Death rates in the APROCO cohort of 1,157 HIV-1 infected adults starting for the first time a protease inhibitor-containing therapy were standardized to the 1996 French general population mortality rates stratified by age and gender. Median follow-up was 23 months and mortality rate was 2.2% person-years (95% confidence interval [CI] = 1.6-2.9). Overall mortality was 7.8 times higher than in the general population (95% CI = 5.7-10.4), 4.7 in men and 19.5 in women. Among the 144 patients considered complete responders, the death rate was 1.2% person-years (95% CI = 0.2-3.5) and mortality remained 5.1 times higher (95% CI = 1.0-14.9) than in the general population. Failure of treatment, long-term adverse effects, or less favorable socio-demographic status could explain these trends.