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

Abstract

Background: Few data are available on the long-term immunologic response to antiretroviral therapy (ART) in resource-limited settings, where ART is being rapidly scaled up using a public health approach, with a limited repertoire of drugs.

Objectives: To describe immunologic response to ART among ART patients in a network of cohorts from sub-Saharan Africa, Latin America, and Asia. STUDY POPULATION/METHODS: Treatment-naive patients aged 15 and older from 27 treatment programs were eligible. Multilevel, linear mixed models were used to assess associations between predictor variables and CD4 cell count trajectories following ART initiation.

Results: Of 29 175 patients initiating ART, 8933 (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 cell count measurements. The median baseline CD4 cell count was 114 cells/microl, with 35% having less than 100 cells/microl. Substantial intersite variation in baseline CD4 cell count was observed (range 61-181 cells/microl). Women had higher median baseline CD4 cell counts than men (121 vs. 104 cells/microl). The median CD4 cell count increased from 114 cells/microl at ART initiation to 230 [interquartile range (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 cell count was the most important determinant of subsequent CD4 cell count trajectories.

Conclusion: 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.

Figure 1

Median CD4 count at ART initiation by sex and cohort.

Figure 2

Median CD4 count over time on ART by sex, age at ART initiation, clinical stage, ART regimen, CD4 count at ART initiation, and status at the end of the follow-up period.

Figure 3

Median CD4 count with time of HAART, stratified by baseline CD4 cell count. The lines give the predicted response for baseline CD4 categories from the mixed-effects model. Fractional polynomials for each baseline CD4 category were modelled with an overall intercept (constant) representing the most common patient group: age 30-39, female and year 2004. The symbols give the overall observed median CD4 cell count in each baseline CD4 category by successive time periods on HAART.