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Background. Human immunodeficiency virus type 1 (HIV-1) persists in latently infected resting CD4+ T cells (rCD4 cells), posing a major barrier to curing HIV-1 infection. Previous studies have quantified this pool of latently infected cells in Americans; however, no study has quantified this reservoir in sub-Saharan Africans, who make up the largest population of HIV-1-infected individuals globally. Methods. Peripheral blood was collected from 70 virally suppressed HIV-1-infected individuals from Rakai District, Uganda, who had initiated antiretroviral therapy (ART) during chronic infection. The quantitative viral outgrowth assay was used to determine frequency of latently infected rCD4 cells containing replication-competent virus. Multivariate regression was used to identify correlates of reservoir size and to compare reservoir size between this Ugandan cohort and a previously studied cohort of individuals from Baltimore, Maryland. Results. The median frequency of latently infected rCD4 cells in this Ugandan cohort was 0.36 infectious units per million cells (IUPM; 95% confidence interval, 0.26-0.55 IUPM), 3-fold lower than the frequency observed in the Baltimore cohort (1.08 IUPM; .72-1.49 IUPM; P < .001). Reservoir size in Ugandans was correlated positively with set-point viral load and negatively with duration of viral suppression. Conclusions. Virally suppressed Ugandans had a 3-fold lower frequency of rCD4 cells latently infected with replication-competent HIV-1, compared with previous observations in a cohort of American patients, also treated with ART during chronic infection. The biological mechanism driving the observed smaller reservoir in Ugandans is of interest and may be of significance to HIV-1 eradication efforts. [ABSTRACT FROM AUTHOR]

HIV-1 infection remains incurable owing to the persistence of a viral reservoir that harbors integrated provirus within host cellular DNA. Increasing evidence links sex-based differences in HIV-1 immune responses and pathogenesis; however, little is known about differences in HIV-1 infection persistence. Here, we quantified persistent HIV-1 infection in 90 adults on suppressive antiretroviral therapy in Rakai, Uganda (57 female patients). Total HIV-1 DNA was quantified by PCR, and replication-competent provirus by quantitative viral outgrowth assay (QVOA). Immune phenotyping of T cell subsets and plasma biomarkers was also performed. We found that whereas both sexes had similar total HIV DNA levels, female patients had significantly fewer resting CD4+ T cells harboring replication-competent virus, as measured by viral outgrowth in the QVOA. Factors associated with viral outgrowth differed by sex; notably, frequency of programmed cell death 1 (PD1+) CD4+ T cells correlated with reservoir size in male but not female patients. The sex-based differences in HIV-1 persistence observed in this cohort warrant additional research, especially given the widespread use of the QVOA to assess reservoir size and current explorations of PD1 agonists in cure protocols. Efforts should be made to power future cure studies to assess outcomes in both male and female patients.

The Phylogenetics And Networks for Generalized HIV Epidemics in Africa (PANGEA-HIV) consortium has been vital in the generation and examination of near full-length HIV-1 sequences generated from Sub-Saharan Africa. In this study, we examined a subset ( n  = 275) of sequences from Rakai, Uganda, collected between August 2011 and January 2015. Sequences were initially screened with COMET for subtyping and then evaluated using bootscanning and phylogenetic inference. Among 275 sequences, 38.6% were subtype D, 19.3% were subtype A, 2.9% were subtype C, and 39.3% were recombinant. The recombinants were structurally diverse in the number of breakpoints observed, the location of recombinant segments, and represented subtypes, with AD recombinants accounting for the majority of all recombinants (29.8%). Within the AD subpopulation, we identified a potential new circulating recombinant form in five individuals where the polymerase gene was subtype D and most of env was subtype A (D-A junctures at HXB2 6760 and 8709). While the breakpoints were identical for the viruses from these individuals, the viral fragments did not cluster together. These results suggest selection for a viral strain where properties of the subtype A and subtype D portions of the virus confer a survival advantage. The continued study of recombinants will increase our breadth of knowledge for the genetic diversity and evolution of HIV-1, which can further contribute to our understanding toward a universal HIV-1 vaccine.