CD4+ Response and Subsequent Risk of Death Among Patients on Antiretroviral Therapy in Lusaka, Zambia

Introduction: Where virologic monitoring is not routinely available, immunologic criteria are commonly used to determine treatment failure while on antiretroviral therapy (ART). However, few have studied CD4(+) response and its relationship to subsequent clinical outcomes in a programmatic setting. Methods: We analyzed cohort data from Zambia to investigate whether 6- and 12-month CD4(+) response after ART initiation was associated with later mortality. We used Cox proportional hazards models that accounted for different strata of baseline CD4(+) counts and adjusted for age, sex, clinical stage, tuberculosis coinfiection, baseline hemoglobin, initial ART regimen, and adherence behavior. Results: We analyzed data from 2 cohorts, from 6 months onward (n = 24,366; median follow-up = 467 days, interquartile range 222-791) and from 12 months onward (n = 17,920; median follow-up = 423 days, interquartile range 191-689). In the post-6-month analysis, hazard for death was significantly higher when absolute CD4(+) response was <100 cells per microliter [adjusted hazard ratio (AHR) = 2.25, 95% confidence interval (Cl): 1.91 to 2.64], relative response was <10% above baseline (AHR = 2.60, 95% CI: 2.12 to 3.19), and absolute CD4(+) count was <100 per microliter (AHR = 2.79, 95% CI: 2.26 to 3.45). In the post-12 month analysis, mortality was associated with rise in absolute CD4(+) cell count <200 per microliter (AHR = 2.41, 95% CI: 1.83 to 3.17), relative rise in CD4(+) cell count of <10% above baseline (AHR = 3.41, 95% CI: 2.51 to 4.64), and absolute CD4(+) count at 12 months <100 per microliter (AHR = 4.11, 95% CI: 2.96 to 5.68). Conclusion: Commonly used definitions for immunologic treatment failure are associated with elevated mortality risk among patients on ART.