New research presented at the HIV Research for Prevention (HIVR4P) conference in Lima, Peru, highlights advancements in HIV prevention and treatment strategies. Studies focused on pre-exposure prophylaxis (PrEP), HIV vaccine development, and understanding HIV reservoirs offer insights into future interventions.
PrEP Strategies and Reproductive Health
Research indicates the monthly dapivirine vaginal ring is safe for cisgender women using it during early pregnancy. A pre-licensure open-label study showed no notable adverse effects among participants or their infants when the ring was used in early pregnancy. Participants discontinued use upon learning of their pregnancy, but remained enrolled for safety monitoring. An analysis of 72 pregnancies supports the growing evidence that the dapivirine vaginal ring is safe to use throughout pregnancy.
Furthermore, a Phase 3 study of long-acting injectable cabotegravir (CAB-LA) PrEP in cisgender women revealed no interactions with long-acting reversible contraceptive (LARC) drugs. The study analyzed blood samples from participants using LARCs such as etonogestrel, medroxyprogesterone acetate, or norethindrone, alongside CAB-LA or oral PrEP (tenofovir disoproxil fumarate and emtricitabine, TDF/FTC). Results indicated no drug interactions between CAB-LA and any of the LARCs. Adherence to TDF/FTC was too low to determine interactions. These findings are clinically significant as CAB-LA and TDF/FTC were previously shown to be safe for use in pregnancy.
Advancing HIV Vaccine Development
Several studies are exploring germline targeting, a strategy to stimulate the immune system to produce broadly neutralizing antibodies (bNAbs) against diverse HIV strains. Early findings in human and animal models suggest that certain immunogens can initiate immune responses capable of generating HIV bNAbs. A study involving 53 HIV-negative participants found that a vaccine containing the nanoparticle immunogen 426.mod.core-C4b was safe and appeared to generate B cells capable of producing bNAbs upon further stimulation. These results are informing the development of more advanced HIV vaccine concepts.
Insights into HIV Reservoirs and Remission
Understanding HIV reservoirs, where the virus hides and persists despite antiretroviral therapy (ART), is crucial for developing curative strategies. Research is focusing on clearing these reservoirs or reducing HIV levels to allow control by the individual's immune system. A small study revealed that monocytes expressing the interleukin 1 beta (IL1B) gene are associated with smaller HIV reservoirs after HIV acquisition. Further research into the influence of IL1B could guide novel HIV remission strategies.
Clinical trials and animal studies are also evaluating interventions designed to maintain HIV viral suppression or remission after ART is paused, known as an analytical treatment interruption (ATI). In a study involving infant monkeys infected with SHIV, different treatment groups received ART with leronlimab and HIV bNAbs (PGT121-LS and VRC07-523-LS). After 27 weeks, an ATI was conducted. Animals receiving ART and both HIV bNAbs experienced rapid SHIV rebound. Two of six animals receiving ART and leronlimab remained free of detectable virus for 20 weeks post-ATI. All animals receiving ART, leronlimab, and both HIV bNAbs remained free of detectable virus 15 weeks after ATI. Monitoring of SHIV reservoirs is ongoing to understand these effects.
Novel PrEP Implant Technology
Beyond oral pills, injectables, and vaginal rings, a novel refillable controlled-release antiretroviral drug (ARV) implant is being developed. This subdermal implant can deliver one or more ARVs. Studies in monkeys demonstrated sustained release of investigational ARVs like islatravir and MK-8527, as well as lenacapavir, bictegravir and dolutegravir. Implants containing islatravir completely protected animals from SHIV challenge for 29 months, highlighting its potential for PrEP and ART.
