Opportunistic Disease and Mortality in Patients Coinfected with Hepatitis B or C Virus in the Strategic Management of Antiretroviral Therapy (SMART) Study

Background. In the Strategic Management of Antiretroviral Therapy (SMART) study, the risk of opportunistic disease (OD) and/or death due to any cause was elevated in the drug conservation (i.e., interrupt antiretroviral therapy until the CD4+ cell count is 6 months and positive for HCV if they tested HCV antibody positive. The rate and hazard ratio (HR) of OD and/or death and its 2 components were compared by hepatitis status and drug conservation versus the viral suppression group. Results. Among 5472 participants enrolled from 8 January 2002 through 11 January 2006, 930 (17%) were HBV positive and/or HCV positive. The relative risk of non-OD death in participants randomized to the drug conservation group versus the viral suppression group was comparable regardless of hepatitis status (HR for coinfected and HIV-monoinfected participants, respectively, 1.9 [95% confidence interval {CI}, 1.0–3.9 and 1.8 [95% CI, 0.9–3.4]). The rate of OD or death was 3.9 events per 100 person-years in the coinfected group and 2.0 per 100 person-years in the HIV-monoinfected group. This excess risk was due to a higher risk of non-OD death among the coinfected participants (HR, 3.6; 95% CI, 2.3–5.6), whereas the risk of OD was comparable (HR, 1.1; 95% CI, 0.7–1.8). The 3 leading causes of non-OD death in coinfected participants were unknown cause, substance abuse, and non–acquired immunodeficiency disease cancer. Conclusions. Interruption of antiretroviral therapy is particularly unsafe in persons with hepatitis virus coinfection. Although HCV- and/or HBV-coinfected participants constituted 17% of participants in the SMART study, almost one-half of all non-OD deaths occurred in this population. Viral hepatitis was an unlikely cause of this excess risk. Clinical trials registration. ClinicalTrials.gov registration no. NCT00027352.