HIV-related immune dysregulation during antiretroviral therapy in sub-Saharan Africa

Since antiretroviral therapy (ART) has become available for people living with HIV (PLWH), millions of deaths have been avoided globally, including in sub-Saharan Africa. However, PLWH remain at increased risk of morbidity and mortality, which is thought to be driven by immune dysregulation, including suboptimal CD4+ T-cell recovery and persistent immune activation. In the Pan African studies to evaluate resistance (PASER)-cohort a prospective cohort of adult PLWH in six African countries who initiated ART in the year(s) 2007 and 2009, we found that despite ART mediated viral suppression the majority had incomplete CD4+ T-cell recovery (<500 cells/µL). In addition, immune activation and inflammation was persistent despite successful ART. To identify markers of poor outcomes during ART we assessed whether soluble markers of immune activation and inflammation were associated with CD4+ T-cell recovery and viral rebound, and whether plasma microRNAs were associated with CD4+ T-cell recovery. The on ART plasma levels of sCD14 and CRP were associated with subsequent poor CD4+ T-cell recovery and the on ART levels of CXCL10 or a limited decline of sCD163 during the first year of ART was associated with virological failure. Finally, we found that the plasma microRNAs hsa-miR-199a-3p, hsa-miR-200c-3p, hsa-miR-17-5p and hsa-miR-501-3p were associated with poor CD4+ T-cell recovery.