Absence of HIV-1 Evolution in the Gut-Associated Lymphoid Tissue from Patients on Combination Antiviral Therapy Initiated during Primary Infection

PLoS Pathogens

Amir Figueroa¹  Teresa H. Evering¹  Saurabh Mehandru¹  Martin Markowitz¹  Hiroshi Mohri¹  Paul Racz²  Klara Tenner-Racz²  Michael A. Poles³ 

[1] Aaron Diamond AIDS Research Center, an affiliate of the Rockefeller University, New York, New York, United States of America;Bernhard-Nocht Institut Fur Tropenmedizin, Hamburg, Germany;Departments of Medicine, Microbiology and Pathology, New York University Medical Center, New York, New York, United States of America

关键词: HIV-1;    T cells;    Viral evolution;    Evolutionary immunology;    Phylogenetic analysis;    Sequence analysis;    Viral replication;    Immune activation;   

DOI  :  10.1371/journal.ppat.1002506

学科分类：生物科学（综合）

来源: Public Library of Science

【 摘 要 】

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 biopsy and CD4+ T cell reconstitution in the peripheral blood. Single genome amplification of full-length HIV-1 envelope was performed for each subject pre- and post-initiation of cART in GALT and PBMC. A total of 280 confirmed single genome sequences (SGS) were analyzed for experimental cases. For each subject, maximum likelihood phylogenetic trees derived from molecular sequence data showed no evidence of evolved forms in the GALT over the study period. During treatment, HIV-1 envelope diversity in GALT-derived SGS did not increase and post-treatment GALT-derived SGS showed no substantial genetic divergence from pre-treatment sequences within transmitted groups. Similar results were obtained from PBMC-derived SGS. Our results reveal that initiation of cART during acute/early HIV-1 infection can result in the interruption of measurable viral evolution in the GALT, suggesting the absence of de-novo rounds of HIV-1 replication in this compartment during suppressive cART.

【 授权许可】

CC BY