HIV-1 transmitters (men with hemophilia) and recipients (their female partners) showed different patterns of HLA associations. In the men, B*35 (especially B*35Px, though B*35PY also tended in the same direction) was detected as a high-risk allele for HIV-1 transmission, whereas B*27 and B*57 were associated with low risk. In female partners, none of the previously detected AIDS-regulating HLA alleles showed an association with susceptibility to HIV-1 infection, consistent with a model in which HLA class I diversity affects outcome after HIV infection, but not infection itself. Although our sample size was small, there were no consistent tendencies for effects of these alleles on infection with those observed for viral load control, AIDS progression, and transmission. Our study was largely composed of European Americans infected with clade B virus, such that our results pertain to this ethnic group. Nevertheless, our data concur with a recent report showing that HLA alleles/haplotypes associated with transmission in an African cohort do not associate with acquisition in their heterosexual partners . The different patterns of genetic associations illustrate that HIV-1 transmission and susceptibility to infection involve different host/viral mechanisms and, therefore, are subject to different genetic influences.
Our null data on susceptibility of heterosexual acquisition of HIV-1 infection among women are also consistent with a study on HLA and mother-to-infant HIV-1 transmission in which the HLA-B genotype of the recipient (the infant) did not alter the risk of transmission, whereas the HLA-B genotype of the HIV transmitter (the mother) was associated with varied risks for HIV-1 transmission . If there is indeed an effect of HLA polymorphism on susceptibility to HIV-1 infection, it may very well differ from that for viral transmission. For example, MHC polymorphism might affect susceptibility by influencing innate immunity against HIV-1 infection through specific interactions with KIR. A larger sample with more HIV-1-infected women is needed to test this hypothesis.
We would like to thank Dr Pat Martin for helpful comments regarding this article. This project has been funded in whole or in part with federal funds from the National Cancer Institute, National Institutes of Health, under Contract No. HHSN261200800001E. The content of this publication does not necessarily reflect the views or policies of the Department of Health and Human Services, nor does mention of trade names, commercial products, or organizations imply endorsement by the US Government. This research was supported in part by the Intramural Research Program of the NIH, National Cancer Institute, Center for Cancer Research.
The MACS is funded by the National Institute of Allergy and Infectious Diseases, with additional supplemental funding from the National Cancer Institute; and the National Heart, Lung, and Blood Institute: UO1-AI-35042, 5-M01-RR-00052 (GCRC), UO1-AI-35043, UO1-AI-37984, UO1-AI-35039, UO1-AI-35040, UO1-AI-37613, and UO1-AI-35041.
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