Long-term immunologic response to antiretroviral therapy in low-income countries: a collaborative analysis of prospective studies

Background: Few data are available on the long-term immunologic response to ART in resource-limited settings, where antiretroviral therapy (ART) is being scaled up using a public health approach, with a limited repertoire of drugs. Objectives: To describe immunologic response to ART in a network of cohorts from sub-Saharan Africa, Latin America, and Asia. Study population/methodsL: Treatment-naïve patients aged 15 and older from 27 treatment programs were eligible. Multi-level, linear mixed models were used to assess associations between predictor variables and CD4 count trajectories following ART initiation. Results: Of 29,175 patients initiating ART, 8,933 patients (31%) were excluded due to insufficient follow-up time and early lost to follow-up or death. The remaining 19,967 patients contributed 39,200 person-years on ART and 71,067 CD4 measurements. The median baseline CD4 count was 114 cells/μL, with 35%<100 cells μL and substantial inter-site variation (range: 61-181 cells/μL). Females had higher median baseline CD4 counts than males (121 vs. 104 cells/μL). The median CD4 count increased from 114 cells/μL at ART initiation to 230 (IQR:144-338) at 6 months, 263 (IQR:175-376) at 1 year, 336 (IQR:224-472) at 2 years, 372 (IQR:242-537) at 3 years, 377 (IQR:221-561) at 4 years, and 395 (IQR:240-592) at 5 years. In multivariable models, baseline CD4 count was the most important determinant of subsequent CD4 count trajectories. Conclusions: These data demonstrate robust and sustained CD4 response to ART among patients remaining on therapy. Public health and programmatic interventions leading to earlier HIV diagnosis and initiation of ART could substantially improve patient outcomes in resource-limited settings.