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Although there have been many studies of gene variant association with different stages of HIV/AIDS progression in United States and European cohorts, few gene-association studies have assessed genic determinants in sub-Saharan African populations, which have the highest density of HIV infections worldwide. We carried out genome-wide association studies on 766 study participants at risk for HIV-1 subtype C (HIV-1C) infection in Botswana. Three gene associations (AP3B1, PTPRA, and NEO1) were shown to have significant association with HIV-1C acquisition. Each gene association was replicated within Botswana or in the United States-African American or United States-European American AIDS cohorts or in both. Each associated gene has a prior reported influence on HIV/AIDS pathogenesis. Thirteen previously discovered AIDS restriction genes were further replicated in the Botswana cohorts, extending our confidence in these prior AIDS restriction gene reports. This work presents an early step toward the identification of genetic variants associated with and affecting HIV acquisition or AIDS progression in the understudied HIV-1C afflicted Botswana population. [ABSTRACT FROM AUTHOR]

Allotypes of the natural killer (NK) cell receptor KIR3DL1 vary in both NK cell expression patterns and inhibitory capacity upon binding to their ligands, HLA-B Bw4 molecules, present on target cells. Using a sample size of over 1,500 human immunodeficiency virus (HIV)+ individuals, we show that various distinct allelic combinations of the KIR3DL1 and HLA-B loci significantly and strongly influence both AIDS progression and plasma HIV RNA abundance in a consistent manner. These genetic data correlate very well with previously defined functional differences that distinguish KIR3DL1 allotypes. The various epistatic effects observed here for common, distinct KIR3DL1 and HLA-B Bw4 combinations are unprecedented with regard to any pair of genetic loci in human disease, and indicate that NK cells may have a critical role in the natural history of HIV infection. [ABSTRACT FROM AUTHOR]

The article studies the influence of AIDS restriction genes and haplotypes of the CCR5 P1 promoter and RANTES variants among HIV-1 infected patients on highly active antiretroviral therapy in the Multicenter AIDS Cohort Study and the Multicenter Hemophilia Cohort Study. It examines a range of genes that were predicted to influence HAART through various interactions with the HIV life cycle and drug metabolism.

Reports the relative contributions to AIDS progression of three promoter haplotypes of CCR2-CCR5. Comparison of the rapid progression with a seroconverter control group including intermediate progressors to AIDS; Data indicating that factors other than CCR5 or CCR2 genetic variants must be responsible for the long-term maintenance of nonprogression.

The article presents a study on the effect of host genetics on human immunodeficiency virus neuroretinal disorder (HIV-NRD) in patients with AIDS. It notes the loss of contrast sensitivity that is sufficient to impair reading speed. It mentions the validated AIDS restriction gene variants in evaluating the effect of host genes on HIV-NRD which has been implicated to influence HIV-1 infection, AIDS progression, therapy response, and antiviral drug metabolism.