Associations of Human Leukocyte Antigen G with Resistance and Susceptibility to HIV-Ilnfection in the Pumwani Sexworker Cohort

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Turk, William John Russell
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HlV/AIDS is currently a global pandemic with an estimated 33.3 million persons living with HlV / AIDS worldwide. One of the best hopes for eliminating the spread of HIV is in developing an effective vaccine. A group of sex trade workers in Pumwani, Kenya are resistant to HIV -1 infection despite frequent exposure and provide an example of natural protective irrununity. Human leukocyte antigens (HLA) class I and II molecules have been shown to be associated with resistance/susceptibility in this cohort. HLA-G is a non-classical class I allele that is primarily involved in mucosal and inflammatory defence. In this study, we examined the influence of HLA-G genotypes on the resistance to HlV -1 infection using a sequenced based method. The G*O 1:0 1:01 genotype was significantly associated with resistance to HIV-I infection (p-value 0.002, OR = 2.11, 95% CIO.259-0.976). The G*01:04:04 genotype was significantly associated with susceptibility to HlV-I infection (p-value 0.039, OR = 0.502, 95% CI 0.259-0.976). Kaplan-Meier survival analysis correlated with these results. G*01:01:01 genotype was associated with significantly slower rate of seroconversion. Alternatively, G*OI :04:04 genotype was significantly associated with an increased rate of seroconversion. Our study showed that functionally active HLA-G alleles play an important role in resistance/susceptibility to HIV -1 infection. Since HLA-G is important in mucosal and inflammatory responses further studies need to be conducted to better understand it's functional significance in HlV -1 transmission.