The systemic immune response and central nervous system (CNS) events occurring during acute HIV likely set the stage for chronic HIV-related CNS injury and the establishment of CNS-relevant HIV reservoirs. Just as the earliest systemic features such as peak plasma HIV RNA, level of T-cell activation, and early loss of CD4 cells are crucial determinants of HIV disease trajectory, CNS processes initiated during the earliest stages may critically inform the establishment of a CNS-relevant viral reservoirs, CNS compartmentalized virus, the hosts'ability to control CNS virus, and the long-term CNS consequences of infection. Logistical challenges have lead to heavy reliance on animal data to define the likely CNS events during acute HIV. In this application, we extend existing partnerships with US Army studies underway in Thailand to define these earliest events in humans and determine factors that influence long-term CNS outcomes. This application proposes to provide intensive CNS characterization for 60 Thai subjects enrolled during acute HIV (<1 month after exposure). In our schema, one-half of subjects will begin HAART immediately after initial assessments for a fixed 18-month course. We will longitudinally characterize CNS clinical events, neurological, neuropsychological, and psychiatric factors, multimodal magnetic resonance imaging, CSF immunology and compartment specific full-genome HIV sequencing to determine how the events that occur in acute HIV impact chronic HIV CNS disorders. We will also determine CNS founder and established viruses and determine if early HAART intervention impacts these relationships. The parent studies include extensive systemic immunological and virological characterization allowing us to determine if the earliest systemic events impact long-term CNS outcomes.

Public Health Relevance

This project will aid in clarifying how the earliest events during HIV infection may affect brain injury during chronic HIV. Defining these events could direct interventions aimed at reducing cognitive disorders for people living with HIV.

National Institute of Health (NIH)
National Institute of Mental Health (NIMH)
Research Project (R01)
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Study Section
Special Emphasis Panel (ZMH1-ERB-M (03))
Program Officer
Joseph, Jeymohan
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University of California San Francisco
Schools of Medicine
San Francisco
United States
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Chan, Phillip; Patel, Payal; Hellmuth, Joanna et al. (2018) Distribution of Human Immunodeficiency Virus (HIV) Ribonucleic Acid in Cerebrospinal Fluid and Blood Is Linked to CD4/CD8 Ratio During Acute HIV. J Infect Dis 218:937-945
Chan, Phillip; Hellmuth, Joanna; Colby, Donn et al. (2018) Safety of lumbar puncture procedure in an international research setting during acute HIV infection. J Virus Erad 4:16-20
Samboju, Vishal; Philippi, Carissa L; Chan, Phillip et al. (2018) Structural and functional brain imaging in acute HIV. Neuroimage Clin 20:327-335
D'Antoni, Michelle L; Byron, Mary Margaret; Chan, Phillip et al. (2018) Normalization of Soluble CD163 Levels After Institution of Antiretroviral Therapy During Acute HIV Infection Tracks with Fewer Neurological Abnormalities. J Infect Dis 218:1453-1463
Kessing, Cari F; Spudich, Serena; Valcour, Victor et al. (2017) High Number of Activated CD8+ T Cells Targeting HIV Antigens Are Present in Cerebrospinal Fluid in Acute HIV Infection. J Acquir Immune Defic Syndr 75:108-117
Sereti, Irini; Krebs, Shelly J; Phanuphak, Nittaya et al. (2017) Persistent, Albeit Reduced, Chronic Inflammation in Persons Starting Antiretroviral Therapy in Acute HIV Infection. Clin Infect Dis 64:124-131
Hellmuth, Joanna; Colby, Donn; Valcour, Victor et al. (2017) Depression and Anxiety are Common in Acute HIV Infection and Associate with Plasma Immune Activation. AIDS Behav 21:3238-3246
Peluso, Michael J; Valcour, Victor; Phanuphak, Nittaya et al. (2017) Immediate initiation of cART is associated with lower levels of cerebrospinal fluid YKL-40, a marker of microglial activation, in HIV-1 infection. AIDS 31:247-252
Chan, Phillip; Hellmuth, Joanna; Spudich, Serena et al. (2016) Cognitive Impairment and Persistent CNS Injury in Treated HIV. Curr HIV/AIDS Rep 13:209-17
Spudich, Serena S (2016) Immune activation in the central nervous system throughout the course of HIV infection. Curr Opin HIV AIDS 11:226-33

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