Analysis of HIV-1 in mucosal tissue in elite suppressors

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DESCRIPTION (provided by applicant): Elite suppressors are HIV-1 infected patients who maintain viral loads of <50 copies/ml without antiretroviral therapy. Despite this excellent control of viral replication, these patients continue to have residual viremia as determined by the presence of latently infected CD4+ T cells that contain replication-competent HIV-1. Interestingly, the frequency of these latently infected cells in peripheral blood is much lower in ES than in patients on suppressive HAART regimens with undetectable viral loads. This might suggest that ES may be the best candidates for strategies that could lead to eradication of these cells. This would only hold true if the total burden of these cells was much lower in ES. We therefore propose to look at two different mucosal sites in ES. Studies have suggested that the frequency of latently infected CD4 T cells in the gut associated lymphoid tissue (GALT) is ten times higher than the frequency in peripheral CD4+ T cells in patients on HAART. We want to determine whether this relationship holds true in ES. We will also look at the frequency of latently infected CD4+ T cells in the lungs of these patients so as to have a better approximation of the total burden of infected cells in ES. We have also recently provided evidence of ongoing HIV-1 replication and evolution of the very low level of HIV-1 present in the plasma of ES. There was very little evolution of the virus obtained from peripheral CD4+ T cells implying that CD4+ T cells in some other compartment are the source of the ongoing replication and evolution that lead to the plasma variants. By analyzing the sequence obtained from each compartment we would be able to determine the source of ongoing replication in the patients. This work will be important because it may suggest that ES are the best candidates for studies that could potentially cure HIV-1 infection by the eradication of latently infected CD4+ T cells. PUBLIC HEALTH RELEVANCE: Most patients infected with HIV-1 will develop a drop in their CD4 counts and frank AIDS as the virus replicates and destroys the immune system, however a unique group of untreated HIV-1-infected patients, termed Elite Suppressors (ES) are able to completely control the virus and do not develop AIDS (1-3). This project plans to measure the number of infected cells present in these patients and to determine the relationship between viruses from different tissues. The results may be applicable to the development of strategies for the eradication of HIV-1.