SEARCH 010: Long-Term CNS Consequences of Treatment During Acute Infection
Overview
Attention is increasingly focused on the very early events in HIV infection as early viruses and innate and adaptive immune responses may play a significant role in shaping disease burden and disease outcome. Based on limited clinical and autopsy data, there is growing evidence that a significant neuropathogenic impact may occur during the earliest stages of infection. The precise timing of brain infection, inflammation, and injury, however, is incompletely understood due to challenges in acquiring very early neurological data during the acute infection period. Our understanding of the earliest events in HIV infection is primarily based on in vitro and animal studies and necessarily remains largely speculative in humans.
The established international operation in Bangkok, Thailand known as the Southeast Asia Research Collaboration with Hawaii (SEARCH) combines the resources of a strong clinical and neuroAIDS base and the on-site intensive immunological and virological laboratories of the Armed Forces Research Institute of Medical Sciences (AFRIMS) of the US Army. SEARCH 010 in particular identifies acute HIV-infected cases who have not yet seroconverted (HIV antibody negative by 1st generation enzyme immunoassay) but are positive by nucleic acid testing. SEARCH 010 captures CSF, neurological, neuropsychological and psychiatric evaluations, structural brain MRI and MR Spectroscopy (MRS) within three weeks of infection. These data will help determine the extent to which central nervous system (CNS) immunological activation and injury are noted in the acute HIV infection period and the degree to which systemic markers of immune activation and intracellular HIV DNA correlate to such injury. .
Enrolled subjects are offered mega-HAART, providing an opportunity to determine the extent to which this intervention impacts our planned neurological parameters. In a longitudinal aspect of this work, SEARCH010 evaluates the extent to which CNS inflammation is controlled with early mega-HAART
Attention is increasingly focused on the very early events in HIV infection as early viruses and innate and adaptive immune responses may play a significant role in shaping disease burden and disease outcome. Based on limited clinical and autopsy data, there is growing evidence that a significant neuropathogenic impact may occur during the earliest stages of infection. The precise timing of brain infection, inflammation, and injury, however, is incompletely understood due to challenges in acquiring very early neurological data during the acute infection period. Our understanding of the earliest events in HIV infection is primarily based on in vitro and animal studies and necessarily remains largely speculative in humans.
The established international operation in Bangkok, Thailand known as the Southeast Asia Research Collaboration with Hawaii (SEARCH) combines the resources of a strong clinical and neuroAIDS base and the on-site intensive immunological and virological laboratories of the Armed Forces Research Institute of Medical Sciences (AFRIMS) of the US Army. SEARCH 010 in particular identifies acute HIV-infected cases who have not yet seroconverted (HIV antibody negative by 1st generation enzyme immunoassay) but are positive by nucleic acid testing. SEARCH 010 captures CSF, neurological, neuropsychological and psychiatric evaluations, structural brain MRI and MR Spectroscopy (MRS) within three weeks of infection. These data will help determine the extent to which central nervous system (CNS) immunological activation and injury are noted in the acute HIV infection period and the degree to which systemic markers of immune activation and intracellular HIV DNA correlate to such injury. .
Enrolled subjects are offered mega-HAART, providing an opportunity to determine the extent to which this intervention impacts our planned neurological parameters. In a longitudinal aspect of this work, SEARCH010 evaluates the extent to which CNS inflammation is controlled with early mega-HAART