absence of hiv-1 evolution in the gut-associated lymphoid tissue from patients on combination antiviral therapy initiated during primary infection缺乏hiv - 1的进化从病人内脏相关的淋巴组织联合抗病毒治疗原发感染期间启动.pdfVIP

Absence of HIV-1 Evolution in the Gut-Associated Lymphoid Tissue from Patients on Combination Antiviral Therapy Initiated during Primary Infection 1 1¤ 2 2 3 Teresa H. Evering , Saurabh Mehandru , Paul Racz , Klara Tenner-Racz , Michael A. Poles , Amir 1 1 1 Figueroa , Hiroshi Mohri , Martin Markowitz * 1 Aaron Diamond AIDS Research Center, an affiliate of the Rockefeller University, New York, New York, United States of America, 2 Bernhard-Nocht Institut Fur Tropenmedizin, Hamburg, Germany, 3 Departments of Medicine, Microbiology and Pathology, New York University Medical Center, New York, New York, United States of America Abstract Mucosal mononuclear (MMC) CCR5+CD4+ T cells of the gastrointestinal (GI) tract are selectively infected and depleted during acute HIV-1 infection. Despite early initiation of combination antiretroviral therapy (cART), gut-associated lymphoid tissue (GALT) CD4+ T cell depletion and activation persist in the majority of HIV-1 positive individuals studied. This may result from ongoing HIV-1 replication and T-cell activation despite effective cART. We hypothesized that ongoing viral replication in the GI tract during cART would result in measurable viral evolution, with divergent populations emerging over time. Subjects treated during early HIV-1 infection underwent phlebotomy and flexible sigmoidoscopy with biopsies prior to and 15–24 months post initiation of cART. At the 2nd biopsy, three GALT phenotypes were noted, characterized by high, intermediate and low levels of immune activation. A representative case from each phenotype was analyzed. Each subject had plasma HIV-1 RNA levels ,50 copies/ml at 2nd GI biop