Reduced Frequency of Cells Latently Infected With Replication-Competent Human Immunodeficiency Virus-1 in Virally Suppressed Individuals Living in Rakai, Uganda

Abstract

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.