| Publication Abstract Display | | Type: Published Abstract | | Title: The influence of HLA on HIV associated neurocognitive impairment in Anhui, China. | | Authors: Schrier R, Gupta S , Rigg P, Cysique L, Letendre S, Jin H, Spector S, Singh K, Wolfson T , Wu Z, Hong K, Yu X, Shi C, Heaton RK, and the HNRC Group | | Year: 2011 | | Publication: 18th Conference on Retroviruses and Opportunistic Infections, Boston, Mass, 02-28-2011 | | Volume: Issue: Pages: | | Abstract:Background: Examination of HLA and HIV associated neurocogntive disorder (HAND) in the US suggested that HLA alleles coding for low CD4 responses (HLA DR*04) predicted HAND, but also lower HIV RNA. The proposed mechanism was that HLA encoded low CD4 T-cell activation limited HIV replication, but also reduced protective CD8 T-cell immune surveillance in the CNS. These studies were extended in a cohort in China.
Methods: 178 HIV+ individuals in Anhui China, who acquired HIV through plasma donation, were HLA typed and underwent annual neurocognitive evaluations using culturally standardized norms, correcting for practice effects. Neuromedical exams, plasma HIV RNA, lymphocyte counts, and anti-retroviral treatment status were assessed at baseline and 12 months of follow-up.
Results: Despite different cultural, educational and linguistic backgrounds from the US cohort, HLA DR*04 was associated with neurocognitive impairment (p=.04), HIV related neurocognitive decline (p=.04), and lower HIV RNA (p=.05) in the Anhui China cohort. Presence of protective HLA Class I alleles (A*03,33,B*27,57,58) was associated with less neurocognitive impairment at baseline (p=.037), month 012 (p=.013) and less decline p=.023. However, presence of the HLA DR*04 genotype reduced the neuroprotective effect of the Class I alleles. An unexpected synergistic effect on neurocognitive status for individuals with both HLA-DR*04 and the Alzheimer associated allele ApoE4 (p=.003) suggested that genetic influences on cognition are complex.
Conclusions: HLA DR*04 predicts neurocognitive impairment and decline, but also lower HIV RNA. Resistance to neurocognitive decline was associated with protective HLA Class I alleles, absence of HLA DR*04 and control of HIV RNA. |
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