Host genetics influences HIV reservoir persistence, treatment outcomes and CCR5 expression in patients on long-term antiretroviral therapy in Ghana

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Objective This study investigated influence of cysteine-cysteine chemokines (CCR5, CCR5-59029A/G, CCR2), and stoma cell derived factor 1 (SDF1); as AIDS restriction genes (ARGs), on treatment outcomes among people with HIV (PWH) on long term antiretroviral therapy (ART) in Ghana. Methods This cross-sectional study was conducted among 167 PWH and receiving ART in Accra, Ghana. Genomic DNA from PBMCs was used to genotype CCR5-Δ32, CCR2-V64I, CCR5 A59029G, and SDF1-3′A variants using polymerase chain reaction-restriction fragment length polymorphism, CCR5 expression was estimated by RT-qPCR. Results All participants carried the wild-type CCR5 genotype. No AIDS Restriction Genes was associated with virologic or immunological outcomes ( p >0.05). However, individuals with the CCR5 A59029G GG genotype exhibited significantly higher proviral DNA levels than those with the AA genotype ( p < 0.05), and the GG genotype independently predicted higher proviral DNA burden in multivariable analysis (β = 0.840, p = 0.011). Conclusion No ARG variant was significantly associated with virologic or immunological outcomes. However, CCR5 A59029G was associated with differences in proviral DNA burden and CCR5 mRNA expression, suggesting a potential role in HIV reservoir dynamics during suppressive ART.

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