Background:  An increasing proportion of deaths in patients on ART are from causes not classified as AIDS-related.

Methods:  Data were combined from 13 cohort studies in Europe and North America (ART Cohort Collaboration). We reviewed available information (International Classification of Disease codes, characteristics at the time of death) on 1876 deaths among 39,272 patients aged >15 years, who started triple ART during 1996 to 2006. Causes were classified ≥2 reviewers according to the CoDe classification, with disagreements resolved after discussion.

Results:  The table shows specific causes that could be assigned for 1597 (85%) deaths. AIDS deaths (46% infection, 30% malignancy, 24% unspecified) accounted for 63% of deaths in the first year of ART, and 43% thereafter. The table also shows hazard ratios (HR) (adjusted for sex, age, viral load, AIDS, year of starting ART, and cohort) comparing those with lower with higher baseline CD4 and patients infected via injection drug use (IDU) with others. Median baseline CD4 was 217 cells/mL (IQR 94 to 343) in survivors and 110 (33 to 247) in those who died. Median time to death was 1.8 (0.6 to 3.8) years. In addition to AIDS, non-AIDS malignancy and renal failure appeared associated with immunodeficiency at baseline. Rates of non-AIDS infection, liver-related, non-AIDS malignancy, violence, heart or vascular and respiratory deaths were markedly elevated in patients infected via IDU. Rates of liver-related death declined (p = 0.03) with year of starting ART:  0.83 (95%CI 0.59 to 1.16) per 1000 years in 1996 to 1997 declining to 0.42 (0.14 to 1.32) in 2004 to 2006. Overall mortality rates increased with age, with very strong associations of older age with non-AIDS malignancy and cardiovascular disease death.

Conclusions:  To achieve further declines in mortality rates among patients treated with ART, causes of non-AIDS death must be addressed. Such causes are of particular importance in patients infected via IDU.