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EARLY INTERVENTION THERAPIES IN HUMANS: ART, ANTIBODIES, AND VACCINES
1Thai Red Cross AIDS Research Center, Bangkok, Thailand
HIV cure is a desirable goal for individuals living with HIV who face stigma and life-long antiretroviral therapy (ART), while treatment costs pose a significant challenge to national health programs and donors. Eliminating all cells capable of producing HIV seems a near unattainable goal with current therapies and a more achievable goal may be HIV remission, i.e. the ability to control HIV after ART interruption to levels below detection. Individuals treated since acute HIV infection (AHI) achieve significantly smaller HIV reservoirs, preserved immune function and little viral escape and are therefore targeted for early intervention therapy studies in humans. Interventions to date include latency reversing agents, harnessing antibodies to induce HIV remission, enhancing CTL-mediated killing of infected cells, and gene editing. The SEARCH 010/RV254 study is a cohort of over 500 individuals, predominantly Thai MSM, treated with ART since the earliest stages of HIV infection (Fiebig I-IV). In this cohort, proof of concept studies with these very interventions, with the exception of gene editing, are taking place, followed by analytic treatment interruption (ATI). Thus far, these single intervention HIV remission studies have demonstrated viral load rebound from 9 days to 10 months after ATI, while ATI appeared safe. This presentation will review the results of these single HIV remission studies as representative of findings of the field to date, including effects of early ART, additional therapeutic interventions, and ATI on endpoints, including timing and magnitude of viral load rebound, and HIV reservoir size. Immune mechanisms associated with these dynamics, such as effector CD8+ T cells contributing to lower viral loads after ATI, will also be described, as will safety parameters associated with ATI including assessment for acute retroviral syndrome, de novo resistance mutations, and virological failure. Given the risks and uncertainties associated with these early stage trials, compounded by the complex concepts of cure and remission, it is critical that community participation and social science studies continue to inform the conduct of these trials.