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, 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.
Department of Pathology, University of California San Diego, La Jolla, California, United States of America. rschrier@ucsd.edu
Rachel D
RD
Schrier
Saurabh
S
Gupta
Patricia
P
Riggs
Lucette A
LA
Cysique
Scott
S
Letendre
Hua
H
Jin
Stephen A
SA
Spector
Kumud K
KK
Singh
Tanya
T
Wolfson
Zunyou
Z
Wu
Kun Xue
KX
Hong
Xin
X
Yu
Chuan
C
Shi
Robert K
RK
Heaton
D015526:AIDS Dementia Complex / Q000150:complications* / Q000235:genetics / Q000276:immunology*; D000483:Alleles; D053327:Apolipoprotein E4 / Q000235:genetics; D001782:Blood Donors; D002681:China; D003072:Cognition Disorders / Q000097:blood / Q000150:complications* / Q000276:immunology* / Q000821:virology; D015331:Cohort Studies; D005260:Female; D014644:Genetic Variation; D015658:HIV Infections / Q000150:complications* / Q000276:immunology; D006684:HLA-DR Antigens / Q000235:genetics* / Q000276:immunology; D006801:Humans; D008297:Male; D012367:RNA, Viral / Q000097:blood; D014766:Viremia / Q000150:complications
D053327:Apolipoprotein E4; D006684:HLA-DR Antigens; D012367:RNA, Viral