Initiation of an Abacavir-Containing Regimen in HIV-Infected Adults Is Associated with a Smaller Decrease in Inflammation and Endothelial Activation Markers Compared to Non-Abacavir-Containing Regimens.
1 MetroHealth Medical Center , Cleveland, Ohio.AIDS research and human retroviruses (Impact Factor: 2.33). 04/2012; 28(12). DOI: 10.1089/AID.2012.0034
Abstract Abacavir has been associated with myocardial infarction in several studies. This may be related to inflammation and endothelial cell activation. We compared changes in inflammation and endothelial activation markers between antiretroviral-naive adults initiating zidovudine, lamivudine, abacavir, and nonnucleoside reverse transcriptase inhibitor (NNRTI) or this regimen without abacavir. Changes in soluble tumor necrosis factor receptors-I, -II (sTNFR-I, -II), high sensitivity C-reactive protein, and soluble vascular cell adhesion molecule-1 (sVCAM-1) from baseline (pre-ART) to a second time point about 24 weeks after initiating antiretroviral therapy (ART) were compared between groups using multivariable linear regression. A total of 37 met eligibility criteria; 12 received abacavir. The median (interquartile range) age was 37 years (27-45). Most were men (32/37), African-American (15/37), or white (15/37). The median nadir CD4(+) and baseline HIV-1 RNA were 230 cells/mm(3) (180-301) and 82,642 copies/ml (34,400-204,703). In all, 15/30 smoked, 7/37 had hypertension, 1/37 had diabetes, and 1/37 had hyperlipidemia. None had coronary or renal disease. Changes in CD4(+) and HIV-1 RNA level and timing of stored samples with regard to ART initiation were not different between groups. In univariable analysis, log transformed percent change in sTNFR-I (p=0.05) and -II (p=0.04) showed significant between-group differences and trended toward significance for sVCAM-1 (p=0.08). These markers decreased less in the abacavir group. After adjustment for confounders, significantly less decrease for sTNFR-II and sVCAM-1 was seen for those receiving the abacavir-containing regimen. When taken with an NNRTI, abacavir induced a smaller decrease in inflammation biomarkers in this cohort, suggesting a possible proinflammatory effect of this nucleoside analogue.
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- "Linked to inflammation is altered coagulation, proposed as a mechanism to explain the association between the guanosine analogue ABC and MI. Initiation of an ABC-containing ART was associated with smaller reductions in inflammatory markers than ART not containing ABC, although this is not a consistent finding across studies. In vitro, ABC increases the adhesion of leukocytes to endothelial cells, through leucocyte activationand also increased platelet reactivity through inhibition of soluble guanylyl cyclase. "
ABSTRACT: As a result of major advances in the management of HIV over the last two decades, patients living with HIV are now encountering comorbidities commonly associated with aging. Cardiovascular disease is the leading cause of death worldwide. As the population living with HIV ages, understanding cardiovascular disease in the setting of HIV is of increasing importance. This review examines the complex interplay between cardiovascular disease, HIV infection and the drugs used to treat it, with particular emphasis on the contribution of dyslipidemia.
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ABSTRACT: Soluble CD14 (sCD14) is a monocyte activation marker associated with increased mortality in HIV infection. We assessed 48-week changes in sCD14 and other inflammatory biomarkers in virologically suppressed, HIV-infected women switching to raltegravir (RAL) from a protease inhibitor (PI) or nonnucleoside reverse transcriptase inhibitor (NNRTI). HIV-infected women with central adiposity and HIV-1 RNA < 50 HIV-1 RNA copies/mL continued their thymidine-sparing nucleoside reverse transcriptase inhibitor (NRTI) backbone and were randomized to switch to open-label RAL at week 0 (immediate) or 24 (delayed). In an exploratory analysis, inflammatory biomarkers were measured on stored fasting plasma. Of the 37 evaluable subjects, 78% were non-White; the median age was 43 years, the median body mass index (BMI) was 32 kg/m(2) and the median CD4 count was 558 cells/μL. At baseline, biomarker values were similar between groups. After 24 weeks, median sCD14 significantly declined in subjects switching to RAL [-21% (P < 0.001) vs. PI/NNRTI -5% (P = 0.49); between-group P < 0.01]. After 48 weeks, immediate-switch subjects maintained this decline and delayed-switch subjects experienced a similar decline following the switch to RAL (-10%; within-group P < 0.01). Immediate-switch subjects also experienced an initial increase in tumour necrosis factor (TNF)-α that was neither maintained after 48 weeks nor seen in delayed-switch subjects. After adjustment for multiple testing, only declines in sCD14 remained significant. In this randomized trial of women with central adiposity, a switch to RAL from a PI or NNRTI was associated with a statistically significant decline in sCD14. Further studies are needed to determine whether integrase inhibitors have improved monocyte activation profiles compared with PIs and/or NNRTIs, and whether measured differences between antiretroviral agents translate to demonstrable clinical benefit.
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ABSTRACT: The objective of this review is to appraise recently published literature that describes the relationship between HIV, biologic and environmental risk factors, and cardiovascular disease (CVD) risk with particular emphasis on the aging HIV population and to demonstrate that these biologic and environmental factors may interact to increase the risk of CVD in the HIV population. The mechanisms linking HIV and CVD are multifactorial and encompass biological and 'environmental' modalities including multimorbid conditions that co-occur with HIV, immunologic alterations associated with HIV, polypharmacy (which affects adherence and increases likelihood of adverse drug-drug interactions) and healthcare disparities in CVD risk reduction by HIV status. Data regarding optimal treatment strategies that balance immunological restoration and CVD risk reduction are needed.
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