This subproject is one of many research subprojects utilizing the resources provided by a Center grant funded by NIH/NCRR. The subproject and investigator (PI) may have received primary funding from another NIH source, and thus could be represented in other CRISP entries. The institution listed is for the Center, which is not necessarily the institution for the investigator. There are several theroetical reasons to expect that HIV-1 in CSF and the brain may be phentopypically and genotypically distinct from viruses in blood, and that these differences may impact the response to therapy and ultimately the likelihood that neurologic disease will develop. Although HIV-1 can be detected in cerebrospinal fluid (CSF) and the brain early in the course of HIV-1 disease, the importance and prognostic value of quantifying virus in the CSF remains unclear. Only limited data are availabe regarding the effect of potent antiretroviral therapy (PART) on CSF HIV levels. The overall goals of this study are: to determine if PART is as effective in reducing HIV in the CSF as it is in plasma; to dteremine whether differences in viral genotype and drug penetration between CSF and blood account for differences in ability of PART to suppress HIV in the CSF compartmetn: to determine the relationship between changes in teh amount of virus andimmune activation markers in CSF and measures of neuropsychological performance. The Primary specific aims are to compare the magnitude and durability of suppression of HIV RNA in the plasma and CSF in response to PART. - to determine if the magnitude and durability of CSF HIV RNA response to PART is associated with improved neuropsychological performance. The secondary aims are to: evaluate the pharmacokinetics of CSF drug penetration. - to determine the association of CSF HIV RNA response with genotype and pharmacokinetic estimates. - to determine if the magnitude and durability of CSF HIV RNA response to PART corresponds with improvement in CSF immune activation markers. - to determine if the response in CSF immune activation markers correlates with improvement in neuropsychological performance. - to determine the long-term relationship between viral evolution in blood and CSF compartmetns. The immune status, and development of cognitive impairment in subjects receiving PART
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