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

Abstract

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 Received for publication March 19, 2009; accepted August 16, 2009. From the *Departamento de Epidemiologia e Bioestatı́stica, Universidade Federal Fluminense, Niterói, Brazil; †Programa de Computac x ão Cientı́fica (PROCC)-Fiocruz, Rio de Janeiro, Brazil; ‡Infectious Diseases Epide- miology Research Unit, Graduate School of Public Health and School of Medicine, University of Pittsburgh, Pittsburgh, PA, USA; §Department of Biostatistics, Graduate School of Public Health, University of Pittsburgh, Pittsburgh, PA, USA; k Department of Social Medicine, Bristol University, UK; {Department of Social and Preventive Medicine, University of Bern, Bern, Switzerland; #Unité INSERM 897, Institut de Santé Publique, Epidémiologie et Développement (ISPED) Université Victor Segalen, Bordeaux, France; **Department of Social and Preventive Medicine, University of Bern, Bern, Switzerland; ††International Center of AIDS Care and Treatment Programs, Columbia University, Mailman School of Public Health, New York, NY, USA; ‡‡Center for Global Health, Massachusetts General Hospital, Global Health Scholars, Harvard Initiative for Global Health, Boston, MA, USA; §§Indiana University School of Medicine, Indianapolis, USA; Moi University School of Medicine, Eldoret, Kenya; Regenstrief Institute for Informatics, Indian- apolis, IN, USA; kk Division of Biostatistics, Indiana University School of Medicine, Indianapolis, IN, USA; {{Institute of Infectious Disease and Molecular Medicine and Department of Medicine, University of Cape Town, Cape Town, South Africa; ##Hospital de Clinicas de Porto Alegre, Universidade Federal do Rio Grande do Sul, Brazil; and ***Hospital Universitario Clementino Fraga Filho Universidade Federal do Rio de Janeiro, Rio de Janeiro, Brazil. The ART-LINC collaboration of the International epidemiological Databases to Evaluate AIDS (IeDEA) is funded by the US National Institutes of Health (Office of AIDS Research and National Institute of Allergy and Infectious Diseases) and the French Agence Nationale de Recherches sur le Sida et les hepatitis virales (ANRS). This study was partially supported by the Fogarty International Center, NIH (grant 3 D43 TW01038). ART-LINC of IeDEA central coordinating team and the Collaborating centers are listed in Appendix 1. Correspondence to: Dr. Mauro Schechter, MD, PhD, Hospital Universitario Clementino Fraga Filho Universidade Federal do Rio de Janeiro, Rua Professor Rodolpho Paulo Rocco, n 255, Ilha do Fundão, Rio de Janeiro—RJ, Brazil 21941.590. (e-mail: maurosch@hucff.ufrj.br). Copyright Ó 2009 by Lippincott Williams & Wilkins 70 | www.jaids.com 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 avail- ability of plasma viral load testing to monitor antiretroviral therapy in these settings. Key Words: antiretroviral therapy, cohort, CD4 lymphocyte count, highly active, low-income population, mortality, treatment outcome,