7 research outputs found
Lipid levels in HIV-positive men receiving anti-retroviral therapy are not associated with copy number variation of reverse cholesterol transport pathway genes
Contribution of genetic background, traditional risk factors, and HIV-related factors to coronary artery disease events in HIV-positive persons.
BACKGROUND: Persons infected with human immunodeficiency virus (HIV) have increased rates of coronary artery disease (CAD). The relative contribution of genetic background, HIV-related factors, antiretroviral medications, and traditional risk factors to CAD has not been fully evaluated in the setting of HIV infection.
METHODS: In the general population, 23 common single-nucleotide polymorphisms (SNPs) were shown to be associated with CAD through genome-wide association analysis. Using the Metabochip, we genotyped 1875 HIV-positive, white individuals enrolled in 24 HIV observational studies, including 571 participants with a first CAD event during the 9-year study period and 1304 controls matched on sex and cohort.
RESULTS: A genetic risk score built from 23 CAD-associated SNPs contributed significantly to CAD (P = 2.9 × 10(-4)). In the final multivariable model, participants with an unfavorable genetic background (top genetic score quartile) had a CAD odds ratio (OR) of 1.47 (95% confidence interval [CI], 1.05-2.04). This effect was similar to hypertension (OR = 1.36; 95% CI, 1.06-1.73), hypercholesterolemia (OR = 1.51; 95% CI, 1.16-1.96), diabetes (OR = 1.66; 95% CI, 1.10-2.49), ≥ 1 year lopinavir exposure (OR = 1.36; 95% CI, 1.06-1.73), and current abacavir treatment (OR = 1.56; 95% CI, 1.17-2.07). The effect of the genetic risk score was additive to the effect of nongenetic CAD risk factors, and did not change after adjustment for family history of CAD.
CONCLUSIONS: In the setting of HIV infection, the effect of an unfavorable genetic background was similar to traditional CAD risk factors and certain adverse antiretroviral exposures. Genetic testing may provide prognostic information complementary to family history of CAD
Differential subcutaneous adipose tissue gene expression patterns in a randomized clinical trial of efavirenz or lopinavir-ritonavir in antiretroviral-naive patients
10.1128/AAC.03481-14Gene expression studies of subcutaneous adipose tissue may help to better understand the mechanisms behind body fat changes in HIV-infected patients who initiate antiretroviral therapy (ART). Here, we evaluated early changes in adipose tissue gene expression and their relationship to fat changes in ART-naive HIV-infected patients randomly assigned to initiate therapy with emtricitabine/tenofovir plus efavirenz (EFV) or ritonavir-boosted lopinavir (LPV/r). Patients had abdominal subcutaneous adipose tissue biopsies at baseline and week 16 and dual-energy-X-ray absorptiometry at baseline and weeks 16 and 48. mRNA changes of 11 genes involved in adipogenesis, lipid and glucose metabolism, mitochondrial energy, and inflammation were assessed through reverse transcription-quantitative PCR (RT-qPCR). Additionally, correlations between gene expression changes and fat changes were evaluated. Fat increased preferentially in the trunk with EFV and in the limbs with LPV/r (P < 0.05). After 16 weeks of exposure to the drug regimen, transcripts of CEBP/A, ADIPOQ, GLUT4, LPL, and COXIV were significantly downregulated in the EFV arm compared to the LPV/r arm (P < 0.05). Significant correlations were observed between LPL expression change and trunk fat change at week 16 in both arms and between CEBP/A or COXIV change and trunk fat change at the same time point only in the EFV arm and not in the LPV/r arm. When combined with emtricitabine/tenofovir as standard backbone therapy, EFV and LPV/r induced differential early expression of genes involved in adipogenesis and energy metabolism. Moreover, these mRNA expression changes correlated with trunk fat change in the EFV arm. (This was a substudy of a randomized clinical trial [LIPOTAR study] registered at ClinicalTr
Elevated expression of miR-146a correlates with high levels of immune cell exhaustion markers and suppresses cellular immune function in chronic HIV-1-infected patients
MicroRNA Profile in CD8+ T-Lymphocytes from HIV-Infected Individuals: Relationship with Antiviral Immune Response and Disease Progression
Background
The relationship between host microRNAs (miRNA), viral control and immune response
has not yet been elucidated in the field of HIV. The aim of this study was to assess the differential
miRNA profile in CD8+ T-cells between HIV-infected individuals who differ in terms of
viral replication control and immune response.
Methods
miRNA profile from resting and CD3/CD28-stimulated CD8+ T-cells from uninfected individuals
(HIV-, n = 11), Elite Controllers (EC, n = 15), Viremic Controllers (VC, n = 15), Viremic
Progressors (VP, n = 13) and HIV-infected patients on therapy (ART, n = 14) was assessed
using Affymetrix miRNA 3.1 arrays. After background correction, quantile normalization and
median polish summarization, normalized data were fit to a linear model. The analysis comprised:
resting samples between groups; stimulated samples between groups; and stimulated
versus resting samples within each group. Enrichment analyses of the putative target
genes were perfomed using bioinformatic algorithms.
Results
A downregulated miRNA pattern was observed when resting samples from all infected
groups were compared to HIV-. A miRNA downregulation was also observed when stimulated
samples from EC, ART and HIV- groups were compared to VP, being hsa-miR-4492
the most downregulated. Although a preferential miRNA downregulation was observed
when stimulated samples were compared to the respective resting samples, VP presented
a differential miRNA expression pattern. In fact, hsa-miR-155 and hsa-miR-181a were
downregulated in VP whereas in the other groups, either an upregulation or no differences
were observed after stimulation, respectively. Overall, functional enrichment analysis
revealed that the predicted target genes were involved in signal transduction pathways,
metabolic regulation, apoptosis, and immune response.
Conclusions
Resting CD8+ T-cells do not exhibit a differential miRNA expression between HIV-infected
individuals but they do differ from non-infected individuals. Moreover, a specific miRNA pattern
is present in stimulated CD8+ T-cells from VP which could reflect a detrimental pattern
in terms of CD8+ T-cell immune response