The 2021 Conference on Retroviruses and Opportunistic Infections (CROI 2021), which took place virtually this year from March 6 through March 10, featured hundreds of presentations highlighting the latest science on a huge array of HIV-related subjects. Here we share bite-sized summaries of several studies selected by our team of editors and correspondents that provide new data pertaining to HIV epidemiology, prevention, and transmission, with a particular focus on U.S.-centric findings.
We will continue to update this article throughout March 2021; new additions will be added to the top of the article. You can also check out our bite-sized summaries of research on HIV complications/comorbidities, HIV treatment and patient care, and HIV and COVID-19.
Efficacy of On-Demand PrEP vs. Daily PrEP: Virtually Indistinguishable
Although on-demand HIV pre-exposure prophylaxis (PrEP) is still not recommended in official U.S. guidelines, data continue to stack up supporting its viability as an HIV prevention strategy alongside daily oral PrEP. The latest evidence of its strength comes via newly presented results of the ANRS Prevenir Study.
The last time we saw ANRS Prevenir findings was in July 2019, when two-year results indicated that both daily and on-demand PrEP were safe and effective. (On-demand PrEP is also called the “2-1-1” approach—i.e., take two PrEP doses between 2 and 24 hours prior to sex, a single dose 24 hours after the first, and a final dose 24 hours after that.) Here at CROI 2021, Jean-Michael Molina, M.D., of Assistance Publique Hôpitaux de Paris, presented three-year study results that complemented those two-year findings.
Molina reported that, after 5,633 total person-years of follow-up (over 2,500 each in the daily PrEP and on-demand PrEP arms) through September 2020, the HIV incidence rate in ANRS Prevenir was 0.12 per 100 patient-years—a rate that was identical between the daily PrEP arm and the on-demand PrEP arm. The average patient follow-up period was about 22 months.
Only six study participants were diagnosed with HIV during the study, three in each arm—and in every case, the person had stopped taking PrEP several weeks prior to their diagnosis. (The ANRS Prevenir study cohort is comprised almost entirely of men who have sex with men.)
Relative to prior research on PrEP efficacy involving a placebo group, Molina and his colleagues estimated that PrEP had averted 361 HIV infections to date within the study cohort.
Molina noted that the impact of PrEP on sexual behavior varied over time, and differed depending on whether a study participant had ever taken PrEP prior to participating in ANRS Prevenir. PrEP-naive participants reported having more sex overall, more condomless sex, and more receptive condomless sex at year 3 than they did at baseline; PrEP-experienced participants only reported more condomless sex. Both groups reported fewer recent sex partners over time.
Perhaps correlated with the increase in condomless sex, Molina also noted a total of 43 viral hepatitis infections (mostly hepatitis C) across the study groups, as well as relatively high rates of sexually transmitted infections, particularly chlamydia and gonorrhea (although those rates dropped dramatically once COVID-19 lockdowns began in France).
Drug-related adverse events continued to be relatively infrequent and generally non-severe. Gastrointestinal events were more common in the on-demand PrEP group (5.83 per 100 person-years) than the daily PrEP group (4.37 per 100 person-years), and led to only three discontinuations across both arms. Lab abnormalities were much more common: ALT elevations occurred more frequently in the daily PrEP group (22.22 per 100-person years) than the on-demand PrEP group (18.33 per 100 person-years), though rates of Grade 3 or 4 ALT were similar between the groups. Creatinine numbers were also similar between the groups.
For conference attendees: watch the oral abstract session, entitled “Prevention 2021”
For everyone else: read the study abstract, entitled “Incidence of HIV Infection With Daily or On-Demand Oral PrEP With TDF/FTC in France”
Summary by Myles Helfand; posted March 9 at 6:56 p.m.
Islatravir Implants for PrEP Deliver High Potency Up to a Year, and Are Well-Tolerated
Randolph Matthews, M.D., Ph.D., from Merck & Co. presented encouraging results of a phase 1 trial of an experimental implant for HIV pre-exposure prophylaxis (PrEP). The implant, which is placed under the skin, releases islatravir (a.k.a. ISL or MK-8591), a high-potency, long-acting antiretroviral.
These data present an update on study findings presented in 2019 (Protocol 007) that were based on a prototype implant (comprised of only islatravir and a polymer) for 12 weeks at two doses, 54 mg and 62 mg. The new study, Protocol 008, involved a more advanced radiopaque implant tested at three doses: 48 mg, 52 mg, and 56 mg. The double-blind, placebo-controlled trial tested these subdermal implants for 12 weeks in 36 low-risk, HIV-negative participants, then followed participants for an additional 8 weeks after removing the implant.
Researchers found that the implants were generally well-tolerated, with no serious adverse events and no discontinuations due to an adverse event. Mild to moderate events were common (reported by 61% of participants) and similar to those of other subdermal implants, most notably localized erythema, induration, pruritis, and pain or tenderness.
Based on the study data, the 56 mg implant was projected to have sufficient islatravir-triphosphate levels for at least one year.
The combination of high potency and long half life of the implant—islatravir remained at effective levels 198 hours after removal of the 56 mg implant, which is similar to the half life of oral islatravir—makes it a potentially attractive option for PrEP, Matthews stated.
For conference attendees: watch the oral abstract session, entitled “HIV Treatment and Prevention: New Opportunities to Optimize Drug Dosing, Adherence, and Antiretroviral Therapy”
For everyone else: read the study abstract, entitled “Next-Generation Islatravir Implants Projected to Provide Yearly HIV Prophylaxis”
Summary by Larry Buhl; posted March 8 at 6:45 p.m., updated March 9 at 4:45 p.m.
HIV Diagnoses and Mortality Trends Among American Indians and Alaska Natives
Among American Indians and Alaska Natives (AI/AN) in the prior decade, HIV diagnoses and mortality decreased, but there were significant variations by age group and geographic area, according to data presented by Sophie Sembajwe, M.S.P.H., of the Indian Health Service, a federal health program within the Department of Health and Human Services (HHS).
From 2014 through 2018, trends in HIV diagnoses and mortality among AI/AN mirrored that of the general population of people living with HIV in the U.S., though AI/AN rates were higher at every time point. For instance, diagnoses peaked at 10.3 per 100,000 people among AI/AN in 2016 compared to 9.2 per 100,000 in the general population, and dropped to 8.2 per 100,000 among AI/AN in 2018 compared to 7.7 per 100,000 in the general population.
A more intricate breakdown of the data revealed substantial decreases in HIV diagnoses among people in the 13-to-24 and 45-to-54 age groups, contrasted by increases in the 25-to-34 and 35-to-44 age groups. In addition, wide gaps were found in HIV diagnosis rates depending on geographical area, with 2018 HIV diagnosis rates highest among people in the Navajo (roughly 14 per 100,000), Albuquerque (~13 per 100,000), Phoenix (~12.5 per 100,000), and Tucson (~12 per 100,000) regions, and lowest in the Nashville (~2 per 100,000), Portland (~3 per 100,000), and Bemidji (~4 per 100,000) regions.
For conference attendees: watch the oral abstract session, entitled “Identifying Disparities and Opportunities in HIV”
For everyone else: read the study abstract, entitled “HIV Trends Among the American Indian/Alaska Natives, 2014-2018”
Summary by Myles Helfand; posted March 8 at 6:45 p.m.