Background:  Successful combination Antiretroviral Therapy (cART) may be associated with a life expectancy of HIV-infected patients approaching that of the uninfected population. We compared age- and gender-specific death rates in HIV-infected adults after initiation of cART according to current CD4 cell count and time spent with CD4 ≥500 cells/mm³, with those of the general population.

Methods:  HIV-infected adults (≥18 years) starting cART from naïve from 1998 onwards, enrolled in COHERE, a collaboration of 25 European observational cohorts and followed ≥1 day were eligible. Standardized mortality ratios (SMR) were estimated with reference to age- and gender-specific mortality rates in country-specific general populations using the Human Mortality Database or WHO data. Time of follow-up was categorized into 4 CD4 strata (<200; 200 to 349; 350 to 499; and ≥500 cells/mm³) using the lowest observed measurement within each year of follow-up. Missing data for CD4 were imputed using simple imputation including last observation carried forward since this method was robust through several sensitivity analyses.

Results:  Among 80,642 adults, (70% men, median (IQR) age at cART initiation 37 (range 31 to 43) years; 42% heterosexual, 33% sex between men, and 16% injecting drug use), baseline median (IQR) CD4 cell count was 225 (107 to 357) cells/mm³, 3,813 (men: 2,979, women: 834) deaths occurred and median (IQR) duration of follow-up 3.5 (1.5 to 6.1) years, ie, 315,340 person-years. For current CD4 <200, 200 to 349, 350 to 499, and ≥500 cells/mm³, SMR (95%CI) were 13.0 (12.5 to 13.5), 3.0 (2.8 to 3.2), 1.8 (1.7 to 2.0), 1.5 (1.4 to 1.7), respectively. Death rates among men with CD4 ≥500 cells/mm³ reached those of the general population after at least 3 years spent above that threshold: SMR (95%CI) were 1.4 (1.2 to 1.6) after 1 year, 1.0 (0.8 to 1.3) after 3 years and 1.1 (0.8 to 1.7) over 5 years. Death rates among women with CD4 ≥500 cells/mm³ remained higher than those of the general population even after 5 years spent above this threshold: 1.9 (1.3 to 2.6) after 1 year, 1.7 (0.9 to 2.9) after 3 years, 2.4 (1.0 to 5.0) after 5 years.

Conclusions:  While HIV-infected men who were successfully treated reached similar mortality rates to those in the general male population after 3 years, this was not the case among women. Though our results might be partly explained by other differences between HIV-infected and uninfected populations, they point to the importance of treatment adherence and early initiation of treatment.