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Combination of niacin and fenofibrate with lifestyle changes improves dyslipidemia and hypoadiponectinemia in HIV patients on antiretroviral therapy: results of "heart positive," a randomized, controlled trial.

ABSTRACT: HIV patients on antiretroviral therapy (ART) have a unique dyslipidemia [elevated triglycerides and non-high-density lipoprotein-cholesterol (HDL-C), low HDL-C] with insulin resistance (characterized by hypoadiponectinemia).The aim was to test a targeted, comprehensive, additive approach to treating the dyslipidemia.We conducted a randomized, double-blind, placebo-controlled, 24-wk trial of lifestyle modification, fenofibrate, and niacin in multiethnic HIV clinics at an academic center.Hypertriglyceridemic adult patients were stratified on three combinations of ART classes. Subjects retained at the first measurement (2 wk) after entry were included in the analysis (n = 191).Subjects were randomized into five treatment groups: usual care (group 1); low-saturated-fat diet and exercise (D/E; group 2); D/E + fenofibrate (group 3); D/E + niacin (group 4); or D/E + fenofibrate + niacin (group 5).We measured changes in fasting triglycerides, HDL-C, and non-HDL-C (primary), and in insulin sensitivity, glycemia, adiponectin, C-reactive protein, energy expenditure, and body composition (secondary). Data were analyzed as a factorial set of treatment combinations using a mixed repeated measures model, last observation carried forward, and complete case approaches (groups 2-5), and as an unstructured set of treatments (groups 1-5).Fenofibrate improved triglycerides (P = 0.002), total cholesterol (P = 0.02), and non-HDL-C (P = 0.003), whereas niacin improved HDL-C (P = 0.03), and both drugs decreased the total cholesterol-to-HDL-C ratio (P = 0.005-0.01). The combination of D/E, fenofibrate, and niacin provided maximal benefit, markedly reducing triglycerides (-52% compared to usual care; P = 0.003), increasing HDL-C (+12%; P < 0.001), and decreasing non-HDL-C (-18.5%; P = 0.003) and total cholesterol-to-HDL-C ratio (-24.5%; P < 0.001). Niacin doubled adiponectin levels.A combination of fenofibrate and niacin with low-saturated-fat D/E is effective and safe in increasing HDL-C, decreasing non-HDL-C and hypertriglyceridemia, and ameliorating hypoadiponectinemia in patients with HIV/ART-associated dyslipidemia.

SUBMITTER: Balasubramanyam A

PROVIDER: S-EPMC3135191 | biostudies-literature | 2011 Jul

REPOSITORIES: biostudies-literature

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Combination of niacin and fenofibrate with lifestyle changes improves dyslipidemia and hypoadiponectinemia in HIV patients on antiretroviral therapy: results of "heart positive," a randomized, controlled trial.

Balasubramanyam Ashok A Coraza Ivonne I Smith E O'Brian EO Scott Lynne W LW Patel Payal P Iyer Dinakar D Taylor Addison A AA Giordano Thomas P TP Sekhar Rajagopal V RV Clark Pamela P Cuevas-Sanchez Edith E Kamble Swarna S Ballantyne Christie M CM Pownall Henry J HJ

The Journal of clinical endocrinology and metabolism 20110511 7

<h4>Context</h4>HIV patients on antiretroviral therapy (ART) have a unique dyslipidemia [elevated triglycerides and non-high-density lipoprotein-cholesterol (HDL-C), low HDL-C] with insulin resistance (characterized by hypoadiponectinemia).<h4>Objective</h4>The aim was to test a targeted, comprehensive, additive approach to treating the dyslipidemia.<h4>Design and setting</h4>We conducted a randomized, double-blind, placebo-controlled, 24-wk trial of lifestyle modification, fenofibrate, and niac ...[more]

PMID: 21565796

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Project description:IMPORTANCE:Dyslipidemia in young adults in the United States during their childbearing years is common, and the consequences for the next generation are poorly understood. Further understanding of the harmful consequences of elevated low-density lipoprotein cholesterol (LDL-C) levels in young adults may help to inform population screening and management strategies. OBJECTIVE:To examine whether adult levels of serum LDL-C are associated with maternal prepregnancy LDL-C levels beyond that attributable to inherited genetic sequence polymorphisms, diet, physical activity, and body mass index. DESIGN, SETTING, AND PARTICIPANTS:The Framingham Heart Study is a multigenerational, population-based inception cohort initiated in 1948 in Framingham, Massachusetts. In this study of families, the analyses included 538 parent-offspring pairs with parental LDL-C levels measured in the study prior to the offspring's birth. Parental prebirth, parental concurrent, and adult offspring assessments occurred in 1971-1983, 1998-2001, and 2002-2005, respectively. Data analyses were conducted between March 1, 2013, and May 30, 2015. EXPOSURES:Maternal prepregnancy LDL-C levels compared with paternal prepregnancy and parental concurrent LDL-C levels in association with adult offspring LDL-C levels. MAIN OUTCOMES AND MEASURES:Adult offspring LDL-C levels were examined as both a continuous and dichotomous outcome (using a threshold of 130 mg/dL). RESULTS:Among the 538 parent-offspring pairs, there were 241 mother-offspring and 297 father-offspring pairs with a mean (SD) offspring age of 26 (3) years. Adult offspring LDL-C levels were associated with maternal prepregnancy LDL-C levels after adjustment for family relatedness and offspring lifestyle, anthropometric factors, and inherited genetic variants (??=?0.32 [SE, 0.05] mg/dL; P?<?.001). After multivariable adjustment, adults who had been exposed to elevated maternal prepregnancy LDL-C levels were at a 3.8 (95% CI, 1.5-9.8) times higher odds of having elevated LDL-C levels (P?=?.005) and had an adjusted LDL-C level of 18 mg/dL (95% CI, 9-27 mg/dL) higher than did those without such exposure. Maternal prepregnancy LDL-C levels explained 13% of the variation in adult offspring LDL-C levels beyond common genetic variants and classic risk factors for elevated LDL-C levels. CONCLUSIONS AND RELEVANCE:Adult offspring dyslipidemia is associated with maternal prepregnancy dyslipidemia in excess of measured lifestyle, anthropometric, and inherited genetic factors. The findings support the possibility of a maternal epigenetic contribution to cardiovascular disease risk in the general population. Further research is warranted to determine whether ongoing public health efforts to identify and reduce dyslipidemia in young adults prior to their childbearing years may have additional potential health benefits for the subsequent generation.

Project description:ObjectivesThis study aimed to describe the epidemiology and risk factors of cholelithiasis and nephrolithiasis among HIV-positive patients in the era of combination antiretroviral therapy.MethodsWe retrospectively reviewed the medical records of HIV-positive patients who underwent routine abdominal sonography for chronic viral hepatitis, fatty liver, or elevated aminotransferases between January 2004 and January 2015. Therapeutic drug monitoring of plasma concentrations of atazanavir was performed and genetic polymorphisms, including UDP-glucuronosyltransferase (UGT) 1A1*28 and multidrug resistance gene 1 (MDR1) G2677T/A, were determined in a subgroup of patients who received ritonavir-boosted or unboosted atazanavir-containing combination antiretroviral therapy. Information on demographics, clinical characteristics, and laboratory testing were collected and analyzed.ResultsDuring the 11-year study period, 910 patients who underwent routine abdominal sonography were included for analysis. The patients were mostly male (96.9%) with a mean age of 42.2 years and mean body-mass index of 22.9 kg/m2 and 85.8% being on antiretroviral therapy. The anchor antiretroviral agents included non-nucleoside reverse-transcriptase inhibitors (49.3%), unboosted atazanavir (34.4%), ritonavir-boosted lopinavir (20.4%), and ritonavir-boosted atazanavir (5.5%). The overall prevalence of cholelithiasis and nephrolithiasis was 12.5% and 8.2%, respectively. Among 680 antiretroviral-experienced patients with both baseline and follow-up sonography, the crude incidence of cholelithiasis and nephrolithiasis was 4.3% and 3.7%, respectively. In multivariate analysis, the independent factors associated with incident cholelithiasis were exposure to ritonavir-boosted atazanavir for >2 years (adjusted odds ratio [AOR], 6.29; 95% confidence interval [CI], 1.12-35.16) and older age (AOR, 1.04; 95% CI, 1.00-1.09). The positive association between duration of exposure to ritonavir-boosted atazanavir and incident cholelithiasis was also found (AOR, per 1-year exposure, 1.49; 95% CI, 1.05-2.10). The associated factors with incident nephrolithiasis were hyperlipidemia (AOR, 3.97; 95% CI, 1.32-11.93), hepatitis B or C coinfection (AOR, 3.41; 95% CI, 1.09-10.62), and exposure to abacavir (AOR, 12.01; 95% CI, 1.54-93.54). Of 180 patients who underwent therapeutic drug monitoring of plasma atazanavir concentrations and pharmacogenetic investigations, we found that the atazanavir concentrations and UGT 1A1*28 and MDR1 G2677T/A polymorphisms were not statistically significantly associated with incident cholelithiasis and nephrolithiasis.ConclusionsIn HIV-positive patients in the era of combination antiretroviral therapy, a high prevalence of cholelithiasis and nephrolithiasis was observed, and exposure to ritonavir-boosted atazanavir for >2 years was associated with incident cholelithiasis.

Project description:Our study aimed to investigate the short-term effect of combination antiretroviral therapy (cART) on cognitive performance and functional and structural connectivity and their relationship to plasma levels of antiretroviral (ARV) drugs. Seventeen ARV treatment-naïve HIV-infected individuals (baseline mean CD4 cell count, 479 ± 48 cells/mm3) were age matched with 17 HIV-uninfected individuals. All subjects underwent a detailed neurocognitive and functional assessment and magnetic resonance imaging. HIV-infected subjects were scanned before starting cART and 12 weeks after initiation of treatment. Uninfected subjects were assessed once at baseline. Functional connectivity (FC) was assessed within the default mode network while structural connectivity was assessed by voxel-wise analysis using tract-based spatial statistics (TBSS) and probabilistic tractography within the DMN. Tenofovir and emtricitabine blood concentration were measured at week 12 of cART. Prior to cART, HIV-infected individuals had significantly lower cognitive performance than control subjects as measured by the total Z-score from the neuropsychological tests assessing six cognitive domains (p = 0.020). After 12 weeks of cART treatment, there remained only a weak cognitive difference between HIV-infected and HIV-uninfected subjects (p = 0.057). Mean FC was lower in HIV-infected individuals compared with those uninfected (p = 0.008), but FC differences became non-significant after treatment (p = 0.197). There were no differences in DTI metrics between HIV-infected and HIV-uninfected individuals using the TBSS approach and limited evidence of decreased structural connectivity within the DMN in HIV-infected individuals. Tenofovir and emtricitabine plasma concentrations did not correlate with either cognitive performance or imaging metrics.ConclusionsTwelve weeks of cART improves cognitive performance and functional connectivity in ARV treatment-naïve HIV-infected individuals with relatively preserved immune function. Longer periods of observation are necessary to assess whether this effect is maintained.

Dataset Information

Combination of niacin and fenofibrate with lifestyle changes improves dyslipidemia and hypoadiponectinemia in HIV patients on antiretroviral therapy: results of "heart positive," a randomized, controlled trial.

Publications

Combination of niacin and fenofibrate with lifestyle changes improves dyslipidemia and hypoadiponectinemia in HIV patients on antiretroviral therapy: results of "heart positive," a randomized, controlled trial.

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