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.
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.
