Impact of Risk Factors for Specific Causes of Death in the First and Subsequent Years of Antiretroviral Therapy Among HIV-Infected Patients

Background. Patterns of cause-specific mortality in HIV-1 positive individuals are changing dramatically in the era of antiretroviral therapy (ART). Methods. 16 cohorts from Europe and North America contributed data on adult patients followed from starting ART. Procedures for coding causes of death were standardised. Estimated hazard ratios (HR) were adjusted for transmission risk group, sex, age, year of ART initiation, baseline CD4 count, viral load and AIDS status, before and after the first year of ART. Results. 4237/65121 (6.5%) patients died (median 4.5 years follow-up). Rates of AIDS death decreased substantially with time since starting ART, but mortality from non-AIDS malignancy increased (rate ratio 1.04 per year: 95% CI 1.0-1.1). Higher mortality in men than women during the first year of ART was mostly due to non-AIDS malignancy and liver-related deaths. Associations with age were strongest for cardiovascular disease, heart/vascular and malignancy deaths. Patients with presumed transmission through IDU had higher rates of all causes of death, particularly for liver-related causes (HRs compared with MSM 18.1: 6.2-52.7 during the first year of ART and 9.1: 5.8-14.2 thereafter). There was a persistent role of CD4 count at baseline and at 12 months in predicting AIDS, non-AIDS infection and non-AIDS malignancy deaths. Lack of viral suppression on ART was associated with AIDS, non-AIDS infection, and other causes of death. Conclusions. Better understanding of patterns of and risk factors for cause-specific mortality in the ART era can help development of appropriate care for HIV-positive individuals and inform guidelines for risk factor management.