Protection versus pathology in aviremic and high viral load HIV-2 infection - The pivotal role of immune activation and T-cell kinetics

Background. Many human immunodeficiency virus (HIV)-2-infected individuals remain aviremic and behave as long-term non-progressors but some progress to AIDS.We hypothesized that immune activation and T-cell turnover would be critical determinants of non-progressor/progressor status. Methods. We studied 37 subjects in The Gambia, West Africa: 10 HIV-negative controls, 10 HIV-2-infected subjects with low viral loads (HIV-2-LV), 7 HIV-2-infected subjects with high viral loads (HIV-2-HV), and 10 with HIV-1 infection. We measured in vivo T-cell turnover using deuterium-glucose labeling, and correlated results with T-cell phenotype (by flow cytometry) and T-cell receptor excision circle (TREC) abundance. Results. Immune activation (HLA-DR/CD38 coexpression) differed between groups with a significant trend: controls <HIV-2-LV <HIV-1 <HIV-2-HV (P < .01 for all cell types). A similar trend was observed in the pattern of in vivo turnover of memory CD4⁺ and CD8⁺ T-cells and TREC depletion in naive CD4⁺ T-cells, although naive T-cell turnover was relatively unaffected by either infection. T-cell turnover, immune activation, and progressor status were closely associated. Conclusions. HIV-2 non-progressors have low rates of T-cell turnover (both CD4⁺ and CD8⁺) and minimal immune activation; high viral load HIV-2 progressors had high values, similar to or exceeding those in HIV-1 infection.