HIV infection significantly reduces lipoprotein lipase which remains low after 6 months of antiretroviral therapy

Purpose of the study Fractional clearance rate of apolipoprotein B100-containing lipoproteins is reduced in HIV infection before and after antiretroviral (ARV) treatment [1]. We compared lipoprotein lipase (LPL) activity and gene expression in HIV-positive subjects before and 6 months after ARV with HIV-negative controls. Methods Fasting blood post heparin total and hepatic lipase activity,adiponectin, leptin, insulin, glucose, and lipid measurementswere made in 32 HIV-infected and 15 HIVnegative controls. LPL was estimated by subtractinghepatic lipase from total lipase. Adiponectin, LPL andhormone sensitive lipase (HSL) gene expression weremeasured from iliac crest subcutaneous fat biopsies.Patients were tested before, and 6 months after randomisation to AZT/3TC (n = 15) or TDF/FTC (n = 17) with EFV.Between-group comparison was by Mann-Whitney andpaired samples by the Wilcoxon signed rank tests. Summary of results There were no differences in gender, ethnicity, baseline BMI, regional fat distribution (whole body DEXA) and visceral (VAT) and subcutaneous fat (SAT) measured by abdominal CT scans between controls and patients. Trunk fat/BMI ratio, VAT and VAT:SAT ratio significantly increased after 6-month ARV therapy (p = 0.01). There were no differences between groups in serum NEFA,HOMA and leptin levels. Selected other results are shown in Table 1. Conclusion Post heparin lipoprotein lipase activity is reduced in HIV and does not return to control levels after 6 months of ARV therapy. AZT-containing regimens are associated with a greater increase in LPL, LPL gene expression and plasma adiponectin than TDF

Differential adipose tissue gene expression profiles in abacavir treated patients that may contribute to the understanding of cardiovascular risk: a microarray study

OBJECTIVE:To compare changes in gene expression by microarray from subcutaneous adipose tissue from HIV treatment naïve patients treated with efavirenz based regimens containing abacavir (ABC), tenofovir (TDF) or zidovidine (AZT). DESIGN:Subcutaneous fat biopsies were obtained before, at 6- and 18-24-months after treatment, and from HIV negative controls. Groups were age, ethnicity, weight, biochemical profile, and pre-treatment CD4 count matched. Microarray data was generated using the Agilent Whole Human Genome Microarray. Identification of differentially expressed genes and genomic response pathways was performed using limma and gene set enrichment analysis. RESULTS:There were significant divergences between ABC and the other two groups 6 months after treatment in genes controlling cell adhesion and environmental information processing, with some convergence at 18-24 months. Compared to controls the ABC group, but not AZT or TDF showed enrichment of genes controlling adherence junction, at 6 months and 18-24 months (adjusted p<0.05) and focal adhesions and tight junction at 6 months (p<0.5). Genes controlling leukocyte transendothelial migration (p<0.05) and ECM-receptor interactions (p = 0.04) were over-expressed in ABC compared to TDF and AZT at 6 months but not at 18-24 months. Enrichment of pathways and individual genes controlling cell adhesion and environmental information processing were specifically dysregulated in the ABC group in comparison with other treatments. There was little difference between AZT and TDF. CONCLUSION:After initiating treatment, there is divergence in the expression of genes controlling cell adhesion and environmental information processing between ABC and both TDF and AZT in subcutaneous adipose tissue. If similar changes are also taking place in other tissues including the coronary vasculature they may contribute to the increased risk of cardiovascular events reported in patients recently started on abacavir-containing regimens

The multi-dimensional scaling plot (MDS) shows that by and large ABC 6 and ABC 18–24 samples are separated from other samples in the study.

<p>Distances in the plot represent root-mean-square deviation (Euclidean distance) for the top 500 genes that best distinguish those samples.</p

Differentially expressed sequences between groups at 6 months and 18–24 months.

<p>Differentially expressed sequences between groups at 6 months and 18–24 months.</p

Volcano plot showing significance versus fold changes in the y- and x-axis respectively for the three treatment groups at 6 months on top row (a-c) and 18 months on bottom row (d-f).

<p>For each comparison the first term is the numerator and the second denominator.</p