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The Influence of HLA on HIV-Associated Neurocognitive Impairment in Anhui, China
BACKGROUND: HLA-DR*04 was identified as a predictor of HIV-Associated neurocognitive disorder (HAND), low CD4 T-cell responses to HIV, and low plasma HIV RNA levels in a U.S. cohort. We hypothesized that low CD4 T-cell activation leads to poor immune control of HIV in the CNS, predisposing to HAND,...
Autores principales: | , , , , , , , , , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
Public Library of Science
2012
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3365058/ https://www.ncbi.nlm.nih.gov/pubmed/22693541 http://dx.doi.org/10.1371/journal.pone.0032303 |
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author | Schrier, Rachel D. Gupta, Saurabh Riggs, Patricia Cysique, Lucette A. Letendre, Scott Jin, Hua Spector, Stephen A. Singh, Kumud K. Wolfson, Tanya Wu, Zunyou Hong, Kun Xue Yu, Xin Shi, Chuan Heaton, Robert K. |
author_facet | Schrier, Rachel D. Gupta, Saurabh Riggs, Patricia Cysique, Lucette A. Letendre, Scott Jin, Hua Spector, Stephen A. Singh, Kumud K. Wolfson, Tanya Wu, Zunyou Hong, Kun Xue Yu, Xin Shi, Chuan Heaton, Robert K. |
author_sort | Schrier, Rachel D. |
collection | PubMed |
description | BACKGROUND: HLA-DR*04 was identified as a predictor of HIV-Associated neurocognitive disorder (HAND), low CD4 T-cell responses to HIV, and low plasma HIV RNA levels in a U.S. cohort. We hypothesized that low CD4 T-cell activation leads to poor immune control of HIV in the CNS, predisposing to HAND, but also provided fewer target (activated CD4 T-cells) for HIV replication. To assess the consistency of these HLA Class II associations in a new cohort and extend analysis to HLA Class I, HLA types, neurocognitive, and virologic status were examined in a cohort of former plasma donors in China. METHODS: 178 HIV infected individuals in Anhui China, were HLA typed and underwent neurocognitive evaluations (using locally standardized norms), neuromedical, treatment and virologic assessments at baseline and at 12 months. RESULTS: HLA DR*04 was associated with a higher rate of baseline neurocognitive impairment (p = 0.04), neurocognitive decline (p = 0.04), and lower levels of HIV RNA in plasma (p = 0.05). HLA Class I alleles (B*27,57,58,A*03,33) that specify a CD8 T-cell response to conserved HIV sequences were neuroprotective, associated with less impairment at baseline (p = 0.037), at month 012 (p = 0.013) and less neurocognitive decline (p = 0.023) in the interval. Consistent with the theory that effective CD8 T-cell responses require CD4 T-cell support, the HLA DR*04 allele reduced the neuroprotective effect of the Class I alleles. The presence of HLA-DR*04 and the Alzheimer associated allele ApoE4 in the same individual had a synergistic negative effect on cognition (p = 0.003). CONCLUSIONS: Despite major background differences between U.S. and Anhui China cohorts, HLA DR*04 predicted neurocognitive impairment and lower plasma HIV RNA levels in both populations. HLA Class I alleles associated with CD8 T-cell control of HIV were associated with protection from HAND, but protection was reduced in the presence of HLA-DR*04. |
format | Online Article Text |
id | pubmed-3365058 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2012 |
publisher | Public Library of Science |
record_format | MEDLINE/PubMed |
spelling | pubmed-33650582012-06-12 The Influence of HLA on HIV-Associated Neurocognitive Impairment in Anhui, China Schrier, Rachel D. Gupta, Saurabh Riggs, Patricia Cysique, Lucette A. Letendre, Scott Jin, Hua Spector, Stephen A. Singh, Kumud K. Wolfson, Tanya Wu, Zunyou Hong, Kun Xue Yu, Xin Shi, Chuan Heaton, Robert K. PLoS One Research Article BACKGROUND: HLA-DR*04 was identified as a predictor of HIV-Associated neurocognitive disorder (HAND), low CD4 T-cell responses to HIV, and low plasma HIV RNA levels in a U.S. cohort. We hypothesized that low CD4 T-cell activation leads to poor immune control of HIV in the CNS, predisposing to HAND, but also provided fewer target (activated CD4 T-cells) for HIV replication. To assess the consistency of these HLA Class II associations in a new cohort and extend analysis to HLA Class I, HLA types, neurocognitive, and virologic status were examined in a cohort of former plasma donors in China. METHODS: 178 HIV infected individuals in Anhui China, were HLA typed and underwent neurocognitive evaluations (using locally standardized norms), neuromedical, treatment and virologic assessments at baseline and at 12 months. RESULTS: HLA DR*04 was associated with a higher rate of baseline neurocognitive impairment (p = 0.04), neurocognitive decline (p = 0.04), and lower levels of HIV RNA in plasma (p = 0.05). HLA Class I alleles (B*27,57,58,A*03,33) that specify a CD8 T-cell response to conserved HIV sequences were neuroprotective, associated with less impairment at baseline (p = 0.037), at month 012 (p = 0.013) and less neurocognitive decline (p = 0.023) in the interval. Consistent with the theory that effective CD8 T-cell responses require CD4 T-cell support, the HLA DR*04 allele reduced the neuroprotective effect of the Class I alleles. The presence of HLA-DR*04 and the Alzheimer associated allele ApoE4 in the same individual had a synergistic negative effect on cognition (p = 0.003). CONCLUSIONS: Despite major background differences between U.S. and Anhui China cohorts, HLA DR*04 predicted neurocognitive impairment and lower plasma HIV RNA levels in both populations. HLA Class I alleles associated with CD8 T-cell control of HIV were associated with protection from HAND, but protection was reduced in the presence of HLA-DR*04. Public Library of Science 2012-05-31 /pmc/articles/PMC3365058/ /pubmed/22693541 http://dx.doi.org/10.1371/journal.pone.0032303 Text en Schrier et al. http://creativecommons.org/licenses/by/4.0/ This is an open-access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are properly credited. |
spellingShingle | Research Article Schrier, Rachel D. Gupta, Saurabh Riggs, Patricia Cysique, Lucette A. Letendre, Scott Jin, Hua Spector, Stephen A. Singh, Kumud K. Wolfson, Tanya Wu, Zunyou Hong, Kun Xue Yu, Xin Shi, Chuan Heaton, Robert K. The Influence of HLA on HIV-Associated Neurocognitive Impairment in Anhui, China |
title | The Influence of HLA on HIV-Associated Neurocognitive Impairment in Anhui, China |
title_full | The Influence of HLA on HIV-Associated Neurocognitive Impairment in Anhui, China |
title_fullStr | The Influence of HLA on HIV-Associated Neurocognitive Impairment in Anhui, China |
title_full_unstemmed | The Influence of HLA on HIV-Associated Neurocognitive Impairment in Anhui, China |
title_short | The Influence of HLA on HIV-Associated Neurocognitive Impairment in Anhui, China |
title_sort | influence of hla on hiv-associated neurocognitive impairment in anhui, china |
topic | Research Article |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3365058/ https://www.ncbi.nlm.nih.gov/pubmed/22693541 http://dx.doi.org/10.1371/journal.pone.0032303 |
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