SUSCEPTIBILITY TO HIV-INFECTION AND PROGRESSION OF AIDS IN RELATION TO VARIANT ALLELES OF MANNOSE-BINDING LECTIN

Background Low serum concentrations of mannose-binding lectin (MBL) ar e associated with increased susceptibility to recurrent infection. Thr ee variant alleles in the MBL gene (B, C, and D), cause low serum conc entrations of the protein. We investigated whether variant alleles of MBL affect susceptibility to infection with HIV and progression of AID S. Methods Between 1983 and 1986, all men who attended two clinics in Copenhagen for HIV screening were invited to take part in our study. W e investigated the prevalence of variant alleles of MBL (detected by P CR) and assessed the prognostic value of these alleles and the corresp onding serum MBL concentrations (measured by ELISA) in 96 homosexual m en with HIV infection and in two control groups (123 healthy adults an d 36 HIV-negative homosexual men at high risk of HIV infection because of their sexual behaviour). Follow-up was for up to 10 years. Finding s Eight (8%) of the HIV-infected men were homozygous for the variant M BL alleles compared with one (0.8%) of the healthy controls (p=0.005) and none of the high-risk homosexual controls (p=0.05). We found no si gnificant association between MBL genotype and time from first positiv e HIV test to progression of AIDS (p=0.8). However, in the 61 HIV-infe cted men who developed AIDS, the median survival time was significantl y shorter after the AIDS diagnosis for men who were carriers of the va riant alleles (both homozygous and heterozygous) than for men homozygo us for the normal MBL allele (11 [IQR 4-21] vs 18 months [9-44], p=0.0 07). Among men who developed AIDS, there was a significant difference in survival time between those with serum MBL concentrations below the lower quartile, those within the IQR, and those above the upper quart ile (p=0.02). Multivariate analysis showed that men who developed AIDS and had low serum concentrations had an increased rate of rapid indep endently of CD4 T-cell counts at AIDS diagnosis. Interpretation Our fi ndings suggest that homozygous carriers of variant MBL alleles are at increased risk of HIV infection, either directly or indirectly because of increased susceptibility to coinfections. These alleles are also a ssociated with a significantly shorter survival time after a diagnosis of AIDS.