Estimation of Mortality among HIV-infected people on antiretroviral therapy treatment in east Africa: a sampling based approach in an observational, multisite, cohort study.

BACKGROUND Mortality after initiation of antiretroviral treatment (ART) among HIV-infected patients in resource limited settings is a critical measure of the effectiveness and comparative effectiveness of the global public health response. Unknown outcomes due to high loss to follow-up (LTFU) preclude accurate accounting of deaths and limit our understanding of effectiveness. METHODS We evaluated in HIV-infected adults on ART in 14 clinics in five settings in Kenya, Uganda and Tanzania using a sampling-based approach in which we intensively traced a random sample of lost patients (> 90 days late for last scheduled visit) and incorporated their vital status outcomes into analyses of the entire clinic population through probability-weighted survival analyses. FINDINGS We followed 34,277 adults on ART from Mbarara and Kampala, Uganda; Eldoret and Kisumu, Kenya; and Morogoro, Tanzania. The median age was 35 years, 34% were men, and median pre-therapy CD4 count was 154 cells/μl. Overall 5,780 (17%) were LTFU, 991 (17%) were randomly selected for tracing and vital status was ascertained in 860 of 991 (87%). Incorporating outcomes among the lost increased estimated 3-year mortality from 3.9% (95% CI: 3.6%-4.2%) to 12.5% (95% CI: 11.8%-13.3%). The sample-corrected, unadjusted 3-year mortality across settings ranged from 7.2% in Mbarara to 23.6% in Morogoro. After adjustment for age, sex, pre-therapy CD4 value, and WHO stage, the sample-corrected hazard ratio comparing the setting with highest vs. lowest mortality was 2.2 (95% CI: 1.5-3.4) and the risk difference for death at 3 years was 11% (95% CI: 5.0%-17.7%). INTERPRETATION A sampling based approach is widely feasible and important for understanding mortality after starting ART. After adjustment for measured biological drivers, mortality differs substantially across settings despite delivery of a similar clinical package of treatment. Implementation research to understand the systems, community, and patient behaviors driving these differences is urgently needed.

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