Both CD31⁺and CD31^- naive CD4⁺ T cells are persistent HIV type 1-infected reservoirs in individuals receiving antiretroviral therapy

Background. Naive T cell recovery is critical for successful immune reconstitution after antiretroviral therapy (ART), but the relative contribution of CD31⁺ and CD31^- naive T cells to immune reconstitution and viral persistence is unknown. Methods. In a cross-sectional (n = 94) and longitudinal (n = 10) study of human immunodeficiency virus (HIV)-infected patients before and after ART, we examined the ratio of CD31⁺ to CD31^- naive CD4⁺ T cells. In the longitudinal cohort we then quantified the concentration of HIV-1 DNA in each cell subset and performed single-genome amplification of virus from memory and naive T cells. Results. Patients receiving ART had a higher proportion of CD31⁺ CD4 ⁺ T cells than HIV-1-infected individuals naive to ART and uninfected control subjects (P<.001 and .007, respectively). After 24 months of ART, the proportion of CD31⁺ naive CD4⁺ T cells did not change, the concentration of HIV-1 DNA in memory CD4⁺ T cells significantly decreased over time (P<.001), and there was no change in the concentration of HIV-1 DNA in CD31⁺ or CD31^- naive CD4⁺ T cells (P = .751 and .251, respectively). Single-genome amplification showed no evidence of virus compartmentalization in memory and naive T cell subsets before or after ART. Conclusions. After ART, both CD31⁺ and CD31 ^- naive CD4⁺ T cells expand, and both subsets represent a stable, persistent reservoir of HIV-1.