Newly presented research supported by the National Institute of Allergy and Infectious Diseases (NIAID) at the 2024 HIV Research for Prevention (HIVR4P) conference in Lima, Peru, showcases significant advancements in HIV discovery and translational findings. This research enriches the understanding of HIV pre-exposure prophylaxis (PrEP) within reproductive health contexts. Below are key highlights from NIAID-supported studies; the full abstracts can be accessed on the official conference website.
PrEP and Contraception in Early Pregnancy
Recent studies have shown that the monthly dapivirine vaginal ring, designed for HIV prevention, is safe for use by cisgender women during early pregnancy. In an open-label study prior to licensing, participants ceased using the ring upon learning they were pregnant, as the study did not cover its use during pregnancy. Nevertheless, these pregnant participants remained part of the study and were monitored for safety. Analysis of data from 72 pregnancies indicated no significant adverse effects for either the mothers or their infants when the ring was used in the early stages of pregnancy. This supports the growing body of evidence suggesting the dapivirine vaginal ring’s safety throughout pregnancy. Prior studies also confirmed its safety when initiated during the second trimester and continued until delivery.
Furthermore, findings from a Phase 3 study on long-acting injectable cabotegravir (CAB-LA) as PrEP indicated no interactions with long-acting reversible contraceptives (LARCs). A subgroup of participants using LARCs like etonogestrel, medroxyprogesterone acetate, or norethindrone provided blood samples for analysis of potential drug interactions with CAB-LA and oral PrEP involving tenofovir disoproxil fumarate and emtricitabine (TDF/FTC). The results showed no interactions between CAB-LA and any of the LARCs. However, interactions between TDF/FTC and LARCs remain inconclusive due to low adherence to TDF/FTC among the cohort. Both CAB-LA and TDF/FTC have previously been deemed safe for use in pregnancy.
Advancements in HIV Vaccine Research
Research on germline targeting, a promising HIV vaccine strategy aimed at stimulating the immune system to create antibodies that can neutralize various HIV strains, yielded important results. Studies involving human and animal models indicated that several immunogens, which are molecules used in vaccines to trigger specific immune responses, began to elicit immune reactions capable of producing broadly neutralizing antibodies (bNAbs) against HIV. One study with 53 HIV-negative participants showed that a vaccine using a nanoparticle immunogen called 426.mod.core-C4b was safe at multiple doses and appeared to activate B cells that could potentially produce bNAbs with further stimulation. These findings are paving the way for more advanced HIV vaccine strategies that incorporate the 426.mod.core-C4b immunogen.
Investigating HIV Reservoirs and Remission Strategies
The challenge of curing HIV lies in the virus’s ability to “hide” within the body, re-emerging in the bloodstream soon after antiretroviral therapy (ART) is stopped. These hiding places, known as reservoirs, are not affected by ART. NIAID-supported researchers are investigating methods to eliminate HIV and its reservoirs or to lower HIV levels to a point where the immune system can suppress the virus. A recent small study found that monocytes—a type of white blood cell—expressing the gene interleukin 1 beta (IL1B) were linked to smaller HIV reservoirs following infection. Understanding how IL1B influences the size of these reservoirs could guide innovative strategies for achieving HIV remission.
In related clinical trials and animal studies aimed at HIV remission, researchers evaluated interventions intended to sustain HIV viral suppression or remission after halting ART, referred to as analytical treatment interruption (ATI). In one study, 16 infant monkeys were infected with a simian version of HIV (SHIV) and placed into three treatment groups, each receiving ART combined with the investigational HIV drug leronlimab and the bNAbs PGT121-LS and VRC07-523-LS. After 27 weeks, an ATI was conducted, revealing that animals receiving ART and both bNAbs experienced a rapid rebound of detectable SHIV. However, two out of six monkeys treated with ART and leronlimab remained free of detectable virus for 20 weeks post-ATI. All monkeys receiving the combined therapy were free of detectable virus at the time of abstract submission, 15 weeks after ATI. The monitoring of SHIV reservoirs in these monkeys is ongoing, and further research is necessary to fully understand the observed effects.
Innovations in PrEP Delivery
Current PrEP options include oral pills, long-acting injectables, and controlled-release vaginal rings. A novel refillable controlled-release implant for antiretroviral drugs (ARVs) has shown promise, proving to be safe and capable of delivering multiple ARVs. This subdermal implant was tested in monkeys and demonstrated sustained release of investigational ARVs, including islatravir and MK-8527, as well as lenacapavir, which is already approved for ART and is undergoing studies for PrEP. Implants containing islatravir were tested for PrEP efficacy, completely protecting the animals from SHIV challenges through 29 months. Ongoing studies are evaluating the implant’s potential for delivering ARVs for both PrEP and ART.
Clinical research on HIV builds on foundational scientific discoveries, preclinical studies, and consultations with affected communities. The contributions of study participants and their supporters are vital to advancing HIV research. NIAID expresses gratitude to all involved in these essential efforts.