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HPTN 069/ACTG A5305: phase II study of maraviroc-containing regimens for HIV PrEP in US women; Postive impact of a randomized controlled trial of the Uthando Lwethu (" Our Love …

Abstract:

Methods: Cynomolgus and rhesus macaques were infected with simian immunodeficiency virus (SIV) and followed longitudinally. Plasma levels of SIV were monitored using qRT-PCR. Bacterial genomic DNA in plasma was characterized and quantified longitudinally using 16S ribosomal deep sequencing and qPCR. ELISA-based assays were used to monitor intestinal permeability (IFABP) and perturbation of bacteria-specific host factors (sCD14 and EndoCab). Flow cytometry was used to track peripheral blood lymphocyte populations. In vitro assays were performed by exposing freshly isolated peripheral blood mononuclear cells to bacterial lysate prepared from major translocators. Effects of bacterial lysate on CD4'T cell activation and CD8'T cell cytotoxicity were measured using flow cytometry. Statistical significance was calculated using ANOVA or Wilcoxon signed-rank testing. Results: Prior to the peak of viremia, we observed a transient highlevel influx of microbial genomic DNA into peripheral blood. This microbial translocation was accompanied by perturbation of bacteria-specific host factors in plasma, as well as expansion of the CD4'CCR5'T cell compartment. Exposure of freshly isolated peripheral blood mononuclear cells to lysate prepared from major translocating taxa revealed differential taxa-specific effects on the CD4'CCR5'T cell compartment and cytotoxic granule expression within CD8'T cells. Conclusions: Altogether, our data identify the influx of microbial products into blood during hyperacute SIV infection as a candidate modifier of early interactions between the antiviral host response and nascent HIV infection. Over the next …