HLA gene loci associated with HIV load in csf and blood plasma in the CHARTER cohort.

Type: Published Abstract
Title: HLA gene loci associated with HIV load in csf and blood plasma in the CHARTER cohort.
Authors: Gelman BB, Ahuja S, Ellis R, Letendre S, Marra C, McArthur J, Morgello S, Clifford D, Grant I, Vaida F
Year: 2014
Publication: Conference on Retroviruses and Opportunistic Infections

Background: Certain polymorphic gene loci in the major histocompatibility complex (HLA) are associated with better control of HIV loading in the blood plasma of patients with European ancestries, but not African ancestries. To determine whether HLA alleles influence HIV replication in the CNS we compared cerebrospinal fluid (CSF) HIV with HLA genotypes.

Methods: HLA-C*-35 (rs9264942) and HLA-B*5701 (rs2395029) were typed using PCR in 564 DNA isolates from HIV-infected patients in the USA CHARTER cohort. HIV gag/pol RNA log10 copy number per ml data was obtained and differences with versus without HLA alleles were assessed using Fisher’s exact test, T test, or Wilcoxon rank sum test. Results: Cross sectional analysis of 48 treatment naïve European subjects showed that the C allele of HLA-C*-35 was associated with lower HIV loading in blood plasma (TT = 4.45, CT = 4.30, CC = 3.60, p < 0.034) but not in CSF (p = 0.61). In 205 European subjects given HAART, HLA-C*-35 was not associated significantly with HIV loads.

Results: For HLA-B*5701 positivity in treatment naïve Europeans resembled HLA-C*-35 results for plasma (+ = 4.49, - = 3.19, p < 0.032) and CSF HIV (p = 0.20). No association between HLA type and HIV loading was present in 33 treatment naïve patients with African ancestries. In 164 treated Africans the C allele of HLA-C*-35 exhibited an unexpected association with greater detection of HIV (worse HIV control) (plasma, p < 0.012; CSF, p < 0.022).

Conclusions: In accord with other reports HLA-C*-35/C and HLA-B*5701/+ alleles provided better control of HIV loading in plasma of treatment naïve Europeans, and this association is not observed in treatment naïve Africans. The same association using CSF HIV instead of plasma HIV was not significant. In treated Europeans HLA genes do not confer an obvious benefit towards improving virological control, likely because the treatment effect overshadows the genetic effect. Unlike treated Europeans the treated Africans with HLA-C*-35 C alleles paradoxically exhibited an innate blunting of the beneficial virological effect of treatment in the two body compartments.