Suboptimal immune recovery during antiretroviral therapy with sustained HIV suppression in sub-Saharan Africa

Objective: To assess incidence, determinants and clinical consequences of suboptimal immune recovery in HIV-1 infected adults in sub-Saharan Africa with sustained viral suppression on antiretroviral therapy (ART). Design: Multicountry prospective cohort. Methods: Suboptimal immune recovery was defined as proportions of participants who failed to attain clinically relevant CD4+cell count thresholds (>200, >350 and >500 cells/μl) despite sustained viral suppression on continuous first-line ART. Participants were censored at the earliest of death, loss to follow-up, last viral load less than 50 copies/ml, or database closure. Determinants of immune recovery were assessed using multivariable Cox regression. We estimated incidence rates of AIDS, pulmonary tuberculosis and all-cause mortality for CD4+strata. Results: One thousand, five hundred and ninety-two participants were included; 60% were women, median age was 37 years (IQR 31-43) and median pre-ART CD4+cell count was 147 cells/μl (IQR 76-215). After 6 years of ART, suboptimal immune recovery at CD4+cell counts less than 200 cells/μl, less than 350 cells/μl, and less than 500 cells/μl occurred in 7, 27, and 57% of participants, respectively. Compared with participants with CD4+cell count greater than 500 cells/μl, on-ART incidence rates were 12.5, 4.1, 0.9 times higher for AIDS and 16.9, 3.5, and 2.3 times higher for pulmonary tuberculosis in participants with CD4+cell count less than 200, 200-349, and 350-499 cells/μl, respectively. All-cause mortality was highest in participants with CD4+cell count less than 200 cells/μl, and comparable across the higher CD4+strata. Older age, male sex, and lower pre-ART CD4+cell count were strongly associated with suboptimal immune recovery. Conclusion: These findings warrant close clinical and laboratory monitoring until adequate immune reconstitution is achieved and support early ART initiation before decline of CD4+cell count.