We studied the relation between the occurrence of adverse reactions to
trimethoprim-sulfamethoxazole (
TMP-SMZ) prophylaxis and the subsequent course of human immunodeficiency virus (
HIV) infection in a cohort of homosexual men. Adverse reactions to
TMP-SMZ were associated with a more rapid progression to
AIDS (P < .001) and death (P < .001) and with a more rapid decline in CD4+ cell counts (P = .001). The median time to progression to
AIDS was 14.9 months in subjects with adverse reactions to
TMP-SMZ and 32.5 months in those without adverse reactions. After exclusion of
Pneumocystis carinii pneumonia (PCP) and
toxoplasmosis from the case definition of
AIDS, the differences in the rate of progression to
AIDS between subjects with and without adverse reactions to
TMP-SMZ were still highly significant (P = .004). A low CD4+ cell count at baseline and the use of
antiretroviral agents before the start of prophylaxis were predictors of adverse reactions to
TMP-SMZ but did not account for the difference in progression to
AIDS between subjects with and without adverse reactions to
TMP-SMZ. In a univariate analysis, the relative hazard of adverse reactions to
TMP-SMZ for progression to
AIDS was 2.54 (95% confidence interval [CI], 1.50-4.28); in a multivariate analysis, it was 2.21 (95% CI, 1.29-3.81). The relative hazards of adverse reactions to
TMP-SMZ for progression to
AIDS with the exclusion of PCP and
toxoplasmosis, CD4+ cell counts of <50/mm3, and death were 2.16 (95% CI, 1.25-3.72), 2.37 (95% CI, 1.36-4.12), and 3.21 (95% CI, 1.80-5.72), respectively. It is unclear whether adverse reactions to
TMP-SMZ induce or merely predict progression of HIV disease.