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.

SummaryImmune compromise can modify the severity and manifestation of some parasitic infections. More widespread use of newer immnosuppressive therapies, the growing population of individuals with immunocompromised states as well as the prolonged survival of these patients have altered the pattern of parasitic infection. This review article discusses the burden and immunology of parasitic infections in patients who are immunocompromised secondary to congenital immunodeficiency, malnutrition, malignancy, and immunosuppressive medications. This review does not address the literature on parasitic infections in the setting of HIV-1 infection.

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Background To understand whether combination antiretroviral therapy (cART) has been optimized, we asked whether 3-drug protease inhibitor (PI)-based cART intensified with raltegravir and maraviroc and initiated during early infection would improve outcomes when compared to similarly applied 3-drug PI-based cART. Methods 40 newly HIV-1 infected patients were randomized 1:2 to receive 3-drug (N=14) or 5-drug (N=26) therapy. The primary endpoint was the percent of subjects with undetectable plasma viremia using standard RT-PCR and the single copy assay (SCA) after 48 weeks. Secondary endpoints included levels of cell-associated HIV-1 DNA and RNA and levels of infectious virus in resting CD4+ T cells at week 96 and quantitative and qualitative immunologic responses. Results At 48 weeks, 34 subjects remained on study and are included in the as-treated analysis. Three of 11 (27.3%) in the 3-drug arm and 9 of 21 (42.9%) in the 5-drug arm had plasma HIV-1 RNA levels below detection by both standard RT-PCR and SCA (P= 0.46, Fishers exact test). No significant differences in absolute levels of proviral DNA or changes in cell-associated RNA were seen during 96-weeks of therapy. Mean levels of infectious HIV-1 in resting CD4+ T cells at week 96 in 7 subjects treated with 3-drugs and 13 with 5-drugs were 0.67 and 0.71 IUPM respectively (P= 0.81). No differences were seen in quantitative or qualitative immunologic determinations including markers of immune activation. Conclusions Intensified 5-drug cART initiated during early infection fails to significantly further impact virologic or immunologic responses beyond those achieved with standard 3-drug PI-based cART.