Increase in Non-AIDS Related Conditions as Causes of Death among HIV-Infected Individuals in the HAART Era in Brazil Antonio G. Pacheco 1,2 *, Suely H. Tuboi 2,3 , Jose ´ C. Faulhaber 3 , Lee H. Harrison 2 , Mauro Schechter 4 1 Department of Epidemiology and Quantitative Methods in Health, National School of Public Health/Scientific Computing Program, Oswaldo Cruz Foundation (FIOCRUZ), Rio de Janeiro, Brazil, 2 Infectious Diseases Epidemiology Research Unit, Graduate School of Public Health and School of Medicine, University of Pittsburgh, Pennsylvania, United States of America, 3 Projeto Prac ¸a Onze, Hospital Escola Sa ˜o Francisco de Assis, Universidade Federal do Rio de Janeiro, Rio de Janeiro, Brazil, 4 AIDS Research Laboratory, Hospital Universitario Clementino Fraga Filho, Universidade Federal do Rio de Janeiro, Rio de Janeiro, Brazil Background. In 1996, Brazil became the first developing country to provide free and universal access to HAART. Although a decrease in overall mortality has been documented, there are no published data on the impact of HAART on causes of death among HIV-infected individuals in Brazil. We assessed temporal trends of mortality due to cardiovascular diseases (CVD), diabetes mellitus (DM) and other conditions generally not associated with HIV-infection among persons with and without HIV infection in Brazil between 1999 and 2004. Methodology/Principal Findings. Odds ratios were used to compare causes of death in individuals who had HIV/AIDS listed on any field of the death certificate with those who did not. Logistic regression models were fitted with generalized estimating equations to account for spatial correlation; co-variables were added to the models to control for potential confounding. Of 5,856,056 deaths reported in Brazil between 1999 and 2004 67,249 (1.15%) had HIV/AIDS listed on the death certificate and non-HIV-related conditions were listed on 16.3% in 1999, increasing to 24.1% by 2004 (p,0.001). The adjusted average yearly increases were 8% and 0.8% for CVD (p,0.001), and 12% and 2.8% for DM (p,0.001), for those who had and did not have HIV/AIDS listed on the death certificate, respectively. Similar results were found for these conditions as underlying causes of death. Conclusions/Significance. In Brazil between 1999 and 2004 conditions usually considered not to be related to HIV-infection appeared to become more likely causes of death over time than reported causes of death among individuals who had HIV/AIDS listed on the death certificate than in those who did not. This observation has important programmatic implications for developing countries that are scaling-up access to antiretroviral therapy. Citation: Pacheco AG, Tuboi SH, Faulhaber JC, Harrison LH, Schechter M (2008) Increase in Non-AIDS Related Conditions as Causes of Death among HIV-Infected Individuals in the HAART Era in Brazil. PLoS ONE 3(1): e1531. doi:10.1371/journal.pone.0001531 INTRODUCTION The introduction and widespread use of highly active antiretroviral therapy (HAART) has had a profound impact on the HIV/AIDS epidemic, turning a fatal disease into a manageable chronic condition. As a consequence, marked decreases in AIDS-related morbidity and mortality have been reported in both low- and high- income settings [1–5]. However, concerns have been raised about the consequences of prolonged exposure to antiretroviral drugs, with some evidence for an association between the use of protease inhibitors (PIs) and diabetes mellitus (DM) [6] and cardiovascular diseases (CVD) [7,8]. It has also been recently suggested that HIV itself may play a contributing role in the pathogenesis of some these conditions [9]. Several recent studies conducted in developed countries have documented changes in mortality patterns after the introduction of HAART. Although causes of death traditionally associated with HIV/AIDS continue to play a predominant role, other conditions, including DM, CVD, cancer, liver and renal diseases have been increasingly reported [10–16]. In 1996, Brazil became the first developing country to provide free and universal access to HAART. In 2004 147,500 patients were receiving HAART through the Brazil public health system [17]. In 2005 WHO estimated that ART coverage in Brazil was in excess of 80% [18]. Although a decrease in overall mortality has been documented [3,4], there are no published data on the impact of HAART on causes of death among HIV-infected individuals in Brazil. To our knowledge, there are no population-based studies that have investigated temporal changes in causes of death among HIV/AIDS patients in developing countries after the introduction of HAART. In the present study, we assessed temporal trends of overall mortality and of selected conditions usually considered not to be related to HIV-infection as causes of death between 1999 and 2004 in individuals who had and who did not have HIV/ AIDS listed on their death certificate. RESULTS A total of 5,856,056 deaths were reported in Brazil between 1999 and 2004. Of these, 67,249 (1.15%) had HIV/AIDS reported in any field of the death certificate, corresponding to a stable rate of approximately 6.4 cases/100,000 inhabitants per year during the study period (p-value for trend = 0.67, Figure 1A, solid circles). According to official figures from the Brazil Ministry of Health [19], the death rate associated with HIV/AIDS decreased from Academic Editor: Thomas Novotny, Center for Tobacco Control Research and Education, United States of America Received November 21, 2007; Accepted January 2, 2008; Published January 30, 2008 Copyright: ß 2008 Pacheco et al. This is an open-access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited. Funding: The authors have no support or funding to report. Competing Interests: The authors have declared that no competing interests exist. * To whom correspondence should be addressed. E-mail: apacheco@fiocruz.br PLoS ONE | www.plosone.org 1 January 2008 | Issue 1 | e1531