User login
OTC cannabidiol products tied to improved pain, sleep, anxiety
Interim findings from Advancing CBD Education and Science, a 100% virtual, open label, randomized, controlled trial, show study participants experienced various degrees of “clinically meaningful” improvements in sleep quality, anxiety, and pain.
“ACES is the largest clinical trial ever conducted on commercially available CBD products and provides first-of-its-kind real world evidence into what conditions users may experience benefit from CBD usage, whether these benefits are clinically meaningful, what attributes of CBD products may impact health outcomes, and what side effects may occur,” study coinvestigator Jessica Saleska, PhD, MPH, director of research at Radicle Science, the company that conducted the study, told this news organization.
Scant evidence
Despite the growing market size of commercially available CBD products “there is still scant data on the effectiveness of over-the-counter cannabinoid products due to the cost, speed, and scale limitations of the current approach to scientific research,” Jeff Chen, MD, MBA, cofounder and CEO of Radicle Science, told this news organization.
One of the study’s goals, said Ethan Russo, MD, a neurologist, founder/CEO of CReDO Science, and scientific adviser for Radicle, is to help consumers make informed decisions before purchasing and using commercially available oral CBD products.
Designed to eliminate all physical infrastructure, which minimizes costs and facilitates faster execution, ACES was conducted much like a phase 4 clinical trial, collating real-world data gathered over 4 weeks.
“The process that Radicle scientists [have] advanced is sort of a crowdsourcing approach to doing clinical science,” Dr. Russo said. “Hopefully, there is going to be a considerable amount of data generated that [will] affect people’s buying options.”
The study also aimed to evaluate product attributes, including composition, mode of use, dosage, dosage timing and frequency, and their correlation to degrees of outcomes.
Dr. Russo explained why product composition is an important factor, especially when dealing with CBD. “What happens with any given [CBD] preparation is going to be totally a function of other components, if any.
“For example, there’s this mistaken notion that cannabidiol is sedating; it is not. Pure cannabidiol is stimulating in low and moderate amounts. Where the confusion has arisen is that the early chemovars containing cannabidiol were also predominant in myrcene, the sedating terpene, [thereby] creating this misimpression that it is good for sleep,” he added.
However, CBD might also affect sleep by reducing anxiety that interferes with it. “What’s clear is that cannabidiol is an antianxiety agent, if you have a sufficient dose,” Dr. Russo said.
The 4-week study included 2,704 participants aged 21 years and older, self-reporting anxiety, chronic pain, or sleep disturbances as a primary reason for taking CBD. Study participants were randomly assigned to receive 1 of 13 commercially available oral CBD extracts.
Participants were allocated to 1 of 14 cohorts, comprising 13 treatment groups with 208 participants each who received a single CBD product, or a wait-list control group of 296 participants who received product at the study’s end.
The primary outcome focused on “clinically meaningful” changes, which were defined as “distinct and palpable improvements in quality of life through improvements in respective health outcomes.”
Secondary outcomes included changes in sleep, anxiety, and pain based on several validated indices, including the PROMIS (Patient-Reported Outcome Measurement Information System) Sleep Short Form; the PROMIS Anxiety Scale; the Patient Global Impression of Change; the Pain, Enjoyment, General Activity scale; and the General Anxiety Disorder–7 scale.
The interim study results are promising, with participants reporting, on average, a 71% improvement in well-being. Additionally, 63% reported clinically meaningful improvements in anxiety, and 61% in sleep quality. The CBD products provided smaller benefits in pain management, with less than half (47%) experiencing meaningful improvements.
In addition to improvement in sleep, pain, and anxiety, these data highlight how rapidly benefits occurred; most were realized during the first week of the study, with up to 61% of treatment group participants reporting a therapeutic effect within 1-4 hours of taking their assigned product.
Overcoming the placebo effect
Commenting on the research, Justin Strickland, PhD, an assistant professor of psychiatry and behavioral sciences at Johns Hopkins University, Baltimore, who was not involved in the research, said without knowing a lot about the pharmacology of the products being tested, early dramatic improvements in these measures, such as sleep impairment, are common.
“There are some data to suggest that there is an expectancy effect when we talk about the therapeutic benefit of cannabinoid products, (i.e., when someone has the expectation that they are going to experience a stronger effect) but this is true of any drug in an open label trial,” Dr. Strickland added.
Dr. Russo took the point a step further. “It’s getting near impossible to look at cannabinoid compounds, even with randomized, controlled trials because of the burgeoning placebo responses. When you couple it with the fact that consumers have the mistaken notion that cannabis-based drugs are miraculous, the expectations are so high that everyone thinks that they’re on the real stuff, even if it’s a placebo group.”
Still, both Dr. Strickland and Dr. Russo highlighted the fact that ACES mirrors real-world experience, which will they hope will inform the use of CBD and CBD-based preparations moving forward. By removing certain barriers like institutional bureaucracy or federal funding restrictions inherent to more traditional randomized controlled trial design, ACES might provide data that bridge the gap between efficacy and effectiveness.
ACES was funded by Radicle Science. Dr. Chen is cofounder and CEO of Radicle Science. Dr. Russo and Dr. Strickland disclosed no relevant financial relationships.
A version of this article first appeared on Medscape.com.
Interim findings from Advancing CBD Education and Science, a 100% virtual, open label, randomized, controlled trial, show study participants experienced various degrees of “clinically meaningful” improvements in sleep quality, anxiety, and pain.
“ACES is the largest clinical trial ever conducted on commercially available CBD products and provides first-of-its-kind real world evidence into what conditions users may experience benefit from CBD usage, whether these benefits are clinically meaningful, what attributes of CBD products may impact health outcomes, and what side effects may occur,” study coinvestigator Jessica Saleska, PhD, MPH, director of research at Radicle Science, the company that conducted the study, told this news organization.
Scant evidence
Despite the growing market size of commercially available CBD products “there is still scant data on the effectiveness of over-the-counter cannabinoid products due to the cost, speed, and scale limitations of the current approach to scientific research,” Jeff Chen, MD, MBA, cofounder and CEO of Radicle Science, told this news organization.
One of the study’s goals, said Ethan Russo, MD, a neurologist, founder/CEO of CReDO Science, and scientific adviser for Radicle, is to help consumers make informed decisions before purchasing and using commercially available oral CBD products.
Designed to eliminate all physical infrastructure, which minimizes costs and facilitates faster execution, ACES was conducted much like a phase 4 clinical trial, collating real-world data gathered over 4 weeks.
“The process that Radicle scientists [have] advanced is sort of a crowdsourcing approach to doing clinical science,” Dr. Russo said. “Hopefully, there is going to be a considerable amount of data generated that [will] affect people’s buying options.”
The study also aimed to evaluate product attributes, including composition, mode of use, dosage, dosage timing and frequency, and their correlation to degrees of outcomes.
Dr. Russo explained why product composition is an important factor, especially when dealing with CBD. “What happens with any given [CBD] preparation is going to be totally a function of other components, if any.
“For example, there’s this mistaken notion that cannabidiol is sedating; it is not. Pure cannabidiol is stimulating in low and moderate amounts. Where the confusion has arisen is that the early chemovars containing cannabidiol were also predominant in myrcene, the sedating terpene, [thereby] creating this misimpression that it is good for sleep,” he added.
However, CBD might also affect sleep by reducing anxiety that interferes with it. “What’s clear is that cannabidiol is an antianxiety agent, if you have a sufficient dose,” Dr. Russo said.
The 4-week study included 2,704 participants aged 21 years and older, self-reporting anxiety, chronic pain, or sleep disturbances as a primary reason for taking CBD. Study participants were randomly assigned to receive 1 of 13 commercially available oral CBD extracts.
Participants were allocated to 1 of 14 cohorts, comprising 13 treatment groups with 208 participants each who received a single CBD product, or a wait-list control group of 296 participants who received product at the study’s end.
The primary outcome focused on “clinically meaningful” changes, which were defined as “distinct and palpable improvements in quality of life through improvements in respective health outcomes.”
Secondary outcomes included changes in sleep, anxiety, and pain based on several validated indices, including the PROMIS (Patient-Reported Outcome Measurement Information System) Sleep Short Form; the PROMIS Anxiety Scale; the Patient Global Impression of Change; the Pain, Enjoyment, General Activity scale; and the General Anxiety Disorder–7 scale.
The interim study results are promising, with participants reporting, on average, a 71% improvement in well-being. Additionally, 63% reported clinically meaningful improvements in anxiety, and 61% in sleep quality. The CBD products provided smaller benefits in pain management, with less than half (47%) experiencing meaningful improvements.
In addition to improvement in sleep, pain, and anxiety, these data highlight how rapidly benefits occurred; most were realized during the first week of the study, with up to 61% of treatment group participants reporting a therapeutic effect within 1-4 hours of taking their assigned product.
Overcoming the placebo effect
Commenting on the research, Justin Strickland, PhD, an assistant professor of psychiatry and behavioral sciences at Johns Hopkins University, Baltimore, who was not involved in the research, said without knowing a lot about the pharmacology of the products being tested, early dramatic improvements in these measures, such as sleep impairment, are common.
“There are some data to suggest that there is an expectancy effect when we talk about the therapeutic benefit of cannabinoid products, (i.e., when someone has the expectation that they are going to experience a stronger effect) but this is true of any drug in an open label trial,” Dr. Strickland added.
Dr. Russo took the point a step further. “It’s getting near impossible to look at cannabinoid compounds, even with randomized, controlled trials because of the burgeoning placebo responses. When you couple it with the fact that consumers have the mistaken notion that cannabis-based drugs are miraculous, the expectations are so high that everyone thinks that they’re on the real stuff, even if it’s a placebo group.”
Still, both Dr. Strickland and Dr. Russo highlighted the fact that ACES mirrors real-world experience, which will they hope will inform the use of CBD and CBD-based preparations moving forward. By removing certain barriers like institutional bureaucracy or federal funding restrictions inherent to more traditional randomized controlled trial design, ACES might provide data that bridge the gap between efficacy and effectiveness.
ACES was funded by Radicle Science. Dr. Chen is cofounder and CEO of Radicle Science. Dr. Russo and Dr. Strickland disclosed no relevant financial relationships.
A version of this article first appeared on Medscape.com.
Interim findings from Advancing CBD Education and Science, a 100% virtual, open label, randomized, controlled trial, show study participants experienced various degrees of “clinically meaningful” improvements in sleep quality, anxiety, and pain.
“ACES is the largest clinical trial ever conducted on commercially available CBD products and provides first-of-its-kind real world evidence into what conditions users may experience benefit from CBD usage, whether these benefits are clinically meaningful, what attributes of CBD products may impact health outcomes, and what side effects may occur,” study coinvestigator Jessica Saleska, PhD, MPH, director of research at Radicle Science, the company that conducted the study, told this news organization.
Scant evidence
Despite the growing market size of commercially available CBD products “there is still scant data on the effectiveness of over-the-counter cannabinoid products due to the cost, speed, and scale limitations of the current approach to scientific research,” Jeff Chen, MD, MBA, cofounder and CEO of Radicle Science, told this news organization.
One of the study’s goals, said Ethan Russo, MD, a neurologist, founder/CEO of CReDO Science, and scientific adviser for Radicle, is to help consumers make informed decisions before purchasing and using commercially available oral CBD products.
Designed to eliminate all physical infrastructure, which minimizes costs and facilitates faster execution, ACES was conducted much like a phase 4 clinical trial, collating real-world data gathered over 4 weeks.
“The process that Radicle scientists [have] advanced is sort of a crowdsourcing approach to doing clinical science,” Dr. Russo said. “Hopefully, there is going to be a considerable amount of data generated that [will] affect people’s buying options.”
The study also aimed to evaluate product attributes, including composition, mode of use, dosage, dosage timing and frequency, and their correlation to degrees of outcomes.
Dr. Russo explained why product composition is an important factor, especially when dealing with CBD. “What happens with any given [CBD] preparation is going to be totally a function of other components, if any.
“For example, there’s this mistaken notion that cannabidiol is sedating; it is not. Pure cannabidiol is stimulating in low and moderate amounts. Where the confusion has arisen is that the early chemovars containing cannabidiol were also predominant in myrcene, the sedating terpene, [thereby] creating this misimpression that it is good for sleep,” he added.
However, CBD might also affect sleep by reducing anxiety that interferes with it. “What’s clear is that cannabidiol is an antianxiety agent, if you have a sufficient dose,” Dr. Russo said.
The 4-week study included 2,704 participants aged 21 years and older, self-reporting anxiety, chronic pain, or sleep disturbances as a primary reason for taking CBD. Study participants were randomly assigned to receive 1 of 13 commercially available oral CBD extracts.
Participants were allocated to 1 of 14 cohorts, comprising 13 treatment groups with 208 participants each who received a single CBD product, or a wait-list control group of 296 participants who received product at the study’s end.
The primary outcome focused on “clinically meaningful” changes, which were defined as “distinct and palpable improvements in quality of life through improvements in respective health outcomes.”
Secondary outcomes included changes in sleep, anxiety, and pain based on several validated indices, including the PROMIS (Patient-Reported Outcome Measurement Information System) Sleep Short Form; the PROMIS Anxiety Scale; the Patient Global Impression of Change; the Pain, Enjoyment, General Activity scale; and the General Anxiety Disorder–7 scale.
The interim study results are promising, with participants reporting, on average, a 71% improvement in well-being. Additionally, 63% reported clinically meaningful improvements in anxiety, and 61% in sleep quality. The CBD products provided smaller benefits in pain management, with less than half (47%) experiencing meaningful improvements.
In addition to improvement in sleep, pain, and anxiety, these data highlight how rapidly benefits occurred; most were realized during the first week of the study, with up to 61% of treatment group participants reporting a therapeutic effect within 1-4 hours of taking their assigned product.
Overcoming the placebo effect
Commenting on the research, Justin Strickland, PhD, an assistant professor of psychiatry and behavioral sciences at Johns Hopkins University, Baltimore, who was not involved in the research, said without knowing a lot about the pharmacology of the products being tested, early dramatic improvements in these measures, such as sleep impairment, are common.
“There are some data to suggest that there is an expectancy effect when we talk about the therapeutic benefit of cannabinoid products, (i.e., when someone has the expectation that they are going to experience a stronger effect) but this is true of any drug in an open label trial,” Dr. Strickland added.
Dr. Russo took the point a step further. “It’s getting near impossible to look at cannabinoid compounds, even with randomized, controlled trials because of the burgeoning placebo responses. When you couple it with the fact that consumers have the mistaken notion that cannabis-based drugs are miraculous, the expectations are so high that everyone thinks that they’re on the real stuff, even if it’s a placebo group.”
Still, both Dr. Strickland and Dr. Russo highlighted the fact that ACES mirrors real-world experience, which will they hope will inform the use of CBD and CBD-based preparations moving forward. By removing certain barriers like institutional bureaucracy or federal funding restrictions inherent to more traditional randomized controlled trial design, ACES might provide data that bridge the gap between efficacy and effectiveness.
ACES was funded by Radicle Science. Dr. Chen is cofounder and CEO of Radicle Science. Dr. Russo and Dr. Strickland disclosed no relevant financial relationships.
A version of this article first appeared on Medscape.com.
Clinician experience, life stressors drive HIV adherence, retention in new patients
A novel twist on the concept of “meeting people where they are” may hold the key to retaining new HIV patients, and even bringing the elusive goal of ending the AIDS epidemic a bit closer. While the concept commonly refers to community outreach and engagement, understanding patient experiences and expectations and personal life stressors in the actual clinic setting may improve overall outcomes, according to new research.
In fact,
“Medical science is not necessarily [at the forefront] of where we want to focus our efforts right now,” Emmanuel Guajardo, MD, lead study author and instructor of infectious diseases at Baylor College of Medicine, Houston, told this news organization.
Rather, “we need to focus on retention in care and adherence to medications. Doubling down on these efforts could really go a long way toward ending the HIV epidemic,” he said.
Study findings were published online Jan. 5, 2022, in AIDS and Behavior.
First time’s a charm
A total of 450 patients attending an HIV clinic in Houston were asked to complete a postvisit survey detailing their experience with the HIV clinician, as well as personal life stressors in the preceding 6 months. Study participants were predominantly non-Hispanic Black (54.2%) or Hispanic (30.7%) and mostly men who have sex with men (MSM), populations that mimic the patients seen at Dr. Guajardo’s clinic. Patients were given the option of survey completion while awaiting discharge, within 2 weeks at the clinic, or (as a last resort) by phone.
Overall scores were based on a composite of validated scales: patient experience scores were defined dichotomously (best experience, most positive experience vs. not the best experience), and life stressor events (death, relationship, economic) were assigned weighted scores based on life change impact (for example, death of a spouse received a score of 100 while moved/changed living location was assigned a score of 25).
“We found that patients who reported better initial experiences with their provider at the first visit were less likely to be lost to follow-up at 6 and 12 months,” explained Dr. Guajardo. “Having fewer life stressors at the first visit [was] also [protective].”
At 6 months, mean overall patient experience scores were 8.60 for those LTFU versus and 8.98 for those not LTFU (P = .011); corresponding mean scores at 12 months were 8.43 and 8.98 respectively (P = .001).
For the dichotomized scoring, patients reporting the best experience with the health care professional were significantly less likely to be LTFU at 6 months (adjusted odd ratio, 0.866; P = .038) and 12 months (aOR, 1.263; P = .029) versus those not reporting the best experience.
Mean life change scores appeared to portend patient drop-off; patients reporting more stressful life events were likelier to be LTFU at 6 months (mean life change score, 129 vs. 100 for those retained in care) and at 12 months (126 vs. 101).
Corresponding multivariate logistic regression models controlling for age, baseline CD4 cell count less than 200, and diagnosis of at least 3 months showed that patients with higher life stressor burdens were significantly more likely to be LTFU at both 6 months (aOR, 1.232, P = .037) and 12 months (aOR, 1.263, P = .029).
Approach matters
“The [study] really hits the nail on the head in terms of identifying a couple of these very salient issues that affect people’s care, especially concerning HIV,” Philip A. Chan, MD, infectious disease specialist and associate professor of medicine at Brown University, Providence, R.I, told this news organization.
“It highlights things that we see on the ground that can interfere with HIV care or [pre-exposure prophylaxis] care, just health care in general, certainly one’s relationship with the physician or provider, and also, you know, real-life stressors,” said Dr. Chan, who was not involved with the study.
Relationship building is especially important for historically underserved populations, a point that’s hardly lost on either Dr. Chan or Dr. Guajardo, who both pointed to higher levels of mistrust among certain patient populations because of their mistreatment by the health care system. The answer? Let the patient lead the initial discussion, allow them to feel comfortable and participate in their care in ways that are most beneficial to them.
“There’s so much miscommunication, misunderstanding, and stigma related to HIV out in the community. So, it’s important to really open the floor for whatever they want to talk about first, before I push any agenda on a new patient.” Dr. Guajardo said. Thereafter, he relies on open-ended questions such as ‘tell me about your sexual partners?’ or ‘what sort of sexual practices do you engage in?’
“At the end of the day, you just need someone dedicated, who can be respectful and listening and caring, and dedicate time to patients to help keep them in care, to listen, and to navigate our incredibly, incredibly complex health care system,” Dr. Chan added.
This study was partly supported by use of the facilities and resources of the Houston Veterans Affairs Center for Innovations in Quality, Effectiveness, and Safety and Harris Health System. Support for the study was also provided by the National Institute of Mental Health and the University of Texas MD Anderson Foundation Chair at Baylor College of Medicine. Dr. Guajardo and Dr. Chan disclosed no relevant financial relationships.
A version of this article first appeared on Medscape.com.
A novel twist on the concept of “meeting people where they are” may hold the key to retaining new HIV patients, and even bringing the elusive goal of ending the AIDS epidemic a bit closer. While the concept commonly refers to community outreach and engagement, understanding patient experiences and expectations and personal life stressors in the actual clinic setting may improve overall outcomes, according to new research.
In fact,
“Medical science is not necessarily [at the forefront] of where we want to focus our efforts right now,” Emmanuel Guajardo, MD, lead study author and instructor of infectious diseases at Baylor College of Medicine, Houston, told this news organization.
Rather, “we need to focus on retention in care and adherence to medications. Doubling down on these efforts could really go a long way toward ending the HIV epidemic,” he said.
Study findings were published online Jan. 5, 2022, in AIDS and Behavior.
First time’s a charm
A total of 450 patients attending an HIV clinic in Houston were asked to complete a postvisit survey detailing their experience with the HIV clinician, as well as personal life stressors in the preceding 6 months. Study participants were predominantly non-Hispanic Black (54.2%) or Hispanic (30.7%) and mostly men who have sex with men (MSM), populations that mimic the patients seen at Dr. Guajardo’s clinic. Patients were given the option of survey completion while awaiting discharge, within 2 weeks at the clinic, or (as a last resort) by phone.
Overall scores were based on a composite of validated scales: patient experience scores were defined dichotomously (best experience, most positive experience vs. not the best experience), and life stressor events (death, relationship, economic) were assigned weighted scores based on life change impact (for example, death of a spouse received a score of 100 while moved/changed living location was assigned a score of 25).
“We found that patients who reported better initial experiences with their provider at the first visit were less likely to be lost to follow-up at 6 and 12 months,” explained Dr. Guajardo. “Having fewer life stressors at the first visit [was] also [protective].”
At 6 months, mean overall patient experience scores were 8.60 for those LTFU versus and 8.98 for those not LTFU (P = .011); corresponding mean scores at 12 months were 8.43 and 8.98 respectively (P = .001).
For the dichotomized scoring, patients reporting the best experience with the health care professional were significantly less likely to be LTFU at 6 months (adjusted odd ratio, 0.866; P = .038) and 12 months (aOR, 1.263; P = .029) versus those not reporting the best experience.
Mean life change scores appeared to portend patient drop-off; patients reporting more stressful life events were likelier to be LTFU at 6 months (mean life change score, 129 vs. 100 for those retained in care) and at 12 months (126 vs. 101).
Corresponding multivariate logistic regression models controlling for age, baseline CD4 cell count less than 200, and diagnosis of at least 3 months showed that patients with higher life stressor burdens were significantly more likely to be LTFU at both 6 months (aOR, 1.232, P = .037) and 12 months (aOR, 1.263, P = .029).
Approach matters
“The [study] really hits the nail on the head in terms of identifying a couple of these very salient issues that affect people’s care, especially concerning HIV,” Philip A. Chan, MD, infectious disease specialist and associate professor of medicine at Brown University, Providence, R.I, told this news organization.
“It highlights things that we see on the ground that can interfere with HIV care or [pre-exposure prophylaxis] care, just health care in general, certainly one’s relationship with the physician or provider, and also, you know, real-life stressors,” said Dr. Chan, who was not involved with the study.
Relationship building is especially important for historically underserved populations, a point that’s hardly lost on either Dr. Chan or Dr. Guajardo, who both pointed to higher levels of mistrust among certain patient populations because of their mistreatment by the health care system. The answer? Let the patient lead the initial discussion, allow them to feel comfortable and participate in their care in ways that are most beneficial to them.
“There’s so much miscommunication, misunderstanding, and stigma related to HIV out in the community. So, it’s important to really open the floor for whatever they want to talk about first, before I push any agenda on a new patient.” Dr. Guajardo said. Thereafter, he relies on open-ended questions such as ‘tell me about your sexual partners?’ or ‘what sort of sexual practices do you engage in?’
“At the end of the day, you just need someone dedicated, who can be respectful and listening and caring, and dedicate time to patients to help keep them in care, to listen, and to navigate our incredibly, incredibly complex health care system,” Dr. Chan added.
This study was partly supported by use of the facilities and resources of the Houston Veterans Affairs Center for Innovations in Quality, Effectiveness, and Safety and Harris Health System. Support for the study was also provided by the National Institute of Mental Health and the University of Texas MD Anderson Foundation Chair at Baylor College of Medicine. Dr. Guajardo and Dr. Chan disclosed no relevant financial relationships.
A version of this article first appeared on Medscape.com.
A novel twist on the concept of “meeting people where they are” may hold the key to retaining new HIV patients, and even bringing the elusive goal of ending the AIDS epidemic a bit closer. While the concept commonly refers to community outreach and engagement, understanding patient experiences and expectations and personal life stressors in the actual clinic setting may improve overall outcomes, according to new research.
In fact,
“Medical science is not necessarily [at the forefront] of where we want to focus our efforts right now,” Emmanuel Guajardo, MD, lead study author and instructor of infectious diseases at Baylor College of Medicine, Houston, told this news organization.
Rather, “we need to focus on retention in care and adherence to medications. Doubling down on these efforts could really go a long way toward ending the HIV epidemic,” he said.
Study findings were published online Jan. 5, 2022, in AIDS and Behavior.
First time’s a charm
A total of 450 patients attending an HIV clinic in Houston were asked to complete a postvisit survey detailing their experience with the HIV clinician, as well as personal life stressors in the preceding 6 months. Study participants were predominantly non-Hispanic Black (54.2%) or Hispanic (30.7%) and mostly men who have sex with men (MSM), populations that mimic the patients seen at Dr. Guajardo’s clinic. Patients were given the option of survey completion while awaiting discharge, within 2 weeks at the clinic, or (as a last resort) by phone.
Overall scores were based on a composite of validated scales: patient experience scores were defined dichotomously (best experience, most positive experience vs. not the best experience), and life stressor events (death, relationship, economic) were assigned weighted scores based on life change impact (for example, death of a spouse received a score of 100 while moved/changed living location was assigned a score of 25).
“We found that patients who reported better initial experiences with their provider at the first visit were less likely to be lost to follow-up at 6 and 12 months,” explained Dr. Guajardo. “Having fewer life stressors at the first visit [was] also [protective].”
At 6 months, mean overall patient experience scores were 8.60 for those LTFU versus and 8.98 for those not LTFU (P = .011); corresponding mean scores at 12 months were 8.43 and 8.98 respectively (P = .001).
For the dichotomized scoring, patients reporting the best experience with the health care professional were significantly less likely to be LTFU at 6 months (adjusted odd ratio, 0.866; P = .038) and 12 months (aOR, 1.263; P = .029) versus those not reporting the best experience.
Mean life change scores appeared to portend patient drop-off; patients reporting more stressful life events were likelier to be LTFU at 6 months (mean life change score, 129 vs. 100 for those retained in care) and at 12 months (126 vs. 101).
Corresponding multivariate logistic regression models controlling for age, baseline CD4 cell count less than 200, and diagnosis of at least 3 months showed that patients with higher life stressor burdens were significantly more likely to be LTFU at both 6 months (aOR, 1.232, P = .037) and 12 months (aOR, 1.263, P = .029).
Approach matters
“The [study] really hits the nail on the head in terms of identifying a couple of these very salient issues that affect people’s care, especially concerning HIV,” Philip A. Chan, MD, infectious disease specialist and associate professor of medicine at Brown University, Providence, R.I, told this news organization.
“It highlights things that we see on the ground that can interfere with HIV care or [pre-exposure prophylaxis] care, just health care in general, certainly one’s relationship with the physician or provider, and also, you know, real-life stressors,” said Dr. Chan, who was not involved with the study.
Relationship building is especially important for historically underserved populations, a point that’s hardly lost on either Dr. Chan or Dr. Guajardo, who both pointed to higher levels of mistrust among certain patient populations because of their mistreatment by the health care system. The answer? Let the patient lead the initial discussion, allow them to feel comfortable and participate in their care in ways that are most beneficial to them.
“There’s so much miscommunication, misunderstanding, and stigma related to HIV out in the community. So, it’s important to really open the floor for whatever they want to talk about first, before I push any agenda on a new patient.” Dr. Guajardo said. Thereafter, he relies on open-ended questions such as ‘tell me about your sexual partners?’ or ‘what sort of sexual practices do you engage in?’
“At the end of the day, you just need someone dedicated, who can be respectful and listening and caring, and dedicate time to patients to help keep them in care, to listen, and to navigate our incredibly, incredibly complex health care system,” Dr. Chan added.
This study was partly supported by use of the facilities and resources of the Houston Veterans Affairs Center for Innovations in Quality, Effectiveness, and Safety and Harris Health System. Support for the study was also provided by the National Institute of Mental Health and the University of Texas MD Anderson Foundation Chair at Baylor College of Medicine. Dr. Guajardo and Dr. Chan disclosed no relevant financial relationships.
A version of this article first appeared on Medscape.com.
FROM AIDS AND BEHAVIOR
FDA approves cabotegravir LA; New HIV PrEP option fills an important gap
SILVER SPRING, MD – .
The priority review approval was based on phase 2b-3 clinical trial data submitted to the agency this past August, after the study was stopped early due to encouraging efficacy results of the first pre-planned interim end-point analysis.
“Although TDF-FTC PrEP could be almost astoundingly effective in preventing HIV acquisition across populations and risk exposures, the adherence to the daily protocols was really challenging and difficult to attain initially and to maintain for some of our most vulnerable populations,” Raphael Landovitz, MD, MDC, lead study investigator and co-director of The Center for HIV Identification, Prevention, and Treatment Services at UCLA, Los Angeles, told this news organization.
Dr. Landovitz noted that population level benefits observed with PrEP were limited to people who were highly engaged in health care and well resourced, but the same benefits were not observed in the most vulnerable, highest-risk populations.
“The idea was, is there anything that we can do to improve ... choices for different options, some of which – like long-acting agents – would remove the obligation to adhere to daily prescribing or a post-coital and be more discreet,” he said.
Data demonstrated superiority versus TDF-FTC
Details of the prospective, phase 2b-3 randomized, double-blind, double-dummy, active-controlled trial among 4,566 cisgender MSM (men who have sex with men) and transgender women highlighted the superiority of CAB 600 mg intramuscularly versus placebo or active TDF-FTC (300 mg/200 mg), with CAB-LA reducing HIV infection risk by 66%. These results were published August 11 in the New England Journal of Medicine and previously reported by this news organization.
Investigators identified HIV infections in 57 participants (including 52 who acquired HIV infections after enrollment). The hazard ratio for incident HIV infection versus TDG-FTC was 0.34, P < .001. Notably, effects were consistent across prespecified subgroups and populations.
Additionally, integrase strand-transfer inhibitor (INSTI) resistance mutations were detected in 1 of 4 of baseline HIV infection cases among CAB participants, while 2 of 39 incident infections in TDF-FTC participants occurred despite drug concentrations indicating good PrEP adherence.
Adverse events, breakthrough infections, and other important considerations
Because the trial was halted early, long-term safety data were lacking, thereby prompting investigators to launch an ongoing, open-label extension. In the initial trial, injection site reactions were reported in 81.4% (1,724) of CAB participants, most beginning a median of 1 day (IQR 0-2 days) post-injection, mild to moderate in severity (60.8% pain, 23.7% tenderness), and lasting a median of 3 days (IQR 2-6 days). In comparison, injection site reactions were reported in 31.3% of TDF-FTC participants (who, incidentally, received at least one placebo injection).
Severe adverse events (grade 3 or higher) were similar between CAB and TDF-FTC groups, They consisted mostly of an increase in creatine kinase level (14.2% with CAB vs. 13.5% with TDF-FTC) and a decrease in creatinine clearance (7.0% with CAB vs. 8.3% with TDF-FTC).
Although weight gain was higher among CAB participants (1.23 kg/year vs. 0.37 kg/year, TDF-FTC participants), most of the differences were observed during the first 40 weeks and were driven by weight loss in the TDF-FDC group. Weight changes were similar (~1 kg/year) thereafter.
Importantly, study participants assigned CAB underwent an oral-tablet, 5-week lead-in phase, which might have contributed to eventual treatment failure.
In a companion piece published Nov. 1 in the Journal of Infectious Diseases, investigators noted that adherence to the oral lead-in was poor in roughly one-third of participants with incident, breakthrough infections. They wrote that the barriers to adherence with daily oral PrEP regimens coupled with the favorable CAB-LA safety profile suggested that “the oral phase before CAB-LA initiation might not be necessary or desirable.”
The question remains as to whether or not strategies entailing viral load or other RNA screening tests at follow-up clinic visits might be warranted.
“It’s one of the biggest sort of ‘what’s next’ questions that’s come out of this study,” Dr. Landovitz said. “We’re now testing the strategy of using viral load or RNA screening at every visit to see if, in fact, we can catch these breakthrough infections earlier and potentially avoid resistance,” he added.
Until more data are available, Dr. Landovitz said that “the guidance for the clinician would be that until you have resistance testing back on someone who breaks through cabotegravir PrEP to use a protease inhibitor-based treatment regimen, at least initially.”
Institutional changes to ensure delivery of injections, tracking, and follow-up to ensure optimal use of long-acting PrEP agents are likely to challenge already overburdened health care systems and may require additional strategies for implementation (for example, pharmacy or at-home administration). Despite these factors, CAB-LA approval is welcome news to clinicians and patients alike.
“We’re constantly searching for new drugs to expand our repertoire of what we can provide patients,” Lina Rosengren-Hovee, MD, MPH, assistant professor of medicine and infectious disease specialist at UNC Health, Chapel Hill, N.C., said in an interview. Dr. Rosengren-Hovee was not involved in the study.
“For folks under 30, the sexual and gender minority, Black, and Latino, they are the ones with the highest need for PrEP, that are in a position that places them at higher risk for HIV. Being able to offer an injectable option is ... a game changer,” she said.
Dr. Rosengren-Hovee reports no relevant financial relationships. Dr. Landovitz has consulting relationships with Gilead, Janssen, Roche, and Cepheus.
A version of this article first appeared on Medscape.com.
SILVER SPRING, MD – .
The priority review approval was based on phase 2b-3 clinical trial data submitted to the agency this past August, after the study was stopped early due to encouraging efficacy results of the first pre-planned interim end-point analysis.
“Although TDF-FTC PrEP could be almost astoundingly effective in preventing HIV acquisition across populations and risk exposures, the adherence to the daily protocols was really challenging and difficult to attain initially and to maintain for some of our most vulnerable populations,” Raphael Landovitz, MD, MDC, lead study investigator and co-director of The Center for HIV Identification, Prevention, and Treatment Services at UCLA, Los Angeles, told this news organization.
Dr. Landovitz noted that population level benefits observed with PrEP were limited to people who were highly engaged in health care and well resourced, but the same benefits were not observed in the most vulnerable, highest-risk populations.
“The idea was, is there anything that we can do to improve ... choices for different options, some of which – like long-acting agents – would remove the obligation to adhere to daily prescribing or a post-coital and be more discreet,” he said.
Data demonstrated superiority versus TDF-FTC
Details of the prospective, phase 2b-3 randomized, double-blind, double-dummy, active-controlled trial among 4,566 cisgender MSM (men who have sex with men) and transgender women highlighted the superiority of CAB 600 mg intramuscularly versus placebo or active TDF-FTC (300 mg/200 mg), with CAB-LA reducing HIV infection risk by 66%. These results were published August 11 in the New England Journal of Medicine and previously reported by this news organization.
Investigators identified HIV infections in 57 participants (including 52 who acquired HIV infections after enrollment). The hazard ratio for incident HIV infection versus TDG-FTC was 0.34, P < .001. Notably, effects were consistent across prespecified subgroups and populations.
Additionally, integrase strand-transfer inhibitor (INSTI) resistance mutations were detected in 1 of 4 of baseline HIV infection cases among CAB participants, while 2 of 39 incident infections in TDF-FTC participants occurred despite drug concentrations indicating good PrEP adherence.
Adverse events, breakthrough infections, and other important considerations
Because the trial was halted early, long-term safety data were lacking, thereby prompting investigators to launch an ongoing, open-label extension. In the initial trial, injection site reactions were reported in 81.4% (1,724) of CAB participants, most beginning a median of 1 day (IQR 0-2 days) post-injection, mild to moderate in severity (60.8% pain, 23.7% tenderness), and lasting a median of 3 days (IQR 2-6 days). In comparison, injection site reactions were reported in 31.3% of TDF-FTC participants (who, incidentally, received at least one placebo injection).
Severe adverse events (grade 3 or higher) were similar between CAB and TDF-FTC groups, They consisted mostly of an increase in creatine kinase level (14.2% with CAB vs. 13.5% with TDF-FTC) and a decrease in creatinine clearance (7.0% with CAB vs. 8.3% with TDF-FTC).
Although weight gain was higher among CAB participants (1.23 kg/year vs. 0.37 kg/year, TDF-FTC participants), most of the differences were observed during the first 40 weeks and were driven by weight loss in the TDF-FDC group. Weight changes were similar (~1 kg/year) thereafter.
Importantly, study participants assigned CAB underwent an oral-tablet, 5-week lead-in phase, which might have contributed to eventual treatment failure.
In a companion piece published Nov. 1 in the Journal of Infectious Diseases, investigators noted that adherence to the oral lead-in was poor in roughly one-third of participants with incident, breakthrough infections. They wrote that the barriers to adherence with daily oral PrEP regimens coupled with the favorable CAB-LA safety profile suggested that “the oral phase before CAB-LA initiation might not be necessary or desirable.”
The question remains as to whether or not strategies entailing viral load or other RNA screening tests at follow-up clinic visits might be warranted.
“It’s one of the biggest sort of ‘what’s next’ questions that’s come out of this study,” Dr. Landovitz said. “We’re now testing the strategy of using viral load or RNA screening at every visit to see if, in fact, we can catch these breakthrough infections earlier and potentially avoid resistance,” he added.
Until more data are available, Dr. Landovitz said that “the guidance for the clinician would be that until you have resistance testing back on someone who breaks through cabotegravir PrEP to use a protease inhibitor-based treatment regimen, at least initially.”
Institutional changes to ensure delivery of injections, tracking, and follow-up to ensure optimal use of long-acting PrEP agents are likely to challenge already overburdened health care systems and may require additional strategies for implementation (for example, pharmacy or at-home administration). Despite these factors, CAB-LA approval is welcome news to clinicians and patients alike.
“We’re constantly searching for new drugs to expand our repertoire of what we can provide patients,” Lina Rosengren-Hovee, MD, MPH, assistant professor of medicine and infectious disease specialist at UNC Health, Chapel Hill, N.C., said in an interview. Dr. Rosengren-Hovee was not involved in the study.
“For folks under 30, the sexual and gender minority, Black, and Latino, they are the ones with the highest need for PrEP, that are in a position that places them at higher risk for HIV. Being able to offer an injectable option is ... a game changer,” she said.
Dr. Rosengren-Hovee reports no relevant financial relationships. Dr. Landovitz has consulting relationships with Gilead, Janssen, Roche, and Cepheus.
A version of this article first appeared on Medscape.com.
SILVER SPRING, MD – .
The priority review approval was based on phase 2b-3 clinical trial data submitted to the agency this past August, after the study was stopped early due to encouraging efficacy results of the first pre-planned interim end-point analysis.
“Although TDF-FTC PrEP could be almost astoundingly effective in preventing HIV acquisition across populations and risk exposures, the adherence to the daily protocols was really challenging and difficult to attain initially and to maintain for some of our most vulnerable populations,” Raphael Landovitz, MD, MDC, lead study investigator and co-director of The Center for HIV Identification, Prevention, and Treatment Services at UCLA, Los Angeles, told this news organization.
Dr. Landovitz noted that population level benefits observed with PrEP were limited to people who were highly engaged in health care and well resourced, but the same benefits were not observed in the most vulnerable, highest-risk populations.
“The idea was, is there anything that we can do to improve ... choices for different options, some of which – like long-acting agents – would remove the obligation to adhere to daily prescribing or a post-coital and be more discreet,” he said.
Data demonstrated superiority versus TDF-FTC
Details of the prospective, phase 2b-3 randomized, double-blind, double-dummy, active-controlled trial among 4,566 cisgender MSM (men who have sex with men) and transgender women highlighted the superiority of CAB 600 mg intramuscularly versus placebo or active TDF-FTC (300 mg/200 mg), with CAB-LA reducing HIV infection risk by 66%. These results were published August 11 in the New England Journal of Medicine and previously reported by this news organization.
Investigators identified HIV infections in 57 participants (including 52 who acquired HIV infections after enrollment). The hazard ratio for incident HIV infection versus TDG-FTC was 0.34, P < .001. Notably, effects were consistent across prespecified subgroups and populations.
Additionally, integrase strand-transfer inhibitor (INSTI) resistance mutations were detected in 1 of 4 of baseline HIV infection cases among CAB participants, while 2 of 39 incident infections in TDF-FTC participants occurred despite drug concentrations indicating good PrEP adherence.
Adverse events, breakthrough infections, and other important considerations
Because the trial was halted early, long-term safety data were lacking, thereby prompting investigators to launch an ongoing, open-label extension. In the initial trial, injection site reactions were reported in 81.4% (1,724) of CAB participants, most beginning a median of 1 day (IQR 0-2 days) post-injection, mild to moderate in severity (60.8% pain, 23.7% tenderness), and lasting a median of 3 days (IQR 2-6 days). In comparison, injection site reactions were reported in 31.3% of TDF-FTC participants (who, incidentally, received at least one placebo injection).
Severe adverse events (grade 3 or higher) were similar between CAB and TDF-FTC groups, They consisted mostly of an increase in creatine kinase level (14.2% with CAB vs. 13.5% with TDF-FTC) and a decrease in creatinine clearance (7.0% with CAB vs. 8.3% with TDF-FTC).
Although weight gain was higher among CAB participants (1.23 kg/year vs. 0.37 kg/year, TDF-FTC participants), most of the differences were observed during the first 40 weeks and were driven by weight loss in the TDF-FDC group. Weight changes were similar (~1 kg/year) thereafter.
Importantly, study participants assigned CAB underwent an oral-tablet, 5-week lead-in phase, which might have contributed to eventual treatment failure.
In a companion piece published Nov. 1 in the Journal of Infectious Diseases, investigators noted that adherence to the oral lead-in was poor in roughly one-third of participants with incident, breakthrough infections. They wrote that the barriers to adherence with daily oral PrEP regimens coupled with the favorable CAB-LA safety profile suggested that “the oral phase before CAB-LA initiation might not be necessary or desirable.”
The question remains as to whether or not strategies entailing viral load or other RNA screening tests at follow-up clinic visits might be warranted.
“It’s one of the biggest sort of ‘what’s next’ questions that’s come out of this study,” Dr. Landovitz said. “We’re now testing the strategy of using viral load or RNA screening at every visit to see if, in fact, we can catch these breakthrough infections earlier and potentially avoid resistance,” he added.
Until more data are available, Dr. Landovitz said that “the guidance for the clinician would be that until you have resistance testing back on someone who breaks through cabotegravir PrEP to use a protease inhibitor-based treatment regimen, at least initially.”
Institutional changes to ensure delivery of injections, tracking, and follow-up to ensure optimal use of long-acting PrEP agents are likely to challenge already overburdened health care systems and may require additional strategies for implementation (for example, pharmacy or at-home administration). Despite these factors, CAB-LA approval is welcome news to clinicians and patients alike.
“We’re constantly searching for new drugs to expand our repertoire of what we can provide patients,” Lina Rosengren-Hovee, MD, MPH, assistant professor of medicine and infectious disease specialist at UNC Health, Chapel Hill, N.C., said in an interview. Dr. Rosengren-Hovee was not involved in the study.
“For folks under 30, the sexual and gender minority, Black, and Latino, they are the ones with the highest need for PrEP, that are in a position that places them at higher risk for HIV. Being able to offer an injectable option is ... a game changer,” she said.
Dr. Rosengren-Hovee reports no relevant financial relationships. Dr. Landovitz has consulting relationships with Gilead, Janssen, Roche, and Cepheus.
A version of this article first appeared on Medscape.com.
Geospatial maps show areas of Africa that need HIV services
Can geospatial mapping fill in the gaps in areas lagging behind in global efforts to end the HIV epidemic?
That’s what Diego Cuadros, PhD, assistant professor of health geography and disease modeling at the University of Cincinnati, set out to learn using geospatial data combined with prevalence data to identify the most underserved areas in Sub-Saharan Africa (SSA) for HIV services.
Study findings, which were published Nov. 24 in PLOS Global Public Health, highlight that as many as 1.5 million people living with HIV (PLHIV) in SSA have more than an hour’s motorized travel time both ways to access care, while roughly 3 million must set aside, at minimum, 30 minutes. When the only mode of transportation is walking, as much as 95.3% of underserved areas are faced with at least 30 minutes travel time.
This is simply the tip of the overall problem, Dr. Cuadros told this news organization.
“We are able to estimate how many people [whose] quality of life is being affected by HIV because they are not on treatment and most probably, HIV incidence is high in those areas. But [it’s not as simple as just] increasing the number of health care facilities,” he said. “We need to find strategies to be able to cover this population.”
Dr. Cuadros also noted that the problem goes both ways. “It’s hard for them to move, and it’s [also] hard to reach them,” he explained.
Mapping care, or lack thereof
Dr. Cuadros and team used two primary sources of data to generate high-resolution maps of underserved SSA areas: estimated number of PLHIV between the ages of 15 and 49 years in 47 SSA countries paired with population density and global map of travel time to the nearest health facility by motorized and nonmotorized (that is, walking) transportation. Combining these data allowed them to then detail the distance from access to care for every 5 km².
The mapping exercise showed that 90.5% of the total territory, in which about 7 million PLHIV resided, had more than 10 minutes motorized travel time to the nearest health care facility, while 74.6% were within 30 minutes, and 58.9% were within 60 minutes. Increases in threshold travel times (from 10 to 60 minutes) corresponded directly to declines in the average proportion of underserved areas (from 80.9% to 42.6%). However, in certain countries like Sudan and Mauritania, 99.4% of the areas were underserved at the 10 minute threshold, while more than 90% were underserved at the 60 minute threshold.
Corresponding rates for nonmotorized access to health services were similar: 88.7% (~17.6 million) PLHIV had 10 minutes walking time to health care services, while 57.8% (~11.5 million) had at least 30 minutes, and 33.0% (~6.6 million), at least 60 minutes. Likewise, as threshold times increased from 10 to 60 minutes, the percentage of affected PLHIV declined (to roughly 50% in two-thirds of the countries). But more than 70% of PLHIV resided in underserved areas in countries like Equatorial Guinea, Eritrea, South Sudan, and Sudan.
Geographical allocation of health service facilities underscores treatment gaps
“We think that most PLHIV live in urban areas or close to urban areas, and most of the health care facilities in Africa are concentrated in those areas. But [roughly 8 million people with HIV] are living in rural areas, and for most, movement is very difficult,” explained Dr. Cuadros, meaning that the majority are not on treatment despite the high incidence of HIV.
Inarguably, the pandemic has interrupted HIV services and treatment substantially on the African continent, further challenging any efforts to translate these study findings into actionable strategies.
“We’ve known for quite a while that distance and travel times and travel expenses are known risks for nonadherence, for lack of access to diagnostics, for people at risk for exposure,” Chris Beyrer, MD, MPH, Desmond M. Tutu Professor of Public Health and Human Rights at the Johns Hopkins Bloomberg School of Public Health, Baltimore, said in an interview. (Dr. Beyrer was not involved in the study.)
“What’s new is the ability to really look at this across geographies and really home in on how many people face very long times and distances for travel. That’s a really important contribution,” he said.
Dr. Cuadros pointed out that these hard-to-reach populations are key to achieving the UNAID’s HIV elimination targets. “We’re going to have these pockets of transmission that are going to be really important for epidemic control,” he explained.
Toward that end, the onus appears to extend well beyond solutions that emphasize difficulty in reaching people from the provider perspective. “There’s quite a lot of what you might want to think of as blaming the victim for when people miss appointments, don’t appear to be adherent, [or] can’t stay reliably suppressed,” said Dr. Beyrer.
“It’s really important for providers in general to include in history and intake how far people have come, what their challenges are with travel, to really pay attention to those issues. Having this elegant analysis, this level of detail, is an important first step,” he added.
Dr. Cuadros has disclosed no relevant financial relationships. Dr. Beyrer reports a consulting agreement with Merck.
A version of this article first appeared on Medscape.com.
Can geospatial mapping fill in the gaps in areas lagging behind in global efforts to end the HIV epidemic?
That’s what Diego Cuadros, PhD, assistant professor of health geography and disease modeling at the University of Cincinnati, set out to learn using geospatial data combined with prevalence data to identify the most underserved areas in Sub-Saharan Africa (SSA) for HIV services.
Study findings, which were published Nov. 24 in PLOS Global Public Health, highlight that as many as 1.5 million people living with HIV (PLHIV) in SSA have more than an hour’s motorized travel time both ways to access care, while roughly 3 million must set aside, at minimum, 30 minutes. When the only mode of transportation is walking, as much as 95.3% of underserved areas are faced with at least 30 minutes travel time.
This is simply the tip of the overall problem, Dr. Cuadros told this news organization.
“We are able to estimate how many people [whose] quality of life is being affected by HIV because they are not on treatment and most probably, HIV incidence is high in those areas. But [it’s not as simple as just] increasing the number of health care facilities,” he said. “We need to find strategies to be able to cover this population.”
Dr. Cuadros also noted that the problem goes both ways. “It’s hard for them to move, and it’s [also] hard to reach them,” he explained.
Mapping care, or lack thereof
Dr. Cuadros and team used two primary sources of data to generate high-resolution maps of underserved SSA areas: estimated number of PLHIV between the ages of 15 and 49 years in 47 SSA countries paired with population density and global map of travel time to the nearest health facility by motorized and nonmotorized (that is, walking) transportation. Combining these data allowed them to then detail the distance from access to care for every 5 km².
The mapping exercise showed that 90.5% of the total territory, in which about 7 million PLHIV resided, had more than 10 minutes motorized travel time to the nearest health care facility, while 74.6% were within 30 minutes, and 58.9% were within 60 minutes. Increases in threshold travel times (from 10 to 60 minutes) corresponded directly to declines in the average proportion of underserved areas (from 80.9% to 42.6%). However, in certain countries like Sudan and Mauritania, 99.4% of the areas were underserved at the 10 minute threshold, while more than 90% were underserved at the 60 minute threshold.
Corresponding rates for nonmotorized access to health services were similar: 88.7% (~17.6 million) PLHIV had 10 minutes walking time to health care services, while 57.8% (~11.5 million) had at least 30 minutes, and 33.0% (~6.6 million), at least 60 minutes. Likewise, as threshold times increased from 10 to 60 minutes, the percentage of affected PLHIV declined (to roughly 50% in two-thirds of the countries). But more than 70% of PLHIV resided in underserved areas in countries like Equatorial Guinea, Eritrea, South Sudan, and Sudan.
Geographical allocation of health service facilities underscores treatment gaps
“We think that most PLHIV live in urban areas or close to urban areas, and most of the health care facilities in Africa are concentrated in those areas. But [roughly 8 million people with HIV] are living in rural areas, and for most, movement is very difficult,” explained Dr. Cuadros, meaning that the majority are not on treatment despite the high incidence of HIV.
Inarguably, the pandemic has interrupted HIV services and treatment substantially on the African continent, further challenging any efforts to translate these study findings into actionable strategies.
“We’ve known for quite a while that distance and travel times and travel expenses are known risks for nonadherence, for lack of access to diagnostics, for people at risk for exposure,” Chris Beyrer, MD, MPH, Desmond M. Tutu Professor of Public Health and Human Rights at the Johns Hopkins Bloomberg School of Public Health, Baltimore, said in an interview. (Dr. Beyrer was not involved in the study.)
“What’s new is the ability to really look at this across geographies and really home in on how many people face very long times and distances for travel. That’s a really important contribution,” he said.
Dr. Cuadros pointed out that these hard-to-reach populations are key to achieving the UNAID’s HIV elimination targets. “We’re going to have these pockets of transmission that are going to be really important for epidemic control,” he explained.
Toward that end, the onus appears to extend well beyond solutions that emphasize difficulty in reaching people from the provider perspective. “There’s quite a lot of what you might want to think of as blaming the victim for when people miss appointments, don’t appear to be adherent, [or] can’t stay reliably suppressed,” said Dr. Beyrer.
“It’s really important for providers in general to include in history and intake how far people have come, what their challenges are with travel, to really pay attention to those issues. Having this elegant analysis, this level of detail, is an important first step,” he added.
Dr. Cuadros has disclosed no relevant financial relationships. Dr. Beyrer reports a consulting agreement with Merck.
A version of this article first appeared on Medscape.com.
Can geospatial mapping fill in the gaps in areas lagging behind in global efforts to end the HIV epidemic?
That’s what Diego Cuadros, PhD, assistant professor of health geography and disease modeling at the University of Cincinnati, set out to learn using geospatial data combined with prevalence data to identify the most underserved areas in Sub-Saharan Africa (SSA) for HIV services.
Study findings, which were published Nov. 24 in PLOS Global Public Health, highlight that as many as 1.5 million people living with HIV (PLHIV) in SSA have more than an hour’s motorized travel time both ways to access care, while roughly 3 million must set aside, at minimum, 30 minutes. When the only mode of transportation is walking, as much as 95.3% of underserved areas are faced with at least 30 minutes travel time.
This is simply the tip of the overall problem, Dr. Cuadros told this news organization.
“We are able to estimate how many people [whose] quality of life is being affected by HIV because they are not on treatment and most probably, HIV incidence is high in those areas. But [it’s not as simple as just] increasing the number of health care facilities,” he said. “We need to find strategies to be able to cover this population.”
Dr. Cuadros also noted that the problem goes both ways. “It’s hard for them to move, and it’s [also] hard to reach them,” he explained.
Mapping care, or lack thereof
Dr. Cuadros and team used two primary sources of data to generate high-resolution maps of underserved SSA areas: estimated number of PLHIV between the ages of 15 and 49 years in 47 SSA countries paired with population density and global map of travel time to the nearest health facility by motorized and nonmotorized (that is, walking) transportation. Combining these data allowed them to then detail the distance from access to care for every 5 km².
The mapping exercise showed that 90.5% of the total territory, in which about 7 million PLHIV resided, had more than 10 minutes motorized travel time to the nearest health care facility, while 74.6% were within 30 minutes, and 58.9% were within 60 minutes. Increases in threshold travel times (from 10 to 60 minutes) corresponded directly to declines in the average proportion of underserved areas (from 80.9% to 42.6%). However, in certain countries like Sudan and Mauritania, 99.4% of the areas were underserved at the 10 minute threshold, while more than 90% were underserved at the 60 minute threshold.
Corresponding rates for nonmotorized access to health services were similar: 88.7% (~17.6 million) PLHIV had 10 minutes walking time to health care services, while 57.8% (~11.5 million) had at least 30 minutes, and 33.0% (~6.6 million), at least 60 minutes. Likewise, as threshold times increased from 10 to 60 minutes, the percentage of affected PLHIV declined (to roughly 50% in two-thirds of the countries). But more than 70% of PLHIV resided in underserved areas in countries like Equatorial Guinea, Eritrea, South Sudan, and Sudan.
Geographical allocation of health service facilities underscores treatment gaps
“We think that most PLHIV live in urban areas or close to urban areas, and most of the health care facilities in Africa are concentrated in those areas. But [roughly 8 million people with HIV] are living in rural areas, and for most, movement is very difficult,” explained Dr. Cuadros, meaning that the majority are not on treatment despite the high incidence of HIV.
Inarguably, the pandemic has interrupted HIV services and treatment substantially on the African continent, further challenging any efforts to translate these study findings into actionable strategies.
“We’ve known for quite a while that distance and travel times and travel expenses are known risks for nonadherence, for lack of access to diagnostics, for people at risk for exposure,” Chris Beyrer, MD, MPH, Desmond M. Tutu Professor of Public Health and Human Rights at the Johns Hopkins Bloomberg School of Public Health, Baltimore, said in an interview. (Dr. Beyrer was not involved in the study.)
“What’s new is the ability to really look at this across geographies and really home in on how many people face very long times and distances for travel. That’s a really important contribution,” he said.
Dr. Cuadros pointed out that these hard-to-reach populations are key to achieving the UNAID’s HIV elimination targets. “We’re going to have these pockets of transmission that are going to be really important for epidemic control,” he explained.
Toward that end, the onus appears to extend well beyond solutions that emphasize difficulty in reaching people from the provider perspective. “There’s quite a lot of what you might want to think of as blaming the victim for when people miss appointments, don’t appear to be adherent, [or] can’t stay reliably suppressed,” said Dr. Beyrer.
“It’s really important for providers in general to include in history and intake how far people have come, what their challenges are with travel, to really pay attention to those issues. Having this elegant analysis, this level of detail, is an important first step,” he added.
Dr. Cuadros has disclosed no relevant financial relationships. Dr. Beyrer reports a consulting agreement with Merck.
A version of this article first appeared on Medscape.com.
HIV prescription mandate controversy reaches the Supreme Court
A firestorm of controversy over access to HIV medications and protection against discriminatory insurance practices has been making its way through U.S. district courts for the past 3 years, pitting HIV patients against pharmacy benefits managers and, ostensibly, the healthcare industry itself.
.
At odds are whether or not mandatory mail-order requirements for specialty medications violate specific provisions of the Patient Protection and Affordable Care Act (ACA) and the Rehabilitation Act of 1973, both of which prohibit discrimination by programs that receive federal funds.
An amicus brief submitted on October 29 by the Center for Health Law and Policy Innovation (CHLPI) of Harvard Law School on behalf of five John Does and a number of medical practitioners and practitioner organizations underscores the degree to which advances in HIV treatment, viral suppression, and care linkage — not to mention the national mandate to end the AIDS epidemic by 2030 — might ultimately be affected.
“We decided to file the brief at the Supreme Court level because we wanted to make sure that the perspectives of people living with HIV, their providers, and advocates were in the record,” Maryanne Tomazic, a clinical instructor at CHLPI, toldthis news organization.
“It’s important for the court to consider why robust access to prescription drug coverage and pharmacy services are so important for people living with HIV, and why it’s not appropriate to compromise access to antiretroviral therapy,” she explained.
A bitter pill, regardless of who swallows it
CVS Pharmacy Inc. v. Doe focuses on a legal concept known as “disparate impact discrimination,” which refers to a policy that appears neutral but unintentionally discriminates against a protected class of people (eg, on the basis of sex, age, or ethnicity).
The Supreme Court’s decision in the case will address a central question: did CVS Pharmacy, Caremark, and Caremark Specialty Pharmacy (“CVS”) discriminate against the respondents by requiring that they obtain specialty medications (including those for HIV) by mail order or drop shipment for pickup, or, alternatively, pay out-of-network prices for these medications at non-CVS pharmacies?
The decision will also address whether the ACA’s inclusion of clause 504 of the Rehabilitation Act, which prohibits protected class discrimination, allows patients to challenge terms and conditions of their healthcare plans, a decision that has broad and far-reaching implications for insurers’ abilities to set plan restrictions and pricing.
A spokesperson for CVS declined to comment when contacted by this news organization but provided a link to an April 9, 2021 SCOTUS blog post about the filing. In its court filing, CVS contended that the program applies to all specialty medications (not just HIV) and simply reflects the cost/complexity of specialty medications.
Not everyone agrees that cost is the most important issue at play. Indeed, a critical take-away for practitioners is how mandated mail-order pharmacy programs can disrupt coordination of care.
“In the traditional model, the physician is talking to the pharmacists [or] talking with the patient, and you have kind of triangular communication model that helps not only the patient stay engaged in care but [also] allows the healthcare provider team to adjust the medication quickly without delay,” said Ms. Tomazic.
The John Doe statements in the original case highlight these concerns. They focus on how mandatory mail orders restrict highly personable relationships with local specialty pharmacists who are familiar with their patients’ medical histories as well as their medication dosing and adjustments and who regularly communicate with the complete care team on the patients’ behalf.
“JOHN DOE THREE and others depend on these types of long standing relationships with local pharmacists to maximize the benefits of HIV/AIDS medications and treat the complex and ever-changing needs of the HIV/AIDS patients,” wrote attorneys in the 2018 class action filing.
Other issues raised by the suit involve the following: privacy with respect to medication pickup; specialty care customer representatives’ lack of understanding and knowledge of HIV medications; incomplete prescription fills; late medication deliveries; exposure of medications to the elements; work and employment interruptions; and restrictions on early fills and reorders, which increase the risk for missed doses and potentially serious health problems, including interruptions in viral suppression and resistance.
Discrimination issues also raised
CHLPI’s amicus joins several others in support of the unique needs of persons with HIV, especially in Black and Hispanic/Latino communities, which are disproportionately affected by HIV.
A press release distributed by the National Association for the Advancement of Colored People Legal Defense and Educational Fund (LDF) reinforces the idea that not only are Black people more likely to have a disability other groups, owing to the country’s legacy of racial inequality, but also that they are likely to encounter unique forms of discrimination and specific barriers to full participation in society, further underscoring the need for disparate impact liability to address unfair policies and practices.
“Inequity in access to resources, including healthcare, further amplifies the instance and persistence of disabilities among Black people,” LDF attorneys wrote in the brief.
“We saw with COVID-19 that [mail-order prescription] programs can serve in a supportive role in access to care,” said Ms. Tomazic. “But we don’t want those programs to be mandated, and we don’t want to forget about communities where these kinds of programs are simply not a viable option,” she said.
Oral arguments in the case begin on December 7. A decision is expected some months later.
No relevant financial relationships have been disclosed.
A version of this article first appeared on Medscape.com.
A firestorm of controversy over access to HIV medications and protection against discriminatory insurance practices has been making its way through U.S. district courts for the past 3 years, pitting HIV patients against pharmacy benefits managers and, ostensibly, the healthcare industry itself.
.
At odds are whether or not mandatory mail-order requirements for specialty medications violate specific provisions of the Patient Protection and Affordable Care Act (ACA) and the Rehabilitation Act of 1973, both of which prohibit discrimination by programs that receive federal funds.
An amicus brief submitted on October 29 by the Center for Health Law and Policy Innovation (CHLPI) of Harvard Law School on behalf of five John Does and a number of medical practitioners and practitioner organizations underscores the degree to which advances in HIV treatment, viral suppression, and care linkage — not to mention the national mandate to end the AIDS epidemic by 2030 — might ultimately be affected.
“We decided to file the brief at the Supreme Court level because we wanted to make sure that the perspectives of people living with HIV, their providers, and advocates were in the record,” Maryanne Tomazic, a clinical instructor at CHLPI, toldthis news organization.
“It’s important for the court to consider why robust access to prescription drug coverage and pharmacy services are so important for people living with HIV, and why it’s not appropriate to compromise access to antiretroviral therapy,” she explained.
A bitter pill, regardless of who swallows it
CVS Pharmacy Inc. v. Doe focuses on a legal concept known as “disparate impact discrimination,” which refers to a policy that appears neutral but unintentionally discriminates against a protected class of people (eg, on the basis of sex, age, or ethnicity).
The Supreme Court’s decision in the case will address a central question: did CVS Pharmacy, Caremark, and Caremark Specialty Pharmacy (“CVS”) discriminate against the respondents by requiring that they obtain specialty medications (including those for HIV) by mail order or drop shipment for pickup, or, alternatively, pay out-of-network prices for these medications at non-CVS pharmacies?
The decision will also address whether the ACA’s inclusion of clause 504 of the Rehabilitation Act, which prohibits protected class discrimination, allows patients to challenge terms and conditions of their healthcare plans, a decision that has broad and far-reaching implications for insurers’ abilities to set plan restrictions and pricing.
A spokesperson for CVS declined to comment when contacted by this news organization but provided a link to an April 9, 2021 SCOTUS blog post about the filing. In its court filing, CVS contended that the program applies to all specialty medications (not just HIV) and simply reflects the cost/complexity of specialty medications.
Not everyone agrees that cost is the most important issue at play. Indeed, a critical take-away for practitioners is how mandated mail-order pharmacy programs can disrupt coordination of care.
“In the traditional model, the physician is talking to the pharmacists [or] talking with the patient, and you have kind of triangular communication model that helps not only the patient stay engaged in care but [also] allows the healthcare provider team to adjust the medication quickly without delay,” said Ms. Tomazic.
The John Doe statements in the original case highlight these concerns. They focus on how mandatory mail orders restrict highly personable relationships with local specialty pharmacists who are familiar with their patients’ medical histories as well as their medication dosing and adjustments and who regularly communicate with the complete care team on the patients’ behalf.
“JOHN DOE THREE and others depend on these types of long standing relationships with local pharmacists to maximize the benefits of HIV/AIDS medications and treat the complex and ever-changing needs of the HIV/AIDS patients,” wrote attorneys in the 2018 class action filing.
Other issues raised by the suit involve the following: privacy with respect to medication pickup; specialty care customer representatives’ lack of understanding and knowledge of HIV medications; incomplete prescription fills; late medication deliveries; exposure of medications to the elements; work and employment interruptions; and restrictions on early fills and reorders, which increase the risk for missed doses and potentially serious health problems, including interruptions in viral suppression and resistance.
Discrimination issues also raised
CHLPI’s amicus joins several others in support of the unique needs of persons with HIV, especially in Black and Hispanic/Latino communities, which are disproportionately affected by HIV.
A press release distributed by the National Association for the Advancement of Colored People Legal Defense and Educational Fund (LDF) reinforces the idea that not only are Black people more likely to have a disability other groups, owing to the country’s legacy of racial inequality, but also that they are likely to encounter unique forms of discrimination and specific barriers to full participation in society, further underscoring the need for disparate impact liability to address unfair policies and practices.
“Inequity in access to resources, including healthcare, further amplifies the instance and persistence of disabilities among Black people,” LDF attorneys wrote in the brief.
“We saw with COVID-19 that [mail-order prescription] programs can serve in a supportive role in access to care,” said Ms. Tomazic. “But we don’t want those programs to be mandated, and we don’t want to forget about communities where these kinds of programs are simply not a viable option,” she said.
Oral arguments in the case begin on December 7. A decision is expected some months later.
No relevant financial relationships have been disclosed.
A version of this article first appeared on Medscape.com.
A firestorm of controversy over access to HIV medications and protection against discriminatory insurance practices has been making its way through U.S. district courts for the past 3 years, pitting HIV patients against pharmacy benefits managers and, ostensibly, the healthcare industry itself.
.
At odds are whether or not mandatory mail-order requirements for specialty medications violate specific provisions of the Patient Protection and Affordable Care Act (ACA) and the Rehabilitation Act of 1973, both of which prohibit discrimination by programs that receive federal funds.
An amicus brief submitted on October 29 by the Center for Health Law and Policy Innovation (CHLPI) of Harvard Law School on behalf of five John Does and a number of medical practitioners and practitioner organizations underscores the degree to which advances in HIV treatment, viral suppression, and care linkage — not to mention the national mandate to end the AIDS epidemic by 2030 — might ultimately be affected.
“We decided to file the brief at the Supreme Court level because we wanted to make sure that the perspectives of people living with HIV, their providers, and advocates were in the record,” Maryanne Tomazic, a clinical instructor at CHLPI, toldthis news organization.
“It’s important for the court to consider why robust access to prescription drug coverage and pharmacy services are so important for people living with HIV, and why it’s not appropriate to compromise access to antiretroviral therapy,” she explained.
A bitter pill, regardless of who swallows it
CVS Pharmacy Inc. v. Doe focuses on a legal concept known as “disparate impact discrimination,” which refers to a policy that appears neutral but unintentionally discriminates against a protected class of people (eg, on the basis of sex, age, or ethnicity).
The Supreme Court’s decision in the case will address a central question: did CVS Pharmacy, Caremark, and Caremark Specialty Pharmacy (“CVS”) discriminate against the respondents by requiring that they obtain specialty medications (including those for HIV) by mail order or drop shipment for pickup, or, alternatively, pay out-of-network prices for these medications at non-CVS pharmacies?
The decision will also address whether the ACA’s inclusion of clause 504 of the Rehabilitation Act, which prohibits protected class discrimination, allows patients to challenge terms and conditions of their healthcare plans, a decision that has broad and far-reaching implications for insurers’ abilities to set plan restrictions and pricing.
A spokesperson for CVS declined to comment when contacted by this news organization but provided a link to an April 9, 2021 SCOTUS blog post about the filing. In its court filing, CVS contended that the program applies to all specialty medications (not just HIV) and simply reflects the cost/complexity of specialty medications.
Not everyone agrees that cost is the most important issue at play. Indeed, a critical take-away for practitioners is how mandated mail-order pharmacy programs can disrupt coordination of care.
“In the traditional model, the physician is talking to the pharmacists [or] talking with the patient, and you have kind of triangular communication model that helps not only the patient stay engaged in care but [also] allows the healthcare provider team to adjust the medication quickly without delay,” said Ms. Tomazic.
The John Doe statements in the original case highlight these concerns. They focus on how mandatory mail orders restrict highly personable relationships with local specialty pharmacists who are familiar with their patients’ medical histories as well as their medication dosing and adjustments and who regularly communicate with the complete care team on the patients’ behalf.
“JOHN DOE THREE and others depend on these types of long standing relationships with local pharmacists to maximize the benefits of HIV/AIDS medications and treat the complex and ever-changing needs of the HIV/AIDS patients,” wrote attorneys in the 2018 class action filing.
Other issues raised by the suit involve the following: privacy with respect to medication pickup; specialty care customer representatives’ lack of understanding and knowledge of HIV medications; incomplete prescription fills; late medication deliveries; exposure of medications to the elements; work and employment interruptions; and restrictions on early fills and reorders, which increase the risk for missed doses and potentially serious health problems, including interruptions in viral suppression and resistance.
Discrimination issues also raised
CHLPI’s amicus joins several others in support of the unique needs of persons with HIV, especially in Black and Hispanic/Latino communities, which are disproportionately affected by HIV.
A press release distributed by the National Association for the Advancement of Colored People Legal Defense and Educational Fund (LDF) reinforces the idea that not only are Black people more likely to have a disability other groups, owing to the country’s legacy of racial inequality, but also that they are likely to encounter unique forms of discrimination and specific barriers to full participation in society, further underscoring the need for disparate impact liability to address unfair policies and practices.
“Inequity in access to resources, including healthcare, further amplifies the instance and persistence of disabilities among Black people,” LDF attorneys wrote in the brief.
“We saw with COVID-19 that [mail-order prescription] programs can serve in a supportive role in access to care,” said Ms. Tomazic. “But we don’t want those programs to be mandated, and we don’t want to forget about communities where these kinds of programs are simply not a viable option,” she said.
Oral arguments in the case begin on December 7. A decision is expected some months later.
No relevant financial relationships have been disclosed.
A version of this article first appeared on Medscape.com.
ANCHOR study findings may usher in new care standards for anal cancer in HIV-infected patients
Can treatment or removal of high-grade squamous intraepithelial lesions (HSIL) reduce the likelihood of developing anal cancer in people living with HIV (PLHIV)?
“In theory, looking for and treating high-grade disease (like we know works in the cervix) is a potential way to prevent anal cancer in high-risk individuals,” Joel Palefsky, MD, lead investigator of the Anal Cancer/HSIL Outcomes Research (ANCHOR) study and founder/director of the University of California, San Francisco’s Anal Neoplasia Clinic, told this news organization. “But we’ve never had any direct evidence that it worked,” he said.
Initial findings from ANCHOR – the first randomized trial to demonstrate that anal cancer can be prevented in high-risk, HIV-infected patients – promise to change that paradigm and may even portend a new standard of care.
Undoubtedly, this is welcome news for the HIV community, who are not only at increased risk for anal HSIL overall, but among whom anal cancer cases have been rising over the past decade. This is especially true for women who are expected to bear a large portion of overall burden of human papillomavirus (HPV)–associated anal squamous cell carcinoma over the next 10 to 20 years.
In the study, 4,446 PLHIV ages 35 and older with precursor anal HSIL were randomly assigned to topical (imiquimod intra-anally, perianally, or both, or fluorouracil) or ablative (infrared coagulation, hyfrecation/electrocautery) treatment, or active surveillance, and followed every 6 months for 5 years. The study population was broadly representative, including men who have sex with men (MSM), women, transgender people, and historically underrepresented minorities, a factor that reinforces the study’s importance in this specific population.
Because the primary endpoint was reached (that is, to determine if HSIL treatment and removal effectively reduces anal cancer incidence in HIV-infected men and women), the Data Safety Board halted accrual and recommended that participants in the surveillance group be offered treatment moving forward. While the investigators are currently working on publication of the results, the study is ongoing.
Still, the ANCHOR study, which is one of the largest malignancy screening studies conducted in PLHIV, has also highlighted significant challenges in how anal cancer is approached in general.
“Anal cancer has many similarities to cervical cancer, where screening for precancerous lesions and treatment have been shown to substantially reduce morbidity and mortality,” said Joseph Sparano, MD, a medical oncologist specializing in HIV and breast cancer at Icahn School of Medicine at Mount Sinai, New York. Dr. Sparano is chair and principal investigator of the AIDS Malignancy Consortium but was not involved in the ANCHOR study.
But, he explained in an interview, “it’s much more difficult and technically challenging to screen for and evaluate the anal canal histology,” noting that
Availability and access to high-resolution anoscopy is limited, said Robert Yarchoan, MD, chief of the HIV and AIDS Malignancy Branch at the National Cancer Institute’s Clinical Cancer Research Division and director of the Office of HIV and AIDS Malignancy (which, incidentally, cosponsored ANCHOR).
“There are relatively few people that do this at this time,” he added in an interview, pointing out that among those who do, most are obstetricians/gynecologists.
A bit of digging into ANCHOR’s backstory revealed that this was a point of contention at the study’s onset. While physicians participating in the study received extensive training in high-resolution anoscopy, ob/gyns were the fastest to achieve competency and/or had the most prior experience, namely because of their experience in cervical cancer screening in women.
But initial objections by the American Board of Obstetricians and Gynecologists (which at the time, insisted that its members only treat women and threatened to remove their certification if they participated in the research), almost threw a wrench into the study’s start, according to a report in The New York Times. While rational minds prevailed and the board reversed its earlier statements, lack of ample training in the procedure may signal future barriers to treatment.
Another challenge lies in how study findings might be applicable to other groups outside of the HIV/AIDS population, such as people with other forms of immunosuppression who have HSIL, or even healthy women or men who are at risk as a result of penetrative/nonpenetrative sexual or nonsexual (for example, vaginal discharge to the anus) contact.
Although he was unable to share specifics at this time, Dr. Palefsky said that when they designed the ANCHOR study, they were aware that “merely showing efficacy wouldn’t necessarily be sufficient for establishing a standard of care, where[as] other pieces of information undoubtedly would be considered by entities that make guidelines” (for example, an examination of adverse events, risks/benefits, and factors that influence quality of life).
“With that in mind, we are doing a quality-of-life study and, in fact, have [collaborated on], developed, and validated what I think is the first anal disease-specific, quality of life instrument,” Dr. Palefsky said. “The work is still ongoing because we did not complete enrollment in the study, but we are continuing it as part of the follow up.”
Study investigators have also collected samples for a biorepository of specimens that will hopefully facilitate a better understanding of the molecular events driving progression from precancer to cancer. “A lot of people with HIV have these high-grade lesions,” Dr. Palefsky said. “If we were able to identify who’s at highest risk of all of them, that would be very important, because we prefer not to treat everybody with high-grade disease,” he noted, adding that the “underlying hope is that the biomarkers we find in the setting will also be relevant for other HPV-related cancers,” especially in women.
Dr. Yarchoan concurred. “One of the challenges is going to be to digest this information and see how to use it to potentially address the growing problem of females with HIV,” he said.
Dr. Palefsky, Dr. Sparano, and Dr. Yarchoan have disclosed no relevant financial relationships.
A version of this article first appeared on Medscape.com.
Can treatment or removal of high-grade squamous intraepithelial lesions (HSIL) reduce the likelihood of developing anal cancer in people living with HIV (PLHIV)?
“In theory, looking for and treating high-grade disease (like we know works in the cervix) is a potential way to prevent anal cancer in high-risk individuals,” Joel Palefsky, MD, lead investigator of the Anal Cancer/HSIL Outcomes Research (ANCHOR) study and founder/director of the University of California, San Francisco’s Anal Neoplasia Clinic, told this news organization. “But we’ve never had any direct evidence that it worked,” he said.
Initial findings from ANCHOR – the first randomized trial to demonstrate that anal cancer can be prevented in high-risk, HIV-infected patients – promise to change that paradigm and may even portend a new standard of care.
Undoubtedly, this is welcome news for the HIV community, who are not only at increased risk for anal HSIL overall, but among whom anal cancer cases have been rising over the past decade. This is especially true for women who are expected to bear a large portion of overall burden of human papillomavirus (HPV)–associated anal squamous cell carcinoma over the next 10 to 20 years.
In the study, 4,446 PLHIV ages 35 and older with precursor anal HSIL were randomly assigned to topical (imiquimod intra-anally, perianally, or both, or fluorouracil) or ablative (infrared coagulation, hyfrecation/electrocautery) treatment, or active surveillance, and followed every 6 months for 5 years. The study population was broadly representative, including men who have sex with men (MSM), women, transgender people, and historically underrepresented minorities, a factor that reinforces the study’s importance in this specific population.
Because the primary endpoint was reached (that is, to determine if HSIL treatment and removal effectively reduces anal cancer incidence in HIV-infected men and women), the Data Safety Board halted accrual and recommended that participants in the surveillance group be offered treatment moving forward. While the investigators are currently working on publication of the results, the study is ongoing.
Still, the ANCHOR study, which is one of the largest malignancy screening studies conducted in PLHIV, has also highlighted significant challenges in how anal cancer is approached in general.
“Anal cancer has many similarities to cervical cancer, where screening for precancerous lesions and treatment have been shown to substantially reduce morbidity and mortality,” said Joseph Sparano, MD, a medical oncologist specializing in HIV and breast cancer at Icahn School of Medicine at Mount Sinai, New York. Dr. Sparano is chair and principal investigator of the AIDS Malignancy Consortium but was not involved in the ANCHOR study.
But, he explained in an interview, “it’s much more difficult and technically challenging to screen for and evaluate the anal canal histology,” noting that
Availability and access to high-resolution anoscopy is limited, said Robert Yarchoan, MD, chief of the HIV and AIDS Malignancy Branch at the National Cancer Institute’s Clinical Cancer Research Division and director of the Office of HIV and AIDS Malignancy (which, incidentally, cosponsored ANCHOR).
“There are relatively few people that do this at this time,” he added in an interview, pointing out that among those who do, most are obstetricians/gynecologists.
A bit of digging into ANCHOR’s backstory revealed that this was a point of contention at the study’s onset. While physicians participating in the study received extensive training in high-resolution anoscopy, ob/gyns were the fastest to achieve competency and/or had the most prior experience, namely because of their experience in cervical cancer screening in women.
But initial objections by the American Board of Obstetricians and Gynecologists (which at the time, insisted that its members only treat women and threatened to remove their certification if they participated in the research), almost threw a wrench into the study’s start, according to a report in The New York Times. While rational minds prevailed and the board reversed its earlier statements, lack of ample training in the procedure may signal future barriers to treatment.
Another challenge lies in how study findings might be applicable to other groups outside of the HIV/AIDS population, such as people with other forms of immunosuppression who have HSIL, or even healthy women or men who are at risk as a result of penetrative/nonpenetrative sexual or nonsexual (for example, vaginal discharge to the anus) contact.
Although he was unable to share specifics at this time, Dr. Palefsky said that when they designed the ANCHOR study, they were aware that “merely showing efficacy wouldn’t necessarily be sufficient for establishing a standard of care, where[as] other pieces of information undoubtedly would be considered by entities that make guidelines” (for example, an examination of adverse events, risks/benefits, and factors that influence quality of life).
“With that in mind, we are doing a quality-of-life study and, in fact, have [collaborated on], developed, and validated what I think is the first anal disease-specific, quality of life instrument,” Dr. Palefsky said. “The work is still ongoing because we did not complete enrollment in the study, but we are continuing it as part of the follow up.”
Study investigators have also collected samples for a biorepository of specimens that will hopefully facilitate a better understanding of the molecular events driving progression from precancer to cancer. “A lot of people with HIV have these high-grade lesions,” Dr. Palefsky said. “If we were able to identify who’s at highest risk of all of them, that would be very important, because we prefer not to treat everybody with high-grade disease,” he noted, adding that the “underlying hope is that the biomarkers we find in the setting will also be relevant for other HPV-related cancers,” especially in women.
Dr. Yarchoan concurred. “One of the challenges is going to be to digest this information and see how to use it to potentially address the growing problem of females with HIV,” he said.
Dr. Palefsky, Dr. Sparano, and Dr. Yarchoan have disclosed no relevant financial relationships.
A version of this article first appeared on Medscape.com.
Can treatment or removal of high-grade squamous intraepithelial lesions (HSIL) reduce the likelihood of developing anal cancer in people living with HIV (PLHIV)?
“In theory, looking for and treating high-grade disease (like we know works in the cervix) is a potential way to prevent anal cancer in high-risk individuals,” Joel Palefsky, MD, lead investigator of the Anal Cancer/HSIL Outcomes Research (ANCHOR) study and founder/director of the University of California, San Francisco’s Anal Neoplasia Clinic, told this news organization. “But we’ve never had any direct evidence that it worked,” he said.
Initial findings from ANCHOR – the first randomized trial to demonstrate that anal cancer can be prevented in high-risk, HIV-infected patients – promise to change that paradigm and may even portend a new standard of care.
Undoubtedly, this is welcome news for the HIV community, who are not only at increased risk for anal HSIL overall, but among whom anal cancer cases have been rising over the past decade. This is especially true for women who are expected to bear a large portion of overall burden of human papillomavirus (HPV)–associated anal squamous cell carcinoma over the next 10 to 20 years.
In the study, 4,446 PLHIV ages 35 and older with precursor anal HSIL were randomly assigned to topical (imiquimod intra-anally, perianally, or both, or fluorouracil) or ablative (infrared coagulation, hyfrecation/electrocautery) treatment, or active surveillance, and followed every 6 months for 5 years. The study population was broadly representative, including men who have sex with men (MSM), women, transgender people, and historically underrepresented minorities, a factor that reinforces the study’s importance in this specific population.
Because the primary endpoint was reached (that is, to determine if HSIL treatment and removal effectively reduces anal cancer incidence in HIV-infected men and women), the Data Safety Board halted accrual and recommended that participants in the surveillance group be offered treatment moving forward. While the investigators are currently working on publication of the results, the study is ongoing.
Still, the ANCHOR study, which is one of the largest malignancy screening studies conducted in PLHIV, has also highlighted significant challenges in how anal cancer is approached in general.
“Anal cancer has many similarities to cervical cancer, where screening for precancerous lesions and treatment have been shown to substantially reduce morbidity and mortality,” said Joseph Sparano, MD, a medical oncologist specializing in HIV and breast cancer at Icahn School of Medicine at Mount Sinai, New York. Dr. Sparano is chair and principal investigator of the AIDS Malignancy Consortium but was not involved in the ANCHOR study.
But, he explained in an interview, “it’s much more difficult and technically challenging to screen for and evaluate the anal canal histology,” noting that
Availability and access to high-resolution anoscopy is limited, said Robert Yarchoan, MD, chief of the HIV and AIDS Malignancy Branch at the National Cancer Institute’s Clinical Cancer Research Division and director of the Office of HIV and AIDS Malignancy (which, incidentally, cosponsored ANCHOR).
“There are relatively few people that do this at this time,” he added in an interview, pointing out that among those who do, most are obstetricians/gynecologists.
A bit of digging into ANCHOR’s backstory revealed that this was a point of contention at the study’s onset. While physicians participating in the study received extensive training in high-resolution anoscopy, ob/gyns were the fastest to achieve competency and/or had the most prior experience, namely because of their experience in cervical cancer screening in women.
But initial objections by the American Board of Obstetricians and Gynecologists (which at the time, insisted that its members only treat women and threatened to remove their certification if they participated in the research), almost threw a wrench into the study’s start, according to a report in The New York Times. While rational minds prevailed and the board reversed its earlier statements, lack of ample training in the procedure may signal future barriers to treatment.
Another challenge lies in how study findings might be applicable to other groups outside of the HIV/AIDS population, such as people with other forms of immunosuppression who have HSIL, or even healthy women or men who are at risk as a result of penetrative/nonpenetrative sexual or nonsexual (for example, vaginal discharge to the anus) contact.
Although he was unable to share specifics at this time, Dr. Palefsky said that when they designed the ANCHOR study, they were aware that “merely showing efficacy wouldn’t necessarily be sufficient for establishing a standard of care, where[as] other pieces of information undoubtedly would be considered by entities that make guidelines” (for example, an examination of adverse events, risks/benefits, and factors that influence quality of life).
“With that in mind, we are doing a quality-of-life study and, in fact, have [collaborated on], developed, and validated what I think is the first anal disease-specific, quality of life instrument,” Dr. Palefsky said. “The work is still ongoing because we did not complete enrollment in the study, but we are continuing it as part of the follow up.”
Study investigators have also collected samples for a biorepository of specimens that will hopefully facilitate a better understanding of the molecular events driving progression from precancer to cancer. “A lot of people with HIV have these high-grade lesions,” Dr. Palefsky said. “If we were able to identify who’s at highest risk of all of them, that would be very important, because we prefer not to treat everybody with high-grade disease,” he noted, adding that the “underlying hope is that the biomarkers we find in the setting will also be relevant for other HPV-related cancers,” especially in women.
Dr. Yarchoan concurred. “One of the challenges is going to be to digest this information and see how to use it to potentially address the growing problem of females with HIV,” he said.
Dr. Palefsky, Dr. Sparano, and Dr. Yarchoan have disclosed no relevant financial relationships.
A version of this article first appeared on Medscape.com.
COVID-19 causes major interruption in global HIV progress
“We’ve been set back by COVID but we’ve seen remarkable resilience, a lot of innovation and creativity,” Siobhan Crowley MD, head of HIV at the Global Fund, said in an interview.
“If you consider that 21.9 million people are getting antiretrovirals at this point through the Global Fund, I think that needs to be appreciated. Ten years ago, that wouldn’t have been the case; all of those people would have disappeared into the ethers,” she said.
Through close partnerships with the U.S. Agency for International Development, the U.S. President’s Emergency Plan for AIDS Relief, and other Western countries and organizations, the Global Fund has invested $22.7 billion in programs to prevent and treat HIV and AIDS, and $3.8 billion in tuberculosis (TB)/HIV programs, according to the organization’s 2021 Results Report.
But the report also underscores the significant effect that the COVID-19 pandemic has had on funded countries’ progress toward achieving renewed 90-90-90 targets for HIV testing/diagnosis, treatment, and viral suppression by 2030.
The setbacks have been challenging and have touched nearly every service from prevention to treatment. According to the report, between 2019 and 2020:
- Voluntary male circumcision declined by 27%.
- Numbers reached by HIV prevention programs fell by 11%.
- 4.5% fewer mothers received medications to prevent HIV transmission to their babies.
- HIV testing services, including initiation, decreased by 22%.
The numbers tell only a part of the story, according to Dr. Crowley.
“We put in place an emergency mechanism to make funds available for countries to do everything except vaccines in support of COVID,” Dr. Crowley explained. (As of August 2021, these funds had been allocated to 107 countries and 16 multicountry programs.)
Countries were advised that they could use the emergency funds three different ways: 1) for COVID-specific purposes (e.g., diagnostics, oxygen, personal protective equipment; 2) to support mitigation strategies geared toward protecting existing HIV, tuberculosis, and malaria programs and getting them back on track; and 3) for so-called “health system fixes,” such as investing in data systems to track COVID, HIV, and other core diseases, as well as the community workforce.
With regard to HIV, each country supported by the Global Fund was asked to ensure that multimonth (3-6 months) dispensing was implemented and/or accelerated so that patients could avoid congested facilities, and, wherever possible, that drugs were delivered or accessed outside the facility. One example of the success of this effort was found in South Africa, where the number of people on antiretrovirals increased almost threefold, from 1.2 million to 4.2 million people.
Countries also were asked to adapt HIV testing procedures by, for example, moving organized testing out of the facilities and into neighborhoods to meet people where they are. Rapid diagnostic testing and triage care linkage using technologies such as WhatsApp were the result, as were opportunities for home testing which, Dr. Crowley noted, remains a critical component of the overall strategy.
“The self-test is important for two reasons, not just because you are trying to find people with HIV, but also, when people know that they’re negative, they know what they can or should do to stay negative,” she said. “It’s quite a powerful motivator.”
Self-testing might also help countries motivate the 6 million people who know that they have HIV but are not on treatment. But there are still 4.1 million residing in these countries who aren’t aware that they are infected, according to the report. This figure is especially troubling, considering that some may also be harboring TB coinfections, including multidrug-resistant TB (MDR-TB).
The imperfect storm globally and in the U.S.
“One of the things that was striking in the report was the decline in the number of people reached with testing and prevention services,” Chris Beyrer, MD, MPH, the Desmond M. Tutu Professor of Public Health and Human Rights at the Johns Hopkins Bloomberg School of Public Health in Baltimore, said in an interview. Dr. Beyrer was not involved in the report’s development.
“You know, a 10% decline in 1 year to reach people in need is substantial,” he said. “Let’s say it continues; many people are predicting that we won’t have reasonable coverage for low-income countries with COVID until 2023. That adds up to a substantial decline in people reached with these services.”
Dr. Beyrer also expressed concern about the convergence of HIV and TB in already overburdened, fragile health care systems. “Globally, the No. 1 cause of death for people living with HIV is TB, and of course, it’s highly transmissible. So, in many high-burden countries, children are exposed, typically from household members early on, and so the number of people with latent TB infection is just enormous.
“If you look at the report, the worst outcomes are MDR-TB. Those multidrug-resistant and extensively-drug-resistant strains are really a threat to everybody,” Dr. Beyrer said.
But it’s not time for U.S. providers to rest on their laurels either. Dr. Beyrer noted that the 22% decline in HIV testing reported by the Global Fund is similar to what has been happening in the United States with elective procedures such as HIV testing and even preventive procedures like medical male circumcision.
“It’s very clear here in the Global Fund data that the majority of new infections worldwide are in key populations [that] include gay and bisexual men, men who have sex with men, transgender women who have sex with men, people who inject drugs, and sex workers of all genders. Those are people who already faced barriers to health care access and were made worse by COVID.”
Dr. Beyrer noted that, according to the Centers for Disease Control and Prevention, in 2019 in the United States, 68% of new HIV infections occurred in gay and bisexual men, and the effect that COVID-19 will have is still unknown. He also noted the similarity between the most marginalized populations in the Global Fund report and African American men, who have not realized the same increase in the use of preexposure prophylaxis or the same decline in new infections as have their White counterparts.
“It’s also where we are seeing the worst of COVID, low immunization coverage, and high rates of hospitalization and death. ... It’s a dark, dark time for many,” Dr. Crowley said. “And there has also been some amazing resilience and adaptation. The weird thing is, the HIV platform is a natural platform; I mean, if we can keep 21.9 million people on treatment, we can probably deliver them a COVID test and a vaccine.”
Dr. Crowley and Dr. Beyrer report no relevant financial relationships.
A version of this article first appeared on Medscape.com.
“We’ve been set back by COVID but we’ve seen remarkable resilience, a lot of innovation and creativity,” Siobhan Crowley MD, head of HIV at the Global Fund, said in an interview.
“If you consider that 21.9 million people are getting antiretrovirals at this point through the Global Fund, I think that needs to be appreciated. Ten years ago, that wouldn’t have been the case; all of those people would have disappeared into the ethers,” she said.
Through close partnerships with the U.S. Agency for International Development, the U.S. President’s Emergency Plan for AIDS Relief, and other Western countries and organizations, the Global Fund has invested $22.7 billion in programs to prevent and treat HIV and AIDS, and $3.8 billion in tuberculosis (TB)/HIV programs, according to the organization’s 2021 Results Report.
But the report also underscores the significant effect that the COVID-19 pandemic has had on funded countries’ progress toward achieving renewed 90-90-90 targets for HIV testing/diagnosis, treatment, and viral suppression by 2030.
The setbacks have been challenging and have touched nearly every service from prevention to treatment. According to the report, between 2019 and 2020:
- Voluntary male circumcision declined by 27%.
- Numbers reached by HIV prevention programs fell by 11%.
- 4.5% fewer mothers received medications to prevent HIV transmission to their babies.
- HIV testing services, including initiation, decreased by 22%.
The numbers tell only a part of the story, according to Dr. Crowley.
“We put in place an emergency mechanism to make funds available for countries to do everything except vaccines in support of COVID,” Dr. Crowley explained. (As of August 2021, these funds had been allocated to 107 countries and 16 multicountry programs.)
Countries were advised that they could use the emergency funds three different ways: 1) for COVID-specific purposes (e.g., diagnostics, oxygen, personal protective equipment; 2) to support mitigation strategies geared toward protecting existing HIV, tuberculosis, and malaria programs and getting them back on track; and 3) for so-called “health system fixes,” such as investing in data systems to track COVID, HIV, and other core diseases, as well as the community workforce.
With regard to HIV, each country supported by the Global Fund was asked to ensure that multimonth (3-6 months) dispensing was implemented and/or accelerated so that patients could avoid congested facilities, and, wherever possible, that drugs were delivered or accessed outside the facility. One example of the success of this effort was found in South Africa, where the number of people on antiretrovirals increased almost threefold, from 1.2 million to 4.2 million people.
Countries also were asked to adapt HIV testing procedures by, for example, moving organized testing out of the facilities and into neighborhoods to meet people where they are. Rapid diagnostic testing and triage care linkage using technologies such as WhatsApp were the result, as were opportunities for home testing which, Dr. Crowley noted, remains a critical component of the overall strategy.
“The self-test is important for two reasons, not just because you are trying to find people with HIV, but also, when people know that they’re negative, they know what they can or should do to stay negative,” she said. “It’s quite a powerful motivator.”
Self-testing might also help countries motivate the 6 million people who know that they have HIV but are not on treatment. But there are still 4.1 million residing in these countries who aren’t aware that they are infected, according to the report. This figure is especially troubling, considering that some may also be harboring TB coinfections, including multidrug-resistant TB (MDR-TB).
The imperfect storm globally and in the U.S.
“One of the things that was striking in the report was the decline in the number of people reached with testing and prevention services,” Chris Beyrer, MD, MPH, the Desmond M. Tutu Professor of Public Health and Human Rights at the Johns Hopkins Bloomberg School of Public Health in Baltimore, said in an interview. Dr. Beyrer was not involved in the report’s development.
“You know, a 10% decline in 1 year to reach people in need is substantial,” he said. “Let’s say it continues; many people are predicting that we won’t have reasonable coverage for low-income countries with COVID until 2023. That adds up to a substantial decline in people reached with these services.”
Dr. Beyrer also expressed concern about the convergence of HIV and TB in already overburdened, fragile health care systems. “Globally, the No. 1 cause of death for people living with HIV is TB, and of course, it’s highly transmissible. So, in many high-burden countries, children are exposed, typically from household members early on, and so the number of people with latent TB infection is just enormous.
“If you look at the report, the worst outcomes are MDR-TB. Those multidrug-resistant and extensively-drug-resistant strains are really a threat to everybody,” Dr. Beyrer said.
But it’s not time for U.S. providers to rest on their laurels either. Dr. Beyrer noted that the 22% decline in HIV testing reported by the Global Fund is similar to what has been happening in the United States with elective procedures such as HIV testing and even preventive procedures like medical male circumcision.
“It’s very clear here in the Global Fund data that the majority of new infections worldwide are in key populations [that] include gay and bisexual men, men who have sex with men, transgender women who have sex with men, people who inject drugs, and sex workers of all genders. Those are people who already faced barriers to health care access and were made worse by COVID.”
Dr. Beyrer noted that, according to the Centers for Disease Control and Prevention, in 2019 in the United States, 68% of new HIV infections occurred in gay and bisexual men, and the effect that COVID-19 will have is still unknown. He also noted the similarity between the most marginalized populations in the Global Fund report and African American men, who have not realized the same increase in the use of preexposure prophylaxis or the same decline in new infections as have their White counterparts.
“It’s also where we are seeing the worst of COVID, low immunization coverage, and high rates of hospitalization and death. ... It’s a dark, dark time for many,” Dr. Crowley said. “And there has also been some amazing resilience and adaptation. The weird thing is, the HIV platform is a natural platform; I mean, if we can keep 21.9 million people on treatment, we can probably deliver them a COVID test and a vaccine.”
Dr. Crowley and Dr. Beyrer report no relevant financial relationships.
A version of this article first appeared on Medscape.com.
“We’ve been set back by COVID but we’ve seen remarkable resilience, a lot of innovation and creativity,” Siobhan Crowley MD, head of HIV at the Global Fund, said in an interview.
“If you consider that 21.9 million people are getting antiretrovirals at this point through the Global Fund, I think that needs to be appreciated. Ten years ago, that wouldn’t have been the case; all of those people would have disappeared into the ethers,” she said.
Through close partnerships with the U.S. Agency for International Development, the U.S. President’s Emergency Plan for AIDS Relief, and other Western countries and organizations, the Global Fund has invested $22.7 billion in programs to prevent and treat HIV and AIDS, and $3.8 billion in tuberculosis (TB)/HIV programs, according to the organization’s 2021 Results Report.
But the report also underscores the significant effect that the COVID-19 pandemic has had on funded countries’ progress toward achieving renewed 90-90-90 targets for HIV testing/diagnosis, treatment, and viral suppression by 2030.
The setbacks have been challenging and have touched nearly every service from prevention to treatment. According to the report, between 2019 and 2020:
- Voluntary male circumcision declined by 27%.
- Numbers reached by HIV prevention programs fell by 11%.
- 4.5% fewer mothers received medications to prevent HIV transmission to their babies.
- HIV testing services, including initiation, decreased by 22%.
The numbers tell only a part of the story, according to Dr. Crowley.
“We put in place an emergency mechanism to make funds available for countries to do everything except vaccines in support of COVID,” Dr. Crowley explained. (As of August 2021, these funds had been allocated to 107 countries and 16 multicountry programs.)
Countries were advised that they could use the emergency funds three different ways: 1) for COVID-specific purposes (e.g., diagnostics, oxygen, personal protective equipment; 2) to support mitigation strategies geared toward protecting existing HIV, tuberculosis, and malaria programs and getting them back on track; and 3) for so-called “health system fixes,” such as investing in data systems to track COVID, HIV, and other core diseases, as well as the community workforce.
With regard to HIV, each country supported by the Global Fund was asked to ensure that multimonth (3-6 months) dispensing was implemented and/or accelerated so that patients could avoid congested facilities, and, wherever possible, that drugs were delivered or accessed outside the facility. One example of the success of this effort was found in South Africa, where the number of people on antiretrovirals increased almost threefold, from 1.2 million to 4.2 million people.
Countries also were asked to adapt HIV testing procedures by, for example, moving organized testing out of the facilities and into neighborhoods to meet people where they are. Rapid diagnostic testing and triage care linkage using technologies such as WhatsApp were the result, as were opportunities for home testing which, Dr. Crowley noted, remains a critical component of the overall strategy.
“The self-test is important for two reasons, not just because you are trying to find people with HIV, but also, when people know that they’re negative, they know what they can or should do to stay negative,” she said. “It’s quite a powerful motivator.”
Self-testing might also help countries motivate the 6 million people who know that they have HIV but are not on treatment. But there are still 4.1 million residing in these countries who aren’t aware that they are infected, according to the report. This figure is especially troubling, considering that some may also be harboring TB coinfections, including multidrug-resistant TB (MDR-TB).
The imperfect storm globally and in the U.S.
“One of the things that was striking in the report was the decline in the number of people reached with testing and prevention services,” Chris Beyrer, MD, MPH, the Desmond M. Tutu Professor of Public Health and Human Rights at the Johns Hopkins Bloomberg School of Public Health in Baltimore, said in an interview. Dr. Beyrer was not involved in the report’s development.
“You know, a 10% decline in 1 year to reach people in need is substantial,” he said. “Let’s say it continues; many people are predicting that we won’t have reasonable coverage for low-income countries with COVID until 2023. That adds up to a substantial decline in people reached with these services.”
Dr. Beyrer also expressed concern about the convergence of HIV and TB in already overburdened, fragile health care systems. “Globally, the No. 1 cause of death for people living with HIV is TB, and of course, it’s highly transmissible. So, in many high-burden countries, children are exposed, typically from household members early on, and so the number of people with latent TB infection is just enormous.
“If you look at the report, the worst outcomes are MDR-TB. Those multidrug-resistant and extensively-drug-resistant strains are really a threat to everybody,” Dr. Beyrer said.
But it’s not time for U.S. providers to rest on their laurels either. Dr. Beyrer noted that the 22% decline in HIV testing reported by the Global Fund is similar to what has been happening in the United States with elective procedures such as HIV testing and even preventive procedures like medical male circumcision.
“It’s very clear here in the Global Fund data that the majority of new infections worldwide are in key populations [that] include gay and bisexual men, men who have sex with men, transgender women who have sex with men, people who inject drugs, and sex workers of all genders. Those are people who already faced barriers to health care access and were made worse by COVID.”
Dr. Beyrer noted that, according to the Centers for Disease Control and Prevention, in 2019 in the United States, 68% of new HIV infections occurred in gay and bisexual men, and the effect that COVID-19 will have is still unknown. He also noted the similarity between the most marginalized populations in the Global Fund report and African American men, who have not realized the same increase in the use of preexposure prophylaxis or the same decline in new infections as have their White counterparts.
“It’s also where we are seeing the worst of COVID, low immunization coverage, and high rates of hospitalization and death. ... It’s a dark, dark time for many,” Dr. Crowley said. “And there has also been some amazing resilience and adaptation. The weird thing is, the HIV platform is a natural platform; I mean, if we can keep 21.9 million people on treatment, we can probably deliver them a COVID test and a vaccine.”
Dr. Crowley and Dr. Beyrer report no relevant financial relationships.
A version of this article first appeared on Medscape.com.
Guideline gives weak support to trying oral medical cannabis for chronic pain
“Evidence alone is not sufficient for clinical decision-making, particularly in chronic pain,” said Jason Busse, DC, PhD, director of Michael G. DeGroote Centre for Medicinal Cannabis Research at McMaster University, Hamilton, Ont., and lead author of a newly released rapid guideline on medical cannabis or cannabinoids for chronic pain.
The recommendations, published online Sept. 9, 2021 in the British Medical Journal, suggest that providers offer patients with chronic pain a trial of noninhaled medical cannabis or cannabinoids if standard care or management is ineffective. However, the “weak” rating attached to the recommendation may compel some clinicians to automatically write off the panel’s recommendations.
“Because of the close balance between benefits and harms and wide variability in patient attitudes, the panel came to the conclusion that [some] patients presented with the current best evidence would likely choose to engage in a trial of medicinal cannabis, if their current care was felt to be suboptimal,” Dr. Busse explained in an interview.
But more importantly, “the recommendation allows for shared decision making to occur, and for different patients to make different decisions based on individual preferences and circumstances,” he said.
Evidence supports improved pain and sleep quality, physical functioning
Evidence supporting the use of medical cannabis in chronic pain is derived from a rigorous systematic review and meta-analysis of 32 studies enrolling 5,174 patients randomized to oral (capsule, spray, sublingual drops) or topical (transdermal cream) medical cannabis or placebo. Of note, three types of cannabinoids were represented: phytocannabinoids, synthetic, and endocannabinoids.
The studies included both patients with chronic noncancer pain (28 studies, n = 3,812) and chronic cancer pain not receiving palliative care (4 studies, n = 1,362). On average, baseline pain scores were a median 6.28 cm on a 10-cm visual analog scale (VAS), and median participant age was 53 years. 60% of trials reporting sex differences enrolled female participants. Overall, patients were followed for roughly 2 months (median, 50 days).
Findings (27 studies, n = 3,939) showed that, compared with placebo, medical cannabis resulted in a small, albeit important, improvement in the proportion of patients experiencing pain relief at or above the minimally important difference (MID) (moderate-certainty evidence, 10% modeled risk difference [RD; 95% confidence interval, 5%-15%] for achieving at least the MID of 1 cm).
Medical cannabis (15 studies, n = 2,425) also provided a small increase in the proportion of patients experiencing improvements in physical functioning at or above the MID (high certainty evidence, 4% modeled RD [95% CI, 0.1%-8%] for achieving at least a MID of 10 points).
Additionally, participants experienced significant improvements in sleep quality, compared with placebo (16 studies, 3,124 participants, high-quality evidence), demonstrating a weighted mean difference of –0.53 cm on a 10-cm VAS (95% CI, –0.75 to –0.30 cm). A total of nine larger trials (n = 2,652, high-certainty evidence) saw a small increase in the proportion of patients experiencing improved sleep quality at or above the MID: 6% modeled RD (95% CI, 2%-9%).
On the other hand, benefits did not extend to emotional, role, or social functioning (high-certainty evidence).
First do no harm: Start low, go slow
While these findings provide a rationale for medical cannabis in chronic pain, exploring options with patients can be challenging. Studies on medical cannabis consistently note that patients want information, but data also show that many providers express a lack of knowledge to provide adequate counseling.
There are also legal hurdles. Despite the authorization of medicinal cannabis across a majority of states and territories, cannabis is still a schedule I substance under the Federal Controlled Substances Act. In addition, the absence of standards around formulations, potency, and dosing has also been cited as a major barrier to recommending medical cannabis, as have concerns about adverse events (AEs), especially with inhaled and tetrahydrocannabinol (THC)-predominant formulations.
Like most medications, medical cannabis dosing should be individualized depending on product, patient, and ability to titrate the dose, but the guidelines provide a general rule of thumb. Providers considering therapeutic noninhaled medical cannabis trials are encouraged to start with a low-dose cannabidiol (CBD) oral tablet, spray, or sublingual oil drops 5 mg twice daily, increasing it by 10 mg every 2-3 days depending on the clinical response (to a maximum daily dose of 40 mg/day). If patient response is unsatisfactory, they should consider adding 1-2.5 mg THC/daily, titrated every 2-7 days to a maximum of 40 mg/day.
Still, an important caveat is whether or not adjunctive CBD alone is effective for chronic pain.
“While we know that one out of seven U.S. adults are using cannabidiol, we know very little about its therapeutic effects when given by itself for pain,” Ziva Cooper, PhD, director of the Cannabis Research Initiative at the University of California, Los Angeles, and an associate professor at-large of psychology and behavioral science, said in an interview. (Dr. Cooper was not involved in the guideline development.)
“But patients tend to self-report that CBD is helpful, and at low doses, we know that it is unlikely to have adverse effects of any significant concern,” Dr. Cooper noted.
Depending on its components, medical cannabis is associated with a wide range of AEs. Studies comprising the evidence base for the guideline reported transient cognitive impairment (relative risk, 2.39; 95% CI, 1.06-5.38), vomiting (RR, 1.46; 95% CI, 1.07-1.99), and drowsiness (RR, 2.14; 95% CI, 1.55-2.95), attention impairment (RR, 4.04; 95% CI, 1.67-9.74), and nausea (RR, 1.59; 95% CI, 1.28-1.99). Of note, findings of a subgroup analysis showed that the risk of dizziness increased with treatment duration, starting at 3 months (test of interaction P = .002).
However, Dr. Cooper explained that, because the included studies were inconsistent in terms of cannabis type (e.g., some looked at synthetic THC or THC-like substances where others looked at a THC/CBD combination) and formulation (capsules, oral mucosal sprays), it’s difficult to tease out component-specific AEs.
“These are really important things to note, especially when you think about different populations that might be using these types of medicines moving forward,” she said.
Toward that end, the guideline specifically states that there is “no reason why the expected benefits would be systematically different among adolescents and emerging adults.”
Among children with cancer, prior study findings reinforce the conclusion that benefits are similar to adults, but studies in this area are limited to end-of-life treatment, childhood cancer with primarily palliative intent, or progressive or relapsed cancer. Because THC’s safety profile is less certain in children, it’s also important to consider adverse neurocognitive effects before initiating a medical cannabis trial in this population.
Navigating the landscape
Although promising, the medical cannabis landscape is undoubtedly difficult to navigate, with land mines ranging from a limited inability to simply pick up a prescribing pad to quality control.
With the exception of three Food and Drug Administration–approved products – dronabinol, cannabidiol Rx, and nabilone – U.S. providers are only able to ‘certify,’ not prescribe, medical cannabis for chronic pain, and only if it is included within the state cannabis board’s list of eligible conditions. (A state-by-state guide is available.)
Quality control also varies by product but is critical. “You want to look for certificates of quality assurance,” Jenny Wilkerson, PhD, a research assistant professor of pharmacodynamics at the University of Florida, Gainesville, said in an interview. (Dr. Wilkerson was not involved in the guideline development.)
“A good dispensary should have that information or at least be willing to get that information, but generally speaking, that is something that patients need to ask for,” she emphasized, noting that “most available mass readouts are not divided by lots.”
Initial counseling and AE monitoring and regular follow-up is important, especially among patients who’ve never tried medical cannabis (or older patients whose prior experience may be limited to weaker recreational marijuana).
Notably, the reliance on medical dispensaries to deliver the right information at the right time may prove to be faulty. While recent data show that frontline dispensary workers regularly provide information to customers on their medical conditions and available products, they rarely, if ever, base recommendations on provider input, and never or rarely discuss potential AEs and other risks.
Per the new guideline, inexperienced patients should be seen monthly until a stable dose is achieved; longer times between visits can be considered in those who are more experienced. Still, patients should be advised to contact their provider when pain relief or other goals are insufficient, or when response or problematic AEs occur. This facilitates down-titration to a previously tolerated dose, up-titration in CBD and/or THC, or a different route of administration/formulation altogether.
Dr. Wilkerson pointed out that follow-up visits also provide an opportunity to do a blood draw and ask the lab to conduct pharmacokinetic analysis.
If possible, “ask patients to [ensure that they] take a standard dose before the visit so that the lab can assess the blood percentage of primary compounds and metabolites in the product that they are using,” she explained, noting that the information is helping to determine how “the different ratios may be affecting therapeutic response in individual patients.”
Granted, the guideline is only a start. But it is a good one.
“A lot of physicians want to be able to hang their hat on evidence of the safety and efficacy of these products, and the analysis that was leveraged for this guideline was very rigorous,” Dr. Cooper said.
Not only do they reinforce that “oral cannabinoids can produce small improvements in pain and provide a dosing structure that minimizes risk to the patient, [but they] should be able to help educate physicians who [are looking] for a sense of what the literature tells us at this time,” she added.
“With chronic pain, we often find that different treatments will show small potential benefits and they have a certain risk profile,” Dr. Busse said.
“It’s almost impossible to know what patients think about this option unless you present them with the evidence and ask them to make a decision based on their values and preferences,” he said.
The Michael G. DeGroote Centre for Medicinal Cannabis Research funded the MAGIC Evidence Ecosystem Foundation to support the creation of the guideline. The center receives no funding from industry Dr. Busse, Dr. Cooper, and Dr. Wilkerson reported having no relevant financial relationships.
“Evidence alone is not sufficient for clinical decision-making, particularly in chronic pain,” said Jason Busse, DC, PhD, director of Michael G. DeGroote Centre for Medicinal Cannabis Research at McMaster University, Hamilton, Ont., and lead author of a newly released rapid guideline on medical cannabis or cannabinoids for chronic pain.
The recommendations, published online Sept. 9, 2021 in the British Medical Journal, suggest that providers offer patients with chronic pain a trial of noninhaled medical cannabis or cannabinoids if standard care or management is ineffective. However, the “weak” rating attached to the recommendation may compel some clinicians to automatically write off the panel’s recommendations.
“Because of the close balance between benefits and harms and wide variability in patient attitudes, the panel came to the conclusion that [some] patients presented with the current best evidence would likely choose to engage in a trial of medicinal cannabis, if their current care was felt to be suboptimal,” Dr. Busse explained in an interview.
But more importantly, “the recommendation allows for shared decision making to occur, and for different patients to make different decisions based on individual preferences and circumstances,” he said.
Evidence supports improved pain and sleep quality, physical functioning
Evidence supporting the use of medical cannabis in chronic pain is derived from a rigorous systematic review and meta-analysis of 32 studies enrolling 5,174 patients randomized to oral (capsule, spray, sublingual drops) or topical (transdermal cream) medical cannabis or placebo. Of note, three types of cannabinoids were represented: phytocannabinoids, synthetic, and endocannabinoids.
The studies included both patients with chronic noncancer pain (28 studies, n = 3,812) and chronic cancer pain not receiving palliative care (4 studies, n = 1,362). On average, baseline pain scores were a median 6.28 cm on a 10-cm visual analog scale (VAS), and median participant age was 53 years. 60% of trials reporting sex differences enrolled female participants. Overall, patients were followed for roughly 2 months (median, 50 days).
Findings (27 studies, n = 3,939) showed that, compared with placebo, medical cannabis resulted in a small, albeit important, improvement in the proportion of patients experiencing pain relief at or above the minimally important difference (MID) (moderate-certainty evidence, 10% modeled risk difference [RD; 95% confidence interval, 5%-15%] for achieving at least the MID of 1 cm).
Medical cannabis (15 studies, n = 2,425) also provided a small increase in the proportion of patients experiencing improvements in physical functioning at or above the MID (high certainty evidence, 4% modeled RD [95% CI, 0.1%-8%] for achieving at least a MID of 10 points).
Additionally, participants experienced significant improvements in sleep quality, compared with placebo (16 studies, 3,124 participants, high-quality evidence), demonstrating a weighted mean difference of –0.53 cm on a 10-cm VAS (95% CI, –0.75 to –0.30 cm). A total of nine larger trials (n = 2,652, high-certainty evidence) saw a small increase in the proportion of patients experiencing improved sleep quality at or above the MID: 6% modeled RD (95% CI, 2%-9%).
On the other hand, benefits did not extend to emotional, role, or social functioning (high-certainty evidence).
First do no harm: Start low, go slow
While these findings provide a rationale for medical cannabis in chronic pain, exploring options with patients can be challenging. Studies on medical cannabis consistently note that patients want information, but data also show that many providers express a lack of knowledge to provide adequate counseling.
There are also legal hurdles. Despite the authorization of medicinal cannabis across a majority of states and territories, cannabis is still a schedule I substance under the Federal Controlled Substances Act. In addition, the absence of standards around formulations, potency, and dosing has also been cited as a major barrier to recommending medical cannabis, as have concerns about adverse events (AEs), especially with inhaled and tetrahydrocannabinol (THC)-predominant formulations.
Like most medications, medical cannabis dosing should be individualized depending on product, patient, and ability to titrate the dose, but the guidelines provide a general rule of thumb. Providers considering therapeutic noninhaled medical cannabis trials are encouraged to start with a low-dose cannabidiol (CBD) oral tablet, spray, or sublingual oil drops 5 mg twice daily, increasing it by 10 mg every 2-3 days depending on the clinical response (to a maximum daily dose of 40 mg/day). If patient response is unsatisfactory, they should consider adding 1-2.5 mg THC/daily, titrated every 2-7 days to a maximum of 40 mg/day.
Still, an important caveat is whether or not adjunctive CBD alone is effective for chronic pain.
“While we know that one out of seven U.S. adults are using cannabidiol, we know very little about its therapeutic effects when given by itself for pain,” Ziva Cooper, PhD, director of the Cannabis Research Initiative at the University of California, Los Angeles, and an associate professor at-large of psychology and behavioral science, said in an interview. (Dr. Cooper was not involved in the guideline development.)
“But patients tend to self-report that CBD is helpful, and at low doses, we know that it is unlikely to have adverse effects of any significant concern,” Dr. Cooper noted.
Depending on its components, medical cannabis is associated with a wide range of AEs. Studies comprising the evidence base for the guideline reported transient cognitive impairment (relative risk, 2.39; 95% CI, 1.06-5.38), vomiting (RR, 1.46; 95% CI, 1.07-1.99), and drowsiness (RR, 2.14; 95% CI, 1.55-2.95), attention impairment (RR, 4.04; 95% CI, 1.67-9.74), and nausea (RR, 1.59; 95% CI, 1.28-1.99). Of note, findings of a subgroup analysis showed that the risk of dizziness increased with treatment duration, starting at 3 months (test of interaction P = .002).
However, Dr. Cooper explained that, because the included studies were inconsistent in terms of cannabis type (e.g., some looked at synthetic THC or THC-like substances where others looked at a THC/CBD combination) and formulation (capsules, oral mucosal sprays), it’s difficult to tease out component-specific AEs.
“These are really important things to note, especially when you think about different populations that might be using these types of medicines moving forward,” she said.
Toward that end, the guideline specifically states that there is “no reason why the expected benefits would be systematically different among adolescents and emerging adults.”
Among children with cancer, prior study findings reinforce the conclusion that benefits are similar to adults, but studies in this area are limited to end-of-life treatment, childhood cancer with primarily palliative intent, or progressive or relapsed cancer. Because THC’s safety profile is less certain in children, it’s also important to consider adverse neurocognitive effects before initiating a medical cannabis trial in this population.
Navigating the landscape
Although promising, the medical cannabis landscape is undoubtedly difficult to navigate, with land mines ranging from a limited inability to simply pick up a prescribing pad to quality control.
With the exception of three Food and Drug Administration–approved products – dronabinol, cannabidiol Rx, and nabilone – U.S. providers are only able to ‘certify,’ not prescribe, medical cannabis for chronic pain, and only if it is included within the state cannabis board’s list of eligible conditions. (A state-by-state guide is available.)
Quality control also varies by product but is critical. “You want to look for certificates of quality assurance,” Jenny Wilkerson, PhD, a research assistant professor of pharmacodynamics at the University of Florida, Gainesville, said in an interview. (Dr. Wilkerson was not involved in the guideline development.)
“A good dispensary should have that information or at least be willing to get that information, but generally speaking, that is something that patients need to ask for,” she emphasized, noting that “most available mass readouts are not divided by lots.”
Initial counseling and AE monitoring and regular follow-up is important, especially among patients who’ve never tried medical cannabis (or older patients whose prior experience may be limited to weaker recreational marijuana).
Notably, the reliance on medical dispensaries to deliver the right information at the right time may prove to be faulty. While recent data show that frontline dispensary workers regularly provide information to customers on their medical conditions and available products, they rarely, if ever, base recommendations on provider input, and never or rarely discuss potential AEs and other risks.
Per the new guideline, inexperienced patients should be seen monthly until a stable dose is achieved; longer times between visits can be considered in those who are more experienced. Still, patients should be advised to contact their provider when pain relief or other goals are insufficient, or when response or problematic AEs occur. This facilitates down-titration to a previously tolerated dose, up-titration in CBD and/or THC, or a different route of administration/formulation altogether.
Dr. Wilkerson pointed out that follow-up visits also provide an opportunity to do a blood draw and ask the lab to conduct pharmacokinetic analysis.
If possible, “ask patients to [ensure that they] take a standard dose before the visit so that the lab can assess the blood percentage of primary compounds and metabolites in the product that they are using,” she explained, noting that the information is helping to determine how “the different ratios may be affecting therapeutic response in individual patients.”
Granted, the guideline is only a start. But it is a good one.
“A lot of physicians want to be able to hang their hat on evidence of the safety and efficacy of these products, and the analysis that was leveraged for this guideline was very rigorous,” Dr. Cooper said.
Not only do they reinforce that “oral cannabinoids can produce small improvements in pain and provide a dosing structure that minimizes risk to the patient, [but they] should be able to help educate physicians who [are looking] for a sense of what the literature tells us at this time,” she added.
“With chronic pain, we often find that different treatments will show small potential benefits and they have a certain risk profile,” Dr. Busse said.
“It’s almost impossible to know what patients think about this option unless you present them with the evidence and ask them to make a decision based on their values and preferences,” he said.
The Michael G. DeGroote Centre for Medicinal Cannabis Research funded the MAGIC Evidence Ecosystem Foundation to support the creation of the guideline. The center receives no funding from industry Dr. Busse, Dr. Cooper, and Dr. Wilkerson reported having no relevant financial relationships.
“Evidence alone is not sufficient for clinical decision-making, particularly in chronic pain,” said Jason Busse, DC, PhD, director of Michael G. DeGroote Centre for Medicinal Cannabis Research at McMaster University, Hamilton, Ont., and lead author of a newly released rapid guideline on medical cannabis or cannabinoids for chronic pain.
The recommendations, published online Sept. 9, 2021 in the British Medical Journal, suggest that providers offer patients with chronic pain a trial of noninhaled medical cannabis or cannabinoids if standard care or management is ineffective. However, the “weak” rating attached to the recommendation may compel some clinicians to automatically write off the panel’s recommendations.
“Because of the close balance between benefits and harms and wide variability in patient attitudes, the panel came to the conclusion that [some] patients presented with the current best evidence would likely choose to engage in a trial of medicinal cannabis, if their current care was felt to be suboptimal,” Dr. Busse explained in an interview.
But more importantly, “the recommendation allows for shared decision making to occur, and for different patients to make different decisions based on individual preferences and circumstances,” he said.
Evidence supports improved pain and sleep quality, physical functioning
Evidence supporting the use of medical cannabis in chronic pain is derived from a rigorous systematic review and meta-analysis of 32 studies enrolling 5,174 patients randomized to oral (capsule, spray, sublingual drops) or topical (transdermal cream) medical cannabis or placebo. Of note, three types of cannabinoids were represented: phytocannabinoids, synthetic, and endocannabinoids.
The studies included both patients with chronic noncancer pain (28 studies, n = 3,812) and chronic cancer pain not receiving palliative care (4 studies, n = 1,362). On average, baseline pain scores were a median 6.28 cm on a 10-cm visual analog scale (VAS), and median participant age was 53 years. 60% of trials reporting sex differences enrolled female participants. Overall, patients were followed for roughly 2 months (median, 50 days).
Findings (27 studies, n = 3,939) showed that, compared with placebo, medical cannabis resulted in a small, albeit important, improvement in the proportion of patients experiencing pain relief at or above the minimally important difference (MID) (moderate-certainty evidence, 10% modeled risk difference [RD; 95% confidence interval, 5%-15%] for achieving at least the MID of 1 cm).
Medical cannabis (15 studies, n = 2,425) also provided a small increase in the proportion of patients experiencing improvements in physical functioning at or above the MID (high certainty evidence, 4% modeled RD [95% CI, 0.1%-8%] for achieving at least a MID of 10 points).
Additionally, participants experienced significant improvements in sleep quality, compared with placebo (16 studies, 3,124 participants, high-quality evidence), demonstrating a weighted mean difference of –0.53 cm on a 10-cm VAS (95% CI, –0.75 to –0.30 cm). A total of nine larger trials (n = 2,652, high-certainty evidence) saw a small increase in the proportion of patients experiencing improved sleep quality at or above the MID: 6% modeled RD (95% CI, 2%-9%).
On the other hand, benefits did not extend to emotional, role, or social functioning (high-certainty evidence).
First do no harm: Start low, go slow
While these findings provide a rationale for medical cannabis in chronic pain, exploring options with patients can be challenging. Studies on medical cannabis consistently note that patients want information, but data also show that many providers express a lack of knowledge to provide adequate counseling.
There are also legal hurdles. Despite the authorization of medicinal cannabis across a majority of states and territories, cannabis is still a schedule I substance under the Federal Controlled Substances Act. In addition, the absence of standards around formulations, potency, and dosing has also been cited as a major barrier to recommending medical cannabis, as have concerns about adverse events (AEs), especially with inhaled and tetrahydrocannabinol (THC)-predominant formulations.
Like most medications, medical cannabis dosing should be individualized depending on product, patient, and ability to titrate the dose, but the guidelines provide a general rule of thumb. Providers considering therapeutic noninhaled medical cannabis trials are encouraged to start with a low-dose cannabidiol (CBD) oral tablet, spray, or sublingual oil drops 5 mg twice daily, increasing it by 10 mg every 2-3 days depending on the clinical response (to a maximum daily dose of 40 mg/day). If patient response is unsatisfactory, they should consider adding 1-2.5 mg THC/daily, titrated every 2-7 days to a maximum of 40 mg/day.
Still, an important caveat is whether or not adjunctive CBD alone is effective for chronic pain.
“While we know that one out of seven U.S. adults are using cannabidiol, we know very little about its therapeutic effects when given by itself for pain,” Ziva Cooper, PhD, director of the Cannabis Research Initiative at the University of California, Los Angeles, and an associate professor at-large of psychology and behavioral science, said in an interview. (Dr. Cooper was not involved in the guideline development.)
“But patients tend to self-report that CBD is helpful, and at low doses, we know that it is unlikely to have adverse effects of any significant concern,” Dr. Cooper noted.
Depending on its components, medical cannabis is associated with a wide range of AEs. Studies comprising the evidence base for the guideline reported transient cognitive impairment (relative risk, 2.39; 95% CI, 1.06-5.38), vomiting (RR, 1.46; 95% CI, 1.07-1.99), and drowsiness (RR, 2.14; 95% CI, 1.55-2.95), attention impairment (RR, 4.04; 95% CI, 1.67-9.74), and nausea (RR, 1.59; 95% CI, 1.28-1.99). Of note, findings of a subgroup analysis showed that the risk of dizziness increased with treatment duration, starting at 3 months (test of interaction P = .002).
However, Dr. Cooper explained that, because the included studies were inconsistent in terms of cannabis type (e.g., some looked at synthetic THC or THC-like substances where others looked at a THC/CBD combination) and formulation (capsules, oral mucosal sprays), it’s difficult to tease out component-specific AEs.
“These are really important things to note, especially when you think about different populations that might be using these types of medicines moving forward,” she said.
Toward that end, the guideline specifically states that there is “no reason why the expected benefits would be systematically different among adolescents and emerging adults.”
Among children with cancer, prior study findings reinforce the conclusion that benefits are similar to adults, but studies in this area are limited to end-of-life treatment, childhood cancer with primarily palliative intent, or progressive or relapsed cancer. Because THC’s safety profile is less certain in children, it’s also important to consider adverse neurocognitive effects before initiating a medical cannabis trial in this population.
Navigating the landscape
Although promising, the medical cannabis landscape is undoubtedly difficult to navigate, with land mines ranging from a limited inability to simply pick up a prescribing pad to quality control.
With the exception of three Food and Drug Administration–approved products – dronabinol, cannabidiol Rx, and nabilone – U.S. providers are only able to ‘certify,’ not prescribe, medical cannabis for chronic pain, and only if it is included within the state cannabis board’s list of eligible conditions. (A state-by-state guide is available.)
Quality control also varies by product but is critical. “You want to look for certificates of quality assurance,” Jenny Wilkerson, PhD, a research assistant professor of pharmacodynamics at the University of Florida, Gainesville, said in an interview. (Dr. Wilkerson was not involved in the guideline development.)
“A good dispensary should have that information or at least be willing to get that information, but generally speaking, that is something that patients need to ask for,” she emphasized, noting that “most available mass readouts are not divided by lots.”
Initial counseling and AE monitoring and regular follow-up is important, especially among patients who’ve never tried medical cannabis (or older patients whose prior experience may be limited to weaker recreational marijuana).
Notably, the reliance on medical dispensaries to deliver the right information at the right time may prove to be faulty. While recent data show that frontline dispensary workers regularly provide information to customers on their medical conditions and available products, they rarely, if ever, base recommendations on provider input, and never or rarely discuss potential AEs and other risks.
Per the new guideline, inexperienced patients should be seen monthly until a stable dose is achieved; longer times between visits can be considered in those who are more experienced. Still, patients should be advised to contact their provider when pain relief or other goals are insufficient, or when response or problematic AEs occur. This facilitates down-titration to a previously tolerated dose, up-titration in CBD and/or THC, or a different route of administration/formulation altogether.
Dr. Wilkerson pointed out that follow-up visits also provide an opportunity to do a blood draw and ask the lab to conduct pharmacokinetic analysis.
If possible, “ask patients to [ensure that they] take a standard dose before the visit so that the lab can assess the blood percentage of primary compounds and metabolites in the product that they are using,” she explained, noting that the information is helping to determine how “the different ratios may be affecting therapeutic response in individual patients.”
Granted, the guideline is only a start. But it is a good one.
“A lot of physicians want to be able to hang their hat on evidence of the safety and efficacy of these products, and the analysis that was leveraged for this guideline was very rigorous,” Dr. Cooper said.
Not only do they reinforce that “oral cannabinoids can produce small improvements in pain and provide a dosing structure that minimizes risk to the patient, [but they] should be able to help educate physicians who [are looking] for a sense of what the literature tells us at this time,” she added.
“With chronic pain, we often find that different treatments will show small potential benefits and they have a certain risk profile,” Dr. Busse said.
“It’s almost impossible to know what patients think about this option unless you present them with the evidence and ask them to make a decision based on their values and preferences,” he said.
The Michael G. DeGroote Centre for Medicinal Cannabis Research funded the MAGIC Evidence Ecosystem Foundation to support the creation of the guideline. The center receives no funding from industry Dr. Busse, Dr. Cooper, and Dr. Wilkerson reported having no relevant financial relationships.
FROM THE BMJ
Injectable cabotegravir PrEP superior to oral TDF-FTC; trial halted early
The future of preexposure prophylaxis (PrEP) is here, according to interim study results demonstrating the superiority of long-acting, injectable cabotegravir (CAB-LA) over the current workhorse, daily oral tenofovir disoproxil fumarate-emtricitabine (TDF-FTC).
In a prospective, phase 2b-3 randomized, double-blind, double-dummy, active-controlled trial among 4,566 cisgender MSM (men who have sex with men) and transgender women, The study was terminated early, owing to strong evidence of efficacy in the first preplanned interim endpoint analysis. The study findings were published Aug. 11 in the New England Journal of Medicine.
“The lesson is not that TDF-FTC doesn’t work or has major problems; it is a very safe, very well-tolerated agent and astonishingly effective if taken as prescribed,” Raphael J. Landovitz, MD, lead author and codirector of the Center for HIV Identification, Prevention, and Treatment Services at the University of California, Los Angeles, said in an interview.
“The reason that we were able to show that cabotegravir was superior is because we enrolled a very young, very highly at-risk, very underresourced, underrepresented, highly sexually active group who weren’t able to take PrEP the way it was prescribed,” he said.
Study participants were assigned to receive either active CAB 600 mg intramuscularly with TDF-FTC placebo or active TDF-FTC (300 mg/200 mg) with a CAB procedure in three phases:
- An oral-tablet 5-week lead-in phase, a blinded injection phase beginning at week 5.
- An injection at week 9 and every 8 weeks thereafter through week 153.
- An open-label “tail” phase consisting of oral TDF/FTC to provide ongoing for participants discontinuing injections.
The median age of study participants was 26 years (interquartile range [IQR], 22-32 years); 12.5% (570) identified as transgender women; 49.8% (845/1,698) of U.S. participants were Black patients.
During follow-up, HIV infections were identified in 57 participants, including 52 who acquired HIV infections after enrollment (13 in the CAB group, incidence 0.41 per 100 person-years, vs. 39 in the TDF-FTC group, incidence 1.22 per 100 person-years). The hazard ratio for incident HIV infection was 0.34 (95% confidence interval, 0.18-0.62) CAB vs. TDF-FTC (P < .001). Consistent effects were observed across prespecified subgroups and populations.
Among participants in the CAB group, integrase strand-transfer inhibitor resistance mutations were detected in one of four of the baseline HIV infection cases. Among participants in the TDF-FTC group, 2 of 39 incident infections occurred despite drug concentration measurements that indicated good PrEP adherence.
Although injection site reactions were reported in 81.4% (1,724) of the CAB group, only 2.4% of patients (50) discontinued treatment. Most reactions began a median of 1 day (IQR, 0-2 days) post injection. They were of mild to moderate severity (60.8% pain, 23.7% tenderness) and lasted a median of 3 days (IQR, 2-6 days). Injection site reactions were reported in 31.3% of the participants in the TDF-FTC group who received at least one placebo injection.
Rates of severe adverse effects (grade 3 or higher) were similar between participants in the CAB and TDF-FTC groups. They consisted mostly of an increase in creatine kinase level (14.2% with CAB vs. 13.5% with TDF-FTC) and a decrease in creatine clearance (7.0% with CAB vs. 8.3% with TDF-FTC).
In a post hoc analysis, the mean annualized weight increase was 1.23 kg/y (95% CI, 1.05-1.42) in the CAB group, compared with 0.37 kg/y (95% CI, 0.18-0.55) in the TDF-FTC group. Most of these differences were observed during the first 40 weeks and were driven by weight loss among TDF-FTC participants; weight changes between groups were similar thereafter (~1 kg/y for both groups).
New modality, new challenges
“We’re constantly searching for new modalities to expand our repertoire of what we can provide patients, especially those folks with the highest need for PrEP,” Lina Rosengren-Hovee, MD, assistant professor of medicine and infectious disease specialist at UNC-Health, Chapel Hill, N.C., said in an interview. “Being able to offer an injectable option is going to be a game changer, but it will be critical to pinpoint structural factors that affect adherence,” she added.
Dr. Rosengren-Hovee also pointed to cases of integrase inhibitor resistance (both in the study and the larger clinical arena), which she believes are concerning. “It’s still a conversation that you’ll want to have with a patient; I wonder if we need more discussion about how we handle that in the clinical setting, even if it’s fairly uncommon,” she said.
When asked, Dr. Landovitz emphasized the rarity of breakthrough cases but acknowledged that there appears to be a pattern whereby the first breakthrough occurs with a trickle of virus and then bursts out with higher levels of virus at some point.
“CDC is actually thinking very hard about whether these long-acting PrEP agents obligate a change to the HIV screening process [e.g., a viral load or RNA-based test] rather than a conventional HIV test,” Dr. Landovitz said. He went on to say that in the ongoing, open-label portion of the study, investigators hope to learn whether one can avoid resistance by catching the first breakthrough earlier. That would help inform clinical implementation, he explained. He said that he challenges practitioners and health care communities to avoid some of the mistakes made with the oral PrEP rollout, namely, universal access without proper implementation of planning and testing protocols.
“By default, PrEP is much more decentralized and demedicalized, especially in primary care,” said Dr. Rosengren-Hovee. “We need more studies looking at real-world scenarios.”
Dr. Rosengren-Hovee reports no relevant financial relationships. Dr. Landovitz has consulting relationships with Gilead, Janssen, Roche, and Cepheus.
A version of this article first appeared on Medscape.com.
The future of preexposure prophylaxis (PrEP) is here, according to interim study results demonstrating the superiority of long-acting, injectable cabotegravir (CAB-LA) over the current workhorse, daily oral tenofovir disoproxil fumarate-emtricitabine (TDF-FTC).
In a prospective, phase 2b-3 randomized, double-blind, double-dummy, active-controlled trial among 4,566 cisgender MSM (men who have sex with men) and transgender women, The study was terminated early, owing to strong evidence of efficacy in the first preplanned interim endpoint analysis. The study findings were published Aug. 11 in the New England Journal of Medicine.
“The lesson is not that TDF-FTC doesn’t work or has major problems; it is a very safe, very well-tolerated agent and astonishingly effective if taken as prescribed,” Raphael J. Landovitz, MD, lead author and codirector of the Center for HIV Identification, Prevention, and Treatment Services at the University of California, Los Angeles, said in an interview.
“The reason that we were able to show that cabotegravir was superior is because we enrolled a very young, very highly at-risk, very underresourced, underrepresented, highly sexually active group who weren’t able to take PrEP the way it was prescribed,” he said.
Study participants were assigned to receive either active CAB 600 mg intramuscularly with TDF-FTC placebo or active TDF-FTC (300 mg/200 mg) with a CAB procedure in three phases:
- An oral-tablet 5-week lead-in phase, a blinded injection phase beginning at week 5.
- An injection at week 9 and every 8 weeks thereafter through week 153.
- An open-label “tail” phase consisting of oral TDF/FTC to provide ongoing for participants discontinuing injections.
The median age of study participants was 26 years (interquartile range [IQR], 22-32 years); 12.5% (570) identified as transgender women; 49.8% (845/1,698) of U.S. participants were Black patients.
During follow-up, HIV infections were identified in 57 participants, including 52 who acquired HIV infections after enrollment (13 in the CAB group, incidence 0.41 per 100 person-years, vs. 39 in the TDF-FTC group, incidence 1.22 per 100 person-years). The hazard ratio for incident HIV infection was 0.34 (95% confidence interval, 0.18-0.62) CAB vs. TDF-FTC (P < .001). Consistent effects were observed across prespecified subgroups and populations.
Among participants in the CAB group, integrase strand-transfer inhibitor resistance mutations were detected in one of four of the baseline HIV infection cases. Among participants in the TDF-FTC group, 2 of 39 incident infections occurred despite drug concentration measurements that indicated good PrEP adherence.
Although injection site reactions were reported in 81.4% (1,724) of the CAB group, only 2.4% of patients (50) discontinued treatment. Most reactions began a median of 1 day (IQR, 0-2 days) post injection. They were of mild to moderate severity (60.8% pain, 23.7% tenderness) and lasted a median of 3 days (IQR, 2-6 days). Injection site reactions were reported in 31.3% of the participants in the TDF-FTC group who received at least one placebo injection.
Rates of severe adverse effects (grade 3 or higher) were similar between participants in the CAB and TDF-FTC groups. They consisted mostly of an increase in creatine kinase level (14.2% with CAB vs. 13.5% with TDF-FTC) and a decrease in creatine clearance (7.0% with CAB vs. 8.3% with TDF-FTC).
In a post hoc analysis, the mean annualized weight increase was 1.23 kg/y (95% CI, 1.05-1.42) in the CAB group, compared with 0.37 kg/y (95% CI, 0.18-0.55) in the TDF-FTC group. Most of these differences were observed during the first 40 weeks and were driven by weight loss among TDF-FTC participants; weight changes between groups were similar thereafter (~1 kg/y for both groups).
New modality, new challenges
“We’re constantly searching for new modalities to expand our repertoire of what we can provide patients, especially those folks with the highest need for PrEP,” Lina Rosengren-Hovee, MD, assistant professor of medicine and infectious disease specialist at UNC-Health, Chapel Hill, N.C., said in an interview. “Being able to offer an injectable option is going to be a game changer, but it will be critical to pinpoint structural factors that affect adherence,” she added.
Dr. Rosengren-Hovee also pointed to cases of integrase inhibitor resistance (both in the study and the larger clinical arena), which she believes are concerning. “It’s still a conversation that you’ll want to have with a patient; I wonder if we need more discussion about how we handle that in the clinical setting, even if it’s fairly uncommon,” she said.
When asked, Dr. Landovitz emphasized the rarity of breakthrough cases but acknowledged that there appears to be a pattern whereby the first breakthrough occurs with a trickle of virus and then bursts out with higher levels of virus at some point.
“CDC is actually thinking very hard about whether these long-acting PrEP agents obligate a change to the HIV screening process [e.g., a viral load or RNA-based test] rather than a conventional HIV test,” Dr. Landovitz said. He went on to say that in the ongoing, open-label portion of the study, investigators hope to learn whether one can avoid resistance by catching the first breakthrough earlier. That would help inform clinical implementation, he explained. He said that he challenges practitioners and health care communities to avoid some of the mistakes made with the oral PrEP rollout, namely, universal access without proper implementation of planning and testing protocols.
“By default, PrEP is much more decentralized and demedicalized, especially in primary care,” said Dr. Rosengren-Hovee. “We need more studies looking at real-world scenarios.”
Dr. Rosengren-Hovee reports no relevant financial relationships. Dr. Landovitz has consulting relationships with Gilead, Janssen, Roche, and Cepheus.
A version of this article first appeared on Medscape.com.
The future of preexposure prophylaxis (PrEP) is here, according to interim study results demonstrating the superiority of long-acting, injectable cabotegravir (CAB-LA) over the current workhorse, daily oral tenofovir disoproxil fumarate-emtricitabine (TDF-FTC).
In a prospective, phase 2b-3 randomized, double-blind, double-dummy, active-controlled trial among 4,566 cisgender MSM (men who have sex with men) and transgender women, The study was terminated early, owing to strong evidence of efficacy in the first preplanned interim endpoint analysis. The study findings were published Aug. 11 in the New England Journal of Medicine.
“The lesson is not that TDF-FTC doesn’t work or has major problems; it is a very safe, very well-tolerated agent and astonishingly effective if taken as prescribed,” Raphael J. Landovitz, MD, lead author and codirector of the Center for HIV Identification, Prevention, and Treatment Services at the University of California, Los Angeles, said in an interview.
“The reason that we were able to show that cabotegravir was superior is because we enrolled a very young, very highly at-risk, very underresourced, underrepresented, highly sexually active group who weren’t able to take PrEP the way it was prescribed,” he said.
Study participants were assigned to receive either active CAB 600 mg intramuscularly with TDF-FTC placebo or active TDF-FTC (300 mg/200 mg) with a CAB procedure in three phases:
- An oral-tablet 5-week lead-in phase, a blinded injection phase beginning at week 5.
- An injection at week 9 and every 8 weeks thereafter through week 153.
- An open-label “tail” phase consisting of oral TDF/FTC to provide ongoing for participants discontinuing injections.
The median age of study participants was 26 years (interquartile range [IQR], 22-32 years); 12.5% (570) identified as transgender women; 49.8% (845/1,698) of U.S. participants were Black patients.
During follow-up, HIV infections were identified in 57 participants, including 52 who acquired HIV infections after enrollment (13 in the CAB group, incidence 0.41 per 100 person-years, vs. 39 in the TDF-FTC group, incidence 1.22 per 100 person-years). The hazard ratio for incident HIV infection was 0.34 (95% confidence interval, 0.18-0.62) CAB vs. TDF-FTC (P < .001). Consistent effects were observed across prespecified subgroups and populations.
Among participants in the CAB group, integrase strand-transfer inhibitor resistance mutations were detected in one of four of the baseline HIV infection cases. Among participants in the TDF-FTC group, 2 of 39 incident infections occurred despite drug concentration measurements that indicated good PrEP adherence.
Although injection site reactions were reported in 81.4% (1,724) of the CAB group, only 2.4% of patients (50) discontinued treatment. Most reactions began a median of 1 day (IQR, 0-2 days) post injection. They were of mild to moderate severity (60.8% pain, 23.7% tenderness) and lasted a median of 3 days (IQR, 2-6 days). Injection site reactions were reported in 31.3% of the participants in the TDF-FTC group who received at least one placebo injection.
Rates of severe adverse effects (grade 3 or higher) were similar between participants in the CAB and TDF-FTC groups. They consisted mostly of an increase in creatine kinase level (14.2% with CAB vs. 13.5% with TDF-FTC) and a decrease in creatine clearance (7.0% with CAB vs. 8.3% with TDF-FTC).
In a post hoc analysis, the mean annualized weight increase was 1.23 kg/y (95% CI, 1.05-1.42) in the CAB group, compared with 0.37 kg/y (95% CI, 0.18-0.55) in the TDF-FTC group. Most of these differences were observed during the first 40 weeks and were driven by weight loss among TDF-FTC participants; weight changes between groups were similar thereafter (~1 kg/y for both groups).
New modality, new challenges
“We’re constantly searching for new modalities to expand our repertoire of what we can provide patients, especially those folks with the highest need for PrEP,” Lina Rosengren-Hovee, MD, assistant professor of medicine and infectious disease specialist at UNC-Health, Chapel Hill, N.C., said in an interview. “Being able to offer an injectable option is going to be a game changer, but it will be critical to pinpoint structural factors that affect adherence,” she added.
Dr. Rosengren-Hovee also pointed to cases of integrase inhibitor resistance (both in the study and the larger clinical arena), which she believes are concerning. “It’s still a conversation that you’ll want to have with a patient; I wonder if we need more discussion about how we handle that in the clinical setting, even if it’s fairly uncommon,” she said.
When asked, Dr. Landovitz emphasized the rarity of breakthrough cases but acknowledged that there appears to be a pattern whereby the first breakthrough occurs with a trickle of virus and then bursts out with higher levels of virus at some point.
“CDC is actually thinking very hard about whether these long-acting PrEP agents obligate a change to the HIV screening process [e.g., a viral load or RNA-based test] rather than a conventional HIV test,” Dr. Landovitz said. He went on to say that in the ongoing, open-label portion of the study, investigators hope to learn whether one can avoid resistance by catching the first breakthrough earlier. That would help inform clinical implementation, he explained. He said that he challenges practitioners and health care communities to avoid some of the mistakes made with the oral PrEP rollout, namely, universal access without proper implementation of planning and testing protocols.
“By default, PrEP is much more decentralized and demedicalized, especially in primary care,” said Dr. Rosengren-Hovee. “We need more studies looking at real-world scenarios.”
Dr. Rosengren-Hovee reports no relevant financial relationships. Dr. Landovitz has consulting relationships with Gilead, Janssen, Roche, and Cepheus.
A version of this article first appeared on Medscape.com.
New guideline for replacement ART: CAB/RPV LA not for everyone
“One of the most important considerations before switching HIV patients to injectable long-acting cabotegravir/rilpivirine [CAB/RPV LA; Cabenuva, ViiV Healthcare] is for the patient and the clinician to arrive at this decision together,” Elliot DeHaan, MD, told this news organization. “This therapy is not necessarily for everyone.”
Dr. DeHaan is lead author of the newly released clinical guideline from the New York State Department of Health AIDS Institute for use of CAB/RPV LA as replacement antiretroviral therapy (ART) in virally suppressed adults with HIV. He explained that the guidance expands upon Health & Human Services’ Feb. 24 CAB/RPV LA recommendations, highlighting some of the most important clinical and patient considerations necessary to implement injectable ART. “There are a lot of things that need to be laid out beforehand,” he said.
Gaining consensus
Approved by the FDA in late January 2021, CAB/RPV LA is considered an optimization strategy for individuals with HIV whose virus is suppressed by oral ART and who might prefer monthly injections to daily oral therapy. While there are various reasons why patients might wish to switch to a long-acting injectable, one of the primary concerns is adherence. Of note, the guidance points to phase 3 clinical study findings that suggest high levels (86%-91%) of patient satisfaction with CAB/RPV LA, which portends a promising future for this therapeutic approach.
With regard to patient preference, recommendations focus on the need to thoroughly discuss several critical requisites with potential candidates, including a 4-week lead-in daily oral ART course (CAB [Vocabria] 30 mg, RPV [Edurant] 25 mg) before initiating a loading dose. Patients should be advised of the potential for development of resistance should dosing be interrupted for any reason (CAB and RPV have extended half-lives ranging from mean 5.6 to 11.5 weeks for CAB and 13 to 28 weeks for RPV), as well as the need to return to oral bridging therapy if subsequent injections are not administered within the 7-day window period. If the maintenance dose is delayed beyond 2 months, a loading dose and restart is necessary.
CAB/RPV LA therapy is administered into opposing gluteal muscles (CAB into one gluteus medius and RPV into the contralateral gluteus medius), and injection-site pain beginning 1 day post-injection and lasting 3-4 days is common. In phase 3 clinical trials, as many as 83% of patients experienced adverse effects (AEs), which also include nodules, induration, and swelling at the injection sites. Fortunately, 99% of AEs were of mild to moderate severity. While pain tends to decline over several injections, Dr. DeHaan said that it’s an important part of the initial discussion about switching therapies.
Other considerations
Prior resistance testing, ART treatment history, and/or baseline genotypic resistance testing that includes both reverse transcriptase and integrase genes should be reviewed or conducted before initiating treatment. K103 mutations alone are not considered exclusionary. Virologic failures (defined as two consecutive plasma HIV-1 RNA measurements greater than 200 copies/mL), while rare, were reported in 13 clinical trial participants. Recent data suggest that patients who developed resistance despite adherence had at least two of three factors: a body mass index greater than 30 kg/m2, the HIV-1 subtype A6/A1, and the presence of proviral RPV RAMS.
CAB/RPV LA does not treat hepatitis B (HBV) coinfections, reinforcing the need for concurrent oral HBV therapy.
And there’s a paucity of data on the safety and efficacy of CAB/RPV in children and adolescents, or during pregnancy/lactation, precluding its use in those patient populations.
Clinical, institutional considerations
Adaptation of CAB/RPV LA as ART requires specific clinical institutional planning, especially in light of current pandemic-related resource and staffing limitations. Monthly dosing must be done within a 7-day window and requires preparations akin to initial loading doses. In addition to pharmacy resources and onsite storage requirements, the guidance points to patient scheduling and reminder systems, access (patient transportation, work constraints, parking), and most importantly, contingency plans for care (including oral bridging therapy) should a clinic be forced to shut down for any reason. Additional factors include billing protocols, insurance or third party authorizations, and provision of counseling and education training.
“Given that this is a completely new way of thinking among providers, we’re all learning together,” said David Koren, PharmD, MPH, a clinical pharmacy specialist in infectious diseases at Temple University, Philadelphia. “The guidelines provide a nice framework for taking the next step to operationalize these processes into practice, taking into account that barriers to implementation are still unknown.” Dr. Koren was not involved in the development of the guidelines.
Dr. DeHaan has disclosed no relevant financial relationships. Dr. Koren disclosed serving on a prior Advisory Panel for ViiV Healthcare US.
A version of this article first appeared on Medscape.com.
“One of the most important considerations before switching HIV patients to injectable long-acting cabotegravir/rilpivirine [CAB/RPV LA; Cabenuva, ViiV Healthcare] is for the patient and the clinician to arrive at this decision together,” Elliot DeHaan, MD, told this news organization. “This therapy is not necessarily for everyone.”
Dr. DeHaan is lead author of the newly released clinical guideline from the New York State Department of Health AIDS Institute for use of CAB/RPV LA as replacement antiretroviral therapy (ART) in virally suppressed adults with HIV. He explained that the guidance expands upon Health & Human Services’ Feb. 24 CAB/RPV LA recommendations, highlighting some of the most important clinical and patient considerations necessary to implement injectable ART. “There are a lot of things that need to be laid out beforehand,” he said.
Gaining consensus
Approved by the FDA in late January 2021, CAB/RPV LA is considered an optimization strategy for individuals with HIV whose virus is suppressed by oral ART and who might prefer monthly injections to daily oral therapy. While there are various reasons why patients might wish to switch to a long-acting injectable, one of the primary concerns is adherence. Of note, the guidance points to phase 3 clinical study findings that suggest high levels (86%-91%) of patient satisfaction with CAB/RPV LA, which portends a promising future for this therapeutic approach.
With regard to patient preference, recommendations focus on the need to thoroughly discuss several critical requisites with potential candidates, including a 4-week lead-in daily oral ART course (CAB [Vocabria] 30 mg, RPV [Edurant] 25 mg) before initiating a loading dose. Patients should be advised of the potential for development of resistance should dosing be interrupted for any reason (CAB and RPV have extended half-lives ranging from mean 5.6 to 11.5 weeks for CAB and 13 to 28 weeks for RPV), as well as the need to return to oral bridging therapy if subsequent injections are not administered within the 7-day window period. If the maintenance dose is delayed beyond 2 months, a loading dose and restart is necessary.
CAB/RPV LA therapy is administered into opposing gluteal muscles (CAB into one gluteus medius and RPV into the contralateral gluteus medius), and injection-site pain beginning 1 day post-injection and lasting 3-4 days is common. In phase 3 clinical trials, as many as 83% of patients experienced adverse effects (AEs), which also include nodules, induration, and swelling at the injection sites. Fortunately, 99% of AEs were of mild to moderate severity. While pain tends to decline over several injections, Dr. DeHaan said that it’s an important part of the initial discussion about switching therapies.
Other considerations
Prior resistance testing, ART treatment history, and/or baseline genotypic resistance testing that includes both reverse transcriptase and integrase genes should be reviewed or conducted before initiating treatment. K103 mutations alone are not considered exclusionary. Virologic failures (defined as two consecutive plasma HIV-1 RNA measurements greater than 200 copies/mL), while rare, were reported in 13 clinical trial participants. Recent data suggest that patients who developed resistance despite adherence had at least two of three factors: a body mass index greater than 30 kg/m2, the HIV-1 subtype A6/A1, and the presence of proviral RPV RAMS.
CAB/RPV LA does not treat hepatitis B (HBV) coinfections, reinforcing the need for concurrent oral HBV therapy.
And there’s a paucity of data on the safety and efficacy of CAB/RPV in children and adolescents, or during pregnancy/lactation, precluding its use in those patient populations.
Clinical, institutional considerations
Adaptation of CAB/RPV LA as ART requires specific clinical institutional planning, especially in light of current pandemic-related resource and staffing limitations. Monthly dosing must be done within a 7-day window and requires preparations akin to initial loading doses. In addition to pharmacy resources and onsite storage requirements, the guidance points to patient scheduling and reminder systems, access (patient transportation, work constraints, parking), and most importantly, contingency plans for care (including oral bridging therapy) should a clinic be forced to shut down for any reason. Additional factors include billing protocols, insurance or third party authorizations, and provision of counseling and education training.
“Given that this is a completely new way of thinking among providers, we’re all learning together,” said David Koren, PharmD, MPH, a clinical pharmacy specialist in infectious diseases at Temple University, Philadelphia. “The guidelines provide a nice framework for taking the next step to operationalize these processes into practice, taking into account that barriers to implementation are still unknown.” Dr. Koren was not involved in the development of the guidelines.
Dr. DeHaan has disclosed no relevant financial relationships. Dr. Koren disclosed serving on a prior Advisory Panel for ViiV Healthcare US.
A version of this article first appeared on Medscape.com.
“One of the most important considerations before switching HIV patients to injectable long-acting cabotegravir/rilpivirine [CAB/RPV LA; Cabenuva, ViiV Healthcare] is for the patient and the clinician to arrive at this decision together,” Elliot DeHaan, MD, told this news organization. “This therapy is not necessarily for everyone.”
Dr. DeHaan is lead author of the newly released clinical guideline from the New York State Department of Health AIDS Institute for use of CAB/RPV LA as replacement antiretroviral therapy (ART) in virally suppressed adults with HIV. He explained that the guidance expands upon Health & Human Services’ Feb. 24 CAB/RPV LA recommendations, highlighting some of the most important clinical and patient considerations necessary to implement injectable ART. “There are a lot of things that need to be laid out beforehand,” he said.
Gaining consensus
Approved by the FDA in late January 2021, CAB/RPV LA is considered an optimization strategy for individuals with HIV whose virus is suppressed by oral ART and who might prefer monthly injections to daily oral therapy. While there are various reasons why patients might wish to switch to a long-acting injectable, one of the primary concerns is adherence. Of note, the guidance points to phase 3 clinical study findings that suggest high levels (86%-91%) of patient satisfaction with CAB/RPV LA, which portends a promising future for this therapeutic approach.
With regard to patient preference, recommendations focus on the need to thoroughly discuss several critical requisites with potential candidates, including a 4-week lead-in daily oral ART course (CAB [Vocabria] 30 mg, RPV [Edurant] 25 mg) before initiating a loading dose. Patients should be advised of the potential for development of resistance should dosing be interrupted for any reason (CAB and RPV have extended half-lives ranging from mean 5.6 to 11.5 weeks for CAB and 13 to 28 weeks for RPV), as well as the need to return to oral bridging therapy if subsequent injections are not administered within the 7-day window period. If the maintenance dose is delayed beyond 2 months, a loading dose and restart is necessary.
CAB/RPV LA therapy is administered into opposing gluteal muscles (CAB into one gluteus medius and RPV into the contralateral gluteus medius), and injection-site pain beginning 1 day post-injection and lasting 3-4 days is common. In phase 3 clinical trials, as many as 83% of patients experienced adverse effects (AEs), which also include nodules, induration, and swelling at the injection sites. Fortunately, 99% of AEs were of mild to moderate severity. While pain tends to decline over several injections, Dr. DeHaan said that it’s an important part of the initial discussion about switching therapies.
Other considerations
Prior resistance testing, ART treatment history, and/or baseline genotypic resistance testing that includes both reverse transcriptase and integrase genes should be reviewed or conducted before initiating treatment. K103 mutations alone are not considered exclusionary. Virologic failures (defined as two consecutive plasma HIV-1 RNA measurements greater than 200 copies/mL), while rare, were reported in 13 clinical trial participants. Recent data suggest that patients who developed resistance despite adherence had at least two of three factors: a body mass index greater than 30 kg/m2, the HIV-1 subtype A6/A1, and the presence of proviral RPV RAMS.
CAB/RPV LA does not treat hepatitis B (HBV) coinfections, reinforcing the need for concurrent oral HBV therapy.
And there’s a paucity of data on the safety and efficacy of CAB/RPV in children and adolescents, or during pregnancy/lactation, precluding its use in those patient populations.
Clinical, institutional considerations
Adaptation of CAB/RPV LA as ART requires specific clinical institutional planning, especially in light of current pandemic-related resource and staffing limitations. Monthly dosing must be done within a 7-day window and requires preparations akin to initial loading doses. In addition to pharmacy resources and onsite storage requirements, the guidance points to patient scheduling and reminder systems, access (patient transportation, work constraints, parking), and most importantly, contingency plans for care (including oral bridging therapy) should a clinic be forced to shut down for any reason. Additional factors include billing protocols, insurance or third party authorizations, and provision of counseling and education training.
“Given that this is a completely new way of thinking among providers, we’re all learning together,” said David Koren, PharmD, MPH, a clinical pharmacy specialist in infectious diseases at Temple University, Philadelphia. “The guidelines provide a nice framework for taking the next step to operationalize these processes into practice, taking into account that barriers to implementation are still unknown.” Dr. Koren was not involved in the development of the guidelines.
Dr. DeHaan has disclosed no relevant financial relationships. Dr. Koren disclosed serving on a prior Advisory Panel for ViiV Healthcare US.
A version of this article first appeared on Medscape.com.