Influence of Antiretroviral Treatment in Acute HIV on Viral Reservoir Formation in the CNS
In the initial days to weeks after infection with HIV, viral RNA enters the central nervous system (CNS) and is thought to form reservoirs in brain tissue that, in the long term, contribute to HIV-associated neurocognitive disorder (HAND) in up to 50% of patients. As patients are usually diagnosed with HIV well after CNS reservoirs have formed, patients with acute HIV (e.g. those diagnosed in the days to weeks after infection) provide an unparalleled opportunity to examine early dynamics of CNS reservoir formation in HIV, thus, providing critical information for cure strategies. This project proposes to evaluate CNS HIV reservoir formation by examining CNS dynamics prior to combination antiretroviral therapy (cART) in acute HIV, as well as before and during analytic treatment interruption (ATI) for acute HIV participants who have been suppressed on cART for at least 24 months as part of novel HIV cure studies underway in Bangkok, Thailand. We will analyze pre-cART, during cART and post ATI assays of CSF HIV RNA (single copy level, when needed), CSF and plasma immune biomarkers, and magnetic resonance spectroscopy (MRS) markers of CNS inflammation and injury to both determine factors that influence success during ATI and to understand the extent of CNS involvement at each stage. Work will be conducted among four separate cure studies underway with the shared leadership of my two mentors and that of the US Military HIV Research Program (US MHRP). My lead mentor is one of the Directors of the research office in Thailand where this work will be conducted and I have spent nearly 6 months in Bangkok evaluating these research subjects. The work proposed is highly novel, tightly linked to my career goals, and likely to transition into K23 funded work in 2016.