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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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
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
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
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Ananworanich, Jintanat; Sacdalan, Carlo P; Pinyakorn, Suteeraporn et al. (2016) Virological and immunological characteristics of HIV-infected individuals at the earliest stage of infection. J Virus Erad 2:43-48
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
Valcour, Victor G; Spudich, Serena S; Sailasuta, Napapon et al. (2015) Neurological Response to cART vs. cART plus Integrase Inhibitor and CCR5 Antagonist Initiated during Acute HIV. PLoS One 10:e0142600
Peluso, Michael J; Valcour, Victor; Ananworanich, Jintanat et al. (2015) Absence of Cerebrospinal Fluid Signs of Neuronal Injury Before and After Immediate Antiretroviral Therapy in Acute HIV Infection. J Infect Dis 212:1759-67

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