Impact of Hiv-Associated Conditions on Mortality in People Commencing Anti-Retroviral Therapy in Resource Limited Settings

Objectives: To identify associations between specific WHO stage 3 and 4 conditions diagnosed after ART initiation and all cause mortality for patients in resource-limited settings (RLS). Design, Setting: Analysis of routine program data collected prospectively from 25 programs in eight countries between 2002 and 2010. Subjects, Participants: 36,664 study participants with median ART follow-up of 1.26 years (IQR 0.55-2.27). Outcome Measures: Using a proportional hazards model we identified factors associated with mortality, including the occurrence of specific WHO clinical stage 3 and 4 conditions during the 6-months following ART initiation. Results: There were 2922 deaths during follow-up (8.0%). The crude mortality rate was 5.41 deaths per 100 person-years (95% CI: 5.21-5.61). The diagnosis of any WHO stage 3 or 4 condition during the first 6 months of ART was associated with increased mortality (HR: 2.21; 95% CI: 1.97-2.47). After adjustment for age, sex, region and pre-ART CD4 count, a diagnosis of extrapulmonary cryptococcosis (aHR: 3.54; 95% CI: 2.74-4.56), HIV wasting syndrome (aHR: 2.92; 95% CI: 2.21 -3.85), non-tuberculous mycobacterial infection (aHR: 2.43; 95% CI: 1.80-3.28) and Pneumocystis pneumonia (aHR: 2.17; 95% CI 1.80-3.28) were associated with the greatest increased mortality. Cerebral toxoplasmosis, pulmonary and extra-pulmonary tuberculosis, Kaposi's sarcoma and oral and oesophageal candidiasis were associated with increased mortality, though at lower rates. Conclusions: A diagnosis of certain WHO stage 3 and 4 conditions is associated with an increased risk of mortality in those initiating ART in RLS. This information will assist initiatives to reduce excess mortality, including prioritization of resources for diagnostics, therapeutic interventions and research.