B-105 Studies of Acute HIV Infection –Insights for Cure

Abstract

The study of acute HIV infection in humans has important implications both for research in acquisition and pathogenesis. In RV217 high risk volunteers from Kenya, Tanzania, Uganda, and Thailand are monitored for HIV infection by nucleic acid testing twice weekly, so that acute HIV infection is diagnosed early (approximately 4 days after previous negative test) and prospectively, so that the first good information on clinical syndromes can be determined. The availability of samples on the upward slope of viral load, and frequently through the establishment of setpoint permit unprecedented correlative studies of viral sequence/quasispecies, epitope specific immune responses, RNA expression analysis, and modeling of the earliest events in human pathogenesis of HIV infection. A different study in Thailand uses a different screening technique to identify and initiate treatment during acute HIV infection (Fiebig Stages I—III). Early and extensive sampling of peripheral blood, CSF, gut, genital fluids, and lymph node have led to the hypothesis that early treatment greatly restricts to pool of integrated HIV, and may limit the seeding of deep, long-lived Tcm reservoirs. A number of intervention studies designed to eliminate the restricted pool of latent provirus are planned and (currently) include: monoclonal antibodies, vaccines, and anti-inflammatory drugs. The potential impact of these interventions and HIV cure related issues will be discussed.