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1277 Results
Background The HIV reservoir in the central nervous system (CNS) poses a significant challenge to cure efforts, mostly by our limited understanding and access to this compartment Methods Tissue samples across 9 CNS regions, including 5 spinal cord (SC) segments (pons, medulla, cervical, lumbosacral, and thoracic spinal cord [TSC], frontal motor cortex [FC], basal ganglia…
Background Long-acting injectables may address barriers to HIV pre-exposure prophylaxis (PrEP), such as stigma and pill burden. In a Phase 3 trial in cisgender women, twice-yearly (Q6M) subcutaneous (SC) lenacapavir (LEN) (927 mg, in two 1.5 mL injections) was safe and 100% efficacious as PrEP, with high adherence among participants. We assessed the pharmacokinetics (PK) and safety…
Background Despite availability of long-acting products for HIV pre-exposure prophylaxis (PrEP), some women may prefer on-demand oral PrEP. Using an existing PK/PD model (Cottrell JID 2016), we previously predicted protective drug exposure would be sustained in the female genital tract (FGT) for 5 days after sex for >80% of the population using the 2-1-1 IPERGAY…
Background In a non-comparative pilot Phase 1b study (NCT04811040), the long-acting HIV-1 capsid inhibitor lenacapavir (LEN) in combination with broadly neutralizing antibodies (bNAbs) teropavimab (TAB, GS-5423) and zinlirvimab (ZAB, GS-2872) maintained virologic suppression (VS; HIV-1 RNA <50 copies/mL) for 6 months after dosing in 18/20 people with HIV-1 (PWH) highly susceptible to both bNAbs. In this Phase…
Background New long-acting antiretroviral therapy (ART) regimens are needed to expand treatment choices for people living with HIV-1. VH4524184 (VH-184) is a third-generation integrase strand transfer inhibitor (INSTI) with an enhanced in vitro resistance profile compared with second-generation INSTIs being developed as a long-acting antiretroviral agent for the treatment of HIV-1. Here, we present data…
Background Studies using the Jurkat T-cell model have identified numerous factors crucial for initiating HIV-1 transcription. However, a significant limitation of transformed cells is their inability to replicate the transitions between active effector cells and quiescent memory T cells, which are the key drivers of HIV latency in vivo. Methods We use refined primary cell…
Background Antiretroviral therapy (ART) can reduce morbidity and mortality but does not eradicate HIV. Developing new therapies that induce HIV remission is crucial to end the epidemic. African women bear a disproportionate burden of the global epidemic yet are rarely included in clinical trials. We conducted a phase 2a HIV cure study to evaluate the…
Background The nuclear import of HIV-1 into the host nucleus marks a milestone of the viral infection, making it a potential drug target for effective prophylaxis and treatment. However, understanding this process has been challenged by its dynamic nature and the scarcity of HIV-1 cores in infected cells. Methods To elucidate the mechanisms underlying the…
Background Residual viremia (RV) persists despite years of effective ART due to the daily activation of latently infected cells. Some people on long-term ART develop nonsuppressible viremia (NSV), characterized by persistently detectable HIV RNA that complicates clinical care, raising concerns for virological failure and HIV transmission. Recent work from our group and others showed that…
Background The CARD8 inflammasome is a key driver of innate immune responses to HIV-1. CARD8, containing HIV-1 protease (PR) cleavage sites, responds to PR upon enforced NNRTI-induced dimerization of the viral Gag-Pol polyprotein and premature PR activation. In the absence of antiretrovirals, the apparent lack of CARD8 activation during HIV-1 assembly along with the observation…