HIV

A new, highly-virulent form of the HIV-1 virus has been discovered in the Netherlands by an international collaboration led by researchers at the University of Oxford’s Big Data Institute.

In a study published in the journal Science, researchers identified a VB variant (virulent subtype B) of HIV-1 linked to higher viral loads, increased transmissibility, and a faster decline in CD4 cell levels, leading to increased immune deficiency.

In light of the ongoing pandemic and current focus on SARS-CoV-19 virus variants such as Delta or Omicron, the discovery provides a salutary reminder that other viral pathogens, including those responsible for many long-standing endemic diseases, undergo a similar process of mutation.

Lead author Dr. Chris Wymant said: “Before this study, the genetics of the HIV virus were known to be relevant for virulence, implying that the evolution of a new variant could change its impact on health. Discovery of the VB variant demonstrated this, providing a rare example of the risk posed by viral virulence evolution.”
 

Global disease, local variants

Human immunodeficiency virus (HIV) infections affect around 38 million people worldwide, with more than half a million  people dying from AIDS-related illnesses each year. The disease-causing retroviruses, of which the HIV-1 virus is most common, destroy CD4+ T cells, causing immune deficiency and leading eventually to AIDS.

RNA viruses such as HIV-1 have long been a particular concern to scientists because their error-prone replication, lacking the error-correcting mechanisms of DNA, results in more spontaneous mutations and so a higher potential for acquiring new characteristics.

The VB variant of HIV-1 was first detected in samples from 2,461 HIV-positive people whose viral genomes were sequenced as part of the ongoing BEEHIVE project. Within this cohort, researchers identified 17 people with very highly elevated viral loads.

As 15 of these individuals came from the Netherlands, the researchers next examined virus gene data from 6,706 HIV-positive patients in a Dutch HIV cohort study (ATHENA), identifying a further 92 people carrying the same VB variant.

By analysing patterns of genetic variation in the samples, researchers estimated that the VB variant first emerged in the Netherlands in the late 1990s, occurring through de novo mutations rather than recombination. It spread more quickly than other HIV variants initially, but cases have been declining since around 2010, most likely due to the availability of more effective combination anti-retroviral treatments.
 

Increased virulence

The researchers found a number of differences in people infected with the VB variant compared with those infected by other HIV variants. Prior to starting anti-retroviral treatment, individuals with the VB variant were found to have:

Around a 3.5- to 5.5-fold increase in viral load (a marker for viral virulence)

Double the rate of CD4 cell decline compared with individuals with other subtype-B strains, even after adjusting for viral load

Increased risk of transmitting the virus (the study used the virus ‘local branching index’ as a proxy for transmissibility).

Reassuringly, after starting anti-retroviral treatment, individuals with the VB variant showed similar CD4 cell recovery and survival to individuals with other HIV variants. However, the authors emphasise that due of the more rapid decline in immune function with the VB variant, it is critical to identify VB-positive individuals early and start treatment promptly.

Senior author Professor Christophe Fraser explained: “Our findings emphasise the importance of World Health Organization guidance that individuals at risk of acquiring HIV have access to regular testing to allow early diagnosis, followed by immediate treatment.

“This limits the amount of time HIV can damage an individual’s immune system and jeopardise their health. It also ensures that HIV is suppressed as quickly as possible, which prevents transmission to other individuals.”

A version of this article first appeared on Medscape.com.

A new, highly-virulent form of the HIV-1 virus has been discovered in the Netherlands by an international collaboration led by researchers at the University of Oxford’s Big Data Institute.

In a study published in the journal Science, researchers identified a VB variant (virulent subtype B) of HIV-1 linked to higher viral loads, increased transmissibility, and a faster decline in CD4 cell levels, leading to increased immune deficiency.

In light of the ongoing pandemic and current focus on SARS-CoV-19 virus variants such as Delta or Omicron, the discovery provides a salutary reminder that other viral pathogens, including those responsible for many long-standing endemic diseases, undergo a similar process of mutation.

Lead author Dr. Chris Wymant said: “Before this study, the genetics of the HIV virus were known to be relevant for virulence, implying that the evolution of a new variant could change its impact on health. Discovery of the VB variant demonstrated this, providing a rare example of the risk posed by viral virulence evolution.”
 

Global disease, local variants

Human immunodeficiency virus (HIV) infections affect around 38 million people worldwide, with more than half a million  people dying from AIDS-related illnesses each year. The disease-causing retroviruses, of which the HIV-1 virus is most common, destroy CD4+ T cells, causing immune deficiency and leading eventually to AIDS.

RNA viruses such as HIV-1 have long been a particular concern to scientists because their error-prone replication, lacking the error-correcting mechanisms of DNA, results in more spontaneous mutations and so a higher potential for acquiring new characteristics.

The VB variant of HIV-1 was first detected in samples from 2,461 HIV-positive people whose viral genomes were sequenced as part of the ongoing BEEHIVE project. Within this cohort, researchers identified 17 people with very highly elevated viral loads.

As 15 of these individuals came from the Netherlands, the researchers next examined virus gene data from 6,706 HIV-positive patients in a Dutch HIV cohort study (ATHENA), identifying a further 92 people carrying the same VB variant.

By analysing patterns of genetic variation in the samples, researchers estimated that the VB variant first emerged in the Netherlands in the late 1990s, occurring through de novo mutations rather than recombination. It spread more quickly than other HIV variants initially, but cases have been declining since around 2010, most likely due to the availability of more effective combination anti-retroviral treatments.
 

Increased virulence

The researchers found a number of differences in people infected with the VB variant compared with those infected by other HIV variants. Prior to starting anti-retroviral treatment, individuals with the VB variant were found to have:

Around a 3.5- to 5.5-fold increase in viral load (a marker for viral virulence)

Double the rate of CD4 cell decline compared with individuals with other subtype-B strains, even after adjusting for viral load

Increased risk of transmitting the virus (the study used the virus ‘local branching index’ as a proxy for transmissibility).

Reassuringly, after starting anti-retroviral treatment, individuals with the VB variant showed similar CD4 cell recovery and survival to individuals with other HIV variants. However, the authors emphasise that due of the more rapid decline in immune function with the VB variant, it is critical to identify VB-positive individuals early and start treatment promptly.

Senior author Professor Christophe Fraser explained: “Our findings emphasise the importance of World Health Organization guidance that individuals at risk of acquiring HIV have access to regular testing to allow early diagnosis, followed by immediate treatment.

“This limits the amount of time HIV can damage an individual’s immune system and jeopardise their health. It also ensures that HIV is suppressed as quickly as possible, which prevents transmission to other individuals.”

A version of this article first appeared on Medscape.com.

A new, highly-virulent form of the HIV-1 virus has been discovered in the Netherlands by an international collaboration led by researchers at the University of Oxford’s Big Data Institute.

In a study published in the journal Science, researchers identified a VB variant (virulent subtype B) of HIV-1 linked to higher viral loads, increased transmissibility, and a faster decline in CD4 cell levels, leading to increased immune deficiency.

In light of the ongoing pandemic and current focus on SARS-CoV-19 virus variants such as Delta or Omicron, the discovery provides a salutary reminder that other viral pathogens, including those responsible for many long-standing endemic diseases, undergo a similar process of mutation.

Lead author Dr. Chris Wymant said: “Before this study, the genetics of the HIV virus were known to be relevant for virulence, implying that the evolution of a new variant could change its impact on health. Discovery of the VB variant demonstrated this, providing a rare example of the risk posed by viral virulence evolution.”
 

Global disease, local variants

Human immunodeficiency virus (HIV) infections affect around 38 million people worldwide, with more than half a million  people dying from AIDS-related illnesses each year. The disease-causing retroviruses, of which the HIV-1 virus is most common, destroy CD4+ T cells, causing immune deficiency and leading eventually to AIDS.

RNA viruses such as HIV-1 have long been a particular concern to scientists because their error-prone replication, lacking the error-correcting mechanisms of DNA, results in more spontaneous mutations and so a higher potential for acquiring new characteristics.

The VB variant of HIV-1 was first detected in samples from 2,461 HIV-positive people whose viral genomes were sequenced as part of the ongoing BEEHIVE project. Within this cohort, researchers identified 17 people with very highly elevated viral loads.

As 15 of these individuals came from the Netherlands, the researchers next examined virus gene data from 6,706 HIV-positive patients in a Dutch HIV cohort study (ATHENA), identifying a further 92 people carrying the same VB variant.

By analysing patterns of genetic variation in the samples, researchers estimated that the VB variant first emerged in the Netherlands in the late 1990s, occurring through de novo mutations rather than recombination. It spread more quickly than other HIV variants initially, but cases have been declining since around 2010, most likely due to the availability of more effective combination anti-retroviral treatments.
 

Increased virulence

The researchers found a number of differences in people infected with the VB variant compared with those infected by other HIV variants. Prior to starting anti-retroviral treatment, individuals with the VB variant were found to have:

Around a 3.5- to 5.5-fold increase in viral load (a marker for viral virulence)

Double the rate of CD4 cell decline compared with individuals with other subtype-B strains, even after adjusting for viral load

Increased risk of transmitting the virus (the study used the virus ‘local branching index’ as a proxy for transmissibility).

Reassuringly, after starting anti-retroviral treatment, individuals with the VB variant showed similar CD4 cell recovery and survival to individuals with other HIV variants. However, the authors emphasise that due of the more rapid decline in immune function with the VB variant, it is critical to identify VB-positive individuals early and start treatment promptly.

Senior author Professor Christophe Fraser explained: “Our findings emphasise the importance of World Health Organization guidance that individuals at risk of acquiring HIV have access to regular testing to allow early diagnosis, followed by immediate treatment.

“This limits the amount of time HIV can damage an individual’s immune system and jeopardise their health. It also ensures that HIV is suppressed as quickly as possible, which prevents transmission to other individuals.”

A version of this article first appeared on Medscape.com.

The U.S. Food and Drug Administration has approved rilpivirine and cabotegravir (Cabenuva) to 2-month dosing for adults living with HIV-1 infection.

Cabenuva was first approved by the FDA in January 2021 to be administered once monthly to treat HIV-1 infection in virologically suppressed adults. The medication was the first injectable complete antiretroviral regimen approved by the FDA.

Cabenuva can replace a current treatment in virologically suppressed adults on a stable antiretroviral regimen with no history of treatment failure and no known or suspected resistance to rilpivirine and cabotegravir, the Janssen Pharmaceutical Companies of Johnson & Johnson said in a press release. Janssen and ViiV Healthcare codeveloped the injectable antiretroviral medication Cabenuva.

The expanded label approval “marks an important step forward in advancing the treatment landscape for people living with HIV,” said Candice Long, the president of infectious diseases and vaccines at Janssen Therapeutics, in a Feb. 1 press release. “With this milestone, adults living with HIV have a treatment option that further reduces the frequency of medication.”

This expanded approval was based on global clinical trial of 1,045 adults with HIV-1, which found Cabenuva administered every 8 weeks (3 mL dose of both cabotegravir and rilpivirine) to be noninferior to the 4-week regimen (2 mL dose of both medicines). At week 48 of the trial, the proportion of participants with viral loads above 50 copies per milliliter was 1.7% in the 2-month arm and 1.0% in the 1-month arm. The study found that rates of virological suppression were similar for both the 1-month and 2-month regimens (93.5% and 94.3%, respectively).

The most common side effects were injection site reactions, pyrexia, fatigue, headache, musculoskeletal pain, nausea, sleep disorders, dizziness, and rash. Adverse reactions reported in individuals receiving the regimen every 2 months or once monthly were similar. Cabenuva is contraindicated for patients with a hypersensitivity reaction to cabotegravir or rilpivirine or for those receiving carbamazepine, oxcarbazepine, phenobarbital, phenytoin, rifabutin, rifampin, rifapentine, St. John’s wort, and more than one dose of systemic dexamethasone.

A version of this article first appeared on Medscape.com.

The U.S. Food and Drug Administration has approved rilpivirine and cabotegravir (Cabenuva) to 2-month dosing for adults living with HIV-1 infection.

Cabenuva was first approved by the FDA in January 2021 to be administered once monthly to treat HIV-1 infection in virologically suppressed adults. The medication was the first injectable complete antiretroviral regimen approved by the FDA.

Cabenuva can replace a current treatment in virologically suppressed adults on a stable antiretroviral regimen with no history of treatment failure and no known or suspected resistance to rilpivirine and cabotegravir, the Janssen Pharmaceutical Companies of Johnson & Johnson said in a press release. Janssen and ViiV Healthcare codeveloped the injectable antiretroviral medication Cabenuva.

The expanded label approval “marks an important step forward in advancing the treatment landscape for people living with HIV,” said Candice Long, the president of infectious diseases and vaccines at Janssen Therapeutics, in a Feb. 1 press release. “With this milestone, adults living with HIV have a treatment option that further reduces the frequency of medication.”

This expanded approval was based on global clinical trial of 1,045 adults with HIV-1, which found Cabenuva administered every 8 weeks (3 mL dose of both cabotegravir and rilpivirine) to be noninferior to the 4-week regimen (2 mL dose of both medicines). At week 48 of the trial, the proportion of participants with viral loads above 50 copies per milliliter was 1.7% in the 2-month arm and 1.0% in the 1-month arm. The study found that rates of virological suppression were similar for both the 1-month and 2-month regimens (93.5% and 94.3%, respectively).

The most common side effects were injection site reactions, pyrexia, fatigue, headache, musculoskeletal pain, nausea, sleep disorders, dizziness, and rash. Adverse reactions reported in individuals receiving the regimen every 2 months or once monthly were similar. Cabenuva is contraindicated for patients with a hypersensitivity reaction to cabotegravir or rilpivirine or for those receiving carbamazepine, oxcarbazepine, phenobarbital, phenytoin, rifabutin, rifampin, rifapentine, St. John’s wort, and more than one dose of systemic dexamethasone.

A version of this article first appeared on Medscape.com.

The U.S. Food and Drug Administration has approved rilpivirine and cabotegravir (Cabenuva) to 2-month dosing for adults living with HIV-1 infection.

Cabenuva was first approved by the FDA in January 2021 to be administered once monthly to treat HIV-1 infection in virologically suppressed adults. The medication was the first injectable complete antiretroviral regimen approved by the FDA.

Cabenuva can replace a current treatment in virologically suppressed adults on a stable antiretroviral regimen with no history of treatment failure and no known or suspected resistance to rilpivirine and cabotegravir, the Janssen Pharmaceutical Companies of Johnson & Johnson said in a press release. Janssen and ViiV Healthcare codeveloped the injectable antiretroviral medication Cabenuva.

The expanded label approval “marks an important step forward in advancing the treatment landscape for people living with HIV,” said Candice Long, the president of infectious diseases and vaccines at Janssen Therapeutics, in a Feb. 1 press release. “With this milestone, adults living with HIV have a treatment option that further reduces the frequency of medication.”

This expanded approval was based on global clinical trial of 1,045 adults with HIV-1, which found Cabenuva administered every 8 weeks (3 mL dose of both cabotegravir and rilpivirine) to be noninferior to the 4-week regimen (2 mL dose of both medicines). At week 48 of the trial, the proportion of participants with viral loads above 50 copies per milliliter was 1.7% in the 2-month arm and 1.0% in the 1-month arm. The study found that rates of virological suppression were similar for both the 1-month and 2-month regimens (93.5% and 94.3%, respectively).

The most common side effects were injection site reactions, pyrexia, fatigue, headache, musculoskeletal pain, nausea, sleep disorders, dizziness, and rash. Adverse reactions reported in individuals receiving the regimen every 2 months or once monthly were similar. Cabenuva is contraindicated for patients with a hypersensitivity reaction to cabotegravir or rilpivirine or for those receiving carbamazepine, oxcarbazepine, phenobarbital, phenytoin, rifabutin, rifampin, rifapentine, St. John’s wort, and more than one dose of systemic dexamethasone.

A version of this article first appeared on Medscape.com.

Four decades into the AIDS epidemic and for some, it’s as if gains in awareness, advances in prevention and treatment, and the concept of undetected equals untransmissable (U=U) never happened. In its place, people living with HIV continue to face discrimination and stigma that affect nearly every aspect of the care continuum, from testing, prevention, and treatment to linkage to sexual, health, and reproductive services.

Accordingly, findings from a Harris poll conducted Oct. 13-18, 2021, among 5,047 adults (18 and older) residing in Australia, Portugal, the United Kingdom, and the United States, reveal that 88% of those surveyed believe that negative perceptions toward people living with HIV persist even though HIV infection can be effectively managed with antiretroviral therapy (ART). Conversely, three-quarters (76%) are unaware of U=U, and the fact that someone with HIV who is taking effective treatment cannot pass it on to their partner. Two-thirds incorrectly believe that a person living with HIV can pass it onto their baby, even when they are ART adherent.

“The survey made me think of people who work in HIV clinics, and how much of a bubble I think that we in the HIV field live in,” Nneka Nwokolo, MBBS, senior global medical director at ViiV Healthcare, London, and practicing consultant in sexual health and HIV medicine, told this news organization. “I think that we generally feel that everyone knows as much as we do or feels the way that we do.”
 

Misconceptions abound across the globe

The online survey, which was commissioned by ViiV Healthcare, also highlights that one in five adults do not know that anyone can acquire HIV regardless of lifestyle, thereby perpetuating the stereotype that HIV is a disease that only affects certain populations, such as men who have sex with men (MSM) or transgender women (TGW). 

Pervasive stereotypes and stigmatization only serve to magnify preexisting social inequities that affect access to appropriate care. A recent editorial published in the journal AIDS and Behavior underscores that stigma experienced by marginalized populations in particular (for example, Black MSM, TGW) is directly linked to decreased access to and use of effective HIV prevention and treatment services. Additionally, once stigma becomes internalized, it might further affect overall well-being, mental health, and social support.

“One of the most significant consequences of the ongoing stigma is that people are scared to test and then they end up coming to services late [when] they’re really ill,” explained Dr. Nwokolo. “It goes back to the early days when HIV was a death sentence ... it’s still there. I have one patient who to this day hates the fact that he has HIV, that he has to come to the clinic – it’s a reminder of why he hates himself.”

Great strides in testing and advances in treatment might be helping to reframe HIV as a chronic but treatable and preventable disease. Nevertheless, survey findings also revealed that nearly three out of five adults incorrectly believe that a person living with HIV will have a shorter lifespan than someone who is HIV negative, even if they are on effective treatment. 

These beliefs are especially true among Dr. Nwokolo’s patient base, most of whom are Africans who’ve immigrated to the United Kingdom from countries that have been devastated by the HIV epidemic. “Those who’ve never tested are reluctant to do so because they are afraid that they will have the same outcome as the people that they know that they’ve left behind,” she said.
 

HIV stigma in the era of 90-90-90

While there has been progress toward achieving UN AID’s 90-90-90 targets (that is, 90% living with HIV know their status, 90% who know their status are on ART, and 90% of people on ART are virally suppressed), exclusion and isolation – the key hallmarks of stigma – may ultimately be the most important barriers preventing a lofty goal to end the AIDS epidemic by the year 2030.

“Here we are, 40 years in and we are still facing such ignorance, some stigma,” Carl Schmid, MBA, former cochair of the Presidential Advisory Council on HIV/AIDS, and executive director of HIV+Policy Institute, told this news organization. “It’s gotten better, but it is really putting a damper on people being tested, getting treated, getting access to PrEP.” Mr. Schmid was not involved in the Harris Poll.

Mr. Schmid also said that, in addition to broader outreach and education as well as dissemination of information about HIV and AIDS from the White House and other government leaders, physician involvement is essential. 

“They’re the ones that need to step up. They have to talk about sex with their patients, [but] they don’t do that, especially in the South among certain populations,” he noted.

Data support the unique challenges faced by at-risk individuals living in the southern United States. Not only do Southern states account for roughly half of all new HIV cases annually, but Black MSM and Black women account for the majority of new diagnoses, according to the Centers for Disease Control and Prevention. Data have also demonstrated discrimination and prejudice toward people with HIV persist among many medical professionals in the South (especially those working in rural areas).

But this is not only a Southern problem; a 2018 review of studies in clinicians across the United States published in AIDS Patient Care and STDs linked provider fear of acquiring HIV through occupational exposure to reduced quality of care, refusal of care, and anxiety, especially among providers with limited awareness of PrEP. Discordant attitudes around making a priority to address HIV-related stigma versus other health care needs also reduced overall care delivery and patient experience.

“I think that the first thing that we as HIV clinicians can and should do – and is definitely within our power to do – is to educate our peers about HIV,” Dr. Nwokolo said, “HIV has gone off the radar, but it’s still out there.”

The study was commissioned by Viiv Healthcare. Dr. Nwokolo is an employee of ViiV Healthcare. Mr. Schmid disclosed no relevant financial relationships.

A version of this article first appeared on Medscape.com.

Four decades into the AIDS epidemic and for some, it’s as if gains in awareness, advances in prevention and treatment, and the concept of undetected equals untransmissable (U=U) never happened. In its place, people living with HIV continue to face discrimination and stigma that affect nearly every aspect of the care continuum, from testing, prevention, and treatment to linkage to sexual, health, and reproductive services.

Accordingly, findings from a Harris poll conducted Oct. 13-18, 2021, among 5,047 adults (18 and older) residing in Australia, Portugal, the United Kingdom, and the United States, reveal that 88% of those surveyed believe that negative perceptions toward people living with HIV persist even though HIV infection can be effectively managed with antiretroviral therapy (ART). Conversely, three-quarters (76%) are unaware of U=U, and the fact that someone with HIV who is taking effective treatment cannot pass it on to their partner. Two-thirds incorrectly believe that a person living with HIV can pass it onto their baby, even when they are ART adherent.

“The survey made me think of people who work in HIV clinics, and how much of a bubble I think that we in the HIV field live in,” Nneka Nwokolo, MBBS, senior global medical director at ViiV Healthcare, London, and practicing consultant in sexual health and HIV medicine, told this news organization. “I think that we generally feel that everyone knows as much as we do or feels the way that we do.”
 

Misconceptions abound across the globe

The online survey, which was commissioned by ViiV Healthcare, also highlights that one in five adults do not know that anyone can acquire HIV regardless of lifestyle, thereby perpetuating the stereotype that HIV is a disease that only affects certain populations, such as men who have sex with men (MSM) or transgender women (TGW). 

Pervasive stereotypes and stigmatization only serve to magnify preexisting social inequities that affect access to appropriate care. A recent editorial published in the journal AIDS and Behavior underscores that stigma experienced by marginalized populations in particular (for example, Black MSM, TGW) is directly linked to decreased access to and use of effective HIV prevention and treatment services. Additionally, once stigma becomes internalized, it might further affect overall well-being, mental health, and social support.

“One of the most significant consequences of the ongoing stigma is that people are scared to test and then they end up coming to services late [when] they’re really ill,” explained Dr. Nwokolo. “It goes back to the early days when HIV was a death sentence ... it’s still there. I have one patient who to this day hates the fact that he has HIV, that he has to come to the clinic – it’s a reminder of why he hates himself.”

Great strides in testing and advances in treatment might be helping to reframe HIV as a chronic but treatable and preventable disease. Nevertheless, survey findings also revealed that nearly three out of five adults incorrectly believe that a person living with HIV will have a shorter lifespan than someone who is HIV negative, even if they are on effective treatment. 

These beliefs are especially true among Dr. Nwokolo’s patient base, most of whom are Africans who’ve immigrated to the United Kingdom from countries that have been devastated by the HIV epidemic. “Those who’ve never tested are reluctant to do so because they are afraid that they will have the same outcome as the people that they know that they’ve left behind,” she said.
 

HIV stigma in the era of 90-90-90

While there has been progress toward achieving UN AID’s 90-90-90 targets (that is, 90% living with HIV know their status, 90% who know their status are on ART, and 90% of people on ART are virally suppressed), exclusion and isolation – the key hallmarks of stigma – may ultimately be the most important barriers preventing a lofty goal to end the AIDS epidemic by the year 2030.

“Here we are, 40 years in and we are still facing such ignorance, some stigma,” Carl Schmid, MBA, former cochair of the Presidential Advisory Council on HIV/AIDS, and executive director of HIV+Policy Institute, told this news organization. “It’s gotten better, but it is really putting a damper on people being tested, getting treated, getting access to PrEP.” Mr. Schmid was not involved in the Harris Poll.

Mr. Schmid also said that, in addition to broader outreach and education as well as dissemination of information about HIV and AIDS from the White House and other government leaders, physician involvement is essential. 

“They’re the ones that need to step up. They have to talk about sex with their patients, [but] they don’t do that, especially in the South among certain populations,” he noted.

Data support the unique challenges faced by at-risk individuals living in the southern United States. Not only do Southern states account for roughly half of all new HIV cases annually, but Black MSM and Black women account for the majority of new diagnoses, according to the Centers for Disease Control and Prevention. Data have also demonstrated discrimination and prejudice toward people with HIV persist among many medical professionals in the South (especially those working in rural areas).

But this is not only a Southern problem; a 2018 review of studies in clinicians across the United States published in AIDS Patient Care and STDs linked provider fear of acquiring HIV through occupational exposure to reduced quality of care, refusal of care, and anxiety, especially among providers with limited awareness of PrEP. Discordant attitudes around making a priority to address HIV-related stigma versus other health care needs also reduced overall care delivery and patient experience.

“I think that the first thing that we as HIV clinicians can and should do – and is definitely within our power to do – is to educate our peers about HIV,” Dr. Nwokolo said, “HIV has gone off the radar, but it’s still out there.”

The study was commissioned by Viiv Healthcare. Dr. Nwokolo is an employee of ViiV Healthcare. Mr. Schmid disclosed no relevant financial relationships.

A version of this article first appeared on Medscape.com.

Four decades into the AIDS epidemic and for some, it’s as if gains in awareness, advances in prevention and treatment, and the concept of undetected equals untransmissable (U=U) never happened. In its place, people living with HIV continue to face discrimination and stigma that affect nearly every aspect of the care continuum, from testing, prevention, and treatment to linkage to sexual, health, and reproductive services.

Accordingly, findings from a Harris poll conducted Oct. 13-18, 2021, among 5,047 adults (18 and older) residing in Australia, Portugal, the United Kingdom, and the United States, reveal that 88% of those surveyed believe that negative perceptions toward people living with HIV persist even though HIV infection can be effectively managed with antiretroviral therapy (ART). Conversely, three-quarters (76%) are unaware of U=U, and the fact that someone with HIV who is taking effective treatment cannot pass it on to their partner. Two-thirds incorrectly believe that a person living with HIV can pass it onto their baby, even when they are ART adherent.

“The survey made me think of people who work in HIV clinics, and how much of a bubble I think that we in the HIV field live in,” Nneka Nwokolo, MBBS, senior global medical director at ViiV Healthcare, London, and practicing consultant in sexual health and HIV medicine, told this news organization. “I think that we generally feel that everyone knows as much as we do or feels the way that we do.”
 

Misconceptions abound across the globe

The online survey, which was commissioned by ViiV Healthcare, also highlights that one in five adults do not know that anyone can acquire HIV regardless of lifestyle, thereby perpetuating the stereotype that HIV is a disease that only affects certain populations, such as men who have sex with men (MSM) or transgender women (TGW). 

Pervasive stereotypes and stigmatization only serve to magnify preexisting social inequities that affect access to appropriate care. A recent editorial published in the journal AIDS and Behavior underscores that stigma experienced by marginalized populations in particular (for example, Black MSM, TGW) is directly linked to decreased access to and use of effective HIV prevention and treatment services. Additionally, once stigma becomes internalized, it might further affect overall well-being, mental health, and social support.

“One of the most significant consequences of the ongoing stigma is that people are scared to test and then they end up coming to services late [when] they’re really ill,” explained Dr. Nwokolo. “It goes back to the early days when HIV was a death sentence ... it’s still there. I have one patient who to this day hates the fact that he has HIV, that he has to come to the clinic – it’s a reminder of why he hates himself.”

Great strides in testing and advances in treatment might be helping to reframe HIV as a chronic but treatable and preventable disease. Nevertheless, survey findings also revealed that nearly three out of five adults incorrectly believe that a person living with HIV will have a shorter lifespan than someone who is HIV negative, even if they are on effective treatment. 

These beliefs are especially true among Dr. Nwokolo’s patient base, most of whom are Africans who’ve immigrated to the United Kingdom from countries that have been devastated by the HIV epidemic. “Those who’ve never tested are reluctant to do so because they are afraid that they will have the same outcome as the people that they know that they’ve left behind,” she said.
 

HIV stigma in the era of 90-90-90

While there has been progress toward achieving UN AID’s 90-90-90 targets (that is, 90% living with HIV know their status, 90% who know their status are on ART, and 90% of people on ART are virally suppressed), exclusion and isolation – the key hallmarks of stigma – may ultimately be the most important barriers preventing a lofty goal to end the AIDS epidemic by the year 2030.

“Here we are, 40 years in and we are still facing such ignorance, some stigma,” Carl Schmid, MBA, former cochair of the Presidential Advisory Council on HIV/AIDS, and executive director of HIV+Policy Institute, told this news organization. “It’s gotten better, but it is really putting a damper on people being tested, getting treated, getting access to PrEP.” Mr. Schmid was not involved in the Harris Poll.

Mr. Schmid also said that, in addition to broader outreach and education as well as dissemination of information about HIV and AIDS from the White House and other government leaders, physician involvement is essential. 

“They’re the ones that need to step up. They have to talk about sex with their patients, [but] they don’t do that, especially in the South among certain populations,” he noted.

Data support the unique challenges faced by at-risk individuals living in the southern United States. Not only do Southern states account for roughly half of all new HIV cases annually, but Black MSM and Black women account for the majority of new diagnoses, according to the Centers for Disease Control and Prevention. Data have also demonstrated discrimination and prejudice toward people with HIV persist among many medical professionals in the South (especially those working in rural areas).

But this is not only a Southern problem; a 2018 review of studies in clinicians across the United States published in AIDS Patient Care and STDs linked provider fear of acquiring HIV through occupational exposure to reduced quality of care, refusal of care, and anxiety, especially among providers with limited awareness of PrEP. Discordant attitudes around making a priority to address HIV-related stigma versus other health care needs also reduced overall care delivery and patient experience.

“I think that the first thing that we as HIV clinicians can and should do – and is definitely within our power to do – is to educate our peers about HIV,” Dr. Nwokolo said, “HIV has gone off the radar, but it’s still out there.”

The study was commissioned by Viiv Healthcare. Dr. Nwokolo is an employee of ViiV Healthcare. Mr. Schmid disclosed no relevant financial relationships.

A version of this article first appeared on Medscape.com.

Human clinical trials have started for an experimental HIV vaccine that uses the same kind of mRNA technology found in Moderna’s successful COVID-19 vaccine, the drug company has announced.

The first vaccinations were given Jan. 27 at George Washington University School of Medicine and Health Sciences, Washington, the company said in a news release. Phase I trials will also be run at the Hope Clinic of Emory Vaccine Center, Atlanta, the Fred Hutchinson Cancer Research Center, Seattle, and the University of Texas Health Science Center, San Antonio.

The vaccine is designed to prompt white blood cells to turn into antibodies that can neutralize HIV, ABC News reported. A booster shot to work with the HIV vaccine is also being studied.

For 4 decades, the human immunodeficiency virus has managed to dodge the immune system’s attempts to destroy it. Scientists have not been able to develop a vaccine, though they have made advancements in treatments, such as long-acting injectables for pre- and post-exposure prevention and treatment. HIV can lead to AIDS, which can be fatal.

The release said 56 healthy HIV-negative adults are taking part in the clinical trial, with 48 getting one or two doses of the mRNA vaccine and 32 also getting the booster. Eight people will just get the booster. All of them will be monitored for up to 6 months after receiving a final dose.

The immunogens – antigens that elicit an immune response – that are being tested were developed by the International AIDS Vaccine Initiative (IAVI) and Scripps Research. They will be delivered using the same messenger RNA (mRNA) technology in Moderna’s successful COVID-19 vaccine, the news release said.

About 1.2 million people in the United States had HIV at the end of 2019, according to the CDC, with more than 36,000 people being diagnosed in 2019.

The World Health Organization says 37.7 million people in the world had HIV in 2020.

“We are tremendously excited to be advancing this new direction in HIV vaccine design with Moderna’s mRNA platform,” Mark Feinberg, MD, president and CEO of IAVI, said in the news release. “The search for an HIV vaccine has been long and challenging, and having new tools in terms of immunogens and platforms could be the key to making rapid progress toward an urgently needed, effective HIV vaccine.”

A version of this article first appeared on WebMD.com.

Human clinical trials have started for an experimental HIV vaccine that uses the same kind of mRNA technology found in Moderna’s successful COVID-19 vaccine, the drug company has announced.

The first vaccinations were given Jan. 27 at George Washington University School of Medicine and Health Sciences, Washington, the company said in a news release. Phase I trials will also be run at the Hope Clinic of Emory Vaccine Center, Atlanta, the Fred Hutchinson Cancer Research Center, Seattle, and the University of Texas Health Science Center, San Antonio.

The vaccine is designed to prompt white blood cells to turn into antibodies that can neutralize HIV, ABC News reported. A booster shot to work with the HIV vaccine is also being studied.

For 4 decades, the human immunodeficiency virus has managed to dodge the immune system’s attempts to destroy it. Scientists have not been able to develop a vaccine, though they have made advancements in treatments, such as long-acting injectables for pre- and post-exposure prevention and treatment. HIV can lead to AIDS, which can be fatal.

The release said 56 healthy HIV-negative adults are taking part in the clinical trial, with 48 getting one or two doses of the mRNA vaccine and 32 also getting the booster. Eight people will just get the booster. All of them will be monitored for up to 6 months after receiving a final dose.

The immunogens – antigens that elicit an immune response – that are being tested were developed by the International AIDS Vaccine Initiative (IAVI) and Scripps Research. They will be delivered using the same messenger RNA (mRNA) technology in Moderna’s successful COVID-19 vaccine, the news release said.

About 1.2 million people in the United States had HIV at the end of 2019, according to the CDC, with more than 36,000 people being diagnosed in 2019.

The World Health Organization says 37.7 million people in the world had HIV in 2020.

“We are tremendously excited to be advancing this new direction in HIV vaccine design with Moderna’s mRNA platform,” Mark Feinberg, MD, president and CEO of IAVI, said in the news release. “The search for an HIV vaccine has been long and challenging, and having new tools in terms of immunogens and platforms could be the key to making rapid progress toward an urgently needed, effective HIV vaccine.”

A version of this article first appeared on WebMD.com.

Human clinical trials have started for an experimental HIV vaccine that uses the same kind of mRNA technology found in Moderna’s successful COVID-19 vaccine, the drug company has announced.

The first vaccinations were given Jan. 27 at George Washington University School of Medicine and Health Sciences, Washington, the company said in a news release. Phase I trials will also be run at the Hope Clinic of Emory Vaccine Center, Atlanta, the Fred Hutchinson Cancer Research Center, Seattle, and the University of Texas Health Science Center, San Antonio.

The vaccine is designed to prompt white blood cells to turn into antibodies that can neutralize HIV, ABC News reported. A booster shot to work with the HIV vaccine is also being studied.

For 4 decades, the human immunodeficiency virus has managed to dodge the immune system’s attempts to destroy it. Scientists have not been able to develop a vaccine, though they have made advancements in treatments, such as long-acting injectables for pre- and post-exposure prevention and treatment. HIV can lead to AIDS, which can be fatal.

The release said 56 healthy HIV-negative adults are taking part in the clinical trial, with 48 getting one or two doses of the mRNA vaccine and 32 also getting the booster. Eight people will just get the booster. All of them will be monitored for up to 6 months after receiving a final dose.

The immunogens – antigens that elicit an immune response – that are being tested were developed by the International AIDS Vaccine Initiative (IAVI) and Scripps Research. They will be delivered using the same messenger RNA (mRNA) technology in Moderna’s successful COVID-19 vaccine, the news release said.

About 1.2 million people in the United States had HIV at the end of 2019, according to the CDC, with more than 36,000 people being diagnosed in 2019.

The World Health Organization says 37.7 million people in the world had HIV in 2020.

“We are tremendously excited to be advancing this new direction in HIV vaccine design with Moderna’s mRNA platform,” Mark Feinberg, MD, president and CEO of IAVI, said in the news release. “The search for an HIV vaccine has been long and challenging, and having new tools in terms of immunogens and platforms could be the key to making rapid progress toward an urgently needed, effective HIV vaccine.”

A version of this article first appeared on WebMD.com.

Tosha Rogers, MD, is a one-woman HIV prevention evangelist. For nearly a decade now, the Atlanta-based ob/gyn has been on a mission to increase her gynecological colleagues’ awareness and prescribing of the oral HIV prevention pill. At the same time, she’s been tracking the development of a flexible vaginal ring loaded with a month’s worth of the HIV prevention medication dapivirine. That, she thought, would fit easily into women’s lives and into the toolbox of methods women already use to prevent pregnancy.

But now she’s not sure when – or if – the ring will find its way to her patients. In December, the ring’s maker, the International Partnership for Microbicides (IPM), pulled its application for FDA approval for the pre-exposure prophylaxis (PrEP) ring. Now, one year after the World Health Organization recommended the ring for member nations, there appears to be no path forward in the United States for either the dapivirine-only ring or an approach Dr. Rogers said would change the game: a vaginal ring that supplies both contraception and HIV prevention.

“It would take things to a whole other level,” she said. “It sucks that this happened, and I do think it was not anything medical. I think it was everything political.”

That leaves cisgender women – especially the Black and Latinx women who make up the vast majority of women who acquire HIV every year – with two HIV prevention options. One is the daily pill, first approved in 2012. It’s now generic but previously sold as Truvada by Gilead Sciences. The other is monthly injectable cabotegravir long-acting (Apretude). Another HIV prevention pill, tenofovir alafenamide/emtricitabine (Descovy), is approved for gay men and transgender women but not cisgender women.
 

Vagina-specific protection from HIV

The WHO recommendation for the vaginal ring was followed last July by a positive opinion from the Committee for Medicinal Products for Human Use (CHMP) of the European Medicines Agency (EMA) for women in low- and middle-income countries outside the European Union.

The flexible silicone ring, similar to the hormonal NuvaRing contraceptive, works by slowly releasing the antiretroviral dapivirine directly into the vaginal canal, thereby protecting women who might be exposed to the virus through vaginal sex only. Because the medicine stays where it’s delivered and doesn’t circulate through the body, it has been found to be extremely safe with few adverse events.

However, in initial studies, the ring was found to be just 27% effective overall. Later studies, where scientists divided women by how much drug was missing from the ring – a proxy for use – found that higher use was associated with higher protection (as much as 54%). By comparison, Truvada has been found to be up to 99% effective when used daily, though it can take up to 21 days to be available in the vagina in high enough concentrations to protect women from vaginal exposure. And the HIV prevention shot was found to be 90% more effective than that in a recent trial of the two methods conducted by the HIV Prevention Trials Network.

This, and an orientation away from topical HIV prevention drugs and toward systemic options, led the National Institute of Allergy and Infectious Diseases (NIAID) to discontinue funding for such projects under its Microbicide Trials Network.

“Clearly you want to counsel women to use the highest efficacy method, and that is part of our label,” Zeda Rosenberg, ScD, IPM’s founder and chief executive officer, told this news organization. “Women should not choose the ring if they can and will use oral PrEP, and I would argue it should be the same thing for [cabotegravir shots]. But if they can’t or don’t want to – and we know that especially many young women don’t want to use systemic methods – then the dapivirine ring is a great option.”

Still, Dr. Rosenberg said that the gap in efficacy, the relatively small number of women affected by HIV in the U.S. compared with gay and bisexual men, and the emergence of products like the HIV prevention shot cabotegravir, made it “very unlikely” that FDA regulators would approve the ring. And rather than be “distracted” by the FDA process, Dr. Rosenberg said IPM chose to concentrate on the countries where the ring has already been approved or where women make up the vast majority of people affected by HIV.

Zimbabwe publicly announced it has approved the ring, and three other countries may have approved it, according to Dr. Rosenberg. She declined to name them, saying they had requested silence while they formulate their new HIV prevention guidelines. Aside from Zimbabwe, the other countries where women participated in the ring clinical trials were South Africa, Malawi, and Uganda.

“The U.S. population ... has widespread access to oral PrEP, which is unlike countries in Africa, and which would have widespread access to injectable cabotegravir,” she said. “The U.S. FDA may not see choice in the same way that African women and African activists and advocates see the need for choice.”

But women’s rates of accessing HIV prevention medications in the U.S. continues to be frustratingly low. At the end of 2018, just 7% of women who could benefit from HIV prevention drugs were taking them, according to Centers for Disease Control and Prevention data.

New CDC guidelines recommend clinicians talk to every sexually active adult and adolescent about HIV prevention medications at least once and prescribe it to anyone who asks for it, whether or not they understand their patients’ HIV risks. However, research continues to show that clinicians struggle with willingness to prescribe PrEP to Black women, and the American College of Obstetrics and Gynecology’s committee opinion on managing women using HIV prevention drugs has not been updated to reflect the new guidelines. And while the HIV prevention shot is approved for women and its maker ViiV Healthcare is already initiating postmarket studies of the ring in key populations including women, there are lots of things that need to line up in order for clinicians to be willing to stock it and prescribe it to women.

From where Dázon Dixon Diallo, executive director of the nonprofit SisterLove, sits, the decision to withdraw the ring from FDA consideration and the FDA’s seeming argument that the epidemiology in the U.S. doesn’t warrant the ring’s approval is a slap in the face to the Black women who have led the movement to end HIV in the U.S. for decades.

“No matter how you slice it, we’re talking about Black women, and then we’re talking about brown women,” said Ms. Diallo. “The value [they place on us] from a government standpoint, from a political standpoint, from a public health standpoint is just woeful. It’s woeful and it’s disrespectful and it’s insulting and I’m sick of it.”
 

‘America sneezes and Africa catches a cold’

When she first heard the decision to pull the ring from FDA consideration, Yvette Raphael, the South Africa-based executive director of Advocates for the Prevention of HIV in Africa, started asking, “What can we do to help our sisters in America get this ring?” And then she started worrying about other women in her own country and those nearby.

“The FDA plays a big role,” she said. “You know, America sneezes and Africa catches a cold.”

She worries that IPM’s decision to withdraw the ring from FDA consideration will signal to regulators in other countries either (a) that they should not approve it or (b) in countries where it’s already been approved but guidelines have not been issued, that they won’t invest money in rolling it out to women in those countries – especially now with the U.S. approval of the prevention shot. In much of Africa, ministries of health prefer to provide injectable contraception, often giving women few or no other options. But women, she said, think about more than administration of the drug. They look at if it’s an easier option for them to manage.

“This is a long journey, an emotional one too, for women in South Africa, because the idea of a microbicide is one of the ideas that came directly from women in South Africa,” she said. “[The jab] can be seen as a solution to all. We can just give jabs to all the women. And after all, we know that women don’t adhere, so we can just grab them.”

Dr. Rosenberg pointed to the positive opinion from the EMA as another “rigorous review” process that she said ought to equally influence ministries of health in countries where women tested the ring. And she pointed to the WHO statement released last month, the same day as IPM’s announcement that it was withdrawing the ring from FDA considerations, recommitting the ring as a good option in sub-Saharan Africa: “The U.S. FDA decision is not based on any new or additional data on efficacy and safety,” it stated. “WHO will continue to support countries as they consider whether to include the [dapivirine vaginal ring]. WHO recognizes that country decisionmaking will vary based on their context and that women’s voices remain central to discussions about their prevention choices.”
 

Dual action ring on the horizon, but not in U.S.

What this means, though, is that the next step in the ring’s development – the combination dapivirine ring with contraceptive levonorgestrel (used in the Mirena intrauterine device) – may not come to the U.S., at least for a long while.

“It’s not out of the question,” Dr. Rosenberg said of conducting HIV/pregnancy prevention ring trials in the U.S. “But without the approval of the dapivirine-only ring by FDA, I imagine they would want to see new efficacy data on dapivirine. That is a very difficult hill to climb. There would have to be an active control group [using oral PrEP or injectable cabotegravir], and it would be very difficult for the dapivirine ring to be able to go head-to-head for either noninferiority and certainly for superiority.”

The study would need to be quite large to get enough results to prove anything, and IPM is a research organization, not a large pharmaceutical company with deep enough pockets to fund that, she said. Raising those funds “would be difficult.”

In addition to NIAID discontinuing its funding for the Microbicides Trials Network, a new 5-year, $85 million research collaboration through USAID hasn’t slated any money to fund trials of the combination HIV prevention and contraceptive ring, according to Dr. Rosenberg.

But that doesn’t mean avenues for its development are closed. NIH’s Eunice Kennedy Shriver National Institute of Child Health and Human Development (NICHD) is currently funding a phase 1/2 trial of the combination ring, and IPM continues to receive funding from research agencies in Germany, the Netherlands, Denmark, and Ireland. And this means, she said, that the E.U. – not the U.S. – is where they would seek approval for a combination ring first.

That leaves Ms. Rafael and Ms. Diallo debating how to work together to push the FDA – and maybe IPM – to reconsider the ring. For instance, Ms. Diallo suggested that instead of seeking an indication for all women, the FDA might consider the ring for women with very high risk of HIV, such as sex workers or women with HIV positive partners not on treatment. And she said that this has to be bigger than HIV prevention. It has to be about the ways in which women’s health issues in general lag at the FDA. For instance, she pointed to the movement to get contraceptive pills available over the counter, fights against FDA rulings on hormone replacement therapy, and fights for emergency contraception.

In the meantime, ob/gyn Dr. Rogers is expecting access to the ring to follow a similar path as the copper IUD, which migrated to the U.S. from Europe, where it has been among the most popular contraceptive methods for women.

“Contrary to what we may think, we are not innovators, especially for something like this,” she said. “Once we see it is working and doing a good job – that women in Europe love it – then someone here is going to pick it up and make it as if it’s the greatest thing. But for now, I think we’re going to have to take a back seat to Europe.”

Ms. Diallo reports receiving fees from Johnson & Johnson, ViiV Healthcare, and Gilead Sciences. Dr. Rosenberg and Dr. Rogers have disclosed no relevant financial relationships.

A version of this article first appeared on Medscape.com.

Tosha Rogers, MD, is a one-woman HIV prevention evangelist. For nearly a decade now, the Atlanta-based ob/gyn has been on a mission to increase her gynecological colleagues’ awareness and prescribing of the oral HIV prevention pill. At the same time, she’s been tracking the development of a flexible vaginal ring loaded with a month’s worth of the HIV prevention medication dapivirine. That, she thought, would fit easily into women’s lives and into the toolbox of methods women already use to prevent pregnancy.

But now she’s not sure when – or if – the ring will find its way to her patients. In December, the ring’s maker, the International Partnership for Microbicides (IPM), pulled its application for FDA approval for the pre-exposure prophylaxis (PrEP) ring. Now, one year after the World Health Organization recommended the ring for member nations, there appears to be no path forward in the United States for either the dapivirine-only ring or an approach Dr. Rogers said would change the game: a vaginal ring that supplies both contraception and HIV prevention.

“It would take things to a whole other level,” she said. “It sucks that this happened, and I do think it was not anything medical. I think it was everything political.”

That leaves cisgender women – especially the Black and Latinx women who make up the vast majority of women who acquire HIV every year – with two HIV prevention options. One is the daily pill, first approved in 2012. It’s now generic but previously sold as Truvada by Gilead Sciences. The other is monthly injectable cabotegravir long-acting (Apretude). Another HIV prevention pill, tenofovir alafenamide/emtricitabine (Descovy), is approved for gay men and transgender women but not cisgender women.
 

Vagina-specific protection from HIV

The WHO recommendation for the vaginal ring was followed last July by a positive opinion from the Committee for Medicinal Products for Human Use (CHMP) of the European Medicines Agency (EMA) for women in low- and middle-income countries outside the European Union.

The flexible silicone ring, similar to the hormonal NuvaRing contraceptive, works by slowly releasing the antiretroviral dapivirine directly into the vaginal canal, thereby protecting women who might be exposed to the virus through vaginal sex only. Because the medicine stays where it’s delivered and doesn’t circulate through the body, it has been found to be extremely safe with few adverse events.

However, in initial studies, the ring was found to be just 27% effective overall. Later studies, where scientists divided women by how much drug was missing from the ring – a proxy for use – found that higher use was associated with higher protection (as much as 54%). By comparison, Truvada has been found to be up to 99% effective when used daily, though it can take up to 21 days to be available in the vagina in high enough concentrations to protect women from vaginal exposure. And the HIV prevention shot was found to be 90% more effective than that in a recent trial of the two methods conducted by the HIV Prevention Trials Network.

This, and an orientation away from topical HIV prevention drugs and toward systemic options, led the National Institute of Allergy and Infectious Diseases (NIAID) to discontinue funding for such projects under its Microbicide Trials Network.

“Clearly you want to counsel women to use the highest efficacy method, and that is part of our label,” Zeda Rosenberg, ScD, IPM’s founder and chief executive officer, told this news organization. “Women should not choose the ring if they can and will use oral PrEP, and I would argue it should be the same thing for [cabotegravir shots]. But if they can’t or don’t want to – and we know that especially many young women don’t want to use systemic methods – then the dapivirine ring is a great option.”

Still, Dr. Rosenberg said that the gap in efficacy, the relatively small number of women affected by HIV in the U.S. compared with gay and bisexual men, and the emergence of products like the HIV prevention shot cabotegravir, made it “very unlikely” that FDA regulators would approve the ring. And rather than be “distracted” by the FDA process, Dr. Rosenberg said IPM chose to concentrate on the countries where the ring has already been approved or where women make up the vast majority of people affected by HIV.

Zimbabwe publicly announced it has approved the ring, and three other countries may have approved it, according to Dr. Rosenberg. She declined to name them, saying they had requested silence while they formulate their new HIV prevention guidelines. Aside from Zimbabwe, the other countries where women participated in the ring clinical trials were South Africa, Malawi, and Uganda.

“The U.S. population ... has widespread access to oral PrEP, which is unlike countries in Africa, and which would have widespread access to injectable cabotegravir,” she said. “The U.S. FDA may not see choice in the same way that African women and African activists and advocates see the need for choice.”

But women’s rates of accessing HIV prevention medications in the U.S. continues to be frustratingly low. At the end of 2018, just 7% of women who could benefit from HIV prevention drugs were taking them, according to Centers for Disease Control and Prevention data.

New CDC guidelines recommend clinicians talk to every sexually active adult and adolescent about HIV prevention medications at least once and prescribe it to anyone who asks for it, whether or not they understand their patients’ HIV risks. However, research continues to show that clinicians struggle with willingness to prescribe PrEP to Black women, and the American College of Obstetrics and Gynecology’s committee opinion on managing women using HIV prevention drugs has not been updated to reflect the new guidelines. And while the HIV prevention shot is approved for women and its maker ViiV Healthcare is already initiating postmarket studies of the ring in key populations including women, there are lots of things that need to line up in order for clinicians to be willing to stock it and prescribe it to women.

From where Dázon Dixon Diallo, executive director of the nonprofit SisterLove, sits, the decision to withdraw the ring from FDA consideration and the FDA’s seeming argument that the epidemiology in the U.S. doesn’t warrant the ring’s approval is a slap in the face to the Black women who have led the movement to end HIV in the U.S. for decades.

“No matter how you slice it, we’re talking about Black women, and then we’re talking about brown women,” said Ms. Diallo. “The value [they place on us] from a government standpoint, from a political standpoint, from a public health standpoint is just woeful. It’s woeful and it’s disrespectful and it’s insulting and I’m sick of it.”
 

‘America sneezes and Africa catches a cold’

When she first heard the decision to pull the ring from FDA consideration, Yvette Raphael, the South Africa-based executive director of Advocates for the Prevention of HIV in Africa, started asking, “What can we do to help our sisters in America get this ring?” And then she started worrying about other women in her own country and those nearby.

“The FDA plays a big role,” she said. “You know, America sneezes and Africa catches a cold.”

She worries that IPM’s decision to withdraw the ring from FDA consideration will signal to regulators in other countries either (a) that they should not approve it or (b) in countries where it’s already been approved but guidelines have not been issued, that they won’t invest money in rolling it out to women in those countries – especially now with the U.S. approval of the prevention shot. In much of Africa, ministries of health prefer to provide injectable contraception, often giving women few or no other options. But women, she said, think about more than administration of the drug. They look at if it’s an easier option for them to manage.

“This is a long journey, an emotional one too, for women in South Africa, because the idea of a microbicide is one of the ideas that came directly from women in South Africa,” she said. “[The jab] can be seen as a solution to all. We can just give jabs to all the women. And after all, we know that women don’t adhere, so we can just grab them.”

Dr. Rosenberg pointed to the positive opinion from the EMA as another “rigorous review” process that she said ought to equally influence ministries of health in countries where women tested the ring. And she pointed to the WHO statement released last month, the same day as IPM’s announcement that it was withdrawing the ring from FDA considerations, recommitting the ring as a good option in sub-Saharan Africa: “The U.S. FDA decision is not based on any new or additional data on efficacy and safety,” it stated. “WHO will continue to support countries as they consider whether to include the [dapivirine vaginal ring]. WHO recognizes that country decisionmaking will vary based on their context and that women’s voices remain central to discussions about their prevention choices.”
 

Dual action ring on the horizon, but not in U.S.

What this means, though, is that the next step in the ring’s development – the combination dapivirine ring with contraceptive levonorgestrel (used in the Mirena intrauterine device) – may not come to the U.S., at least for a long while.

“It’s not out of the question,” Dr. Rosenberg said of conducting HIV/pregnancy prevention ring trials in the U.S. “But without the approval of the dapivirine-only ring by FDA, I imagine they would want to see new efficacy data on dapivirine. That is a very difficult hill to climb. There would have to be an active control group [using oral PrEP or injectable cabotegravir], and it would be very difficult for the dapivirine ring to be able to go head-to-head for either noninferiority and certainly for superiority.”

The study would need to be quite large to get enough results to prove anything, and IPM is a research organization, not a large pharmaceutical company with deep enough pockets to fund that, she said. Raising those funds “would be difficult.”

In addition to NIAID discontinuing its funding for the Microbicides Trials Network, a new 5-year, $85 million research collaboration through USAID hasn’t slated any money to fund trials of the combination HIV prevention and contraceptive ring, according to Dr. Rosenberg.

But that doesn’t mean avenues for its development are closed. NIH’s Eunice Kennedy Shriver National Institute of Child Health and Human Development (NICHD) is currently funding a phase 1/2 trial of the combination ring, and IPM continues to receive funding from research agencies in Germany, the Netherlands, Denmark, and Ireland. And this means, she said, that the E.U. – not the U.S. – is where they would seek approval for a combination ring first.

That leaves Ms. Rafael and Ms. Diallo debating how to work together to push the FDA – and maybe IPM – to reconsider the ring. For instance, Ms. Diallo suggested that instead of seeking an indication for all women, the FDA might consider the ring for women with very high risk of HIV, such as sex workers or women with HIV positive partners not on treatment. And she said that this has to be bigger than HIV prevention. It has to be about the ways in which women’s health issues in general lag at the FDA. For instance, she pointed to the movement to get contraceptive pills available over the counter, fights against FDA rulings on hormone replacement therapy, and fights for emergency contraception.

In the meantime, ob/gyn Dr. Rogers is expecting access to the ring to follow a similar path as the copper IUD, which migrated to the U.S. from Europe, where it has been among the most popular contraceptive methods for women.

“Contrary to what we may think, we are not innovators, especially for something like this,” she said. “Once we see it is working and doing a good job – that women in Europe love it – then someone here is going to pick it up and make it as if it’s the greatest thing. But for now, I think we’re going to have to take a back seat to Europe.”

Ms. Diallo reports receiving fees from Johnson & Johnson, ViiV Healthcare, and Gilead Sciences. Dr. Rosenberg and Dr. Rogers have disclosed no relevant financial relationships.

A version of this article first appeared on Medscape.com.

Tosha Rogers, MD, is a one-woman HIV prevention evangelist. For nearly a decade now, the Atlanta-based ob/gyn has been on a mission to increase her gynecological colleagues’ awareness and prescribing of the oral HIV prevention pill. At the same time, she’s been tracking the development of a flexible vaginal ring loaded with a month’s worth of the HIV prevention medication dapivirine. That, she thought, would fit easily into women’s lives and into the toolbox of methods women already use to prevent pregnancy.

But now she’s not sure when – or if – the ring will find its way to her patients. In December, the ring’s maker, the International Partnership for Microbicides (IPM), pulled its application for FDA approval for the pre-exposure prophylaxis (PrEP) ring. Now, one year after the World Health Organization recommended the ring for member nations, there appears to be no path forward in the United States for either the dapivirine-only ring or an approach Dr. Rogers said would change the game: a vaginal ring that supplies both contraception and HIV prevention.

“It would take things to a whole other level,” she said. “It sucks that this happened, and I do think it was not anything medical. I think it was everything political.”

That leaves cisgender women – especially the Black and Latinx women who make up the vast majority of women who acquire HIV every year – with two HIV prevention options. One is the daily pill, first approved in 2012. It’s now generic but previously sold as Truvada by Gilead Sciences. The other is monthly injectable cabotegravir long-acting (Apretude). Another HIV prevention pill, tenofovir alafenamide/emtricitabine (Descovy), is approved for gay men and transgender women but not cisgender women.
 

Vagina-specific protection from HIV

The WHO recommendation for the vaginal ring was followed last July by a positive opinion from the Committee for Medicinal Products for Human Use (CHMP) of the European Medicines Agency (EMA) for women in low- and middle-income countries outside the European Union.

The flexible silicone ring, similar to the hormonal NuvaRing contraceptive, works by slowly releasing the antiretroviral dapivirine directly into the vaginal canal, thereby protecting women who might be exposed to the virus through vaginal sex only. Because the medicine stays where it’s delivered and doesn’t circulate through the body, it has been found to be extremely safe with few adverse events.

However, in initial studies, the ring was found to be just 27% effective overall. Later studies, where scientists divided women by how much drug was missing from the ring – a proxy for use – found that higher use was associated with higher protection (as much as 54%). By comparison, Truvada has been found to be up to 99% effective when used daily, though it can take up to 21 days to be available in the vagina in high enough concentrations to protect women from vaginal exposure. And the HIV prevention shot was found to be 90% more effective than that in a recent trial of the two methods conducted by the HIV Prevention Trials Network.

This, and an orientation away from topical HIV prevention drugs and toward systemic options, led the National Institute of Allergy and Infectious Diseases (NIAID) to discontinue funding for such projects under its Microbicide Trials Network.

“Clearly you want to counsel women to use the highest efficacy method, and that is part of our label,” Zeda Rosenberg, ScD, IPM’s founder and chief executive officer, told this news organization. “Women should not choose the ring if they can and will use oral PrEP, and I would argue it should be the same thing for [cabotegravir shots]. But if they can’t or don’t want to – and we know that especially many young women don’t want to use systemic methods – then the dapivirine ring is a great option.”

Still, Dr. Rosenberg said that the gap in efficacy, the relatively small number of women affected by HIV in the U.S. compared with gay and bisexual men, and the emergence of products like the HIV prevention shot cabotegravir, made it “very unlikely” that FDA regulators would approve the ring. And rather than be “distracted” by the FDA process, Dr. Rosenberg said IPM chose to concentrate on the countries where the ring has already been approved or where women make up the vast majority of people affected by HIV.

Zimbabwe publicly announced it has approved the ring, and three other countries may have approved it, according to Dr. Rosenberg. She declined to name them, saying they had requested silence while they formulate their new HIV prevention guidelines. Aside from Zimbabwe, the other countries where women participated in the ring clinical trials were South Africa, Malawi, and Uganda.

“The U.S. population ... has widespread access to oral PrEP, which is unlike countries in Africa, and which would have widespread access to injectable cabotegravir,” she said. “The U.S. FDA may not see choice in the same way that African women and African activists and advocates see the need for choice.”

But women’s rates of accessing HIV prevention medications in the U.S. continues to be frustratingly low. At the end of 2018, just 7% of women who could benefit from HIV prevention drugs were taking them, according to Centers for Disease Control and Prevention data.

New CDC guidelines recommend clinicians talk to every sexually active adult and adolescent about HIV prevention medications at least once and prescribe it to anyone who asks for it, whether or not they understand their patients’ HIV risks. However, research continues to show that clinicians struggle with willingness to prescribe PrEP to Black women, and the American College of Obstetrics and Gynecology’s committee opinion on managing women using HIV prevention drugs has not been updated to reflect the new guidelines. And while the HIV prevention shot is approved for women and its maker ViiV Healthcare is already initiating postmarket studies of the ring in key populations including women, there are lots of things that need to line up in order for clinicians to be willing to stock it and prescribe it to women.

From where Dázon Dixon Diallo, executive director of the nonprofit SisterLove, sits, the decision to withdraw the ring from FDA consideration and the FDA’s seeming argument that the epidemiology in the U.S. doesn’t warrant the ring’s approval is a slap in the face to the Black women who have led the movement to end HIV in the U.S. for decades.

“No matter how you slice it, we’re talking about Black women, and then we’re talking about brown women,” said Ms. Diallo. “The value [they place on us] from a government standpoint, from a political standpoint, from a public health standpoint is just woeful. It’s woeful and it’s disrespectful and it’s insulting and I’m sick of it.”
 

‘America sneezes and Africa catches a cold’

When she first heard the decision to pull the ring from FDA consideration, Yvette Raphael, the South Africa-based executive director of Advocates for the Prevention of HIV in Africa, started asking, “What can we do to help our sisters in America get this ring?” And then she started worrying about other women in her own country and those nearby.

“The FDA plays a big role,” she said. “You know, America sneezes and Africa catches a cold.”

She worries that IPM’s decision to withdraw the ring from FDA consideration will signal to regulators in other countries either (a) that they should not approve it or (b) in countries where it’s already been approved but guidelines have not been issued, that they won’t invest money in rolling it out to women in those countries – especially now with the U.S. approval of the prevention shot. In much of Africa, ministries of health prefer to provide injectable contraception, often giving women few or no other options. But women, she said, think about more than administration of the drug. They look at if it’s an easier option for them to manage.

“This is a long journey, an emotional one too, for women in South Africa, because the idea of a microbicide is one of the ideas that came directly from women in South Africa,” she said. “[The jab] can be seen as a solution to all. We can just give jabs to all the women. And after all, we know that women don’t adhere, so we can just grab them.”

Dr. Rosenberg pointed to the positive opinion from the EMA as another “rigorous review” process that she said ought to equally influence ministries of health in countries where women tested the ring. And she pointed to the WHO statement released last month, the same day as IPM’s announcement that it was withdrawing the ring from FDA considerations, recommitting the ring as a good option in sub-Saharan Africa: “The U.S. FDA decision is not based on any new or additional data on efficacy and safety,” it stated. “WHO will continue to support countries as they consider whether to include the [dapivirine vaginal ring]. WHO recognizes that country decisionmaking will vary based on their context and that women’s voices remain central to discussions about their prevention choices.”
 

Dual action ring on the horizon, but not in U.S.

What this means, though, is that the next step in the ring’s development – the combination dapivirine ring with contraceptive levonorgestrel (used in the Mirena intrauterine device) – may not come to the U.S., at least for a long while.

“It’s not out of the question,” Dr. Rosenberg said of conducting HIV/pregnancy prevention ring trials in the U.S. “But without the approval of the dapivirine-only ring by FDA, I imagine they would want to see new efficacy data on dapivirine. That is a very difficult hill to climb. There would have to be an active control group [using oral PrEP or injectable cabotegravir], and it would be very difficult for the dapivirine ring to be able to go head-to-head for either noninferiority and certainly for superiority.”

The study would need to be quite large to get enough results to prove anything, and IPM is a research organization, not a large pharmaceutical company with deep enough pockets to fund that, she said. Raising those funds “would be difficult.”

In addition to NIAID discontinuing its funding for the Microbicides Trials Network, a new 5-year, $85 million research collaboration through USAID hasn’t slated any money to fund trials of the combination HIV prevention and contraceptive ring, according to Dr. Rosenberg.

But that doesn’t mean avenues for its development are closed. NIH’s Eunice Kennedy Shriver National Institute of Child Health and Human Development (NICHD) is currently funding a phase 1/2 trial of the combination ring, and IPM continues to receive funding from research agencies in Germany, the Netherlands, Denmark, and Ireland. And this means, she said, that the E.U. – not the U.S. – is where they would seek approval for a combination ring first.

That leaves Ms. Rafael and Ms. Diallo debating how to work together to push the FDA – and maybe IPM – to reconsider the ring. For instance, Ms. Diallo suggested that instead of seeking an indication for all women, the FDA might consider the ring for women with very high risk of HIV, such as sex workers or women with HIV positive partners not on treatment. And she said that this has to be bigger than HIV prevention. It has to be about the ways in which women’s health issues in general lag at the FDA. For instance, she pointed to the movement to get contraceptive pills available over the counter, fights against FDA rulings on hormone replacement therapy, and fights for emergency contraception.

In the meantime, ob/gyn Dr. Rogers is expecting access to the ring to follow a similar path as the copper IUD, which migrated to the U.S. from Europe, where it has been among the most popular contraceptive methods for women.

“Contrary to what we may think, we are not innovators, especially for something like this,” she said. “Once we see it is working and doing a good job – that women in Europe love it – then someone here is going to pick it up and make it as if it’s the greatest thing. But for now, I think we’re going to have to take a back seat to Europe.”

Ms. Diallo reports receiving fees from Johnson & Johnson, ViiV Healthcare, and Gilead Sciences. Dr. Rosenberg and Dr. Rogers have 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, accounting for both expectations and life stressors may help physicians predict which patients will be lost to follow-up (LTFU) in the first year of HIV care.

“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, accounting for both expectations and life stressors may help physicians predict which patients will be lost to follow-up (LTFU) in the first year of HIV care.

“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, accounting for both expectations and life stressors may help physicians predict which patients will be lost to follow-up (LTFU) in the first year of HIV care.

“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.

Liver or kidney transplant recipients who are HIV-positive show outcomes that are similar to those without HIV at 15-years post-transplant, in new research that represents some of the longest follow-up on these patients to date.

The findings further support the inclusion of people with HIV in transplant resource allocation, say the researchers.

“Overall, the excellent outcomes following liver and kidney transplant recipients in HIV-infected recipients justify the utilization of a scarce resource,” senior author Peter G. Stock, MD, PhD, surgical director of the Kidney and Pancreas Transplant Program and surgical director of the Pediatric Renal Transplant Program at the University of California, San Francisco (UCSF), said in an interview.

“Many centers still view HIV as a strict contraindication [for transplantation]. This data shows it is not,” he emphasized.

The study, published in JAMA Surgery, involved HIV-positive patients who received kidney or liver transplants between 2000 and 2019 at UCSF, which has unique access to some of the longest-term data on those outcomes.

“UCSF was the first U.S. center to do transplants routinely in people with HIV, and based on the large volume of transplants that are performed, we were able to use propensity matching to address the comparison of HIV-positive and negative liver and kidney transplant recipients at a single center,” Dr. Stock explained.

“To the best of our knowledge, there are no long-term reports [greater than 10 years] on [transplant] outcomes in the HIV-positive population.”

Commenting on the study, David Klassen, MD, chief medical officer of the United Network for Organ Sharing (UNOS), noted that the findings “confirm previous research done at UCSF and reported in the New England Journal of Medicine” in 2010. “It extends the previous findings.”

“The take-home message is that these HIV-positive patients can be successfully transplanted with expected good outcomes and will derive substantial benefit from transplantation,” Dr. Klassen said.
 

Kidney transplant patient survival lower, graft survival similar

For the kidney transplant analysis, 119 HIV-positive recipients were propensity matched with 655 recipients who were HIV-negative, with the patients’ mean age about 52 and approximately 70% male.

At 15-years post-transplant, patient survival was 53.6% among the HIV-positive patients versus 79.6% for HIV-negative (P = .03).

Graft survival among the kidney transplant patients was proportionally higher among HIV-positive patients after 15 years (75% vs. 57%); however, the difference was not statistically significant (P = .77).

First author Arya Zarinsefat, MD, of the Department of Surgery at UCSF, speculated that the lower long-term patient survival among HIV-positive kidney transplant recipients may reflect known cardiovascular risks among those patients.

“We postulated that part of this may be due to the fact that HIV-positive patients certainly have additional comorbidities, specifically cardiovascular” ones, he told this news organization.

“When looking at the survival curve, survival was nearly identical at 5 years and only started to diverge at 10 years post-transplant,” he noted.

A further evaluation of patients with HIV who were co-infected with hepatitis C (HCV) showed that those with HIV-HCV co-infection prior to the center’s introduction of anti-HCV direct-acting antiviral (DAA) medications in 2014 had the lowest survival rate of all subgroups, at 57.1% at 5 years post-transplant (P = .045 vs. those treated after 2014).
 

Liver transplant patient survival similar

In terms of liver transplant outcomes, among 83 HIV-positive recipients who were propensity-matched with 468 HIV-negative recipients, the mean age was about 53 and about 66% were male.

The patient survival rates at 15 years were not significantly different between the groups, at 70% for HIV-positive and 75.7% for HIV-negative, (P = .12).

Similar to the kidney transplant recipients, the worst survival among all liver transplant subgroups was among HIV-HCV co-infected patients prior to access to HCV direct-acting antivirals in 2014, with a 5-year survival of 59.5% (P = .04).

“Since the advent of HCV direct-acting antivirals, liver transplant outcomes in HCV mono-infected patients are comparable to HCV/HIV co-infected recipients,” Dr. Stock said.
 

Acute rejection rates higher with HIV-positivity versus national averages

The rates of acute rejection at 1 year in the kidney and liver transplant, HIV-positive groups – at about 20% and 30%, respectively – were, however, higher than national average incidence rates of about 10% at 1 year.

Long-term data on those patients showed the acute rejection affected graft survival outcomes with kidney transplant recipients: HIV-positive kidney transplant recipients who had at least one episode of acute rejection had a graft survival of just 52.8% at 15 years post-transplant, compared with 91.8% among recipients without acute rejection.

Such differences were not observed among HIV-positive liver transplant recipients.

The authors note that the increased risk of acute rejection in HIV-positive kidney transplant patients is consistent with previous studies, with causes that may be multifactorial.

Top theories include drug interactions with protease inhibitors, resulting in some centers transitioning HIV-infected patients from those regimens to integrase-based regimens prior to transplant.

“The management and prevention of acute rejection in HIV-positive kidney transplant [patients] will therefore continue to be a key component in the care of these patients,” the authors note in their study.

The study was supported in part by the National Institutes of Health. The study authors and Dr. Klassen have disclosed no relevant financial relationships.

A version of this article first appeared on Medscape.com.

Liver or kidney transplant recipients who are HIV-positive show outcomes that are similar to those without HIV at 15-years post-transplant, in new research that represents some of the longest follow-up on these patients to date.

The findings further support the inclusion of people with HIV in transplant resource allocation, say the researchers.

“Overall, the excellent outcomes following liver and kidney transplant recipients in HIV-infected recipients justify the utilization of a scarce resource,” senior author Peter G. Stock, MD, PhD, surgical director of the Kidney and Pancreas Transplant Program and surgical director of the Pediatric Renal Transplant Program at the University of California, San Francisco (UCSF), said in an interview.

“Many centers still view HIV as a strict contraindication [for transplantation]. This data shows it is not,” he emphasized.

The study, published in JAMA Surgery, involved HIV-positive patients who received kidney or liver transplants between 2000 and 2019 at UCSF, which has unique access to some of the longest-term data on those outcomes.

“UCSF was the first U.S. center to do transplants routinely in people with HIV, and based on the large volume of transplants that are performed, we were able to use propensity matching to address the comparison of HIV-positive and negative liver and kidney transplant recipients at a single center,” Dr. Stock explained.

“To the best of our knowledge, there are no long-term reports [greater than 10 years] on [transplant] outcomes in the HIV-positive population.”

Commenting on the study, David Klassen, MD, chief medical officer of the United Network for Organ Sharing (UNOS), noted that the findings “confirm previous research done at UCSF and reported in the New England Journal of Medicine” in 2010. “It extends the previous findings.”

“The take-home message is that these HIV-positive patients can be successfully transplanted with expected good outcomes and will derive substantial benefit from transplantation,” Dr. Klassen said.
 

Kidney transplant patient survival lower, graft survival similar

For the kidney transplant analysis, 119 HIV-positive recipients were propensity matched with 655 recipients who were HIV-negative, with the patients’ mean age about 52 and approximately 70% male.

At 15-years post-transplant, patient survival was 53.6% among the HIV-positive patients versus 79.6% for HIV-negative (P = .03).

Graft survival among the kidney transplant patients was proportionally higher among HIV-positive patients after 15 years (75% vs. 57%); however, the difference was not statistically significant (P = .77).

First author Arya Zarinsefat, MD, of the Department of Surgery at UCSF, speculated that the lower long-term patient survival among HIV-positive kidney transplant recipients may reflect known cardiovascular risks among those patients.

“We postulated that part of this may be due to the fact that HIV-positive patients certainly have additional comorbidities, specifically cardiovascular” ones, he told this news organization.

“When looking at the survival curve, survival was nearly identical at 5 years and only started to diverge at 10 years post-transplant,” he noted.

A further evaluation of patients with HIV who were co-infected with hepatitis C (HCV) showed that those with HIV-HCV co-infection prior to the center’s introduction of anti-HCV direct-acting antiviral (DAA) medications in 2014 had the lowest survival rate of all subgroups, at 57.1% at 5 years post-transplant (P = .045 vs. those treated after 2014).
 

Liver transplant patient survival similar

In terms of liver transplant outcomes, among 83 HIV-positive recipients who were propensity-matched with 468 HIV-negative recipients, the mean age was about 53 and about 66% were male.

The patient survival rates at 15 years were not significantly different between the groups, at 70% for HIV-positive and 75.7% for HIV-negative, (P = .12).

Similar to the kidney transplant recipients, the worst survival among all liver transplant subgroups was among HIV-HCV co-infected patients prior to access to HCV direct-acting antivirals in 2014, with a 5-year survival of 59.5% (P = .04).

“Since the advent of HCV direct-acting antivirals, liver transplant outcomes in HCV mono-infected patients are comparable to HCV/HIV co-infected recipients,” Dr. Stock said.
 

Acute rejection rates higher with HIV-positivity versus national averages

The rates of acute rejection at 1 year in the kidney and liver transplant, HIV-positive groups – at about 20% and 30%, respectively – were, however, higher than national average incidence rates of about 10% at 1 year.

Long-term data on those patients showed the acute rejection affected graft survival outcomes with kidney transplant recipients: HIV-positive kidney transplant recipients who had at least one episode of acute rejection had a graft survival of just 52.8% at 15 years post-transplant, compared with 91.8% among recipients without acute rejection.

Such differences were not observed among HIV-positive liver transplant recipients.

The authors note that the increased risk of acute rejection in HIV-positive kidney transplant patients is consistent with previous studies, with causes that may be multifactorial.

Top theories include drug interactions with protease inhibitors, resulting in some centers transitioning HIV-infected patients from those regimens to integrase-based regimens prior to transplant.

“The management and prevention of acute rejection in HIV-positive kidney transplant [patients] will therefore continue to be a key component in the care of these patients,” the authors note in their study.

The study was supported in part by the National Institutes of Health. The study authors and Dr. Klassen have disclosed no relevant financial relationships.

A version of this article first appeared on Medscape.com.

Liver or kidney transplant recipients who are HIV-positive show outcomes that are similar to those without HIV at 15-years post-transplant, in new research that represents some of the longest follow-up on these patients to date.

The findings further support the inclusion of people with HIV in transplant resource allocation, say the researchers.

“Overall, the excellent outcomes following liver and kidney transplant recipients in HIV-infected recipients justify the utilization of a scarce resource,” senior author Peter G. Stock, MD, PhD, surgical director of the Kidney and Pancreas Transplant Program and surgical director of the Pediatric Renal Transplant Program at the University of California, San Francisco (UCSF), said in an interview.

“Many centers still view HIV as a strict contraindication [for transplantation]. This data shows it is not,” he emphasized.

The study, published in JAMA Surgery, involved HIV-positive patients who received kidney or liver transplants between 2000 and 2019 at UCSF, which has unique access to some of the longest-term data on those outcomes.

“UCSF was the first U.S. center to do transplants routinely in people with HIV, and based on the large volume of transplants that are performed, we were able to use propensity matching to address the comparison of HIV-positive and negative liver and kidney transplant recipients at a single center,” Dr. Stock explained.

“To the best of our knowledge, there are no long-term reports [greater than 10 years] on [transplant] outcomes in the HIV-positive population.”

Commenting on the study, David Klassen, MD, chief medical officer of the United Network for Organ Sharing (UNOS), noted that the findings “confirm previous research done at UCSF and reported in the New England Journal of Medicine” in 2010. “It extends the previous findings.”

“The take-home message is that these HIV-positive patients can be successfully transplanted with expected good outcomes and will derive substantial benefit from transplantation,” Dr. Klassen said.
 

Kidney transplant patient survival lower, graft survival similar

For the kidney transplant analysis, 119 HIV-positive recipients were propensity matched with 655 recipients who were HIV-negative, with the patients’ mean age about 52 and approximately 70% male.

At 15-years post-transplant, patient survival was 53.6% among the HIV-positive patients versus 79.6% for HIV-negative (P = .03).

Graft survival among the kidney transplant patients was proportionally higher among HIV-positive patients after 15 years (75% vs. 57%); however, the difference was not statistically significant (P = .77).

First author Arya Zarinsefat, MD, of the Department of Surgery at UCSF, speculated that the lower long-term patient survival among HIV-positive kidney transplant recipients may reflect known cardiovascular risks among those patients.

“We postulated that part of this may be due to the fact that HIV-positive patients certainly have additional comorbidities, specifically cardiovascular” ones, he told this news organization.

“When looking at the survival curve, survival was nearly identical at 5 years and only started to diverge at 10 years post-transplant,” he noted.

A further evaluation of patients with HIV who were co-infected with hepatitis C (HCV) showed that those with HIV-HCV co-infection prior to the center’s introduction of anti-HCV direct-acting antiviral (DAA) medications in 2014 had the lowest survival rate of all subgroups, at 57.1% at 5 years post-transplant (P = .045 vs. those treated after 2014).
 

Liver transplant patient survival similar

In terms of liver transplant outcomes, among 83 HIV-positive recipients who were propensity-matched with 468 HIV-negative recipients, the mean age was about 53 and about 66% were male.

The patient survival rates at 15 years were not significantly different between the groups, at 70% for HIV-positive and 75.7% for HIV-negative, (P = .12).

Similar to the kidney transplant recipients, the worst survival among all liver transplant subgroups was among HIV-HCV co-infected patients prior to access to HCV direct-acting antivirals in 2014, with a 5-year survival of 59.5% (P = .04).

“Since the advent of HCV direct-acting antivirals, liver transplant outcomes in HCV mono-infected patients are comparable to HCV/HIV co-infected recipients,” Dr. Stock said.
 

Acute rejection rates higher with HIV-positivity versus national averages

The rates of acute rejection at 1 year in the kidney and liver transplant, HIV-positive groups – at about 20% and 30%, respectively – were, however, higher than national average incidence rates of about 10% at 1 year.

Long-term data on those patients showed the acute rejection affected graft survival outcomes with kidney transplant recipients: HIV-positive kidney transplant recipients who had at least one episode of acute rejection had a graft survival of just 52.8% at 15 years post-transplant, compared with 91.8% among recipients without acute rejection.

Such differences were not observed among HIV-positive liver transplant recipients.

The authors note that the increased risk of acute rejection in HIV-positive kidney transplant patients is consistent with previous studies, with causes that may be multifactorial.

Top theories include drug interactions with protease inhibitors, resulting in some centers transitioning HIV-infected patients from those regimens to integrase-based regimens prior to transplant.

“The management and prevention of acute rejection in HIV-positive kidney transplant [patients] will therefore continue to be a key component in the care of these patients,” the authors note in their study.

The study was supported in part by the National Institutes of Health. The study authors and Dr. Klassen have disclosed no relevant financial relationships.

A version of this article first appeared on Medscape.com.

A global study led by researchers at University College London, published Dec. 30, 2021, in the New England Journal of Medicine, found that a regimen based on a once-a-day small dolutegravir tablet was more effective at suppressing HIV than standard treatments. Dolutegravir suppresses HIV by inhibiting integrase, an enzyme that the virus needs to replicate.

The pill-based regimen, which researchers described as easier to take than standard treatment, reduced the chances of treatment failure among children aged 3-18 years by about 40%, compared with other treatments. Dolutegravir is already used for the suppression of HIV in adults.

“About 1.8 million children live with HIV but they have had limited treatment options, with medicines that taste unpalatable, that need to be taken twice a day, or that come in large pills that are difficult to swallow” said lead author Anna Turkova, MD, from the MRC clinical trials unit at UCL. “Dolutegravir is given in small tablets usually once a day and the baby pills can be dispersed in water, meaning it’s a lot easier for young children to take. This is important in encouraging uptake of the treatment and adherence to it over many years.

“Sadly, only about half of children living with HIV are currently receiving treatment, and those who are not treated face high risks of impaired immunity and worsening health.”
 

Study details

The randomized controlled trial, called ODYSSEY, involved more than 700 children from 29 clinical centers located in Africa, Europe, and Asia. The children were given either dolutegravir or standard anti-HIV drugs, and were followed up for at least 2 years.

The study showed that 14% of children receiving dolutegravir experienced treatment failure over 2 years, compared with 22% of those receiving standard treatment. Treatment failure was deemed to occur if measurable virus appeared in the blood or if the child had symptoms of HIV-related illness.

“Our findings provide strong evidence for the global rollout of dolutegravir for children with HIV,” said Diana Gibb, MD, also from the MRC clinical trials unit at UCL, principal investigator of the trial and one of the senior authors of the paper.

“Medical treatments for children often lag woefully behind those of adults because of the separate formulations and studies that are needed,” she added. “With the evidence from ODYSSEY which used simplified dosing of both adult and baby pills, this treatment gap has been reduced and we hope that countries can quickly scale up access to children globally.”
 

Simplified dosing

“Simplifying the dosing is crucial,” concurred Cissy Kityo Mutuluuza, MD, from the Joint Clinical Research Centre in Uganda, the country enrolling most children in the trial. “Older children being able to take the same tablets as adults immediately opens access to dolutegravir for the majority of children living with HIV. It greatly simplifies procurement for national health systems in low- and middle-income countries, and lowers costs.”

Evidence from adults shows dolutegravir has a high genetic barrier to resistance, meaning viruses are less likely to become resistant to it over time. This was confirmed in the ODYSSEY trial, with much less resistance occurring among children and adolescents on dolutegravir-based treatment. In addition, past studies of the drug have shown that it may be associated with weight gain in adults, but the findings were reassuring for children. Those given dolutegravir gained on average 1 kg more and grew 1 cm higher over the study period, indicating better growth rather than abnormal weight gain.

Early findings from the trial have informed new guidance by the World Health Organization, recommending the use of dolutegravir for children.

The study was sponsored by the Penta Foundation, an international independent research network, and funded by specialist pharmaceutical company ViiV Healthcare.

A version of this article first appeared on Medscape.com.

A global study led by researchers at University College London, published Dec. 30, 2021, in the New England Journal of Medicine, found that a regimen based on a once-a-day small dolutegravir tablet was more effective at suppressing HIV than standard treatments. Dolutegravir suppresses HIV by inhibiting integrase, an enzyme that the virus needs to replicate.

The pill-based regimen, which researchers described as easier to take than standard treatment, reduced the chances of treatment failure among children aged 3-18 years by about 40%, compared with other treatments. Dolutegravir is already used for the suppression of HIV in adults.

“About 1.8 million children live with HIV but they have had limited treatment options, with medicines that taste unpalatable, that need to be taken twice a day, or that come in large pills that are difficult to swallow” said lead author Anna Turkova, MD, from the MRC clinical trials unit at UCL. “Dolutegravir is given in small tablets usually once a day and the baby pills can be dispersed in water, meaning it’s a lot easier for young children to take. This is important in encouraging uptake of the treatment and adherence to it over many years.

“Sadly, only about half of children living with HIV are currently receiving treatment, and those who are not treated face high risks of impaired immunity and worsening health.”
 

Study details

The randomized controlled trial, called ODYSSEY, involved more than 700 children from 29 clinical centers located in Africa, Europe, and Asia. The children were given either dolutegravir or standard anti-HIV drugs, and were followed up for at least 2 years.

The study showed that 14% of children receiving dolutegravir experienced treatment failure over 2 years, compared with 22% of those receiving standard treatment. Treatment failure was deemed to occur if measurable virus appeared in the blood or if the child had symptoms of HIV-related illness.

“Our findings provide strong evidence for the global rollout of dolutegravir for children with HIV,” said Diana Gibb, MD, also from the MRC clinical trials unit at UCL, principal investigator of the trial and one of the senior authors of the paper.

“Medical treatments for children often lag woefully behind those of adults because of the separate formulations and studies that are needed,” she added. “With the evidence from ODYSSEY which used simplified dosing of both adult and baby pills, this treatment gap has been reduced and we hope that countries can quickly scale up access to children globally.”
 

Simplified dosing

“Simplifying the dosing is crucial,” concurred Cissy Kityo Mutuluuza, MD, from the Joint Clinical Research Centre in Uganda, the country enrolling most children in the trial. “Older children being able to take the same tablets as adults immediately opens access to dolutegravir for the majority of children living with HIV. It greatly simplifies procurement for national health systems in low- and middle-income countries, and lowers costs.”

Evidence from adults shows dolutegravir has a high genetic barrier to resistance, meaning viruses are less likely to become resistant to it over time. This was confirmed in the ODYSSEY trial, with much less resistance occurring among children and adolescents on dolutegravir-based treatment. In addition, past studies of the drug have shown that it may be associated with weight gain in adults, but the findings were reassuring for children. Those given dolutegravir gained on average 1 kg more and grew 1 cm higher over the study period, indicating better growth rather than abnormal weight gain.

Early findings from the trial have informed new guidance by the World Health Organization, recommending the use of dolutegravir for children.

The study was sponsored by the Penta Foundation, an international independent research network, and funded by specialist pharmaceutical company ViiV Healthcare.

A version of this article first appeared on Medscape.com.

A global study led by researchers at University College London, published Dec. 30, 2021, in the New England Journal of Medicine, found that a regimen based on a once-a-day small dolutegravir tablet was more effective at suppressing HIV than standard treatments. Dolutegravir suppresses HIV by inhibiting integrase, an enzyme that the virus needs to replicate.

The pill-based regimen, which researchers described as easier to take than standard treatment, reduced the chances of treatment failure among children aged 3-18 years by about 40%, compared with other treatments. Dolutegravir is already used for the suppression of HIV in adults.

“About 1.8 million children live with HIV but they have had limited treatment options, with medicines that taste unpalatable, that need to be taken twice a day, or that come in large pills that are difficult to swallow” said lead author Anna Turkova, MD, from the MRC clinical trials unit at UCL. “Dolutegravir is given in small tablets usually once a day and the baby pills can be dispersed in water, meaning it’s a lot easier for young children to take. This is important in encouraging uptake of the treatment and adherence to it over many years.

“Sadly, only about half of children living with HIV are currently receiving treatment, and those who are not treated face high risks of impaired immunity and worsening health.”
 

Study details

The randomized controlled trial, called ODYSSEY, involved more than 700 children from 29 clinical centers located in Africa, Europe, and Asia. The children were given either dolutegravir or standard anti-HIV drugs, and were followed up for at least 2 years.

The study showed that 14% of children receiving dolutegravir experienced treatment failure over 2 years, compared with 22% of those receiving standard treatment. Treatment failure was deemed to occur if measurable virus appeared in the blood or if the child had symptoms of HIV-related illness.

“Our findings provide strong evidence for the global rollout of dolutegravir for children with HIV,” said Diana Gibb, MD, also from the MRC clinical trials unit at UCL, principal investigator of the trial and one of the senior authors of the paper.

“Medical treatments for children often lag woefully behind those of adults because of the separate formulations and studies that are needed,” she added. “With the evidence from ODYSSEY which used simplified dosing of both adult and baby pills, this treatment gap has been reduced and we hope that countries can quickly scale up access to children globally.”
 

Simplified dosing

“Simplifying the dosing is crucial,” concurred Cissy Kityo Mutuluuza, MD, from the Joint Clinical Research Centre in Uganda, the country enrolling most children in the trial. “Older children being able to take the same tablets as adults immediately opens access to dolutegravir for the majority of children living with HIV. It greatly simplifies procurement for national health systems in low- and middle-income countries, and lowers costs.”

Evidence from adults shows dolutegravir has a high genetic barrier to resistance, meaning viruses are less likely to become resistant to it over time. This was confirmed in the ODYSSEY trial, with much less resistance occurring among children and adolescents on dolutegravir-based treatment. In addition, past studies of the drug have shown that it may be associated with weight gain in adults, but the findings were reassuring for children. Those given dolutegravir gained on average 1 kg more and grew 1 cm higher over the study period, indicating better growth rather than abnormal weight gain.

Early findings from the trial have informed new guidance by the World Health Organization, recommending the use of dolutegravir for children.

The study was sponsored by the Penta Foundation, an international independent research network, and funded by specialist pharmaceutical company ViiV Healthcare.

A version of this article first appeared on Medscape.com.

SILVER SPRING, MD – The FDA issued approval for long-acting, injectable cabotegravir (CAB-LA) on Dec. 21, providing an alternative to daily oral tenofovir disoproxil fumarate-emtricitabine (TDC-FTC) for pre-exposure prophylaxis (PrEP) against HIV acquisition.

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 FDA issued approval for long-acting, injectable cabotegravir (CAB-LA) on Dec. 21, providing an alternative to daily oral tenofovir disoproxil fumarate-emtricitabine (TDC-FTC) for pre-exposure prophylaxis (PrEP) against HIV acquisition.

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 FDA issued approval for long-acting, injectable cabotegravir (CAB-LA) on Dec. 21, providing an alternative to daily oral tenofovir disoproxil fumarate-emtricitabine (TDC-FTC) for pre-exposure prophylaxis (PrEP) against HIV acquisition.

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.

The Food and Drug Administration has stopped trials of oral and implant formulations of islatravir for HIV, the investigational drug’s developer, Merck, announced in a press release.

Investigational new drug applications were halted for the oral and implant formulations of islatravir, a nucleoside reverse transcriptase translocation inhibitor, for pre-exposure prophylaxis (PrEP); the injectable formulation of islatravir for treatment and prophylaxis; and the oral doravirine/islatravir (DOR/ISL) once-daily treatment, the company announced.

The FDA’s hold followed observations that total lymphocyte and T-cell counts had dropped in some participants receiving islatravir in clinical studies.

The trials have dealt a major setback to Merck’s HIV program momentum: Thirteen trials are now on hold (six on partial hold and seven on full hold). Seven of the trials were in phase 3. But primarily the news is disappointing for patients looking for options with the confounding disease.

Tristan Barber, MD, an HIV consultant with Royal Free London National Health Service Foundation Trust, told this news organization that “the hold on these studies is a blow for those hoping for longer-acting therapies for HIV treatment and prevention. Islatravir and [investigational drug] MK-8507 were being explored in oral and other formulations and potentially would offer a non-integrase, two-drug option, increasing options for people with HIV. Whilst we don’t know the clinical significance of these CD4 drops, [Merck] made the correct decision in pausing these studies until the data is clearer.”

Merck announced in November that it had stopped dosing in the phase 2 IMAGINE-DR clinical trial of islatravir in combination with MK-8507. MK-8507 and islatravir, alone and combined, are investigational and not approved for use.

In that trial as well, decreases were observed in total lymphocyte and T-cell counts in study participants randomly assigned to receive the combination. A review by the external Data Monitoring Committee determined that the drop was related to treatment with the combination.

“We are grateful to the participants and the study investigators for their ongoing contributions to this research,” Joan Butterton, MD, vice president of infectious diseases in Global Clinical Development at Merck Research Laboratories, said in a statement. “Merck continues to investigate the potential of islatravir and nucleoside reverse transcriptase translocation inhibitors and remains committed to helping to address unmet needs in HIV treatment and prevention.”

In light of the hold, no new studies using islatravir may be initiated. People currently receiving islatravir as part of the studies for PrEP, as well as injectable islatravir for treatment and prophylaxis, will no longer receive the study drug, and T-cell and lymphocyte counts will be monitored for recovery.

Those participating in the PrEP studies will be offered approved, once-daily, oral PrEP and those in studies of DOR/ISL who already started treatment will continue to receive study medication under a partial clinical hold.

A full list of the trials that have been placed on full or partial clinical holds can be found in the press release.

In an interview with this news organization, Monica Gandhi, MD, MPH, director of University of California, San Francisco’s Gladstone Center for AIDS Research, described the news of the islatravir trial holds as “very disappointing.”

“There were high hopes for this drug,” she said, adding that the hope was it would be paired with Gilead’s lenacapavir (another long-acting agent) for treatment and be able to give a once-weekly option for HIV treatment.

Lenacapavir is Gilead’s potential first-in-class, long-acting HIV-1 capsid inhibitor in development for treatment and prevention of HIV.

“Moreover,” she said, “additional hope was that, because of [islatravir’s] long half-life, it could be used as a monthly medication for pre-exposure prophylaxis.”

Gilead and Merck have decided to stop all dosing of participants in the phase 2 clinical trial evaluating an oral, weekly combination treatment of islatravir and lenacapavir in people living with HIV who are virologically suppressed on antiretroviral therapy, according to Merck’s press release.

Participants in that trial will stop taking the study drug and restart their previous antiretroviral regimen. According to the press release, both companies are considering whether a different dosing of islatravir combined with lenacapavir may become a once-weekly oral therapy option for people living with HIV.

Neither Merck nor Gilead representatives responded to request for comment by publication time.

Dr. Barber reported conference support, speaker fees, and advisory board honoraria from Gilead, Janssen, Merck, Roche, Thera, and ViiV and research/educational grants from Gilead, Roche, and ViiV. Dr. Gandhi has disclosed no relevant financial relationships.

A version of this article first appeared on Medscape.com.

The Food and Drug Administration has stopped trials of oral and implant formulations of islatravir for HIV, the investigational drug’s developer, Merck, announced in a press release.

Investigational new drug applications were halted for the oral and implant formulations of islatravir, a nucleoside reverse transcriptase translocation inhibitor, for pre-exposure prophylaxis (PrEP); the injectable formulation of islatravir for treatment and prophylaxis; and the oral doravirine/islatravir (DOR/ISL) once-daily treatment, the company announced.

The FDA’s hold followed observations that total lymphocyte and T-cell counts had dropped in some participants receiving islatravir in clinical studies.

The trials have dealt a major setback to Merck’s HIV program momentum: Thirteen trials are now on hold (six on partial hold and seven on full hold). Seven of the trials were in phase 3. But primarily the news is disappointing for patients looking for options with the confounding disease.

Tristan Barber, MD, an HIV consultant with Royal Free London National Health Service Foundation Trust, told this news organization that “the hold on these studies is a blow for those hoping for longer-acting therapies for HIV treatment and prevention. Islatravir and [investigational drug] MK-8507 were being explored in oral and other formulations and potentially would offer a non-integrase, two-drug option, increasing options for people with HIV. Whilst we don’t know the clinical significance of these CD4 drops, [Merck] made the correct decision in pausing these studies until the data is clearer.”

Merck announced in November that it had stopped dosing in the phase 2 IMAGINE-DR clinical trial of islatravir in combination with MK-8507. MK-8507 and islatravir, alone and combined, are investigational and not approved for use.

In that trial as well, decreases were observed in total lymphocyte and T-cell counts in study participants randomly assigned to receive the combination. A review by the external Data Monitoring Committee determined that the drop was related to treatment with the combination.

“We are grateful to the participants and the study investigators for their ongoing contributions to this research,” Joan Butterton, MD, vice president of infectious diseases in Global Clinical Development at Merck Research Laboratories, said in a statement. “Merck continues to investigate the potential of islatravir and nucleoside reverse transcriptase translocation inhibitors and remains committed to helping to address unmet needs in HIV treatment and prevention.”

In light of the hold, no new studies using islatravir may be initiated. People currently receiving islatravir as part of the studies for PrEP, as well as injectable islatravir for treatment and prophylaxis, will no longer receive the study drug, and T-cell and lymphocyte counts will be monitored for recovery.

Those participating in the PrEP studies will be offered approved, once-daily, oral PrEP and those in studies of DOR/ISL who already started treatment will continue to receive study medication under a partial clinical hold.

A full list of the trials that have been placed on full or partial clinical holds can be found in the press release.

In an interview with this news organization, Monica Gandhi, MD, MPH, director of University of California, San Francisco’s Gladstone Center for AIDS Research, described the news of the islatravir trial holds as “very disappointing.”

“There were high hopes for this drug,” she said, adding that the hope was it would be paired with Gilead’s lenacapavir (another long-acting agent) for treatment and be able to give a once-weekly option for HIV treatment.

Lenacapavir is Gilead’s potential first-in-class, long-acting HIV-1 capsid inhibitor in development for treatment and prevention of HIV.

“Moreover,” she said, “additional hope was that, because of [islatravir’s] long half-life, it could be used as a monthly medication for pre-exposure prophylaxis.”

Gilead and Merck have decided to stop all dosing of participants in the phase 2 clinical trial evaluating an oral, weekly combination treatment of islatravir and lenacapavir in people living with HIV who are virologically suppressed on antiretroviral therapy, according to Merck’s press release.

Participants in that trial will stop taking the study drug and restart their previous antiretroviral regimen. According to the press release, both companies are considering whether a different dosing of islatravir combined with lenacapavir may become a once-weekly oral therapy option for people living with HIV.

Neither Merck nor Gilead representatives responded to request for comment by publication time.

Dr. Barber reported conference support, speaker fees, and advisory board honoraria from Gilead, Janssen, Merck, Roche, Thera, and ViiV and research/educational grants from Gilead, Roche, and ViiV. Dr. Gandhi has disclosed no relevant financial relationships.

A version of this article first appeared on Medscape.com.

The Food and Drug Administration has stopped trials of oral and implant formulations of islatravir for HIV, the investigational drug’s developer, Merck, announced in a press release.

Investigational new drug applications were halted for the oral and implant formulations of islatravir, a nucleoside reverse transcriptase translocation inhibitor, for pre-exposure prophylaxis (PrEP); the injectable formulation of islatravir for treatment and prophylaxis; and the oral doravirine/islatravir (DOR/ISL) once-daily treatment, the company announced.

The FDA’s hold followed observations that total lymphocyte and T-cell counts had dropped in some participants receiving islatravir in clinical studies.

The trials have dealt a major setback to Merck’s HIV program momentum: Thirteen trials are now on hold (six on partial hold and seven on full hold). Seven of the trials were in phase 3. But primarily the news is disappointing for patients looking for options with the confounding disease.

Tristan Barber, MD, an HIV consultant with Royal Free London National Health Service Foundation Trust, told this news organization that “the hold on these studies is a blow for those hoping for longer-acting therapies for HIV treatment and prevention. Islatravir and [investigational drug] MK-8507 were being explored in oral and other formulations and potentially would offer a non-integrase, two-drug option, increasing options for people with HIV. Whilst we don’t know the clinical significance of these CD4 drops, [Merck] made the correct decision in pausing these studies until the data is clearer.”

Merck announced in November that it had stopped dosing in the phase 2 IMAGINE-DR clinical trial of islatravir in combination with MK-8507. MK-8507 and islatravir, alone and combined, are investigational and not approved for use.

In that trial as well, decreases were observed in total lymphocyte and T-cell counts in study participants randomly assigned to receive the combination. A review by the external Data Monitoring Committee determined that the drop was related to treatment with the combination.

“We are grateful to the participants and the study investigators for their ongoing contributions to this research,” Joan Butterton, MD, vice president of infectious diseases in Global Clinical Development at Merck Research Laboratories, said in a statement. “Merck continues to investigate the potential of islatravir and nucleoside reverse transcriptase translocation inhibitors and remains committed to helping to address unmet needs in HIV treatment and prevention.”

In light of the hold, no new studies using islatravir may be initiated. People currently receiving islatravir as part of the studies for PrEP, as well as injectable islatravir for treatment and prophylaxis, will no longer receive the study drug, and T-cell and lymphocyte counts will be monitored for recovery.

Those participating in the PrEP studies will be offered approved, once-daily, oral PrEP and those in studies of DOR/ISL who already started treatment will continue to receive study medication under a partial clinical hold.

A full list of the trials that have been placed on full or partial clinical holds can be found in the press release.

In an interview with this news organization, Monica Gandhi, MD, MPH, director of University of California, San Francisco’s Gladstone Center for AIDS Research, described the news of the islatravir trial holds as “very disappointing.”

“There were high hopes for this drug,” she said, adding that the hope was it would be paired with Gilead’s lenacapavir (another long-acting agent) for treatment and be able to give a once-weekly option for HIV treatment.

Lenacapavir is Gilead’s potential first-in-class, long-acting HIV-1 capsid inhibitor in development for treatment and prevention of HIV.

“Moreover,” she said, “additional hope was that, because of [islatravir’s] long half-life, it could be used as a monthly medication for pre-exposure prophylaxis.”

Gilead and Merck have decided to stop all dosing of participants in the phase 2 clinical trial evaluating an oral, weekly combination treatment of islatravir and lenacapavir in people living with HIV who are virologically suppressed on antiretroviral therapy, according to Merck’s press release.

Participants in that trial will stop taking the study drug and restart their previous antiretroviral regimen. According to the press release, both companies are considering whether a different dosing of islatravir combined with lenacapavir may become a once-weekly oral therapy option for people living with HIV.

Neither Merck nor Gilead representatives responded to request for comment by publication time.

Dr. Barber reported conference support, speaker fees, and advisory board honoraria from Gilead, Janssen, Merck, Roche, Thera, and ViiV and research/educational grants from Gilead, Roche, and ViiV. Dr. Gandhi has disclosed no relevant financial relationships.

A version of this article first appeared on Medscape.com.