Content: NIAID Now•Published: October 10, 2024•6 minute read
TopicsNIAID National Institute of Allergy and Infectious DiseasesNIHNational Institutes of HealthPrEP Pre-Exposure Prophylaxis Prevention Study
Transmission electron micrograph of HIV-1 virions (pink) replicating from the cell membrane of an H9 T cell (purple). Image taken at the NIAID Integrated Research Facility at Fort Detrick, Maryland. Credit: NIAID
Reprinted from: NIAID Now Blog
The NIAID-supported new science presented at the 2024 HIV Prevention Research (HIVR4P) conference in Lima, Peru, features a wide range of HIV discovery and translational discoveries, and includes research on HIV pre-exposure in the context of reproductive health. Enriching the evidence base for prevention (PrEP). Highlights of the science supported by the institute are summarized below. A complete summary of HIVR4P is available in the End Disclaimer.
Using PrEP modalities during early pregnancy in conjunction with contraception
A monthly dapivirine vaginal ring for HIV prevention was safe for cisgender women who used the ring during early pregnancy and then discontinued use as soon as they discovered they were pregnant. In a pre-approval, open-label study of the dapivirine vaginal ring, participants discontinued its use if they became pregnant, as use of the ring during pregnancy was beyond the scope of the study. Pregnant study participants continued to enroll after discontinuing the ring and were monitored for safety throughout their pregnancy. An analysis of pregnancy data from 72 people found that using the ring during the first trimester had no noticeable adverse effects on the participants or their infants. These findings further strengthen the evidence that the dapivirine vaginal ring is safe to use throughout pregnancy. Data presented from another study previously confirmed the safety of the ring when participants started using it during the second trimester and continued to use it until birth.
Analysis of a phase 3 trial of long-acting injectable cabotegravir (CAB-LA) PrEP in cisgender women shows that the drug does not interact with long-acting reversible contraceptives (LARCs). It turns out. A subset of study participants taking LARC’s etonogestrel, medroxyprogesterone acetate or norethindrone were treated by the research team with LARC and CAB-LA or tenofovir disoproxil fumarate and emtricitabine (TDF/FTC). An additional blood sample was provided so that we could analyze the effects of taking LARC with oral PrEP (TDF/FTC). Levels of antiretroviral drugs and contraceptives in the body. There were no drug interactions between CAB-LA and any LARC. Due to low adherence to TDF/FTC in the participating cohort, interactions between TDF/FTC and LARC could not be determined. CAB-LA and TDF/FTC have previously been shown to be safe for use during pregnancy.
Early discoveries about an HIV vaccine that produces antibodies that broadly neutralize HIV
Several studies on germline targeting, a promising HIV vaccine strategy that stimulates the immune system to generate antibodies that can neutralize diverse HIV strains, report results that will inform the next steps in vaccine development. It was done. Results from studies in humans and animal models show that some immunogens (molecules used in vaccines to elicit specific immune system responses) can generate broadly neutralizing antibodies (bNAbs) against HIV. It showed that it was starting to stimulate an immune response. In one study of 53 participants without HIV, a vaccine containing a nanoparticle immunogen called 426.mod.core-C4b was safe at multiple dose levels and, upon further stimulation, increased bNAb release. It seemed to generate B cells that could produce. These findings are informing the development of more advanced HIV vaccine concepts, including the 426.mod.core-C4b immunogen.
Understanding HIV carriers and HIV remission with antiretroviral therapy
HIV is difficult to treat because the virus is adept at “hiding” in the body and can reemerge in the bloodstream as soon as antiretroviral therapy (ART) is stopped. These hiding places are called reservoirs and are not affected by ART. Scientists supported by NIAID are exploring strategies to eliminate HIV and its reservoirs from the body, or to reduce HIV to levels that can be suppressed by a person’s own immune system. A new small study has found that monocytes, a type of white blood cell that expresses a gene called interleukin-1 beta (IL1B), are associated with reduced HIV carriage after HIV infection. Further understanding of the influence of IL1B on HIV reservoir size may guide new HIV remission strategies in the future.
Clinical trials and animal studies of HIV remission approaches have reported outcomes for interventions designed to maintain HIV viral suppression or remission after pausing ART. Suspension of ART in HIV remission studies is referred to as analytical treatment interruption (ATI). In one study, researchers infected 16 infant monkeys with the simian version of HIV (SHIV) and then administered ART with various combinations of the investigational HIV drug leronlimab and an HIV bNAb called PGT121-LS and VRC07. Divided into three different treatment groups. -523-LS. After 27 weeks of treatment, the research team conducted an ATI and observed the results for each treatment group. Animals receiving both ART and HIV bNAbs experienced a rapid rebound of detectable SHIV. Two of the six animals receiving ART and leronlimab had no detectable virus throughout 20 weeks post-ATI. All animals receiving ART, leronlimab, and two HIV bNAbs had no detectable virus at the time of abstract submission, 15 weeks after ATI. According to the authors, monitoring and evaluation of SHIV reservoirs in monkeys is ongoing and further research is needed to understand the observed effects.
New PrEP implant technology
Currently available PrEP methods include oral tablets, long-acting injectables, and extended-release vaginal ring formulations. A new refillable controlled-release antiretroviral (ARV) implant has been found to be safe and capable of delivering more than one ARV. The implant, placed subcutaneously (just under the skin), was tested in monkeys and allows sustained release of the investigational ARVs islatravir and MK-8527, as well as lenacapavir, which is approved for ART and is being studied for PrEP. It has been proven that. Bictegravir and dolutegravir, both approved for ART. The islatravir-containing implant was evaluated for its effectiveness as PrEP and was found to fully protect animals from SHIV challenge (direct administration of the virus into the vagina and rectum) for 29 months. This implant is being studied for the delivery of ARVs for PrEP and ART.
HIV clinical research is built on basic science discoveries, preclinical research, and consultation with communities affected by HIV. Additionally, clinical research relies on the dedicated efforts of research participants and those who support them. NIAID is grateful to everyone who has contributed to the advancement of HIV research.
References
P. Ehrenberg et al. Single-cell analysis revealed that monocyte gene expression influences HIV-1 reservoir size in acute treatment cohorts. HIV Prevention Research Conference. Tuesday, October 8, 2024.
W. Hahn et al. Vaccination with a new escalating dose strategy improves the initial humoral response with a new germline-targeted HIV vaccine (426.mod.core-C4b): HVTN 301. HIV Research for Prevention Conference. Preliminary results. Wednesday, October 9, 2024.
N. Haigwood et al. Short-term combination immunotherapy with broadly neutralizing antibodies and CCR5 inhibition mediates ART-free viral control in infant rhesus macaques. HIV Prevention Research Conference. Wednesday, October 9, 2024.
M Marzinke et al. Evaluation of potential pharmacological interactions between CAB-LA or TDF/FTC and hormonal contraceptives: a tertiary analysis of HPTN 084. HIV Prevention Research Council. Thursday, October 10, 2024.
Mayo et al. Pregnancy and infant outcomes in individuals exposed to dapivirine ring during the first trimester in the MTN-025/HOPE open-label extension study. HIV Prevention Research Conference. Thursday, October 10, 2024.
F. Pons Faudoua et al. A drug-independent transdermal refillable subcutaneous implant for ultra-long-acting delivery of antiretroviral drugs for HIV prevention. HIV Prevention Research Conference. Wednesday, October 9, 2024.
