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1.  The Influence of HLA on HIV-Associated Neurocognitive Impairment in Anhui, China 
PLoS ONE  2012;7(5):e32303.
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.
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.
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).
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.
PMCID: PMC3365058  PMID: 22693541
2.  Are Time- and Event-based Prospective Memory Comparably Affected in HIV Infection?† 
According to the multi-process theory of prospective memory (ProM), time-based tasks rely more heavily on strategic processes dependent on prefrontal systems than do event-based tasks. Given the prominent frontostriatal pathophysiology of HIV infection, one would expect HIV-infected individuals to demonstrate greater deficits in time-based versus event-based ProM. However, the two prior studies examining this question have produced variable results. We evaluated this hypothesis in 143 individuals with HIV infection and 43 demographically similar seronegative adults (HIV−) who completed the research version of the Memory for Intentions Screening Test, which yields parallel subscales of time- and event-based ProM. Results showed main effects of HIV serostatus and cue type, but no interaction between serostatus and cue. Planned pair-wise comparisons showed a significant effect of HIV on time-based ProM and a trend-level effect on event-based ProM that was driven primarily by the subset of participants with HIV-associated neurocognitive disorders. Nevertheless, time-based ProM was more strongly correlated with measures of executive functions, attention/working memory, and verbal fluency in HIV-infected persons. Although HIV-associated deficits in time- and event-based ProM appear to be of comparable severity, the cognitive architecture of time-based ProM may be more strongly influenced by strategic monitoring and retrieval processes.
PMCID: PMC3081684  PMID: 21459901
AIDS dementia complex; Episodic memory; Executive functions; Neuropsychological assessment
3.  195APOE ε4 and MBL-2 O/O Genotypes are Associated with Neurocognitive Impairment in HIV-Infected Plasma Donors from Anhui Province, China 
AIDS (London, England)  2010;24(10):1471-1479.
Host genetic factors are important determinants for risk of HIV-1 infection and disease progression. This study examined associations of host genetic variants and neurocognitive impairment in Chinese subjects infected through contaminated blood products.
201 HIV-infected subjects from Anhui, China had neuropsychological (NP) tests at baseline and 12 months. DNA was genotyped for APOE ε2, ε3 and ε4 alleles, MBL2-A/O,CCR5-wt/Δ32, CCR5-59029-G/A, CCR2-180-G/A, SDF-1-G/A, IL4-589-C/T, MCP-1-2518-A/G, CX3CR1-745-G/A, -849-C/T polymorphisms and CCL3L1 copy number variants (CNVs) using real-time PCR. Univariate and multivariate analyses were performed.
The cohort was 61% males, mean education: 5.5 years, AIDS diagnosis: 113(55%), on antiretrovirals: 114(56%), mean baseline CD4+ count: 349/mm3 and mean log10 RNA 4.09. At baseline, 37% had global NP impairment increasing to 44% after 12 months. Of 43 subjects with the APOE ε4 allele, 58% were cognitively impaired versus 31% without the ε4 allele (P=0.001, OR: 3.09; 95% CI: 1.54, 6.18). The mean GDS for ε4 positive participants on antiretrovirals for 12 months was 0.88 (0.55) versus 0.63 (.54) for ε4 negatives (P = 0.053, 95%CI: -0.004, 0.51). For MBL2, 52% of subjects with the O/O genotype declined in cognitive function over 12 months versus 23% with A/A (OR = 3.62. 95% CI: 1.46, 9.03; P=0.004). No associations were observed for the other genetic variants.
The APOE ε4 allele was associated with increased risk for cognitive deficits, while the MBL2 O/O genotype was associated with increased risk for progressive cognitive decline in Chinese subjects infected with HIV through contaminated blood products.
PMCID: PMC3063510  PMID: 20442634
APOE; MBL-2; HIV; cognitive impairment; host genetics; China
4.  Serum Interleukin-6 (IL-6), IL-10, Tumor Necrosis Factor (TNF) Alpha, Soluble Type II TNF Receptor, and Transforming Growth Factor Beta Levels in Human Immunodeficiency Virus Type 1-Infected Individuals with Mycobacterium avium Complex Disease 
Journal of Clinical Microbiology  2001;39(1):298-303.
To characterize changes in serum cytokine levels in human immunodeficiency virus type 1 (HIV-1)-infected persons with Mycobacterium avium complex (MAC) bacteremia, the levels of IL-1α (interleukin-1α), IL-6, IL-10, tumor necrosis factor alpha (TNF-α), soluble type II TNF receptor (sTNF-RII), and transforming growth factor β (TGF-β) in serum were measured in two cohorts of HIV-1-infected persons with MAC bacteremia. The first cohort was part of a MAC prophylaxis study. Patients with bacteremia were matched with controls without bacteremia. Elevated IL-6, IL-10, TNF-α, sTNF-RII, and TGF-β levels were noted at baseline for all subjects, a result consistent with advanced HIV-1 disease. IL-1α was not detected. No differences in cytokine levels in serum were noted at baseline and at the time of bacteremia between patients with MAC and controls. In the second cohort, subjects had serum samples collected at the time of MAC bacteremia and thereafter while on macrolide therapy. Serum samples at time of bacteremia were collected from HIV-1-infected persons at a time when neither highly active antiretroviral therapy (HAART) nor MAC prophylaxis was used routinely. MAC treatment resulted in decreased levels of IL-6 and TNF-α in serum, which were evident for IL-6 by 4 to 6 weeks and for TNF-α by 8 to 16 weeks. Thus, antibiotic treatment for MAC results in decreased levels of IL-6 and TNF-α in serum in HIV-1-infected persons who are not on HAART.
PMCID: PMC87718  PMID: 11136787

Results 1-4 (4)