Pre-AIDS mortality from natural causes associated with HIV disease progression: evidence from the European Seroconverter Study among injecting drug users

Objectives: To study differences in pre-AIDS mortality between European cohorts of injecting drug users (IDU) and to evaluate whether pre-AIDS mortality increased with time since HIV seroconversion and decreasing CD4 count. Methods: The study population consisted of 664 IDU with documented intervals of HIV seroconversion from eight cohort studies. Differences in pre-AIDS mortality were studied between European sites; an evaluation of whether pre-AIDS mortality increased with time since HIV seroconversion and decreasing CD4 count was carried out using Poisson regression. Results: One hundred and seven IDU died, of whom 57 did not have AIDS. Pre-AIDS causes of death were overdose/suicide (49%), natural causes-such as bacterial infections/cirrhosis (40%), and unintentional injuries/unknown (11%). Considering pre-AIDS death and AIDS as competing risks, 14.7% were expected to have died without AIDS and 17.3% to have developed AIDS at 7 years from seroconversion. No statistically significant differences in pre-AIDS mortality were found between European regions, men and women, age categories and calendar time periods. Overall pre-AIDS mortality did not increase with time since seroconversion, but did increase with decreasing CD4 count. Evaluating cause-specific mortality, only pre-AIDS mortality from natural causes appeared to be associated with time since seroconversion as well as immunosuppression. For natural causes, the death rate per 100 person-years was 0.13 the first 2 years after seroconversion, 0.73 in years 2-4 [risk relative (RR) to years 0-2, 5.6], 1.83 in years 4-6 (RR, 14.0) and 1.54 for greater than or equal to 6 years (RR, 11.7). This rate was 0 for a CD4 cell count greater than or equal to 500 x 10(6)/l, 1.06 for 200-500 x 10(6)/l and 4.06 for < 200 x 10(6)/l (RR versus greater than or equal to 200 x 10(6)/l, 7.0). In multivariate analysis, both CD4 count and time since seroconversion appeared to be independently associated with death from natural causes; CD4 count appeared to be the strongest predictor (adjusted RR, 5.9). Conclusions: A high pre-AIDS mortality rate was observed among IDU. No significant differences were observed across European sites. Pre-AIDS mortality from natural causes but not from overdose and suicide was associated with HIV disease progression.