%0 Journal Article
%T Lack of Mucosal Immune Reconstitution during Prolonged Treatment of Acute and Early HIV-1 Infection
%A Saurabh Mehandru
%A Michael A Poles
%A Klara Tenner-Racz
%A Patrick Jean-Pierre
%A Victoria Manuelli
%A Peter Lopez
%A Anita Shet
%A Andrea Low
%A Hiroshi Mohri
%A Daniel Boden
%A Paul Racz
%A Martin Markowitz
%J PLOS Medicine
%D 2006
%I Public Library of Science (PLoS)
%R 10.1371/journal.pmed.0030484
%X Background During acute and early HIV-1 infection (AEI), up to 60% of CD4+ T cells in the lamina propria of the lower gastrointestinal (GI) tract are lost as early as 2每4 wk after infection. Reconstitution in the peripheral blood during therapy with highly active antiretroviral therapy (HAART) is well established. However, the extent of immune reconstitution in the GI tract is unknown. Methods and Findings Fifty-four AEI patients and 18 uninfected control participants underwent colonic biopsy. Forty of the 54 AEI patients were followed after initiation of antiretroviral therapy (18 were studied longitudinally with sequential biopsies over a 3-y period after beginning HAART, and 22 were studied cross sectionally after 1每7 y of uninterrupted therapy). Lymphocyte subsets, markers of immune activation and memory in the peripheral blood and GI tract were determined by flow cytometry and immunohistochemistry. In situ hybridization was performed in order to identify persistent HIV-1 RNA expression. Of the patients studied, 70% maintained, on average, a 50%每60% depletion of lamina propria lymphocytes despite 1每7 y of HAART. Lymphocytes expressing CCR5 and both CCR5 and CXCR4 were persistently and preferentially depleted. Levels of immune activation in the memory cell population, CD45RO+ HLA-DR+, returned to levels seen in the uninfected control participants in the peripheral blood, but were elevated in the GI tract of patients with persistent CD4+ T cell depletion despite therapy. Rare HIV-1 RNA每expressing cells were detected by in situ hybridization. Conclusions Apparently suppressive treatment with HAART during acute and early infection does not lead to complete immune reconstitution in the GI mucosa in the majority of patients studied, despite immune reconstitution in the peripheral blood. Though the mechanism remains obscure, the data suggest that there is either viral or immune-mediated accelerated T cell destruction or, possibly, alterations in T cell homing to the GI tract. Although clinically silent over the short term, the long-term consequences of the persistence of this lesion may emerge as the HIV-1每infected population survives longer owing to the benefits of HAART.
%U http://www.plosmedicine.org/article/info%3Adoi%2F10.1371%2Fjournal.pmed.0030484