Mortality of HIV-infected patients starting potent antiretroviral therapy: comparison with the general population in nine industrialized countries

Abstract

Background: Mortality in HIV-infected patients has declined substantially with combination antiretroviral therapy (ART), but it is unclear whether it has reached that of the general population. We compared mortality in patients starting ART in nine countries of Europe and North America with the corresponding general population, taking into account their response to ART.

Methods: Eligible patients were enrolled in prospective cohort studies participating in the ART Cohort Collaboration. We calculated the ratio of observed to expected deaths from all causes [standardized mortality ratio (SMR)], measuring time from 6 months after starting ART, according to risk group, clinical stage at the start of ART and CD4 cell count and viral load at 6 months. Expected numbers of deaths were obtained from age-, sex- and country-specific mortality rates.

Results: Among 29 935 eligible patients, 1134 deaths were recorded in 131 510 person-years of follow-up. The median age was 37 years, 8162 (27%) patients were females, 4400 (15%) were injecting drug users (IDUs) and 6738 (23%) had AIDS when starting ART. At 6 months, 23 539 patients (79%) had viral load measurements <or=500 copies/ml. The lowest SMR, 1.05 [95% confidence interval (CI) 0.82-1.35] was found for men who have sex with men (MSM) who started ART free of AIDS, reached a CD4 cell count of >or=350 cells/microL and suppressed viral replication to <or=500 copies/ml by the sixth month. In contrast, the SMR was 73.7 (95% CI 46.4-116.9) in IDUs who failed to suppress viral replication and had CD4 cell counts <50 cells/microL at 6 months. The percentage of patients with SMRs <2 was 46% for MSM, 42% for heterosexually infected patients and 0% for patients with a history of injection drug use. Corresponding percentages for SMRs >10 were 4, 14 and 47%.

Conclusions: In industrialized countries, the mortality experience of HIV-infected patients who start ART and survive the first 6 months continues to be higher than in the general population, but for many patients excess mortality is moderate and comparable with patients having other chronic conditions. Much of the excess mortality might be prevented by earlier diagnosis of HIV followed by timely initiation of ART.

Figure 1

(a–c) Cumulative frequency distribution of SMRs for the three main HIV transmission groups