Protective effect of HLA-B∗ 5701 and HLA-C-35 genetic variants in HIV-positive Caucasians from Northern Poland

Abstract

Aim of the Study: Association of two HLA class I variants with HIV-1 pretreatment viremia, CD4+ T cell count at the care-entry and CD4+ T cell nadir. Methods: 414 HIV-positive Caucasians (30% women) aged 19-73 years were genotyped for HLA-C-35 (rs9264942) and HLA-B∗5701 variants. HIV-1 viral load, as well as CD4+ T cell count at care-entry and nadir, were compared across alleles, genotypes and haplotypes. Results: HLA-C -35 C/C genotype was found in 17.6% patients, C/T genotype in 48.1%, and T/T genotype in 34.3% patients. HLA-B∗5701 variant was present in 5.8% of studied population. HIV plasma viremia in the group with C allele was significantly lower (p=0.0002) compared to T/T group [mean:4.66 log (SD:1.03) vs. 5.07 (SD:0.85) log HIV-RNA copies/ml, respectively], while CD4+ T cell count at baseline was notably higher among C allele carriers compared to T/T homozygotes [median: 318 (IQR:127-537) cells/μl vs. median: 203 (IQR:55-410) cells/μl, respectively] (p=0.0007). Moreover, CD4+ T cell nadir among patients with C allele [median: 205 (IQR:83.5-390) cells/μl] was significantly higher compared to T/T group [median: 133 (IQR:46-328) cells/μl] (p=0.006). Among cases with HLA-B∗5701 allele, significantly lower pretreatment viremia and higher baseline CD4+ T cell count were found (mean: 4.08 [SD: 1.2] vs. mean: 4.84 [SD:0.97] log HIV-RNA copies/ml, p=0.003 and 431 vs. 270 cells/μl, p=0.04, respectively) compared to HLA-B∗5701 negative individuals. The lowest viremia (mean: 3.85 log [SD:1.3]) HIV-RNA copies/ml and the highest baseline and nadir CD4+ T cell [median: 476 (IQR:304-682) vs. median: 361 (IQR: 205-574) cells/μl, respectively) were found in individuals with HLA-B∗5701(+)/HLA-C-35 C/C haplotype. Conclusions: HLA-C -35 C and HLA-B∗5701 allele exert a favorable effect on the immunological (higher baseline and nadir CD4+ T cell count) and virologic (lower pretreatment HIV viral load) variables. This protective effect is additive for the compound HLA-B∗5701(+)/HLA-C -35 C/C haplotype.