RESUMO
Genetic variation at the human leukocyte antigen (HLA) loci has been shown to be an important risk factor for progression to HIV disease, but its significance in infection is less well understood. We have investigated its role in HIV transmission in a cohort of individuals at risk for heterosexual infection. Analysis of over 80 individuals revealed that that the degree of concordance at HLA A, B, and DR loci differs significantly between transmitting and nontransmitting couples at risk for heterosexual HIV transmission (p <.02), suggesting that allogeneic immune responses may confer a degree of protection against HIV infection. Analysis of the frequencies of specific alleles at the A, B, and DR loci revealed a significantly higher frequency of HLA DR5 among exposed uninfected individuals, relative to population controls.
Assuntos
Infecções por HIV/transmissão , Antígenos HLA/genética , Alelos , Estudos de Coortes , Progressão da Doença , Suscetibilidade a Doenças , Feminino , Frequência do Gene , Genes Recessivos , Predisposição Genética para Doença , Variação Genética , Infecções por HIV/genética , Infecções por HIV/prevenção & controle , Antígenos HLA/imunologia , Antígenos HLA-A/genética , Antígenos HLA-A/imunologia , Antígenos HLA-B/genética , Antígenos HLA-B/imunologia , Antígenos HLA-DR/genética , Antígenos HLA-DR/imunologia , Heterossexualidade , Heterozigoto , Humanos , Masculino , Fatores de RiscoRESUMO
To assess the effect of mutations at the CCR-2 and CCR-5 loci on heterosexual human immunodeficiency virus (HIV) transmission, 144 persons heterosexually exposed to HIV (infected and uninfected [EU]) and 57 HIV-positive index partners were genotyped. A significantly higher frequency of 64I heterozygotes at CCR-2 was observed in HIV-positive than in EU women (P=.02, relative risk=1.6). The allele frequency of 64I in women was 8% in HIV-positive contacts and 1% in EUs (P<.02). At CCR-5, no difference in the frequency of Delta32 was seen between groups, and the CCR-5 genotypes did not differ in accumulated "at-risk" exposure in EUs. Combining the analysis of the Delta32 and 64I mutations in index partners suggested an additive effect on transmission (P=.10). Thus heterozygosity for 64I at CCR-2 acts as a risk factor for HIV infection of women after heterosexual contact but heterozygosity for Delta32 at CCR-5 has no detectable effect.