Synergy between mannose-binding lectin gene polymorphisms and supplementation with vitamin A influences susceptibility to HIV infection in infants born to HIV-positive mothers.

Mannose-binding lectin (MBL-2) allele variants are associated with deficiencies in innate immunity and have been found to be correlated with HIV infection in adults and children. We tested whether MBL-2 variants among infants born to HIV-positive mothers have an increased susceptibility to HIV. MBL-2 allele variants were measured among 225 infants born to HIV-positive mothers enrolled in a trial in Durban, South Africa. Mothers of 108 infants were randomly assigned to receive vitamin A and beta-carotene supplementation and 117 to receive placebo. Infants were followed with regular HIV tests to determine rates of mother-to-child HIV transmission. A high proportion of infants were either homozygous (10.7%) or heterozygous (32.4%) for MBL-2 variants. MBL-2 variants within the placebo arm were associated with an increased risk of HIV transmission (odds ratio: 3.09; 95% CI: 1.21, 7.86); however, MBL-2 variants within the supplementation arm were not associated with an increased risk of transmission (P = 0.04; test of interaction). Among infants with MBL-2 variants, supplementation was associated with a decreased risk of HIV transmission (odds ratio: 0.37; 95% CI: 0.15, 0.91). We observed what appears to be a gene-environment interaction between MBL-2 variants and an intervention with vitamin A plus beta-carotene that is relevant to mother-to-child HIV transmission.