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Background  Immunological and clinical outcomes can vary considerably at the individual and population levels during both treated and untreated HIV-1 infection. Cytokines encoded by the interleukin-10 gene ( IL10)  family have broad immunomodulatory function in viral persistence, and several SNPs in the  IL10  promoter sequence have been reported to influence pathogenesis or acquisition of HIV-1 infection.    Methodology/Principal Findings  We examined 104 informative SNPs in  IL10, IL19, IL20, IL24, IL10RA  and  IL10RB  among 250 HIV-1 seropositive and 106 high-risk seronegative African American adolescents in the REACH cohort. In subsequent evaluation of five different immunological and virological outcomes related to HIV-1 infection, 25 SNPs were associated with a single outcome and three were associated with two different outcomes. One SNP, rs2243191 in the  IL19  open reading frame (Ser to Phe substitution) was associated with CD4 +  T-cell increase during treatment. Another SNP rs2244305 in  IL10RB  (in strong linkage disequilibrium with rs443498) was associated with an initial decrease in CD4 +  T-cell by 23±9% and 29±9% every 3 months (for AA and AG genotypes, respectively, compared with GG) during ART-free period. These associations were reversed during treatment, as CD4 +  T-cell increased by 31±0.9% and 17±8% every 3 months for AA and AG genotype, respectively.    Conclusions/Significance  In African Americans, variants in  IL10  and related genes might influence multiple outcomes of HIV-1 infection, especially immunological response to HAART. Fine mapping coupled with analysis of gene expression and function should help reveal the immunological importance of the  IL10  gene family to HIV-1/AIDS.

Interleukin-10 (IL-10) Pathway: Genetic Variants and Outcomes of HIV-1 Infection in African American Adolescents