It is increasingly evident that the events which occur during acute HIV infection have a lasting impact on HIV disease course. Brain injury may occur in this very early stage, a factor that is sometime clinically evident with neurological manifestations of disease and is thought to have long-standing consequences. To date, our understanding of these earliest CNS effects are limited since capturing clinical data in the weeks following infection requires extensive resources and since such individuals seldom succumb to autopsy. Information relating to the first few weeks following infection is particularly lacking as few centers are able to identify infection in this very early phase. Intensive neurological and psychological characterization of acute infection would greatly advance our understanding of brain injury in HIV. Our collaborative organization in Bangkok, Thailand, known as the Southeast Asia Research Collaboration with Hawaii (SEARCH), will launch a US Department of Defense-funded protocol in the fall of 2008 to capture up to thirty acute HIV-infected cases in 2 years. All individuals will have been infected within the three weeks prior to enrollment (HIV antibody negative, nucleic acid positive). Broadly focused on vaccine development goals to characterize immunological changes associated with acute infection and the potential impact of mega- HAART in early infection, this cohort provides an unmatched opportunity to assess the neurological manifestations of HIV during acute HIV infection in a predominantly non-subtype B epidemic. In this application, we propose to acquire MR Spectroscopy, neurological assessments, neuropsychological testing, psychiatric characterization and cerebrospinal fluid (CSF) in twenty such cases at baseline and longitudinally for 96 weeks. Our primary goal is to quantify brain injury and CNS inflammation during this early phase of infection and to correlate these parameters to intracellular HIV DNA and systemic immune status during the acute HIV infection period. We will also store peripheral blood mononuclear cells (PBMC) and CSF for future collaborative studies with particular interest in viral sequencing in blood and CSF.

Public Health Relevance

This project will aid in clarifying the earliest events during HIV infection with regard to brain injury to determine the extent to which the brain is affected immediately after infection.

Agency
National Institute of Health (NIH)
Institute
National Institute of Mental Health (NIMH)
Type
Exploratory/Developmental Grants (R21)
Project #
5R21MH086341-02
Application #
7880896
Study Section
NeuroAIDS and other End-Organ Diseases Study Section (NAED)
Program Officer
Joseph, Jeymohan
Project Start
2009-07-01
Project End
2013-05-31
Budget Start
2010-06-01
Budget End
2013-05-31
Support Year
2
Fiscal Year
2010
Total Cost
$174,478
Indirect Cost
Name
University of California San Francisco
Department
Neurology
Type
Schools of Medicine
DUNS #
094878337
City
San Francisco
State
CA
Country
United States
Zip Code
94143
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
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
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
Kore, Idil; Ananworanich, Jintanat; Valcour, Victor et al. (2015) Neuropsychological Impairment in Acute HIV and the Effect of Immediate Antiretroviral Therapy. J Acquir Immune Defic Syndr 70:393-9
Hellmuth, Joanna; Valcour, Victor; Spudich, Serena (2015) CNS reservoirs for HIV: implications for eradication. J Virus Erad 1:67-71
Sailasuta, Napapon; Ross, William; Ananworanich, Jintanat et al. (2012) Change in brain magnetic resonance spectroscopy after treatment during acute HIV infection. PLoS One 7:e49272
Valcour, Victor; Chalermchai, Thep; Sailasuta, Napapon et al. (2012) Central nervous system viral invasion and inflammation during acute HIV infection. J Infect Dis 206:275-82