New treatments, HIV remission insights, etc.

Gilead's one-time lenacapavir formulation demonstrates the sustained efficacy of HIV PREP in a phase 1 study

Moupali Das, MD, and MPH presented the results of two phase 1 studies of two single intramuscular (IM) formulations of HIV pre-exposure prophylaxis (PREP) renacapavir. Both formulations exhibit a strong pharmacokinetic profile, with lenacapavir concentrations maintained above the effective threshold of 95% for over 56 weeks, and double the subcutaneous (SC) formulation per year. Median trough concentrations at week 52 for one annual formulation were 57 ng/ml and 65.6 ng/mL, compared to the SC version of 23.4 ng/ml. Furthermore, peak plasma concentrations were significantly higher in one annual formulation (247 ng/ml and 336 ng/ml) compared to twice the annual SC formulation (67.3 ng/ml). These findings suggest that once-at-a-minute formulations of lenacapavir not only last longer, but also maintain higher plasma concentrations, suggesting the potential for improved efficacy and improved HIV prevention. This study confirmed that the formulation is well tolerated and pain at the injection site is the most common mild to moderate adverse event.

Bictegravir vs Darunavir in Advanced HIV: Laptop Trial Results

Georg Behrens, MD, and PhD presented the results of laptop trials comparing Bictegravir (BIC) and Darunavir (DRV) in individuals suitable for treatment with advanced HIV disease. This trial, a multicenter Europe study, showed that BIC-based regimens (in combination with tenophovir-alafenamide and emtricitabine) outweighed DRV-based regimens (cobicistat, FTC, and TAF) in terms of virological suppression and immune recovery. Participants in the BIC group had a percentage of HIV RNA levels below 50 copies/ml, increasing the speed of CD4 recovery. Despite the challenge of recruiting participants with advanced HIV disease, this study demonstrated that the high genetic barriers and favourable safety profiles of BICs are potentially effective and safe treatment options compared to DRV. Behrens emphasized that while the benefits of Bictegravir are clear, more long-term research is needed to assess its continued efficacy and safety, especially in a diverse patient population.

Immunocore reports some of the PWHs achieving reductions in viral control and dose-dependent active HIV reservoirs in the IMC-M113V trial

Immunocore has announced early detection from the first stage effort trial of IMC-M113V, a replication therapy for HIV-targeted T-cell receptors. IMC-M113V uses a bispecific protein with one end targeting HIV-infected cells, and the other end recruits T cells to destroy these cells, specifically targeting the HLA-A*02:01-gag complex. In the trial, 16 HIV-positive participants who were stable on ART showed dose-dependent viral control after ART discontinuation. In particular, three participants experienced a delay in viral rebound, resulting in a reduced viral load to approximately 200 copies/ml, although the results were not generally seen in untreated individuals. This treatment also results in a decrease in CD4+ T cell-associated HIV GAG RNA, indicating a decrease in viral reservoirs. At high doses there is a decreasing trend in intact HIV DNA, suggesting the possibility of a decrease in the reservoir. Despite mild cytokine release syndrome (CRS) at high doses, treatment was well tolerated. These findings support further investigation into the ability of IMC-M113V to reduce viral reservoirs and potentially achieve functional therapy.

Fresh research tests new HIV remission strategies in South African women

Thumbi ndung'u, BVM, and PhD presented the results of a fresh study, study examining the combination of two broadly neutralizing antibodies (BNAB), VRC07-523LS, and CAP256V2LS. The study involved 20 women with acute HIV-1 infection who had been taking antiretroviral therapy (ART) for at least 12 months. The regimen was well tolerated, with one case of mild infusion-related reactions and grade 1 cytokine release syndrome. Six participants maintained art disruptions for up to 48 weeks, while four continued without ART for 55 weeks. Although this combination was not entirely effective for all participants, the subset demonstrated partial virological control. These findings suggest the potential of BNAB and Vesatolimod as part of HIV treatment strategies, particularly for women who are underestimated in clinical trials. Ndung'u highlighted the potential impact on regions like sub-Saharan Africa, and highlighted the importance of conducting HIV treatment research in resource-limited settings. Further research will focus on understanding the immune mechanisms behind virological control and improving treatment for broader use.

Targeting soluble GP120 to combat immune dysfunction in people living with HIV

Medie Benrabi, a doctoral student at Monttoriol University, discussed the role of soluble GP120 (SGP120) in immune dysfunction in people living with HIV (PLWH). He explained that even with undetectable viral loads of ART, SGP120 persists in the body, contributing to chronic inflammation, and preventing CD4+ T-cell recovery. This insight led to the development of a reboot study co-designed with Andrés Finzi PhD to investigate whether the small molecule inhibitor Fostemsavir can neutralize the toxic effects of SGP120 by blocking interaction with the CD4 receptor. MADELEINE DURAND, MD, MSC, Associate Professor of MSC at Chum Research Center, highlighted the potential for research to improve immune recovery in PLWH and reduce cardiovascular risk, particularly by assessing the effects of fostemsavir on immune function and coronary atherosclerosis.