Mortality among urban drug users and the impact of highly active antiretroviral therapy.

Received 1 June 2005; accepted 2 June 2005; electronically published 16 August 2005. Reprints or correspondence: Dr. David Celentano, Johns Hopkins Bloomberg School of Public Health, 615 N. Wolfe St., E-6547, Baltimore, MD 21205 (dcelenta@jhsph.edu). Clinical Infectious Diseases 2005; 41:873–4 2005 by the Infectious Diseases Society of America. All rights reserved. 1058-4838/2005/4106-0018$15.00 HAART has been shown to improve the course of HIV disease by reducing viral load and increasing the CD4 T lymphocyte count [1, 2]. Consequently, there have been decreases in the rate of progression to AIDS and subsequent significant decreases in the mortality rate [3]. Most of the published literature on the effectiveness of HAART on improved health status is restricted to white men, and only a few studies have directly addressed the survival benefit of HAART for injection drug users and women, who today constitute a substantial proportion of adults with HIV infection [4, 5]. In this issue of Clinical Infectious Diseases, Kolhi et al. [6], of the Montefiore Medical Center and Albert Einstein College of Medicine in New York, report the mortality among a cohort of drug users observed prospectively from 1996 through 2001. They examine mortality rates over this 6-year interval and investigate the causes of death and their predictors among 398 HIV-infected and 656 HIVseronegative drug users recruited from methadone maintenance programs. The HIV Epidemiologic Research on Outcomes (HERO) study is a large, epidemiologic cohort study that began enrollment in June 1985 [7] and was one of the first investigations to report the risk factors for HIV infection among injection drug users in the United States. The present study takes advantage of the strength of the cohort study design in which both time-varying and time-independent risk factors for all-cause mortality are simultaneously considered. The rigor of the analysis, the well-characterized cohort, and the features of the design yield data that clearly answer the study questions. The death rates in the HERO study decreased 150% over the 6-year period. All of the survival benefit was attributable to a decrease in the mortality rate among HIV-infected participants, because the death rate among HIV-seronegative participants was steady (∼1.5 deaths per 100 person-years). Importantly, overall, there were no differences related to race/ethnicity or sex. The cause of death was determined with use of hospital records, a search of the National Death Index database, or communication with a designated contact provided by the participant. This led to a very high ascertainment rate, which is commendable. Aside from the fact that 38% of deaths were attributed to AIDS in the HIV-infected cohort, HIVinfected participants had higher rates of mortality associated with substance abuse, bacterial infection, and other medical illnesses than did HIV-uninfected participants who had a similar history of substance abuse. HAART was clearly associated with greater survival rates in the HERO study, but only for those persons who started therapy at a CD4 lymphocyte count of 200 cells/mm. Unlike other studies, initiation of HAART at higher CD4 lymphocyte counts (e.g., 350 cells/mm) provided no survival advantage. This is in contrast to the findings from a large cohort study of injection drug users recruited in Baltimore at approximately the same historical time period, for which there was a survival advantage in the comparison of patients with CD4 lymphocyte counts 350 cells/mm with HIV-uninfected persons, compared with patients with lower CD4 cell counts [8]. In Cox proportional hazards analysis, only HIV infection status and older age were associated with all-cause mortality in this study conducted in the Bronx. When restricted to HIV-infected participants, predictors of mortality included only recent (i.e., at last study visit) HAART use and high CD4 lymphocyte count. What is perhaps as important as the statistically significant independent predictors of death were the nonsignificant findings; there were no differences in hazard ratios for all-cause mortality among HIV-in-