OBJECTIVE: To examine the association between mannose-binding lectin (MBL) polymorphism and progression to AIDS and death in HIV-1 infection. DESIGN AND METHODS: In 131 HIV-1-infected homosexual seroconverters, survival analyses were performed to determine both the association between MBL genotype and time from HIV-1 seroconversion to AIDS and death, and time from AIDS to death. RESULTS: Of the 131 seroconverters, of whom 61 developed AIDS, 76 were typed as homozygous wild-type and 55 as carriers of variant alleles (52 heterozygous and three homozygous variant alleles). A Survival analyses suggested that HIV-1-infected men with the variant alleles progressed somewhat slower to AIDS [relative hazard (RH), 0.62; 95% confidence interval (CI), 0.36-1.10] and death (RH, 0.73; 95% CI, 0.42-1.25). Interestingly, CD4+ T-cell count determined at the moment of AIDS was found to be significantly lower among persons with the mutation (97 x 10(6)/l versus 204 x 10(6)/l; P=0.03). Furthermore, when AIDS-free times before the diagnosis of an opportunistic infection were compared with those preceding a diagnosis of Kaposi's sarcoma, Kaposi's sarcoma diagnosis was more postponed than that of an opportunistic infection (RH, 0.21; 95% CI, 0.05-0.95; versus RH, 0.67; 95% CI, 0.35-1.27). CONCLUSION: Indications for a weak pre-AIDS protective effect of variant MBL alleles were demonstrated.