This subproject is one of many research subprojects utilizing theresources provided by a Center grant funded by NIH/NCRR. The subproject andinvestigator (PI) may have received primary funding from another NIH source,and thus could be represented in other CRISP entries. The institution listed isfor the Center, which is not necessarily the institution for the investigator.There is a growing appreciation of the fact that up to 25% of people initiating HAART, who have virologic suppression, have an insignificant level of immune reconstitution. Examination of lymphatic tissues from HIV+ persons reveals an early and significant depletion of CD4+ T-cells in the lymphatic reservoir in virtually every patient examined. Preliminary studies have suggested the observed variablility in immune reconstitution is correlated with measures of damage to the LT architecture. We believe that a process of chronic inflammation occurs in some individuals at the time of HIV-1 infection that disrupts the TZ niche through deposition of collagen and destruction of the reticulin network. The goal of this study is to examine this hypothesis in detail with a prospective study of ART naive individuals. We will collect LT from patients at multiple time points before and after starting HAART. We will determine if a single measurement of the amount of collagen in the TZ before treatment will predict the change in CD4 cell count as a measure of immune reconstitution. We will determine if these architectural changes are reversible with HAART. We will examine the phenotype subsets of CD4+ cells in LT and peripheral blood at multiple time points before and after starting HAART to determine the source and fate of CD4+ T cells that repopulate the LT. Successful collegen might predict success of HAART and suggest that reoutine biopsy before therapy is begun might help to determine optimal timing of initiation of therapy. In addition, these studies may provide additional insight into the mechanism of immune reconstitution with HAART and why some individuals have incomplete responses. We are requesting permission to use the GCRC resources and nursing services for the inpatient stays between Day 0 and Day 3, for both inpatient and outpatient blood draws, and for pre-op and recovery of the outpatient surgical procedures.
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