Mortality associated with discordant responses to antiretroviral therapy in resource-constrained settings

Tuboi, Suely Hiromi; Pacheco, Antonio Guilherme; Harrison, Lee H; Stone, Roslyn A; May, Margaret; Brinkhof, Martin W G; Dabis, François; Egger, Matthias; Nash, Denis; Bangsberg, David; Braitstein, Paula; Yiannoutsos, Constantin T; Wood, Robin; Sprinz, Eduardo; Schechter, Mauro (2010). Mortality associated with discordant responses to antiretroviral therapy in resource-constrained settings. Journal of acquired immune deficiency syndromes JAIDS, 53(1), pp. 70-77. Philadelphia, Pa.: Lippincott Williams & Wilkins 10.1097/QAI.0b013e3181c22d19

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Objectives: We assessed mortality associated with immunologic and virologic patterns of response at 6 months of highly active antiretroviral therapy (HAART) in HIV-infected individuals from resource-limited countries in Africa and South America.

Methods: Patients who initiated HAART between 1996 and 2007, aged 16 years or older, and had at least 1 measurement (HIV-1 RNA plasma viral load or CD4 cell count) at 6 months of therapy (3-9 month window) were included. Therapy response was categorized as complete, discordant (virologic only or immunologic only), and absent. Associations between 6-month response to therapy and all-cause mortality were assessed by Cox proportional hazards regression. Robust standard errors were calculated to account for intrasite correlation.

Results: A total of 7160 patients, corresponding to 15,107 person-years, were analyzed. In multivariable analysis adjusted for age at HAART initiation, baseline clinical stage and CD4 cell count, year of HAART initiation, clinic, occurrence of an AIDS-defining condition within the first 6 months of treatment, and discordant and absent responses were associated with increased risk of death.

Conclusions: Similar to reports from high-income countries, discordant immunologic and virologic responses were associated with intermediate risk of death compared with complete and no response in this large cohort of HIV-1 patients from resource-limited countries. Our results support a recommendation for wider availability of plasma viral load testing to monitor antiretroviral therapy in these settings.

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