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From HIVR4P // Virtual 2021, Investigational Strategies for Expanding PrEP Options

Kenneth Mayer, MD

Infectious Disease Attending
Beth Israel Deaconess Medical Center
Professor of Medicine
Harvard Medical School
Medical Research Director
Fenway Community Health
Boston, Massachusetts

Kenneth Mayer, MD, has disclosed that he has received consulting fees from Gilead Sciences and Merck and funds for research support from Gilead Sciences, Janssen, and Merck.

View ClinicalThoughts from this Author

Released: February 18, 2021

Current medications for preventing HIV infection—oral emtricitabine coformulated with either tenofovir disoproxil fumarate or tenofovir alafenamide—are effective when used as directed, but they have several features that limit their utility for some individuals. They are expensive in many countries, there is a risk of long-term adverse events for some patients, and adherence can be challenging for others. The use of monoclonal antibody infusions to provide passive immunity is an alternative approach currently under investigation for preventing HIV infection. Here, I describe promising new data on antibody infusion and other investigational prevention strategies presented at the 4th HIV Research for Prevention Conference (HIVR4P // Virtual).

Phase IIb AMP Studies: In Vitro Susceptibility of HIV-1 Isolates to bnAb VRC01 Predicts HIV Prevention Efficacy in MSM, Transgender Persons, and Cisgender Women
The Antibody Mediated Prevention (AMP) studies tested VRC01, a human broadly neutralizing monoclonal antibody (bnAb) to the CD4-binding site on the HIV-1 envelope surface. The antibody was derived from a patient who had been infected with HIV for more than 15 years while remaining immunologically stable (a long-term nonprogressor). The monoclonal antibody has previously been shown to be well tolerated in healthy adults, to neutralize HIV-1 isolates in vitro, and to protect against SHIV infection challenge in rhesus macaques. In the randomized, placebo-controlled, phase IIb AMP studies, 2 different concentrations were tested as an infusion compared with a matched placebo, each given every 8 weeks for a total of 10 infusions to cisgender women in Africa or to men who have sex with men and transgender persons who have sex with men in Europe and the Americas.

The AMP studies provided some important insights about the use of antibodies to prevent HIV infection. Overall, there were no significant differences between rates of new HIV infections among those who received VRC01 and those who received placebo infusions. However, with virus strains that were sensitive or moderately sensitive to VRC01 in vitro (80% inhibitory concentration [IC80] < 1 µg/mL), there was a substantial 75% reduction in the risk of acquiring HIV in the pooled VRC01 arms vs the placebo arm. Because most of the HIV strains circulating in the study locations were not sufficiently sensitive to VRC01 (IC80 > 1 µg/mL), the study was underpowered to detect an overall protective benefit.

As proof-of-concept studies, these trials were successful. They demonstrated that bnAb administration could safely prevent HIV infection, but that preventing infection depends on how susceptible the circulating strains were to the bnAb. The results also showed that an in vitro neutralization test could predict whether strains were sufficiently susceptible to impart in vivo protection against HIV infection. For future studies, multiple potent antibodies may need to be combined to make a useful preventive agent. Trials are currently underway to determine the most promising combination bnAb regimen for future efficacy trials.

MPTs for Sexual and Reproductive Health
Another approach to enhance the uptake of HIV prevention interventions is through the development of multipurpose prevention technologies (MPTs). These products combine drugs that prevent HIV with agents that prevent pregnancy or other infections such as human papillomavirus, herpes simplex virus 2, chlamydia, or gonorrhea. Several MPTs are under investigation in clinical trials and many more are in earlier stages of development. Several delivery methods are being tested, including oral tablets, implants, patches, intravaginal rings, vaginal and rectal gels, vaginal films, and fast-dissolving vaginal or rectal inserts. Several products in the latest stages of clinical development use intravaginal rings, which have shown acceptability in previous studies. In regions where HIV stigma is strong, it may be more culturally acceptable if HIV prevention is combined with contraception. Ultimately, MPTs need to be safe, affordable, and easy to use.

MPTs for Substance Use Disorder Treatment and HIV Prevention
Another MPT combines prevention for HIV and treatment for substance use disorder. Combining these interventions may have synergistic effects in enhancing engagement in care and medication adherence. Opioid agonist therapy (OAT), particularly methadone or buprenorphine, not only reduces overdoses by more than 3-fold, but also reduces HIV and hepatitis C virus transmission by more than 50%. OAT is also associated with increased ART use, adherence, and viral suppression in people with HIV and opioid use disorder. The development of long-acting ARVs for prevention could be coupled with long-acting OAT, which may enhance clinical interactions with difficult-to-reach populations.

Currently, people who inject drugs are undertreated for HIV for many reasons, including stigma. They tend to receive care in specialty clinics rather than in primary care settings, and undertreatment of other conditions is common. This may contribute to early death, on average 25 years earlier than the general population. Moreover, pre-exposure prophylaxis (PrEP) use is almost nonexistent in this population.

Because of the current COVID-19 pandemic, clinics for people who inject drugs have streamlined procedures, requiring fewer patient visits by using telehealth, checking in by text, and medication delivery to home or shelter. Recent small pilot projects have suggested that this procedure resulted in better patient engagement and improved outcomes. Based on these projects, a streamlined model for HIV prevention and treatment in people who inject drugs was proposed, with assessment for OAT and PrEP, laboratory testing, and prescriptions on Day 1; review of laboratory results, initial adverse events, and dosing on Day 3; assessment of adverse events, dosing, and adherence on Day 7; and monitoring PrEP laboratory tests and refilling OAT on Day 30. Once individuals are stabilized on prevention/treatment, investigators propose that they could be transitioned to long-acting injectables. Possible combination therapies in the future might include cabotegravir and rilpivirine for HIV and XR-buprenorphine, XR-naltrexone, implantable naltrexone, or implantable buprenorphine for opioid use disorder.

In summary, new data from the recent HIVR4P // Virtual conference underscore the evolving nature of HIV prevention, with new approaches being tested, such bnAb immunoprophylaxis, and the development of MPTs, which can simultaneously address several health concerns for key populations.

Your Thoughts?
Which new data from HIVR4P // Virtual do you expect will help improve HIV prevention efficacy in your community? Answer the polling question and join the conversation by posting a comment in the discussion section. 

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Produced in collaboration with
Educational grant provided by:
Gilead Sciences, Inc.
Janssen Therapeutics, Division of Janssen Products, LP
Merck Sharp & Dohme Corp.
ViiV Healthcare

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