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Nucleic acid testing before PrEP urged to detect occult HIV
SEATTLE – Almost a third of patients who developed HIV while on pre-exposure prophylaxis (PrEP) had strains that were resistant to emtricitabine – a component of the PrEP medication Truvada along with tenofovir – at time of diagnosis, compared with just 2% of those not on PrEP, in a review of more than 3,500 newly diagnosed HIV cases in New York.
The finding points to a growing concern as use of PrEP becomes more common: the induction of resistance to HIV treatments.
PrEP is highly effective, so it’s likely that the PrEP patients already had HIV when they started treatment. Nucleic acid amplification testing (NAAT) is the only way to rule it out definitively, but only 5% of PrEP users in the study were screened with NAAT within 2 days of initiation.
The usual test – HIV antibody screening – returns a false negative in the window between HIV exposure and active infection, when antibodies turn positive, which can take months. NAAT, on the other hand, looks for evidence of the virus directly.
The findings led the investigators to urge routine NAAT screening before PrEP, something that New York State guidelines currently recommend only if patients present with symptoms of acute HIV infection or report condomless sex in the previous 4 weeks.
To prevent drug resistance, “rigorous screening that includes NAAT is critical.” It reduces “the likelihood of PrEP start during undetected HIV infection,” said lead investigator Kavita Misra, PhD, MPH, a senior epidemiologist at the New York City Department of Health and Mental Hygiene.
Her team reviewed 3,685 people in New York who were diagnosed with HIV from November 2015 to August 2017; 91 had been on PrEP beforehand for a median of 106 days.
Postdiagnosis genotyping was available for 75% of PrEP users and 63% in the no-PrEP group. Resistance mutations to emtricitabine were significantly more prevalent with PrEP than without (29% versus 2%, respectively; P less than .0001). None of the PrEP users, but four in the no-PrEP group, had resistance to the other component of Truvada, tenofovir.
PrEP users were more likely to be diagnosed with HIV in the acute phase of infection than were those not using PrEP (33% versus 9%; P less than .0001), probably because they were also more likely to have regular office visits while on PrEP.
Skeptics at the Conference on Retroviruses and Opportunistic Infections, where the study was presented, wondered whether emtricitabine resistance would have been more common in the no-PrEP group if the infection had been picked up earlier because resistance fades as the infection progresses.
Dr. Misra said it was a good question and that her team will look into it. However, she stood by her conclusions.
PrEP use was most common among white men who have sex with men and among people under 30 years old.
There was no external funding, and the investigators didn’t have any disclosures.
SOURCE: Misra K et al. 2019 CROI, Abstract 107.
SEATTLE – Almost a third of patients who developed HIV while on pre-exposure prophylaxis (PrEP) had strains that were resistant to emtricitabine – a component of the PrEP medication Truvada along with tenofovir – at time of diagnosis, compared with just 2% of those not on PrEP, in a review of more than 3,500 newly diagnosed HIV cases in New York.
The finding points to a growing concern as use of PrEP becomes more common: the induction of resistance to HIV treatments.
PrEP is highly effective, so it’s likely that the PrEP patients already had HIV when they started treatment. Nucleic acid amplification testing (NAAT) is the only way to rule it out definitively, but only 5% of PrEP users in the study were screened with NAAT within 2 days of initiation.
The usual test – HIV antibody screening – returns a false negative in the window between HIV exposure and active infection, when antibodies turn positive, which can take months. NAAT, on the other hand, looks for evidence of the virus directly.
The findings led the investigators to urge routine NAAT screening before PrEP, something that New York State guidelines currently recommend only if patients present with symptoms of acute HIV infection or report condomless sex in the previous 4 weeks.
To prevent drug resistance, “rigorous screening that includes NAAT is critical.” It reduces “the likelihood of PrEP start during undetected HIV infection,” said lead investigator Kavita Misra, PhD, MPH, a senior epidemiologist at the New York City Department of Health and Mental Hygiene.
Her team reviewed 3,685 people in New York who were diagnosed with HIV from November 2015 to August 2017; 91 had been on PrEP beforehand for a median of 106 days.
Postdiagnosis genotyping was available for 75% of PrEP users and 63% in the no-PrEP group. Resistance mutations to emtricitabine were significantly more prevalent with PrEP than without (29% versus 2%, respectively; P less than .0001). None of the PrEP users, but four in the no-PrEP group, had resistance to the other component of Truvada, tenofovir.
PrEP users were more likely to be diagnosed with HIV in the acute phase of infection than were those not using PrEP (33% versus 9%; P less than .0001), probably because they were also more likely to have regular office visits while on PrEP.
Skeptics at the Conference on Retroviruses and Opportunistic Infections, where the study was presented, wondered whether emtricitabine resistance would have been more common in the no-PrEP group if the infection had been picked up earlier because resistance fades as the infection progresses.
Dr. Misra said it was a good question and that her team will look into it. However, she stood by her conclusions.
PrEP use was most common among white men who have sex with men and among people under 30 years old.
There was no external funding, and the investigators didn’t have any disclosures.
SOURCE: Misra K et al. 2019 CROI, Abstract 107.
SEATTLE – Almost a third of patients who developed HIV while on pre-exposure prophylaxis (PrEP) had strains that were resistant to emtricitabine – a component of the PrEP medication Truvada along with tenofovir – at time of diagnosis, compared with just 2% of those not on PrEP, in a review of more than 3,500 newly diagnosed HIV cases in New York.
The finding points to a growing concern as use of PrEP becomes more common: the induction of resistance to HIV treatments.
PrEP is highly effective, so it’s likely that the PrEP patients already had HIV when they started treatment. Nucleic acid amplification testing (NAAT) is the only way to rule it out definitively, but only 5% of PrEP users in the study were screened with NAAT within 2 days of initiation.
The usual test – HIV antibody screening – returns a false negative in the window between HIV exposure and active infection, when antibodies turn positive, which can take months. NAAT, on the other hand, looks for evidence of the virus directly.
The findings led the investigators to urge routine NAAT screening before PrEP, something that New York State guidelines currently recommend only if patients present with symptoms of acute HIV infection or report condomless sex in the previous 4 weeks.
To prevent drug resistance, “rigorous screening that includes NAAT is critical.” It reduces “the likelihood of PrEP start during undetected HIV infection,” said lead investigator Kavita Misra, PhD, MPH, a senior epidemiologist at the New York City Department of Health and Mental Hygiene.
Her team reviewed 3,685 people in New York who were diagnosed with HIV from November 2015 to August 2017; 91 had been on PrEP beforehand for a median of 106 days.
Postdiagnosis genotyping was available for 75% of PrEP users and 63% in the no-PrEP group. Resistance mutations to emtricitabine were significantly more prevalent with PrEP than without (29% versus 2%, respectively; P less than .0001). None of the PrEP users, but four in the no-PrEP group, had resistance to the other component of Truvada, tenofovir.
PrEP users were more likely to be diagnosed with HIV in the acute phase of infection than were those not using PrEP (33% versus 9%; P less than .0001), probably because they were also more likely to have regular office visits while on PrEP.
Skeptics at the Conference on Retroviruses and Opportunistic Infections, where the study was presented, wondered whether emtricitabine resistance would have been more common in the no-PrEP group if the infection had been picked up earlier because resistance fades as the infection progresses.
Dr. Misra said it was a good question and that her team will look into it. However, she stood by her conclusions.
PrEP use was most common among white men who have sex with men and among people under 30 years old.
There was no external funding, and the investigators didn’t have any disclosures.
SOURCE: Misra K et al. 2019 CROI, Abstract 107.
REPORTING FROM CROI 2019
PrEP adherence lowest among Medicaid patients, others
SEATTLE – Female sex, young age, residing in a rural location, black race, and Medicaid insurance were all associated with reduced adherence to HIV pre-exposure prophylaxis in a study from the Centers for Disease Control and Prevention.
Daily pre-exposure prophylaxis (PrEP) with emtricitabine/tenofovir (Truvada) prevents infection, but not everyone sticks with it. The investigators wanted to find out who struggles the most with adherence to help focus future intervention efforts.
The team identified 7,250 commercially insured and 349 Medicaid PrEP users in IBM MarketScan databases during 2011-2016. They tracked them from their initial PrEP prescription until there was a gap of 30 days or more in their PrEP refills, at which point they met the study’s definition of nonpersistence.
Overall, “commercially insured nonpersistent PrEP users were young, female, and rural. Medicaid insured nonpersistent users were young, female, and black,” said lead investigator Ya-Lin Huang, PhD, a health scientist in the CDC Division of HIV/AIDS Prevention.
“It is concerning that some populations with low persistence were among those with the highest rates of HIV diagnosis, such as young, black men. Research is needed to understand reasons for discontinuing PrEP. Interventions tailored for priority populations are needed to improve PrEP persistence,” she said at the Conference on Retroviruses and Opportunistic Infections.
Her team found that commercially insured patients stuck with PrEP longer than did those on Medicaid, a median of 14.5 months, with 56% still filling their prescriptions after a year, versus a median Medicaid persistence of 7.6 months, with only a third of Medicaid patients still on PrEP after 12 months.
Men were more persistent with PrEP than were women in both groups, as were older people versus younger. The median length of adherence among commercially insured patients aged 45-54 years, for instance, was 20.5 months, versus 8.6 months among people aged 18-24 years. Older PrEP users persisted longer among Medicaid patients as well, a median of 10 versus 4 months.
Also in the Medicaid group, white patients stuck with PrEP longer than did black patients, a median of 8.5 months versus 4.1 months. There were no racial differences with commercial insurance.
The findings held even when the team used gaps of 60 and 90 days, instead of 30 days, to define nonpersistence.
The study says nothing about why people stopped PrEP, or why there were such stark differences between the groups.
Perhaps, in some cases, people quit risky behavior or entered new relationships. Maybe PrEP was too expensive for some, or transportation to the clinic was an issue. Side effects might have been a problem, or people could have lost their insurance coverage, or maybe didn’t want to deal with the hassle. It’s impossible to know from the data, Dr. Huang said.
She said her team wants to figure it out, so they can help people overcome barriers to treatment, which likely vary across subgroups.
The study also was limited to patients who were enrolled in coverage at least 6 months before and 6 months after their first PrEP prescription; the investigators want to exam the situation for people with less consistent coverage, and no coverage at all.
The work was funded by the Centers for Disease Control and Prevention. The investigators had no disclosures.
SOURCE: Huang YA et al. CROI 2019, Abstract 106.
SEATTLE – Female sex, young age, residing in a rural location, black race, and Medicaid insurance were all associated with reduced adherence to HIV pre-exposure prophylaxis in a study from the Centers for Disease Control and Prevention.
Daily pre-exposure prophylaxis (PrEP) with emtricitabine/tenofovir (Truvada) prevents infection, but not everyone sticks with it. The investigators wanted to find out who struggles the most with adherence to help focus future intervention efforts.
The team identified 7,250 commercially insured and 349 Medicaid PrEP users in IBM MarketScan databases during 2011-2016. They tracked them from their initial PrEP prescription until there was a gap of 30 days or more in their PrEP refills, at which point they met the study’s definition of nonpersistence.
Overall, “commercially insured nonpersistent PrEP users were young, female, and rural. Medicaid insured nonpersistent users were young, female, and black,” said lead investigator Ya-Lin Huang, PhD, a health scientist in the CDC Division of HIV/AIDS Prevention.
“It is concerning that some populations with low persistence were among those with the highest rates of HIV diagnosis, such as young, black men. Research is needed to understand reasons for discontinuing PrEP. Interventions tailored for priority populations are needed to improve PrEP persistence,” she said at the Conference on Retroviruses and Opportunistic Infections.
Her team found that commercially insured patients stuck with PrEP longer than did those on Medicaid, a median of 14.5 months, with 56% still filling their prescriptions after a year, versus a median Medicaid persistence of 7.6 months, with only a third of Medicaid patients still on PrEP after 12 months.
Men were more persistent with PrEP than were women in both groups, as were older people versus younger. The median length of adherence among commercially insured patients aged 45-54 years, for instance, was 20.5 months, versus 8.6 months among people aged 18-24 years. Older PrEP users persisted longer among Medicaid patients as well, a median of 10 versus 4 months.
Also in the Medicaid group, white patients stuck with PrEP longer than did black patients, a median of 8.5 months versus 4.1 months. There were no racial differences with commercial insurance.
The findings held even when the team used gaps of 60 and 90 days, instead of 30 days, to define nonpersistence.
The study says nothing about why people stopped PrEP, or why there were such stark differences between the groups.
Perhaps, in some cases, people quit risky behavior or entered new relationships. Maybe PrEP was too expensive for some, or transportation to the clinic was an issue. Side effects might have been a problem, or people could have lost their insurance coverage, or maybe didn’t want to deal with the hassle. It’s impossible to know from the data, Dr. Huang said.
She said her team wants to figure it out, so they can help people overcome barriers to treatment, which likely vary across subgroups.
The study also was limited to patients who were enrolled in coverage at least 6 months before and 6 months after their first PrEP prescription; the investigators want to exam the situation for people with less consistent coverage, and no coverage at all.
The work was funded by the Centers for Disease Control and Prevention. The investigators had no disclosures.
SOURCE: Huang YA et al. CROI 2019, Abstract 106.
SEATTLE – Female sex, young age, residing in a rural location, black race, and Medicaid insurance were all associated with reduced adherence to HIV pre-exposure prophylaxis in a study from the Centers for Disease Control and Prevention.
Daily pre-exposure prophylaxis (PrEP) with emtricitabine/tenofovir (Truvada) prevents infection, but not everyone sticks with it. The investigators wanted to find out who struggles the most with adherence to help focus future intervention efforts.
The team identified 7,250 commercially insured and 349 Medicaid PrEP users in IBM MarketScan databases during 2011-2016. They tracked them from their initial PrEP prescription until there was a gap of 30 days or more in their PrEP refills, at which point they met the study’s definition of nonpersistence.
Overall, “commercially insured nonpersistent PrEP users were young, female, and rural. Medicaid insured nonpersistent users were young, female, and black,” said lead investigator Ya-Lin Huang, PhD, a health scientist in the CDC Division of HIV/AIDS Prevention.
“It is concerning that some populations with low persistence were among those with the highest rates of HIV diagnosis, such as young, black men. Research is needed to understand reasons for discontinuing PrEP. Interventions tailored for priority populations are needed to improve PrEP persistence,” she said at the Conference on Retroviruses and Opportunistic Infections.
Her team found that commercially insured patients stuck with PrEP longer than did those on Medicaid, a median of 14.5 months, with 56% still filling their prescriptions after a year, versus a median Medicaid persistence of 7.6 months, with only a third of Medicaid patients still on PrEP after 12 months.
Men were more persistent with PrEP than were women in both groups, as were older people versus younger. The median length of adherence among commercially insured patients aged 45-54 years, for instance, was 20.5 months, versus 8.6 months among people aged 18-24 years. Older PrEP users persisted longer among Medicaid patients as well, a median of 10 versus 4 months.
Also in the Medicaid group, white patients stuck with PrEP longer than did black patients, a median of 8.5 months versus 4.1 months. There were no racial differences with commercial insurance.
The findings held even when the team used gaps of 60 and 90 days, instead of 30 days, to define nonpersistence.
The study says nothing about why people stopped PrEP, or why there were such stark differences between the groups.
Perhaps, in some cases, people quit risky behavior or entered new relationships. Maybe PrEP was too expensive for some, or transportation to the clinic was an issue. Side effects might have been a problem, or people could have lost their insurance coverage, or maybe didn’t want to deal with the hassle. It’s impossible to know from the data, Dr. Huang said.
She said her team wants to figure it out, so they can help people overcome barriers to treatment, which likely vary across subgroups.
The study also was limited to patients who were enrolled in coverage at least 6 months before and 6 months after their first PrEP prescription; the investigators want to exam the situation for people with less consistent coverage, and no coverage at all.
The work was funded by the Centers for Disease Control and Prevention. The investigators had no disclosures.
SOURCE: Huang YA et al. CROI 2019, Abstract 106.
REPORTING FROM CROI 2019
Making HIV Transmission a Rare Event
About 80% of new HIV transmissions are from people who do not know they have HIV or are not receiving regular care, according to a CDC report. That makes improvements in early detection and “rapid entry into care” key to ending the HIV epidemic within 10 years—the current US Department of Health and Human Services goal.
Recent studies have shown that viral suppression prevents sexual transmission of HIV, the researchers say. The studies found no HIV transmissions attributable to sex between HIV-discordant couples when the HIV-infected partner was maintaining viral suppression through treatment—even when the HIV-negative partner was not using preexposure prophylaxis. Those findings mean HIV transmission can become a “rare event,” the researchers say.
Today’s treatments have gotten simpler than the hills of pills that patients used to take. Sometimes the patient needs only a single-tablet regimen. Most people, according to the CDC, can achieve viral suppression within 6 months of starting treatment.
But many of the 1.1 million people with HIV infection are not effectively treated. In 2015, the CDC researchers say, 14.5% of people with HIV infection did not have a diagnosis, and 37.2% were not in care (receiving ≥ 1 CD4 tests in a measurement year). Nearly half were not virally suppressed. Lack of effective treatment results in worse outcomes and higher rates of transmission: It was associated with 38,700 new HIV infections in 2016.
The researchers used a model to estimate transmission rates in 2016 along the HIV continuum of care. Overall, the rate was 3.5 per 100 person-years. Among 9,600 people who were acutely infected and unaware of their infection, the rate was 16.1 per 100 person-years. Among 154,400 people who were nonacutely infected and unaware, the rate was 8.4.
Of the nearly 250,000 people who were aware of HIV infection but not in care, 16,500 transmissions were generated (6.6/100 person-years). Among the 125,300 who were receiving HIV care but not virally suppressed, 7,700 transmissions were generated (6.1).
The transmission rate was 0 for patients who were virally suppressed. The researchers note that 100% efficacy was assumed based on trial results for sexual transmission; no data are available on the efficacy of viral suppression on reducing HIV transmission from IV drug use.
Better detection and linkage to treatment will address most of the problem, but what about the patients who do not maintain viral suppression? Among patients in clinical care, about 80% were virally suppressed at their most recent visit, but about one-third did not sustain viral suppression over 1 year. For those patients, the researchers say, a tailored approach aimed at the barriers that are most relevant for the patient is critical to improving adherence.
The CDC recommends routine screening of all Americans aged 13 to 64 years at least once in their life and at least annual testing for those at high risk. In addition, the researchers say, it is important to spread the word that maintaining viral suppression prevents sexual transmission. Sharing this knowledge more generally might reduce the stigma associated with HIV and help engage patients in consistent care.
About 80% of new HIV transmissions are from people who do not know they have HIV or are not receiving regular care, according to a CDC report. That makes improvements in early detection and “rapid entry into care” key to ending the HIV epidemic within 10 years—the current US Department of Health and Human Services goal.
Recent studies have shown that viral suppression prevents sexual transmission of HIV, the researchers say. The studies found no HIV transmissions attributable to sex between HIV-discordant couples when the HIV-infected partner was maintaining viral suppression through treatment—even when the HIV-negative partner was not using preexposure prophylaxis. Those findings mean HIV transmission can become a “rare event,” the researchers say.
Today’s treatments have gotten simpler than the hills of pills that patients used to take. Sometimes the patient needs only a single-tablet regimen. Most people, according to the CDC, can achieve viral suppression within 6 months of starting treatment.
But many of the 1.1 million people with HIV infection are not effectively treated. In 2015, the CDC researchers say, 14.5% of people with HIV infection did not have a diagnosis, and 37.2% were not in care (receiving ≥ 1 CD4 tests in a measurement year). Nearly half were not virally suppressed. Lack of effective treatment results in worse outcomes and higher rates of transmission: It was associated with 38,700 new HIV infections in 2016.
The researchers used a model to estimate transmission rates in 2016 along the HIV continuum of care. Overall, the rate was 3.5 per 100 person-years. Among 9,600 people who were acutely infected and unaware of their infection, the rate was 16.1 per 100 person-years. Among 154,400 people who were nonacutely infected and unaware, the rate was 8.4.
Of the nearly 250,000 people who were aware of HIV infection but not in care, 16,500 transmissions were generated (6.6/100 person-years). Among the 125,300 who were receiving HIV care but not virally suppressed, 7,700 transmissions were generated (6.1).
The transmission rate was 0 for patients who were virally suppressed. The researchers note that 100% efficacy was assumed based on trial results for sexual transmission; no data are available on the efficacy of viral suppression on reducing HIV transmission from IV drug use.
Better detection and linkage to treatment will address most of the problem, but what about the patients who do not maintain viral suppression? Among patients in clinical care, about 80% were virally suppressed at their most recent visit, but about one-third did not sustain viral suppression over 1 year. For those patients, the researchers say, a tailored approach aimed at the barriers that are most relevant for the patient is critical to improving adherence.
The CDC recommends routine screening of all Americans aged 13 to 64 years at least once in their life and at least annual testing for those at high risk. In addition, the researchers say, it is important to spread the word that maintaining viral suppression prevents sexual transmission. Sharing this knowledge more generally might reduce the stigma associated with HIV and help engage patients in consistent care.
About 80% of new HIV transmissions are from people who do not know they have HIV or are not receiving regular care, according to a CDC report. That makes improvements in early detection and “rapid entry into care” key to ending the HIV epidemic within 10 years—the current US Department of Health and Human Services goal.
Recent studies have shown that viral suppression prevents sexual transmission of HIV, the researchers say. The studies found no HIV transmissions attributable to sex between HIV-discordant couples when the HIV-infected partner was maintaining viral suppression through treatment—even when the HIV-negative partner was not using preexposure prophylaxis. Those findings mean HIV transmission can become a “rare event,” the researchers say.
Today’s treatments have gotten simpler than the hills of pills that patients used to take. Sometimes the patient needs only a single-tablet regimen. Most people, according to the CDC, can achieve viral suppression within 6 months of starting treatment.
But many of the 1.1 million people with HIV infection are not effectively treated. In 2015, the CDC researchers say, 14.5% of people with HIV infection did not have a diagnosis, and 37.2% were not in care (receiving ≥ 1 CD4 tests in a measurement year). Nearly half were not virally suppressed. Lack of effective treatment results in worse outcomes and higher rates of transmission: It was associated with 38,700 new HIV infections in 2016.
The researchers used a model to estimate transmission rates in 2016 along the HIV continuum of care. Overall, the rate was 3.5 per 100 person-years. Among 9,600 people who were acutely infected and unaware of their infection, the rate was 16.1 per 100 person-years. Among 154,400 people who were nonacutely infected and unaware, the rate was 8.4.
Of the nearly 250,000 people who were aware of HIV infection but not in care, 16,500 transmissions were generated (6.6/100 person-years). Among the 125,300 who were receiving HIV care but not virally suppressed, 7,700 transmissions were generated (6.1).
The transmission rate was 0 for patients who were virally suppressed. The researchers note that 100% efficacy was assumed based on trial results for sexual transmission; no data are available on the efficacy of viral suppression on reducing HIV transmission from IV drug use.
Better detection and linkage to treatment will address most of the problem, but what about the patients who do not maintain viral suppression? Among patients in clinical care, about 80% were virally suppressed at their most recent visit, but about one-third did not sustain viral suppression over 1 year. For those patients, the researchers say, a tailored approach aimed at the barriers that are most relevant for the patient is critical to improving adherence.
The CDC recommends routine screening of all Americans aged 13 to 64 years at least once in their life and at least annual testing for those at high risk. In addition, the researchers say, it is important to spread the word that maintaining viral suppression prevents sexual transmission. Sharing this knowledge more generally might reduce the stigma associated with HIV and help engage patients in consistent care.
Harness EHRs to identify PrEP candidates
SEATTLE – Kaiser Permanente Northern California has developed an EHR program that automatically flags patients at high risk for HIV.
The idea was to come up with a way to help clinicians focus their pre-exposure prophylaxis (PrEP) outreach on the people who need it most. PrEP prevents HIV, but often “it’s difficult for providers to identify patients who are at risk. Prediction models using EHR data can identify patients who are at high risk but not using PrEP,” said study lead Julia Marcus, PhD, an assistant professor in the department of population medicine at Harvard Medical School, Boston.
She proved that assertion in a presentation at the Conference on Retroviruses & Opportunistic Infections.
The Kaiser program uses 44 variables routinely collected in EHRs from five categories: demographics, social history, lab data, medication use, and diagnoses. Specific variables include living in a zip code with high HIV incidence; men who have sex with men (MSM); black race; urine tests positive for cocaine or methadone; use of erectile dysfunction medications; and diagnoses of depression, anal warts, and other conditions.
The development cohort included 3,143,963 Kaiser members from 2007 to 2014 with 2 or more years of enrollment; at least one outpatient visit; no prior PrEP use; and no HIV diagnosis.
There were 701 incident HIV cases; the model did a good job at predicting them, with a C-statistic of 0.86 (95% confidence interval, 0.85-0.87). A score of 1.0 would be perfect prediction, and 0.5 no predictive value. Previous efforts at HIV prediction – relying generally on just MSM status and STD history – have C-statistics of around 0.6; prediction models commonly used for cardiovascular and other diseases often have C-statistics of around 0.7, Dr. Marcus explained.
The model was validated in 606,701 Kaiser members during 2015-2017. The validation cohort was slightly younger than the development cohort, with a mean age of 37 versus 45 years, and slightly more diverse, with fewer white patients, 44% versus 52%. Both cohorts had slightly more women than men.
There were 83 new HIV diagnoses in the validation cohort. The C-statistic for HIV prediction was 0.84 (95% CI, 0.8-0.89). The model predicted 32 of 69 (46%) incident HIV cases among men tagged as high risk – at least a 0.2% chance of contracting HIV within 3 years – or very high risk, a 1% chance or higher, which is more than 50 times the risk among the general population. Relying on just MSM and STD history predicted 32% of cases.
Overall, “our model identified nearly half of new HIV cases among males by flagging only 2% of the general population. The results suggest our model would perform well if implemented today. You could replicate our approach in any health system with an EHR. Our specific variables may not translate to every setting, but any health care system can develop this model based on the EHR data they do have,” Dr. Marcus said.
“You could embed this in any EHR system and have it update in real time to flag providers to do a sexual history and talk with patients about PrEP,” she said.
The next step is a pilot project at Kaiser Permanente San Francisco to evaluate the impact on PrEP prescribing and HIV incidence. The model failed to predict 14 incident HIV cases among women in the validation cohort, a problem that also needs to be addressed.
The work was funded by the National Institutes of Health and Kaiser Permanente. Dr. Marcus didn’t have any relevant disclosures.
SOURCE: Marcus JL et al. CROI 2019, Abstract 105.
SEATTLE – Kaiser Permanente Northern California has developed an EHR program that automatically flags patients at high risk for HIV.
The idea was to come up with a way to help clinicians focus their pre-exposure prophylaxis (PrEP) outreach on the people who need it most. PrEP prevents HIV, but often “it’s difficult for providers to identify patients who are at risk. Prediction models using EHR data can identify patients who are at high risk but not using PrEP,” said study lead Julia Marcus, PhD, an assistant professor in the department of population medicine at Harvard Medical School, Boston.
She proved that assertion in a presentation at the Conference on Retroviruses & Opportunistic Infections.
The Kaiser program uses 44 variables routinely collected in EHRs from five categories: demographics, social history, lab data, medication use, and diagnoses. Specific variables include living in a zip code with high HIV incidence; men who have sex with men (MSM); black race; urine tests positive for cocaine or methadone; use of erectile dysfunction medications; and diagnoses of depression, anal warts, and other conditions.
The development cohort included 3,143,963 Kaiser members from 2007 to 2014 with 2 or more years of enrollment; at least one outpatient visit; no prior PrEP use; and no HIV diagnosis.
There were 701 incident HIV cases; the model did a good job at predicting them, with a C-statistic of 0.86 (95% confidence interval, 0.85-0.87). A score of 1.0 would be perfect prediction, and 0.5 no predictive value. Previous efforts at HIV prediction – relying generally on just MSM status and STD history – have C-statistics of around 0.6; prediction models commonly used for cardiovascular and other diseases often have C-statistics of around 0.7, Dr. Marcus explained.
The model was validated in 606,701 Kaiser members during 2015-2017. The validation cohort was slightly younger than the development cohort, with a mean age of 37 versus 45 years, and slightly more diverse, with fewer white patients, 44% versus 52%. Both cohorts had slightly more women than men.
There were 83 new HIV diagnoses in the validation cohort. The C-statistic for HIV prediction was 0.84 (95% CI, 0.8-0.89). The model predicted 32 of 69 (46%) incident HIV cases among men tagged as high risk – at least a 0.2% chance of contracting HIV within 3 years – or very high risk, a 1% chance or higher, which is more than 50 times the risk among the general population. Relying on just MSM and STD history predicted 32% of cases.
Overall, “our model identified nearly half of new HIV cases among males by flagging only 2% of the general population. The results suggest our model would perform well if implemented today. You could replicate our approach in any health system with an EHR. Our specific variables may not translate to every setting, but any health care system can develop this model based on the EHR data they do have,” Dr. Marcus said.
“You could embed this in any EHR system and have it update in real time to flag providers to do a sexual history and talk with patients about PrEP,” she said.
The next step is a pilot project at Kaiser Permanente San Francisco to evaluate the impact on PrEP prescribing and HIV incidence. The model failed to predict 14 incident HIV cases among women in the validation cohort, a problem that also needs to be addressed.
The work was funded by the National Institutes of Health and Kaiser Permanente. Dr. Marcus didn’t have any relevant disclosures.
SOURCE: Marcus JL et al. CROI 2019, Abstract 105.
SEATTLE – Kaiser Permanente Northern California has developed an EHR program that automatically flags patients at high risk for HIV.
The idea was to come up with a way to help clinicians focus their pre-exposure prophylaxis (PrEP) outreach on the people who need it most. PrEP prevents HIV, but often “it’s difficult for providers to identify patients who are at risk. Prediction models using EHR data can identify patients who are at high risk but not using PrEP,” said study lead Julia Marcus, PhD, an assistant professor in the department of population medicine at Harvard Medical School, Boston.
She proved that assertion in a presentation at the Conference on Retroviruses & Opportunistic Infections.
The Kaiser program uses 44 variables routinely collected in EHRs from five categories: demographics, social history, lab data, medication use, and diagnoses. Specific variables include living in a zip code with high HIV incidence; men who have sex with men (MSM); black race; urine tests positive for cocaine or methadone; use of erectile dysfunction medications; and diagnoses of depression, anal warts, and other conditions.
The development cohort included 3,143,963 Kaiser members from 2007 to 2014 with 2 or more years of enrollment; at least one outpatient visit; no prior PrEP use; and no HIV diagnosis.
There were 701 incident HIV cases; the model did a good job at predicting them, with a C-statistic of 0.86 (95% confidence interval, 0.85-0.87). A score of 1.0 would be perfect prediction, and 0.5 no predictive value. Previous efforts at HIV prediction – relying generally on just MSM status and STD history – have C-statistics of around 0.6; prediction models commonly used for cardiovascular and other diseases often have C-statistics of around 0.7, Dr. Marcus explained.
The model was validated in 606,701 Kaiser members during 2015-2017. The validation cohort was slightly younger than the development cohort, with a mean age of 37 versus 45 years, and slightly more diverse, with fewer white patients, 44% versus 52%. Both cohorts had slightly more women than men.
There were 83 new HIV diagnoses in the validation cohort. The C-statistic for HIV prediction was 0.84 (95% CI, 0.8-0.89). The model predicted 32 of 69 (46%) incident HIV cases among men tagged as high risk – at least a 0.2% chance of contracting HIV within 3 years – or very high risk, a 1% chance or higher, which is more than 50 times the risk among the general population. Relying on just MSM and STD history predicted 32% of cases.
Overall, “our model identified nearly half of new HIV cases among males by flagging only 2% of the general population. The results suggest our model would perform well if implemented today. You could replicate our approach in any health system with an EHR. Our specific variables may not translate to every setting, but any health care system can develop this model based on the EHR data they do have,” Dr. Marcus said.
“You could embed this in any EHR system and have it update in real time to flag providers to do a sexual history and talk with patients about PrEP,” she said.
The next step is a pilot project at Kaiser Permanente San Francisco to evaluate the impact on PrEP prescribing and HIV incidence. The model failed to predict 14 incident HIV cases among women in the validation cohort, a problem that also needs to be addressed.
The work was funded by the National Institutes of Health and Kaiser Permanente. Dr. Marcus didn’t have any relevant disclosures.
SOURCE: Marcus JL et al. CROI 2019, Abstract 105.
REPORTING FROM CROI 2019
Genetic data boost HIV surveillance efforts
SEATTLE – Advances in genetic sequencing are boosting efforts to identify new clusters of HIV infections and guiding public health interventions to address them. The method relies on resistance testing at diagnosis and virologic failure and allows public health researchers to determine the genetic relatedness of viruses responsible for new infections. If the viruses are genetically, geographically, and temporally associated, it indicates a previously unknown transmission cluster.
“The presence of a cluster indicates gaps in our preventative services, which we must address to improve service delivery and stop transmission,” Alexandra M. Oster, MD, Division of HIV/AIDS Prevention, Surveillance, and Epidemiology at the Centers for Disease Control and Prevention, Atlanta, said during a talk at the Conference on Retroviruses and Opportunistic Infections.
She noted that HIV brings special challenges to outbreak detection. The median delay between infection and diagnosis is 3 years. Individuals are highly mobile, and signals of new outbreaks can be quickly drowned out in high-burden areas. But these challenges aren’t unique. Tuberculosis has a similarly lengthy latency period, yet more than 75% of new TB outbreaks are now identified through the use of genetic data. Sequencing also is used to track food-borne illness. The CDC’s PulseNet is a network of laboratories that examines DNA sequences from bacterial infections in search of previously unrecognized outbreaks.
In the HIV setting, molecular surveillance has great potential in identifying and intervening in evolving networks of HIV transmission, but also carries ethical and other challenges.
Nevertheless, “I hope to make the case that cluster detection and response [using molecular surveillance] can help bring the nation closer to ending the HIV epidemic,” said Dr. Oster.
Molecular surveillance obtains most of its data from drug resistance testing, both at entry to care and after virologic failure, which then gets passed to the U.S. National HIV Surveillance System. The data are then stripped of patient identifying information and submitted to the CDC.
With data from multiple individuals in hand, researchers create a phylogenetic tree, in which closely-related viruses appear as close neighbors on a branch. “By tracing back along the tree, you can see the inferred ancestor of [individual strains], and also the inferred ancestor of all strains on the tree,” said Dr. Oster. Together with geographical data, that information allows researchers to identify clusters of patients connected in a transmission network, and that information can be passed along to federal, state, and local agencies to prevent infections and improve care.
From 1997 through 2012, the CDC’s molecular surveillance program focused on drug resistance patterns, but in 2013 the agency decided to expand to include transmission clusters. It now uses a tool called HIV Trace, which helps public health workers with no background in bioinformatics to visualize the DNA sequences and potential clusters, though Dr. Oster cautioned against overinterpretation of the results. “The links shown can easily be misinterpreted as actual social connections,” she said.
As proof of the approach’s potential, an analysis of the clusters identified showed their potential for HIV spread. On average in the United States, four new HIV infections occur per 100 people living with HIV. In the first 13 clusters that CDC identified, the number of infections was 33 per 100 person-years. The first 60 clusters had an average of 44 transmissions per 100 person-years. “None of these clusters had been found by [standard] epidemiologic methods, demonstrating that rapid transmission can be hard to detect without molecular data,” said Dr. Oster.
In 2018, all health departments began collecting sequencing data, and almost 40% of newly diagnosed patients have had sequencing data reported, more than 340,000 patients in total. Researchers have identified 145 priority clusters.
But use of molecular data is not the only method available. The CDC monitors increases in diagnoses in specific areas and conducts time-space analyses. These more traditional methods are particularly useful in areas with small populations or low HIV burden.
With a cluster identified, public health officials can attempt to identify all of the members of the network and help them to access services, such as testing, preexposure prophylaxis (PrEP), syringe service programs, and linkage to care.
In San Antonio, Tex., an analysis identified a cluster of 24 gay and bisexual men, and further analysis revealed an extended network of 87 sexual or needle-sharing partners. Researchers also identified missed opportunities for diagnosis of acute infection as well as low access to PrEP, so the health department sent out an alert clarifying diagnosis testing guidelines, highlighting the concern over acute infection, and containing PrEP educational material.
Analysis of another network in Michigan found that all identified individuals were virally suppressed, even though the network continued to grow. That suggested that there were unidentified individuals who were contributing to transmission, which prompted efforts by providers to encourage testing, linkage to care, and prevention.
All of these developments are good news for efforts to eradicate HIV, but they come with pitfalls. Local communities have expressed concerned that molecular data could be used to identify direction of transmission and for prosecution, since there are HIV laws that criminalize lack of disclosure and potential exposure to the virus, even when transmission doesn’t occur. “These laws are not aligned with current science and have not been found to help curb HIV,” said Dr. Oster.
She noted that current molecular methods are incapable of identifying direction of transmission. Still, the CDC is reemphasizing efforts to protect public health data from nonpublic health use. “CDC and health departments implement unprecedented policies and procedures to ensure confidentiality and security of the data,” Dr. Oster said.
She reported having no relevant disclosures.
SEATTLE – Advances in genetic sequencing are boosting efforts to identify new clusters of HIV infections and guiding public health interventions to address them. The method relies on resistance testing at diagnosis and virologic failure and allows public health researchers to determine the genetic relatedness of viruses responsible for new infections. If the viruses are genetically, geographically, and temporally associated, it indicates a previously unknown transmission cluster.
“The presence of a cluster indicates gaps in our preventative services, which we must address to improve service delivery and stop transmission,” Alexandra M. Oster, MD, Division of HIV/AIDS Prevention, Surveillance, and Epidemiology at the Centers for Disease Control and Prevention, Atlanta, said during a talk at the Conference on Retroviruses and Opportunistic Infections.
She noted that HIV brings special challenges to outbreak detection. The median delay between infection and diagnosis is 3 years. Individuals are highly mobile, and signals of new outbreaks can be quickly drowned out in high-burden areas. But these challenges aren’t unique. Tuberculosis has a similarly lengthy latency period, yet more than 75% of new TB outbreaks are now identified through the use of genetic data. Sequencing also is used to track food-borne illness. The CDC’s PulseNet is a network of laboratories that examines DNA sequences from bacterial infections in search of previously unrecognized outbreaks.
In the HIV setting, molecular surveillance has great potential in identifying and intervening in evolving networks of HIV transmission, but also carries ethical and other challenges.
Nevertheless, “I hope to make the case that cluster detection and response [using molecular surveillance] can help bring the nation closer to ending the HIV epidemic,” said Dr. Oster.
Molecular surveillance obtains most of its data from drug resistance testing, both at entry to care and after virologic failure, which then gets passed to the U.S. National HIV Surveillance System. The data are then stripped of patient identifying information and submitted to the CDC.
With data from multiple individuals in hand, researchers create a phylogenetic tree, in which closely-related viruses appear as close neighbors on a branch. “By tracing back along the tree, you can see the inferred ancestor of [individual strains], and also the inferred ancestor of all strains on the tree,” said Dr. Oster. Together with geographical data, that information allows researchers to identify clusters of patients connected in a transmission network, and that information can be passed along to federal, state, and local agencies to prevent infections and improve care.
From 1997 through 2012, the CDC’s molecular surveillance program focused on drug resistance patterns, but in 2013 the agency decided to expand to include transmission clusters. It now uses a tool called HIV Trace, which helps public health workers with no background in bioinformatics to visualize the DNA sequences and potential clusters, though Dr. Oster cautioned against overinterpretation of the results. “The links shown can easily be misinterpreted as actual social connections,” she said.
As proof of the approach’s potential, an analysis of the clusters identified showed their potential for HIV spread. On average in the United States, four new HIV infections occur per 100 people living with HIV. In the first 13 clusters that CDC identified, the number of infections was 33 per 100 person-years. The first 60 clusters had an average of 44 transmissions per 100 person-years. “None of these clusters had been found by [standard] epidemiologic methods, demonstrating that rapid transmission can be hard to detect without molecular data,” said Dr. Oster.
In 2018, all health departments began collecting sequencing data, and almost 40% of newly diagnosed patients have had sequencing data reported, more than 340,000 patients in total. Researchers have identified 145 priority clusters.
But use of molecular data is not the only method available. The CDC monitors increases in diagnoses in specific areas and conducts time-space analyses. These more traditional methods are particularly useful in areas with small populations or low HIV burden.
With a cluster identified, public health officials can attempt to identify all of the members of the network and help them to access services, such as testing, preexposure prophylaxis (PrEP), syringe service programs, and linkage to care.
In San Antonio, Tex., an analysis identified a cluster of 24 gay and bisexual men, and further analysis revealed an extended network of 87 sexual or needle-sharing partners. Researchers also identified missed opportunities for diagnosis of acute infection as well as low access to PrEP, so the health department sent out an alert clarifying diagnosis testing guidelines, highlighting the concern over acute infection, and containing PrEP educational material.
Analysis of another network in Michigan found that all identified individuals were virally suppressed, even though the network continued to grow. That suggested that there were unidentified individuals who were contributing to transmission, which prompted efforts by providers to encourage testing, linkage to care, and prevention.
All of these developments are good news for efforts to eradicate HIV, but they come with pitfalls. Local communities have expressed concerned that molecular data could be used to identify direction of transmission and for prosecution, since there are HIV laws that criminalize lack of disclosure and potential exposure to the virus, even when transmission doesn’t occur. “These laws are not aligned with current science and have not been found to help curb HIV,” said Dr. Oster.
She noted that current molecular methods are incapable of identifying direction of transmission. Still, the CDC is reemphasizing efforts to protect public health data from nonpublic health use. “CDC and health departments implement unprecedented policies and procedures to ensure confidentiality and security of the data,” Dr. Oster said.
She reported having no relevant disclosures.
SEATTLE – Advances in genetic sequencing are boosting efforts to identify new clusters of HIV infections and guiding public health interventions to address them. The method relies on resistance testing at diagnosis and virologic failure and allows public health researchers to determine the genetic relatedness of viruses responsible for new infections. If the viruses are genetically, geographically, and temporally associated, it indicates a previously unknown transmission cluster.
“The presence of a cluster indicates gaps in our preventative services, which we must address to improve service delivery and stop transmission,” Alexandra M. Oster, MD, Division of HIV/AIDS Prevention, Surveillance, and Epidemiology at the Centers for Disease Control and Prevention, Atlanta, said during a talk at the Conference on Retroviruses and Opportunistic Infections.
She noted that HIV brings special challenges to outbreak detection. The median delay between infection and diagnosis is 3 years. Individuals are highly mobile, and signals of new outbreaks can be quickly drowned out in high-burden areas. But these challenges aren’t unique. Tuberculosis has a similarly lengthy latency period, yet more than 75% of new TB outbreaks are now identified through the use of genetic data. Sequencing also is used to track food-borne illness. The CDC’s PulseNet is a network of laboratories that examines DNA sequences from bacterial infections in search of previously unrecognized outbreaks.
In the HIV setting, molecular surveillance has great potential in identifying and intervening in evolving networks of HIV transmission, but also carries ethical and other challenges.
Nevertheless, “I hope to make the case that cluster detection and response [using molecular surveillance] can help bring the nation closer to ending the HIV epidemic,” said Dr. Oster.
Molecular surveillance obtains most of its data from drug resistance testing, both at entry to care and after virologic failure, which then gets passed to the U.S. National HIV Surveillance System. The data are then stripped of patient identifying information and submitted to the CDC.
With data from multiple individuals in hand, researchers create a phylogenetic tree, in which closely-related viruses appear as close neighbors on a branch. “By tracing back along the tree, you can see the inferred ancestor of [individual strains], and also the inferred ancestor of all strains on the tree,” said Dr. Oster. Together with geographical data, that information allows researchers to identify clusters of patients connected in a transmission network, and that information can be passed along to federal, state, and local agencies to prevent infections and improve care.
From 1997 through 2012, the CDC’s molecular surveillance program focused on drug resistance patterns, but in 2013 the agency decided to expand to include transmission clusters. It now uses a tool called HIV Trace, which helps public health workers with no background in bioinformatics to visualize the DNA sequences and potential clusters, though Dr. Oster cautioned against overinterpretation of the results. “The links shown can easily be misinterpreted as actual social connections,” she said.
As proof of the approach’s potential, an analysis of the clusters identified showed their potential for HIV spread. On average in the United States, four new HIV infections occur per 100 people living with HIV. In the first 13 clusters that CDC identified, the number of infections was 33 per 100 person-years. The first 60 clusters had an average of 44 transmissions per 100 person-years. “None of these clusters had been found by [standard] epidemiologic methods, demonstrating that rapid transmission can be hard to detect without molecular data,” said Dr. Oster.
In 2018, all health departments began collecting sequencing data, and almost 40% of newly diagnosed patients have had sequencing data reported, more than 340,000 patients in total. Researchers have identified 145 priority clusters.
But use of molecular data is not the only method available. The CDC monitors increases in diagnoses in specific areas and conducts time-space analyses. These more traditional methods are particularly useful in areas with small populations or low HIV burden.
With a cluster identified, public health officials can attempt to identify all of the members of the network and help them to access services, such as testing, preexposure prophylaxis (PrEP), syringe service programs, and linkage to care.
In San Antonio, Tex., an analysis identified a cluster of 24 gay and bisexual men, and further analysis revealed an extended network of 87 sexual or needle-sharing partners. Researchers also identified missed opportunities for diagnosis of acute infection as well as low access to PrEP, so the health department sent out an alert clarifying diagnosis testing guidelines, highlighting the concern over acute infection, and containing PrEP educational material.
Analysis of another network in Michigan found that all identified individuals were virally suppressed, even though the network continued to grow. That suggested that there were unidentified individuals who were contributing to transmission, which prompted efforts by providers to encourage testing, linkage to care, and prevention.
All of these developments are good news for efforts to eradicate HIV, but they come with pitfalls. Local communities have expressed concerned that molecular data could be used to identify direction of transmission and for prosecution, since there are HIV laws that criminalize lack of disclosure and potential exposure to the virus, even when transmission doesn’t occur. “These laws are not aligned with current science and have not been found to help curb HIV,” said Dr. Oster.
She noted that current molecular methods are incapable of identifying direction of transmission. Still, the CDC is reemphasizing efforts to protect public health data from nonpublic health use. “CDC and health departments implement unprecedented policies and procedures to ensure confidentiality and security of the data,” Dr. Oster said.
She reported having no relevant disclosures.
EXPERT ANALYSIS FROM CROI 2019
STIs pose complex challenge to HIV efforts
SEATTLE – Sexually-transmitted infections (STIs) such as gonorrhea, chlamydia, and syphilis are on the rise among HIV-infected individuals, and emerging antimicrobial resistance in these organisms is presenting serious challenges to physicians. The issue may be traceable to the introduction of preexposure prophylaxis (PrEP) in 2011, which previous studies have shown to be associated with less condom use.
In the United States, a 2017 report by the Centers for Disease Control and Prevention showed rising incidences of chlamydia (+5% from 2015 to 2017), gonorrhea (+19%), and syphilis (+18%). “We have an incidence among men who have sex with men [MSM] that is above the pre-AIDS era estimates, and we have evidence of spread into heterosexual networks, and a very scary collision with the methamphetamine and heroine using networks,” said Jeanne Marrazzo, MD, professor of infectious diseases at the University of Alabama at Birmingham.
But the numbers alone don’t tell the whole story. “It’s not just the burden of these infections. What’s characterizing these trends is that we have continuing evolution of microbial resistance, which is really a crisis,” Dr. Marrazzo added during a plenary she delivered at the Conference on Retroviruses & Opportunistic Infections.
These infections also remain intricately linked with HIV. An analysis of syphilis cases found that 88% occurred in men. Of those, 80% were MSM. Of the cases in MSM, 46% were coinfected with HIV. “Those are incredible rates,” said Dr. Marrazzo. Among women, the trends are even more alarming. There has been a greater than 150% increase in primary/secondary and congenital syphilis between 2013 and 2017.
Resistance to ceftriaxone and azithromycin remains on the rise in gonorrhea, with 24% of countries reporting at least a 5% incidence of strains that are less susceptible or resistant to ceftriaxone, and 81% of countries reporting similar trends with azithromycin.
In the absence of new drugs to overcome that resistance, or vaccines that can prevent gonorrhea and other infections, what are clinicians to do?
One option may be postexposure doxycycline. One trial in MSM showed that a 200-mg dose taken 24-72 hours after sex was associated with about a 70% increase in both time to first chlamydia and time to first syphilis infection, though no effect was seen on gonorrhea infections. “We shouldn’t be surprised. We know that gonorrhea is classically resistant to tetracyclines, and the MSM population has the highest prevalence of antimicrobial resistance in gonorrhea,” said Dr. Marrazzo.
There are pros and cons to this strategy, of course. On the one hand, doxycycline works for chlamydia and syphilis, it’s safe, and it’s easy to administer. “We’re up a tree when it comes to syphilis, so why not?” opined Dr. Marrazzo. In fact, some MSM have read the literature and are already using it prophylactically. But there are downsides, including adverse effects such as esophagitis/ulceration and photosensitivity, and it is contraindicated in pregnant women. And then there’s the potential for evolving greater resistance. “The horse is out of the barn with respect to gonorrhea, but I think it’s worth thinking about resistance to other pathogens, where we still rely on doxycycline [to treat] in rare cases,” said Dr. Marrazzo.
Finally, Dr. Marrazzo discussed the role of STI treatment in the effort to eradicate HIV. Should the Getting to 0 strategies include aggressive prevention and treatment of STIs? Despite the potentiating role of some STIs in the spread HIV, some urban areas are approaching zero new infections even as other STIs remain a problem. It could be that undetectable = untransmittable, regardless of the presence an STI. Some view targeting STIs as a regressive practice in a setting where the U=U mantra has opened up an era of sexual freedom living with or at risk of HIV.
On the other hand, there are also good arguments to target STIs while trying to eliminate HIV. Results from high-resource locales such as San Francisco and New York City are unlikely to be replicated in places like Sub-Saharan Africa. The public health burden of STIs is extensive, and antibiotic resistance and antibiotic shortages can make treatment difficult. The situation is also different for women, who may experience impacts on fertility or pregnancies, and do not have the same freedom as men in many countries. “Stigma is highly operative and I would wager that sexual pleasure and freedom remain a very elusive goal for women across the globe,” said Dr. Marrazzo.
Dr. Marrazzo has a research grant/grant pending from Cepheid, and is on the advisory panels of BioFire and Gilead.
SEATTLE – Sexually-transmitted infections (STIs) such as gonorrhea, chlamydia, and syphilis are on the rise among HIV-infected individuals, and emerging antimicrobial resistance in these organisms is presenting serious challenges to physicians. The issue may be traceable to the introduction of preexposure prophylaxis (PrEP) in 2011, which previous studies have shown to be associated with less condom use.
In the United States, a 2017 report by the Centers for Disease Control and Prevention showed rising incidences of chlamydia (+5% from 2015 to 2017), gonorrhea (+19%), and syphilis (+18%). “We have an incidence among men who have sex with men [MSM] that is above the pre-AIDS era estimates, and we have evidence of spread into heterosexual networks, and a very scary collision with the methamphetamine and heroine using networks,” said Jeanne Marrazzo, MD, professor of infectious diseases at the University of Alabama at Birmingham.
But the numbers alone don’t tell the whole story. “It’s not just the burden of these infections. What’s characterizing these trends is that we have continuing evolution of microbial resistance, which is really a crisis,” Dr. Marrazzo added during a plenary she delivered at the Conference on Retroviruses & Opportunistic Infections.
These infections also remain intricately linked with HIV. An analysis of syphilis cases found that 88% occurred in men. Of those, 80% were MSM. Of the cases in MSM, 46% were coinfected with HIV. “Those are incredible rates,” said Dr. Marrazzo. Among women, the trends are even more alarming. There has been a greater than 150% increase in primary/secondary and congenital syphilis between 2013 and 2017.
Resistance to ceftriaxone and azithromycin remains on the rise in gonorrhea, with 24% of countries reporting at least a 5% incidence of strains that are less susceptible or resistant to ceftriaxone, and 81% of countries reporting similar trends with azithromycin.
In the absence of new drugs to overcome that resistance, or vaccines that can prevent gonorrhea and other infections, what are clinicians to do?
One option may be postexposure doxycycline. One trial in MSM showed that a 200-mg dose taken 24-72 hours after sex was associated with about a 70% increase in both time to first chlamydia and time to first syphilis infection, though no effect was seen on gonorrhea infections. “We shouldn’t be surprised. We know that gonorrhea is classically resistant to tetracyclines, and the MSM population has the highest prevalence of antimicrobial resistance in gonorrhea,” said Dr. Marrazzo.
There are pros and cons to this strategy, of course. On the one hand, doxycycline works for chlamydia and syphilis, it’s safe, and it’s easy to administer. “We’re up a tree when it comes to syphilis, so why not?” opined Dr. Marrazzo. In fact, some MSM have read the literature and are already using it prophylactically. But there are downsides, including adverse effects such as esophagitis/ulceration and photosensitivity, and it is contraindicated in pregnant women. And then there’s the potential for evolving greater resistance. “The horse is out of the barn with respect to gonorrhea, but I think it’s worth thinking about resistance to other pathogens, where we still rely on doxycycline [to treat] in rare cases,” said Dr. Marrazzo.
Finally, Dr. Marrazzo discussed the role of STI treatment in the effort to eradicate HIV. Should the Getting to 0 strategies include aggressive prevention and treatment of STIs? Despite the potentiating role of some STIs in the spread HIV, some urban areas are approaching zero new infections even as other STIs remain a problem. It could be that undetectable = untransmittable, regardless of the presence an STI. Some view targeting STIs as a regressive practice in a setting where the U=U mantra has opened up an era of sexual freedom living with or at risk of HIV.
On the other hand, there are also good arguments to target STIs while trying to eliminate HIV. Results from high-resource locales such as San Francisco and New York City are unlikely to be replicated in places like Sub-Saharan Africa. The public health burden of STIs is extensive, and antibiotic resistance and antibiotic shortages can make treatment difficult. The situation is also different for women, who may experience impacts on fertility or pregnancies, and do not have the same freedom as men in many countries. “Stigma is highly operative and I would wager that sexual pleasure and freedom remain a very elusive goal for women across the globe,” said Dr. Marrazzo.
Dr. Marrazzo has a research grant/grant pending from Cepheid, and is on the advisory panels of BioFire and Gilead.
SEATTLE – Sexually-transmitted infections (STIs) such as gonorrhea, chlamydia, and syphilis are on the rise among HIV-infected individuals, and emerging antimicrobial resistance in these organisms is presenting serious challenges to physicians. The issue may be traceable to the introduction of preexposure prophylaxis (PrEP) in 2011, which previous studies have shown to be associated with less condom use.
In the United States, a 2017 report by the Centers for Disease Control and Prevention showed rising incidences of chlamydia (+5% from 2015 to 2017), gonorrhea (+19%), and syphilis (+18%). “We have an incidence among men who have sex with men [MSM] that is above the pre-AIDS era estimates, and we have evidence of spread into heterosexual networks, and a very scary collision with the methamphetamine and heroine using networks,” said Jeanne Marrazzo, MD, professor of infectious diseases at the University of Alabama at Birmingham.
But the numbers alone don’t tell the whole story. “It’s not just the burden of these infections. What’s characterizing these trends is that we have continuing evolution of microbial resistance, which is really a crisis,” Dr. Marrazzo added during a plenary she delivered at the Conference on Retroviruses & Opportunistic Infections.
These infections also remain intricately linked with HIV. An analysis of syphilis cases found that 88% occurred in men. Of those, 80% were MSM. Of the cases in MSM, 46% were coinfected with HIV. “Those are incredible rates,” said Dr. Marrazzo. Among women, the trends are even more alarming. There has been a greater than 150% increase in primary/secondary and congenital syphilis between 2013 and 2017.
Resistance to ceftriaxone and azithromycin remains on the rise in gonorrhea, with 24% of countries reporting at least a 5% incidence of strains that are less susceptible or resistant to ceftriaxone, and 81% of countries reporting similar trends with azithromycin.
In the absence of new drugs to overcome that resistance, or vaccines that can prevent gonorrhea and other infections, what are clinicians to do?
One option may be postexposure doxycycline. One trial in MSM showed that a 200-mg dose taken 24-72 hours after sex was associated with about a 70% increase in both time to first chlamydia and time to first syphilis infection, though no effect was seen on gonorrhea infections. “We shouldn’t be surprised. We know that gonorrhea is classically resistant to tetracyclines, and the MSM population has the highest prevalence of antimicrobial resistance in gonorrhea,” said Dr. Marrazzo.
There are pros and cons to this strategy, of course. On the one hand, doxycycline works for chlamydia and syphilis, it’s safe, and it’s easy to administer. “We’re up a tree when it comes to syphilis, so why not?” opined Dr. Marrazzo. In fact, some MSM have read the literature and are already using it prophylactically. But there are downsides, including adverse effects such as esophagitis/ulceration and photosensitivity, and it is contraindicated in pregnant women. And then there’s the potential for evolving greater resistance. “The horse is out of the barn with respect to gonorrhea, but I think it’s worth thinking about resistance to other pathogens, where we still rely on doxycycline [to treat] in rare cases,” said Dr. Marrazzo.
Finally, Dr. Marrazzo discussed the role of STI treatment in the effort to eradicate HIV. Should the Getting to 0 strategies include aggressive prevention and treatment of STIs? Despite the potentiating role of some STIs in the spread HIV, some urban areas are approaching zero new infections even as other STIs remain a problem. It could be that undetectable = untransmittable, regardless of the presence an STI. Some view targeting STIs as a regressive practice in a setting where the U=U mantra has opened up an era of sexual freedom living with or at risk of HIV.
On the other hand, there are also good arguments to target STIs while trying to eliminate HIV. Results from high-resource locales such as San Francisco and New York City are unlikely to be replicated in places like Sub-Saharan Africa. The public health burden of STIs is extensive, and antibiotic resistance and antibiotic shortages can make treatment difficult. The situation is also different for women, who may experience impacts on fertility or pregnancies, and do not have the same freedom as men in many countries. “Stigma is highly operative and I would wager that sexual pleasure and freedom remain a very elusive goal for women across the globe,” said Dr. Marrazzo.
Dr. Marrazzo has a research grant/grant pending from Cepheid, and is on the advisory panels of BioFire and Gilead.
EXPERT ANALYSIS FROM CROI 2019
Noninfected children of HIV-positive mothers have high rates of obesity
NEW ORLEANS – than are those with no such exposure, according to research that provides a compelling link between inflammatory activity in utero and subsequent risk of metabolic disorders.
Most supportive of that link was a near-linear inverse relationship between CD4 counts during the time of pregnancy and risk of both obesity and reactive respiratory disease more than a decade later, according to research presented by Lindsay Fourman, MD, an instructor in medicine at Massachusetts General Hospital, Boston, during the annual meeting of the Endocrine Society.
In this video interview, Dr. Fourman discusses the effort to understand the long-term health consequences of being exposed to HIV and antiretroviral therapies while in utero, a group known by the acronym HIV-exposed uninfected (HEU). With effective therapies now routinely preventing mother-to-child transmission, this population of children is growing quickly.
For this study, 50 HEU individuals were identified from a patient database. They were matched in a 3:1 ratio to a control group for a variety of demographic and socioeconomic variables. At a median age of 18 years, the HEU population was found to have a “strikingly” higher rate of obesity, compared with controls (42% vs. 25%, respectively; P = .04). The rate of reactive airway disease was similarly increased in the HEU group (40% vs. 24%; P = .04).
These data are important for considering health risks in an HEU population, but Dr. Fourman explained that it provides support for looking at metabolic risks from other in utero exposures linked to upregulated inflammation, such as gestational diabetes or obesity.
Dr Fourman and her colleagues reported no disclosures or financial conflicts of interest.
SOURCE: Fourman L et al. ENDO 2019, Session P10 (SAT-256).
NEW ORLEANS – than are those with no such exposure, according to research that provides a compelling link between inflammatory activity in utero and subsequent risk of metabolic disorders.
Most supportive of that link was a near-linear inverse relationship between CD4 counts during the time of pregnancy and risk of both obesity and reactive respiratory disease more than a decade later, according to research presented by Lindsay Fourman, MD, an instructor in medicine at Massachusetts General Hospital, Boston, during the annual meeting of the Endocrine Society.
In this video interview, Dr. Fourman discusses the effort to understand the long-term health consequences of being exposed to HIV and antiretroviral therapies while in utero, a group known by the acronym HIV-exposed uninfected (HEU). With effective therapies now routinely preventing mother-to-child transmission, this population of children is growing quickly.
For this study, 50 HEU individuals were identified from a patient database. They were matched in a 3:1 ratio to a control group for a variety of demographic and socioeconomic variables. At a median age of 18 years, the HEU population was found to have a “strikingly” higher rate of obesity, compared with controls (42% vs. 25%, respectively; P = .04). The rate of reactive airway disease was similarly increased in the HEU group (40% vs. 24%; P = .04).
These data are important for considering health risks in an HEU population, but Dr. Fourman explained that it provides support for looking at metabolic risks from other in utero exposures linked to upregulated inflammation, such as gestational diabetes or obesity.
Dr Fourman and her colleagues reported no disclosures or financial conflicts of interest.
SOURCE: Fourman L et al. ENDO 2019, Session P10 (SAT-256).
NEW ORLEANS – than are those with no such exposure, according to research that provides a compelling link between inflammatory activity in utero and subsequent risk of metabolic disorders.
Most supportive of that link was a near-linear inverse relationship between CD4 counts during the time of pregnancy and risk of both obesity and reactive respiratory disease more than a decade later, according to research presented by Lindsay Fourman, MD, an instructor in medicine at Massachusetts General Hospital, Boston, during the annual meeting of the Endocrine Society.
In this video interview, Dr. Fourman discusses the effort to understand the long-term health consequences of being exposed to HIV and antiretroviral therapies while in utero, a group known by the acronym HIV-exposed uninfected (HEU). With effective therapies now routinely preventing mother-to-child transmission, this population of children is growing quickly.
For this study, 50 HEU individuals were identified from a patient database. They were matched in a 3:1 ratio to a control group for a variety of demographic and socioeconomic variables. At a median age of 18 years, the HEU population was found to have a “strikingly” higher rate of obesity, compared with controls (42% vs. 25%, respectively; P = .04). The rate of reactive airway disease was similarly increased in the HEU group (40% vs. 24%; P = .04).
These data are important for considering health risks in an HEU population, but Dr. Fourman explained that it provides support for looking at metabolic risks from other in utero exposures linked to upregulated inflammation, such as gestational diabetes or obesity.
Dr Fourman and her colleagues reported no disclosures or financial conflicts of interest.
SOURCE: Fourman L et al. ENDO 2019, Session P10 (SAT-256).
REPORTING FROM ENDO 2019
One HCV infection leads to another in HIV+ MSM
SEATTLE – Once HIV positive men who have sex with men contract the hepatitis C virus, they are more likely to get it again, according a study of 305 men in New York.
Overall, 38 men (12%) picked up another HCV infection a median of 1.9 years after clearance of their first, yielding a reinfection rate was 4.4/100 person-years, “a solid seven times higher than the primary infection rate” among HIV-positive men who have sex with men (MSM), said senior investigator Daniel Fierer, MD, an associate professor of infectious diseases at Mount Sinai Hospital, New York.
Thirty-three men cleared their second infection. Of those, six picked up a third infection at a median of 1.1 years, yielding an overall third infection incidence of 8.7/100 person-years.
The results held no matter how the men cleared HCV, whether spontaneously, as in about 10%, or by interferon before 2013, and direct-acting antivirals (DAAs) after.
Most reinfections occurred within 2 years of initial clearance, but some occurred more than a decade later.
The results suggest that there’s a particular need for HCV prevention efforts among men who have previously cleared the infection. For those patients, testing for HCV at an annual HIV checkup might not be frequent enough, Dr. Fierer said at the Conference on Retroviruses and Opportunistic Infections.
“Long-term surveillance is warranted for all HIV-infected MSM after clearance of HCV infection. Further, strategies to reduce HCV reinfections are needed to meet the goal of eliminating HCV in these men,” he said.
Also, “the large difference between primary” and secondary infection “rates suggests HCV risk is not distributed evenly between HIV-infected MSM, but concentrated among a small subpopulation. By definition, this subpopulation would have a higher prevalence” of risky behavior, such as condomless receptive anal sex and sexualized injection methamphetamine use, he said.
The high reinfection rate “tells us basically that we have not done a good job of” preventing infection and reinfection among at risk, HIV-positive men. There’s an “inadequate level of HCV treatment ... we need to eliminate restrictions on DAA” access, Dr. Fierer said.
As far as prevention goes, “I believe we just don’t know what to do. I tell all of my patients about the body fluids that have HCV in them,” which is a good start, he said.
The median age at first clearance was about 45 years, 82% of the men were white, and there was about a 50-50 split between people with private and public insurance.
The work was funded by Gilead. Dr. Fierer did not mention any disclosures.
SOURCE: Carollo JR et al. CROI 2019, Abstract 86
SEATTLE – Once HIV positive men who have sex with men contract the hepatitis C virus, they are more likely to get it again, according a study of 305 men in New York.
Overall, 38 men (12%) picked up another HCV infection a median of 1.9 years after clearance of their first, yielding a reinfection rate was 4.4/100 person-years, “a solid seven times higher than the primary infection rate” among HIV-positive men who have sex with men (MSM), said senior investigator Daniel Fierer, MD, an associate professor of infectious diseases at Mount Sinai Hospital, New York.
Thirty-three men cleared their second infection. Of those, six picked up a third infection at a median of 1.1 years, yielding an overall third infection incidence of 8.7/100 person-years.
The results held no matter how the men cleared HCV, whether spontaneously, as in about 10%, or by interferon before 2013, and direct-acting antivirals (DAAs) after.
Most reinfections occurred within 2 years of initial clearance, but some occurred more than a decade later.
The results suggest that there’s a particular need for HCV prevention efforts among men who have previously cleared the infection. For those patients, testing for HCV at an annual HIV checkup might not be frequent enough, Dr. Fierer said at the Conference on Retroviruses and Opportunistic Infections.
“Long-term surveillance is warranted for all HIV-infected MSM after clearance of HCV infection. Further, strategies to reduce HCV reinfections are needed to meet the goal of eliminating HCV in these men,” he said.
Also, “the large difference between primary” and secondary infection “rates suggests HCV risk is not distributed evenly between HIV-infected MSM, but concentrated among a small subpopulation. By definition, this subpopulation would have a higher prevalence” of risky behavior, such as condomless receptive anal sex and sexualized injection methamphetamine use, he said.
The high reinfection rate “tells us basically that we have not done a good job of” preventing infection and reinfection among at risk, HIV-positive men. There’s an “inadequate level of HCV treatment ... we need to eliminate restrictions on DAA” access, Dr. Fierer said.
As far as prevention goes, “I believe we just don’t know what to do. I tell all of my patients about the body fluids that have HCV in them,” which is a good start, he said.
The median age at first clearance was about 45 years, 82% of the men were white, and there was about a 50-50 split between people with private and public insurance.
The work was funded by Gilead. Dr. Fierer did not mention any disclosures.
SOURCE: Carollo JR et al. CROI 2019, Abstract 86
SEATTLE – Once HIV positive men who have sex with men contract the hepatitis C virus, they are more likely to get it again, according a study of 305 men in New York.
Overall, 38 men (12%) picked up another HCV infection a median of 1.9 years after clearance of their first, yielding a reinfection rate was 4.4/100 person-years, “a solid seven times higher than the primary infection rate” among HIV-positive men who have sex with men (MSM), said senior investigator Daniel Fierer, MD, an associate professor of infectious diseases at Mount Sinai Hospital, New York.
Thirty-three men cleared their second infection. Of those, six picked up a third infection at a median of 1.1 years, yielding an overall third infection incidence of 8.7/100 person-years.
The results held no matter how the men cleared HCV, whether spontaneously, as in about 10%, or by interferon before 2013, and direct-acting antivirals (DAAs) after.
Most reinfections occurred within 2 years of initial clearance, but some occurred more than a decade later.
The results suggest that there’s a particular need for HCV prevention efforts among men who have previously cleared the infection. For those patients, testing for HCV at an annual HIV checkup might not be frequent enough, Dr. Fierer said at the Conference on Retroviruses and Opportunistic Infections.
“Long-term surveillance is warranted for all HIV-infected MSM after clearance of HCV infection. Further, strategies to reduce HCV reinfections are needed to meet the goal of eliminating HCV in these men,” he said.
Also, “the large difference between primary” and secondary infection “rates suggests HCV risk is not distributed evenly between HIV-infected MSM, but concentrated among a small subpopulation. By definition, this subpopulation would have a higher prevalence” of risky behavior, such as condomless receptive anal sex and sexualized injection methamphetamine use, he said.
The high reinfection rate “tells us basically that we have not done a good job of” preventing infection and reinfection among at risk, HIV-positive men. There’s an “inadequate level of HCV treatment ... we need to eliminate restrictions on DAA” access, Dr. Fierer said.
As far as prevention goes, “I believe we just don’t know what to do. I tell all of my patients about the body fluids that have HCV in them,” which is a good start, he said.
The median age at first clearance was about 45 years, 82% of the men were white, and there was about a 50-50 split between people with private and public insurance.
The work was funded by Gilead. Dr. Fierer did not mention any disclosures.
SOURCE: Carollo JR et al. CROI 2019, Abstract 86
REPORTING FROM CROI 2019
Long-acting injectables noninferior to tablet integrase for HIV
SEATTLE – A long-acting, injectable combination of the novel integrase inhibitor cabotegravir (CAB) and the second-generation nonnucleoside reverse transcriptase inhibitor rilpivirine (RPV) was noninferior to dolutegravir/abacavir/lamivudine (DTG/ABC/3TC) in one phase 3 study (FLAIR) and to three-drug oral antiretroviral therapy (ART) more broadly in the companion ATLAS phase 3 study. Patient acceptance of the injectable formulation was surprisingly high, although researchers admitted there was likely some selection bias because patients already interested in receiving an injection would have been predisposed to entering the trials.
Still, the numbers were impressive: 99% of patients who received the intramuscular injection expressed more satisfaction with it than with their previous oral regimen in the FLAIR study, and 98% expressed a similar opinion in the ATLAS study. Circumstantial evidence also suggests there may be some demand, according to Joseph Eron, MD, professor of medicine at the University of North Carolina at Chapel Hill, who commented during a press conference at the Conference on Retroviruses & Opportunistic Infections. “These studies didn’t take a long time to accrue. People were very interested, so it wasn’t as if people had to go around and beat the bushes to try to find people [to participate],” said Dr. Eron, who was not an author on either report.
“My patients tell me that they like not having to worry about taking their pills every day. There may be some relief from the stigma of HIV. You don’t have to think about it,” Susan Swindells, MBBS, medical director of the Specialty Care Clinic at the University of Nebraska Medical Center in Omaha and first author of the ATLAS trial, said during the press conference.
There were some injection site reactions, but they were generally mild and most resolved within 7 days. In the ATLAS study, 75% of participants reported injection site pain, and 1% discontinued as a result. In the FLAIR study, 82% in the CAB/RPV arm experienced an injection site reaction, with a median duration of 3 days; 99% of reactions were grade 1 or 2.
Should the combination achieve regulatory approval, it remains to be seen how challenging it will be to manage patients with monthly injections and ensure they stick to the schedule. The injections must be administered by a health care provider.
“In terms of generalizability outside of the study, it would be a paradigm shift in our therapy,” Chloe Orkin, MBBCh, said at a press conference. Dr. Orkin is the first author on the FLAIR trial report and a consultant in HIV Medicine at Barts Health National Health Service Trust. She pointed to the example of injectable contraception. “It can be done. It’s just that we haven’t done it. It will require some thought,” Dr. Orkin added.
In the ATLAS study, 616 participants taking two nucleoside reverse transcriptase inhibitor (NRTIs) and an integrase inhibitor, a non-NRTI, or a protease inhibitor, were randomized 1:1 to continue their regimen (CART arm) or switch to CAB/RPV, following a 4-week safety monitoring period of oral CAB/RPV. After 48 weeks, 1.6% in the CAB/RPV arm and 1.0% in the CART arm had HIV-1 RNA greater than or equal to 50 copies/mL, which met the prespecified noninferiority margin. Of patients in the CAB/RPV arm, 93% had HIV-1 RNA less than 50 copies/mL at week 48 versus 95% in the CART arm, and the difference was not statistically significant. Grade 3 or 4 events were seen in 11% of CAB/RPV and 7% of CART patients.
The FLAIR study randomized 566 ART-naive patients to receive either CAB/RPV or DTG/ABC/3TC after a 20-week induction phase, followed by a 4-week safety monitoring period for those going into the CAB/RPV arm. At week 48, 2.1% in the CAB/RPV arm and 2.5% in the DTG/ABC/3TC arm had HIV-1 RNA greater than or equal to 50 copies/mL, which met the prespecified noninferiority margin, while 94% in the CAB/RPV arm and 93% in the DTG/ABC/3TC arm had HIV-1 RNA less than 50 copies/mL. Confirmed virologic failure occurred in four patients (1.4%) in the CAB/RPV arm, and three of those patients had mutations in the NNRTI+INSTI domains, while the fourth patient was not tested. Three failures occurred in the DTG/ABC/3TC arm, and none of those patients had INSTI resistance mutations. A total of 82% of CAB/RPV patients had injection site reactions, 99% of which were grade 1 or 2, and the median duration was 3 days.
The ATLAS and FLAIR studies were sponsored by ViiV. Janssen and GlaxoSmithKline were collaborators.
SOURCES: Swindells S et al. CROI 2019, Abstract 139 LB. Orkin C et al. CROI 2019, Abstract 140.
SEATTLE – A long-acting, injectable combination of the novel integrase inhibitor cabotegravir (CAB) and the second-generation nonnucleoside reverse transcriptase inhibitor rilpivirine (RPV) was noninferior to dolutegravir/abacavir/lamivudine (DTG/ABC/3TC) in one phase 3 study (FLAIR) and to three-drug oral antiretroviral therapy (ART) more broadly in the companion ATLAS phase 3 study. Patient acceptance of the injectable formulation was surprisingly high, although researchers admitted there was likely some selection bias because patients already interested in receiving an injection would have been predisposed to entering the trials.
Still, the numbers were impressive: 99% of patients who received the intramuscular injection expressed more satisfaction with it than with their previous oral regimen in the FLAIR study, and 98% expressed a similar opinion in the ATLAS study. Circumstantial evidence also suggests there may be some demand, according to Joseph Eron, MD, professor of medicine at the University of North Carolina at Chapel Hill, who commented during a press conference at the Conference on Retroviruses & Opportunistic Infections. “These studies didn’t take a long time to accrue. People were very interested, so it wasn’t as if people had to go around and beat the bushes to try to find people [to participate],” said Dr. Eron, who was not an author on either report.
“My patients tell me that they like not having to worry about taking their pills every day. There may be some relief from the stigma of HIV. You don’t have to think about it,” Susan Swindells, MBBS, medical director of the Specialty Care Clinic at the University of Nebraska Medical Center in Omaha and first author of the ATLAS trial, said during the press conference.
There were some injection site reactions, but they were generally mild and most resolved within 7 days. In the ATLAS study, 75% of participants reported injection site pain, and 1% discontinued as a result. In the FLAIR study, 82% in the CAB/RPV arm experienced an injection site reaction, with a median duration of 3 days; 99% of reactions were grade 1 or 2.
Should the combination achieve regulatory approval, it remains to be seen how challenging it will be to manage patients with monthly injections and ensure they stick to the schedule. The injections must be administered by a health care provider.
“In terms of generalizability outside of the study, it would be a paradigm shift in our therapy,” Chloe Orkin, MBBCh, said at a press conference. Dr. Orkin is the first author on the FLAIR trial report and a consultant in HIV Medicine at Barts Health National Health Service Trust. She pointed to the example of injectable contraception. “It can be done. It’s just that we haven’t done it. It will require some thought,” Dr. Orkin added.
In the ATLAS study, 616 participants taking two nucleoside reverse transcriptase inhibitor (NRTIs) and an integrase inhibitor, a non-NRTI, or a protease inhibitor, were randomized 1:1 to continue their regimen (CART arm) or switch to CAB/RPV, following a 4-week safety monitoring period of oral CAB/RPV. After 48 weeks, 1.6% in the CAB/RPV arm and 1.0% in the CART arm had HIV-1 RNA greater than or equal to 50 copies/mL, which met the prespecified noninferiority margin. Of patients in the CAB/RPV arm, 93% had HIV-1 RNA less than 50 copies/mL at week 48 versus 95% in the CART arm, and the difference was not statistically significant. Grade 3 or 4 events were seen in 11% of CAB/RPV and 7% of CART patients.
The FLAIR study randomized 566 ART-naive patients to receive either CAB/RPV or DTG/ABC/3TC after a 20-week induction phase, followed by a 4-week safety monitoring period for those going into the CAB/RPV arm. At week 48, 2.1% in the CAB/RPV arm and 2.5% in the DTG/ABC/3TC arm had HIV-1 RNA greater than or equal to 50 copies/mL, which met the prespecified noninferiority margin, while 94% in the CAB/RPV arm and 93% in the DTG/ABC/3TC arm had HIV-1 RNA less than 50 copies/mL. Confirmed virologic failure occurred in four patients (1.4%) in the CAB/RPV arm, and three of those patients had mutations in the NNRTI+INSTI domains, while the fourth patient was not tested. Three failures occurred in the DTG/ABC/3TC arm, and none of those patients had INSTI resistance mutations. A total of 82% of CAB/RPV patients had injection site reactions, 99% of which were grade 1 or 2, and the median duration was 3 days.
The ATLAS and FLAIR studies were sponsored by ViiV. Janssen and GlaxoSmithKline were collaborators.
SOURCES: Swindells S et al. CROI 2019, Abstract 139 LB. Orkin C et al. CROI 2019, Abstract 140.
SEATTLE – A long-acting, injectable combination of the novel integrase inhibitor cabotegravir (CAB) and the second-generation nonnucleoside reverse transcriptase inhibitor rilpivirine (RPV) was noninferior to dolutegravir/abacavir/lamivudine (DTG/ABC/3TC) in one phase 3 study (FLAIR) and to three-drug oral antiretroviral therapy (ART) more broadly in the companion ATLAS phase 3 study. Patient acceptance of the injectable formulation was surprisingly high, although researchers admitted there was likely some selection bias because patients already interested in receiving an injection would have been predisposed to entering the trials.
Still, the numbers were impressive: 99% of patients who received the intramuscular injection expressed more satisfaction with it than with their previous oral regimen in the FLAIR study, and 98% expressed a similar opinion in the ATLAS study. Circumstantial evidence also suggests there may be some demand, according to Joseph Eron, MD, professor of medicine at the University of North Carolina at Chapel Hill, who commented during a press conference at the Conference on Retroviruses & Opportunistic Infections. “These studies didn’t take a long time to accrue. People were very interested, so it wasn’t as if people had to go around and beat the bushes to try to find people [to participate],” said Dr. Eron, who was not an author on either report.
“My patients tell me that they like not having to worry about taking their pills every day. There may be some relief from the stigma of HIV. You don’t have to think about it,” Susan Swindells, MBBS, medical director of the Specialty Care Clinic at the University of Nebraska Medical Center in Omaha and first author of the ATLAS trial, said during the press conference.
There were some injection site reactions, but they were generally mild and most resolved within 7 days. In the ATLAS study, 75% of participants reported injection site pain, and 1% discontinued as a result. In the FLAIR study, 82% in the CAB/RPV arm experienced an injection site reaction, with a median duration of 3 days; 99% of reactions were grade 1 or 2.
Should the combination achieve regulatory approval, it remains to be seen how challenging it will be to manage patients with monthly injections and ensure they stick to the schedule. The injections must be administered by a health care provider.
“In terms of generalizability outside of the study, it would be a paradigm shift in our therapy,” Chloe Orkin, MBBCh, said at a press conference. Dr. Orkin is the first author on the FLAIR trial report and a consultant in HIV Medicine at Barts Health National Health Service Trust. She pointed to the example of injectable contraception. “It can be done. It’s just that we haven’t done it. It will require some thought,” Dr. Orkin added.
In the ATLAS study, 616 participants taking two nucleoside reverse transcriptase inhibitor (NRTIs) and an integrase inhibitor, a non-NRTI, or a protease inhibitor, were randomized 1:1 to continue their regimen (CART arm) or switch to CAB/RPV, following a 4-week safety monitoring period of oral CAB/RPV. After 48 weeks, 1.6% in the CAB/RPV arm and 1.0% in the CART arm had HIV-1 RNA greater than or equal to 50 copies/mL, which met the prespecified noninferiority margin. Of patients in the CAB/RPV arm, 93% had HIV-1 RNA less than 50 copies/mL at week 48 versus 95% in the CART arm, and the difference was not statistically significant. Grade 3 or 4 events were seen in 11% of CAB/RPV and 7% of CART patients.
The FLAIR study randomized 566 ART-naive patients to receive either CAB/RPV or DTG/ABC/3TC after a 20-week induction phase, followed by a 4-week safety monitoring period for those going into the CAB/RPV arm. At week 48, 2.1% in the CAB/RPV arm and 2.5% in the DTG/ABC/3TC arm had HIV-1 RNA greater than or equal to 50 copies/mL, which met the prespecified noninferiority margin, while 94% in the CAB/RPV arm and 93% in the DTG/ABC/3TC arm had HIV-1 RNA less than 50 copies/mL. Confirmed virologic failure occurred in four patients (1.4%) in the CAB/RPV arm, and three of those patients had mutations in the NNRTI+INSTI domains, while the fourth patient was not tested. Three failures occurred in the DTG/ABC/3TC arm, and none of those patients had INSTI resistance mutations. A total of 82% of CAB/RPV patients had injection site reactions, 99% of which were grade 1 or 2, and the median duration was 3 days.
The ATLAS and FLAIR studies were sponsored by ViiV. Janssen and GlaxoSmithKline were collaborators.
SOURCES: Swindells S et al. CROI 2019, Abstract 139 LB. Orkin C et al. CROI 2019, Abstract 140.
REPORTING FROM CROI 2019
Universal “Test-and-Treat” Strategy Cuts Down New HIV Infections
The findings suggest that a universal “test-and-treat” strategy could be “an important addition to our toolbox of proven HIV prevention modalities,” said Anthony Fauci, MD, director of the National Institute of Allergy and Infectious Diseases.
The National Institute of Allergy and Infectious Diseases (NIAID)-sponsored study, Population Effects of Antiretroviral Therapy to Reduce HIV Transmission (PopART), was conducted from 2013 to 2018 in 21 urban and peri-urban communities in Zambia and South Africa, each with about 50,000 residents.
The communities were grouped as 7 “triplets” matched by geographic location and estimated HIV prevalence. The first group received annual house-to-house voluntary HIV testing and counseling, linkage to care for those testing positive, and the offer of a suite of proven prevention measures for those who tested negative. The second group received the same services as the first except treatment was offered according to national guidelines. The third group served as a control and received HIV prevention and testing services according to the local standard of care and HIV treatment according to national guidelines.
At the start of the study, the national guidelines for HIV treatment in Zambia and South Africa specified starting ART when the CD4+ T-cell count had declined to 350 cells/µL. In 2014, that threshold was raised to 500 cells/µL. In 2016, both countries recommended that everyone diagnosed with HIV begin ART immediately regardless of CD4+ T-cell count. Consequently, the first and second groups received the same intervention during the last 2 years of the study.
The researchers also recruited a random sample of about 2,300 adults from each community and visited them once a year for 3 years to collect data and test blood.
In the first 3 years, during nearly 40,000 person-years of follow-up, 553 people developed HIV infection (1.4 infections per 100 person-years). HIV incidence was 7% lower in group 1 than in the control group, although the difference was not statistically significant. However, HIV incidence was 30% lower in group 2 compared with that in the control group—a highly statistically significant and consistent result. (The researchers can’t explain why new HIV infections didn’t decline in all the communities where people who tested positive were offered immediate treatment.)
Of participants who tested positive by year 2, 72% of group 1, 68% of group 2, and 60% of the control group had achieved viral suppression.
The findings suggest that a universal “test-and-treat” strategy could be “an important addition to our toolbox of proven HIV prevention modalities,” said Anthony Fauci, MD, director of the National Institute of Allergy and Infectious Diseases.
The National Institute of Allergy and Infectious Diseases (NIAID)-sponsored study, Population Effects of Antiretroviral Therapy to Reduce HIV Transmission (PopART), was conducted from 2013 to 2018 in 21 urban and peri-urban communities in Zambia and South Africa, each with about 50,000 residents.
The communities were grouped as 7 “triplets” matched by geographic location and estimated HIV prevalence. The first group received annual house-to-house voluntary HIV testing and counseling, linkage to care for those testing positive, and the offer of a suite of proven prevention measures for those who tested negative. The second group received the same services as the first except treatment was offered according to national guidelines. The third group served as a control and received HIV prevention and testing services according to the local standard of care and HIV treatment according to national guidelines.
At the start of the study, the national guidelines for HIV treatment in Zambia and South Africa specified starting ART when the CD4+ T-cell count had declined to 350 cells/µL. In 2014, that threshold was raised to 500 cells/µL. In 2016, both countries recommended that everyone diagnosed with HIV begin ART immediately regardless of CD4+ T-cell count. Consequently, the first and second groups received the same intervention during the last 2 years of the study.
The researchers also recruited a random sample of about 2,300 adults from each community and visited them once a year for 3 years to collect data and test blood.
In the first 3 years, during nearly 40,000 person-years of follow-up, 553 people developed HIV infection (1.4 infections per 100 person-years). HIV incidence was 7% lower in group 1 than in the control group, although the difference was not statistically significant. However, HIV incidence was 30% lower in group 2 compared with that in the control group—a highly statistically significant and consistent result. (The researchers can’t explain why new HIV infections didn’t decline in all the communities where people who tested positive were offered immediate treatment.)
Of participants who tested positive by year 2, 72% of group 1, 68% of group 2, and 60% of the control group had achieved viral suppression.
The findings suggest that a universal “test-and-treat” strategy could be “an important addition to our toolbox of proven HIV prevention modalities,” said Anthony Fauci, MD, director of the National Institute of Allergy and Infectious Diseases.
The National Institute of Allergy and Infectious Diseases (NIAID)-sponsored study, Population Effects of Antiretroviral Therapy to Reduce HIV Transmission (PopART), was conducted from 2013 to 2018 in 21 urban and peri-urban communities in Zambia and South Africa, each with about 50,000 residents.
The communities were grouped as 7 “triplets” matched by geographic location and estimated HIV prevalence. The first group received annual house-to-house voluntary HIV testing and counseling, linkage to care for those testing positive, and the offer of a suite of proven prevention measures for those who tested negative. The second group received the same services as the first except treatment was offered according to national guidelines. The third group served as a control and received HIV prevention and testing services according to the local standard of care and HIV treatment according to national guidelines.
At the start of the study, the national guidelines for HIV treatment in Zambia and South Africa specified starting ART when the CD4+ T-cell count had declined to 350 cells/µL. In 2014, that threshold was raised to 500 cells/µL. In 2016, both countries recommended that everyone diagnosed with HIV begin ART immediately regardless of CD4+ T-cell count. Consequently, the first and second groups received the same intervention during the last 2 years of the study.
The researchers also recruited a random sample of about 2,300 adults from each community and visited them once a year for 3 years to collect data and test blood.
In the first 3 years, during nearly 40,000 person-years of follow-up, 553 people developed HIV infection (1.4 infections per 100 person-years). HIV incidence was 7% lower in group 1 than in the control group, although the difference was not statistically significant. However, HIV incidence was 30% lower in group 2 compared with that in the control group—a highly statistically significant and consistent result. (The researchers can’t explain why new HIV infections didn’t decline in all the communities where people who tested positive were offered immediate treatment.)
Of participants who tested positive by year 2, 72% of group 1, 68% of group 2, and 60% of the control group had achieved viral suppression.