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; Coraza, Ivonne; Smith, E. O’Brian; Scott, Lynne W.; Patel, Pooja; Iyer, Dinakar; Taylor, Addison A.; Giordano, Thomas P.; Sekhar, Rajagopal V.; Clark, Pamela; Cuevas-Sanchez, Edith; Kamble, Swarna; Ballantyne, Christie M.; Pownall, Henry J.

doi:10.1210/jc.2010-3067

Cited by 57 publications

(102 citation statements)

References 42 publications

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“…Analysis of variance confirmed that the lipid profiles at baseline for the five groups, assigned at random upon enrollment in the Heart Positive Study, were not significantly different. As reported for the entire Heart Positive study 16 treatment with fenofibrate + D&E (Group 3), niacin + D&E (Group 4) and the combined therapy of fenofibrate + niacin + D&E (Group 5) significantly reduced plasma TG, with median reductions of 35 – 42 %. Treatments including niacin with or without fenofibrate increased median HDL-C by 21 – 24%.…”

Section: Resultssupporting

confidence: 57%

Impaired Lipoprotein Processing in HIV Patients on Antiretroviral Therapy

Gillard

Raya

Ruiz-Esponda

et al. 2013

ATVB

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Objective HIV patients on antiretroviral therapy (HIV/ART) exhibit a unique atherogenic dyslipidemic profile with hypertriglyceridemia (HTG) and low plasma concentrations of high density lipoprotein-cholesterol (HDL-C). In the Heart Positive Study of HIV/ART patients, a hypolipidemic therapy of fenofibrate, niacin, diet, and exercise reduced HTG and plasma non-HDL-C concentrations and raised plasma HDL-C and adiponectin concentrations. We tested the hypothesis that HIV/ART HDL have abnormal structures and properties and are dysfunctional. Approach and Results Hypolipidemic therapy reduced the TG contents of LDL and HDL. At baseline, HIV/ART low density lipoproteins (LDL) were more triglyceride (TG)-rich and HDL were more TG- and cholesteryl ester (CE)-rich than the corresponding lipoproteins from normolipidemic (NL) subjects. Very low density lipoproteins, LDL and HDL were larger than the corresponding lipoproteins from NL subjects; HIV/ART HDL were less stable than NL HDL. HDL-[3H]CE uptake by Huh7 hepatocytes was used to assess HDL functionality. HIV/ART plasma were found to contain significantly less competitive inhibition activity for hepatocyte HDL-CE uptake than did NL plasma (p<0.001). Conclusion Compared to NL subjects, lipoproteins from HIV/ART patients are larger and more neutral lipid-rich, and their HDL are less stable and less receptor-competent. Based on this work and previous studies of lipase activity in HIV, we present a model in which plasma lipolytic activities and/or hepatic CE uptake are impaired in HIV/ART patients. These findings provide a rationale to determine whether the distinctive lipoprotein structure, properties and function of HIV/ART HDL predict atherosclerosis as assessed by carotid artery intimal medial thickness.

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Section: Resultssupporting

confidence: 57%

Impaired Lipoprotein Processing in HIV Patients on Antiretroviral Therapy

Gillard

Raya

Ruiz-Esponda

et al. 2013

ATVB

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“…Thirteen of the 20 included studies (65%) assessed cardiorespiratory outcomes [26–31, 33, 37, 38, 41, 43, 44, 49]. Sixteen studies (80%) assessed strength outcomes [27–29, 31–33, 35–39, 41–44, 49].…”

Section: Resultsmentioning

confidence: 99%

“…Five studies (25%) had low risk for detection bias because authors reported that outcome assessors were blinded to group allocation [26–28, 31, 32] (Fig. 2).…”

Section: Resultsmentioning

confidence: 99%

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Effectiveness of Progressive Resistive Exercise (PRE) in the context of HIV: systematic review and meta-analysis using the Cochrane Collaboration protocol

O’Brien

Tynan²,

Nixon

et al. 2017

BMC Infect Dis

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BackgroundHIV is increasingly considered a chronic illness. More individuals are living longer and aging with the health-related consequences associated with HIV and multi-morbidity. Exercise is a self-management approach that can promote health for people aging with HIV. We examined the safety and effectiveness of progressive resistive exercise (PRE) interventions on immunological, virological, cardiorespiratory, strength, weight, body composition, and psychological outcomes in adults living with HIV.MethodsWe conducted a systematic review using the Cochrane Collaboration protocol. Searching databases up to April 2013, we included randomized controlled trials that compared PRE with no exercise or another intervention performed at least three times per week for at least four weeks with adults living with HIV. Two reviewers independently determined study eligibility. We extracted data from included studies and assessed risk of bias using the Cochrane Collaboration risk of bias tool. Meta-analyses were conducted using random effects models with Review Manager (RevMan) computer software.ResultsTwenty studies met inclusion criteria (n = 764 participants at study completion); the majority of participants were men (77%) taking antiretroviral therapy (14/20 included studies). Exercise interventions included PRE alone (8 studies) or a combination of resistive and aerobic exercise (12 studies) ranging from 6 to 52 weeks in duration. Thirty-four meta-analyses were performed. Results demonstrated statistically significant improvements in cardiorespiratory status (maximum oxygen consumption, exercise time), strength (chest press, knee flexion), weight, and body composition (arm and thigh girth, leg muscle area) among exercisers versus non-exercisers. We found no significant differences in change in CD4 count and viral load. We were unable to perform meta-analyses for psychological outcomes however results from individual studies demonstrated improvements in health-related quality of life with exercisers compared with non-exercisers.ConclusionsPerforming progressive resistive exercise (PRE) or a combination of resistive and aerobic exercise at least three times per week for at least six weeks is safe and can lead to improvements in cardiorespiratory fitness, strength, weight, and body composition for adults with HIV. Exercise may be considered a safe and beneficial for enhancing the health of medically stable adults aging with HIV.Electronic supplementary materialThe online version of this article (doi:10.1186/s12879-017-2342-8) contains supplementary material, which is available to authorized users.

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“…Niacin is known to control lipoprotein metabolism and suppress synthesis of TG and patients treated with low-fat diet, exercise and niacin had significantly increased plasma concentrations of HDL-C and TC compared to the controls after 24 weeks [146,147]. However, niacin appeared to increase the risk of insulin resistance in HIV patients [146].…”

Section: Nutritional Therapymentioning

confidence: 99%

Highly Active Antiretroviral Therapy-Associated Metabolic Syndrome and Lipodystrophy: Pathophysiology and Current Therapeutic Interventions

et al. 2017

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The use of highly active antiretroviral therapy (HAART) has extremely enhanced the clinical outcome of HIV disease with a decrease in mortality and morbidity. However, the inclusion of protease inhibitors (PIs) and nucleoside reverse transcriptase inhibitors (tNRTIs) has strongly been linked to the development of metabolic abnormalities and lipodystrophy. Lipodystrophy is defined by the loss of peripheral subcutaneous fat and central adiposity, mainly in the abdomen, breast and dorsocervical region. These disorders are reported to be cosmetically distressing and socially stigmatizing to many patients leading to decreased adherence to antiretroviral therapy. Metabolic syndrome precedes lipodystrophy leading to increased risk of diabetes and cardiovascular diseases. With a shifted trajectory of HIV/AIDS morbidity from immunodeficiency and opportunistic infections to metabolic complications, clinical management of these patients has therefore become more complex. Currently there are no evidence-based standard guidelines for the management of HIV-associated lipodystrophy. Several pharmacological interventions such as using anti-diabetic, anti-dyslipidemic drugs or hormone replacement therapy have been tried to effectively improve metabolic syndrome and lipodystrophy but have been hampered by low efficacy, drug interactions, or unwanted side-effects. Non-pharmacological interventions including surgical manipulations, dietary and lifestyle modifications have also been tried with limited success. This review focuses on the proposed mechanisms involved in the development of metabolic syndrome and lipodystrophy, and highlights suggested potential therapeutic interventions to prevent lipodystrophy associated with HAART.

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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: 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.

Cited by 57 publications

References 42 publications

Impaired Lipoprotein Processing in HIV Patients on Antiretroviral Therapy

Impaired Lipoprotein Processing in HIV Patients on Antiretroviral Therapy

Effectiveness of Progressive Resistive Exercise (PRE) in the context of HIV: systematic review and meta-analysis using the Cochrane Collaboration protocol

Highly Active Antiretroviral Therapy-Associated Metabolic Syndrome and Lipodystrophy: Pathophysiology and Current Therapeutic Interventions

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