Reducing mortality with cotrimoxazole preventive therapy at initiation of antiretroviral therapy in South Africa

Abstract

To assess the effectiveness of cotrimoxazole preventive therapy (CPT) among individuals with CD4 cell count above 200 cells/microl and varying WHO clinical stages in reducing mortality during combination antiretroviral therapy (cART). A cohort study. Using proportional hazards modeling, we compared mortality during the first 12 months after cART initiation among patients receiving CPT with patients not receiving CPT. We adjusted for clinic level confounding throughout. We included 14 097 patients starting cART between January 2003 and January 2008, 62% of whom were men, the median CD4 cell count was 132 cells/microl, and 1289 died (11%). The baseline median CD4 cell count was lower (118 vs. 153 cells/microl) among the 7508 patients who received CPT compared with the 6589 patients who did not. In adjusted multivariate modeling, stratifying for baseline CD4 cell count and WHO stage, CPT reduced mortality overall (hazard ratio 0.64, P < 0.001) and for all individuals with CD4 cell count below 200 cells/microl or WHO clinical stage 3 or 4 conditions but did not reduce mortality for patients with both CD4 cell count above 200 cells/microl and WHO clinical stage 1 or 2. We demonstrated a 36% reduction in mortality extending to patients associated with CPT when used with cART that extended to patients with CD4 cell count above 350 cells/microl in a setting with minimal malaria and high rates of cotrimoxazole-resistant bacteria. This provides important additional data toward efforts to increase CPT provision among all cART initiators in resource limited settings.