Causes of death in HIV-1 infected patients treated with antiretroviral therapy 1996-2006: collaborative analysis of 13 HIV cohort studies

Background: We examined specific causes of mortality in HIV-1-infected patients who initiated antiretroviral therapy (ART) in Europe and North America between 1996 and 2006 and quantified associations of prognostic factors with cause-specific mortality. Methods: Retrospective classification of all deaths among 39,272 patients enrolled in 13 HIV cohorts (154,667 person years of follow up) into the categories specified in the Cause of Death (CoDe) project protocol. Results: In 85% (1597) of 1876 deaths a definitive cause of death could be assigned. Among these, 792 deaths (49.5%) were AIDS-related, followed by non-AIDS malignancies (189, 11.8%), non-AIDS infections (131, 8.2%), violence/drug-related (124, 7.7%), liver disease (113, 7.0%) and cardiovascular disease (103, 6.5%). Rates of AIDS-related death (HR per 100 cell decrease1.43 (95% CI 1.34-1.53)) and death from renal failure (1.73, 1.18-2.55) were strongly inversely related to CD4 count at initiation of ART, while rates of death from AIDS (HR viral load >5 v.5 log copies/mL than in other patients. Rates of each cause of death were higher in patients with presumed transmission via injection drug use (IDU) than other patients, with marked increases in rates of liver- (HR IDU v. non-IDU 6.06, 4.03-9.09) and respiratory-tract (4.94, 1.96-12.45) related mortality. The proportion of deaths classified as AIDS-related declined with increasing duration of ART. Conclusions: Important contributors to non-AIDS mortality in treated HIV-1-infected individuals must be addressed if declines in mortality rates are to continue.