Background:  With the reductions in mortality seen among HIV-infected patients in countries with good access to treatment, it is of increasing interest to evaluate changes in the mortality gap between HIV-infected individuals and the general uninfected population.

Methods:  Mortality following HIV seroconversion in a large collaboration of HIV seroconverter cohorts (CASCADE) was compared with expected mortality in a hypothetical general population cohort matched on demographic factors, by applying general population death rates to the latter. A Poisson-based model adjusted for duration of infection was constructed to assess changes over calendar time in the excess mortality among HIV-infected individuals, and prognostic factors.

Results:  Of 15,779 individuals, 2475 died, compared with 226 deaths expected in an equivalent general population cohort. The excess hazard ratio (95%CI) of death compared with pre-1996 was 0.52 (0.47 to 0.59) in 1996 to 1997 when HAART was introduced, falling in each subsequent calendar period to 0.06 (0.05 to 0.08) in 2004 to 2006. By 2004 to 2006, there was no evidence of excess mortality in the first 5 years from seroconversion among those infected sexually, but an excess probability of death remained over the longer term (5.2% in the first 10 years among those aged 15 to 24 years). Injecting drug users were at increasingly elevated risk compared with other groups in later calendar periods (p <0.001).

Conclusions:  Mortality rates for HIV-infected persons have become much closer to general mortality rates since the introduction of HAART. HIV-infected persons in developed countries now appear to experience similar rates to their uninfected counterparts in the first 5 years from infection, though a mortality excess remains as HIV infection duration lengthens.