A Comparison of the Effects of Nevirapine and Nelfinavir on Metabolism and Body Habitus in Antiretroviral-Naive Human Immunodeficiency Virus-Infected Patients: A Randomized Controlled Study

Fisac, Cesar; Virgili, N.; Ferrer, Elena; Barberà, María Jesús; Fumero, Emilio; Vilarasau, Concepcio; Podzamczer, Daniel

doi:10.1210/jc.2002-021830

Cited by 49 publications

(38 citation statements)

References 46 publications

(38 reference statements)

Supporting

Mentioning

Contrasting

Unclassified

Order By: Relevance

“…The INTERHEART study reported that non-fasting ApoB:ApoA1 ratio was superior to any of the cholesterol Patients with HDL-c ratios for estimation of the risk of acute MI in all ethnic groups, in both sexes and at all ages [29]. In the AMORIS study, the strongest single variable that related to increased risk of fatal MI was the ApoB:ApoA1 ratio [30], while the MONICA/KORA study also found the ApoB:ApoA1 ratio to be an independent risk factor [33].The greater increase in HDL-c and greater decrease in TC:HDL-c in patients receiving NVP compared with those on ATZ/r is supported by the findings of a number of other studies in which patients were treated with NVP [32,33]. Furthermore, a study by Franssen et al reported that NVP increases ApoAI production, suggesting this as a mechanism that contributes to the HDL-c increases observed after the introduction of NVP-containing regimens [17].…”

mentioning

confidence: 71%

Lipid profiles for nevirapine vs. atazanavir/ritonavir, both combined with tenofovir disoproxil fumarate and emtricitabine over 48 weeks, in treatment-naïve HIV-1-infected patients (the ARTEN study)

et al. 2011

View full text Add to dashboard Cite

ObjectivesDyslipidaemic effects of antiretrovirals (ARVs) may contribute to increased cardiovascular risk (CR) in HIV-1-infected patients. The ARTEN (atazanavir/ritonavir on a background of tenofovir and emtricitabine vs. nevirapine on the same background, in naïve HIV-1-infected patients) study compared prospectively ritonavir-boosted atazanavir (ATZ/r) 300 mg/100 mg once daily (qd) with immediate release nevirapine (NVP) 200 mg twice daily or 400 mg qd, each combined with fixed-dose tenofovir 300 mg/emtricitabine 200 mg qd in 569 ARV-naïve HIV-1-infected patients. Lipid profiles and CR from baseline to week 48 are reported. MethodsChanges from baseline to week 48 in fasting plasma levels of total cholesterol (TC), high-density lipoprotein cholesterol (HDL-c), low-density lipoprotein cholesterol (LDL-c), TC:HDL-c ratio, apolipoprotein A1 (ApoA1), apolipoprotein B (ApoB) and total triglycerides (TG) were determined. The Framingham algorithm was used to estimate CR. Analysis was by intention-to-treat (ITT) with last observation carried forward (LOCF) for missing data. ResultsAt week 48, NVP treatment resulted in significantly greater mean increases from baseline in TC (24.4 vs. 19.6 mg/dL; P 5 0.038), HDL-c (9.7 vs. 3.9 mg/dL; Po0.0001), LDL-c (15.0 vs. 10.4 mg/dL; P 5 0.011) and ApoA1 (0.18 vs. 0.08 g/L; Po0.0001) but not ApoB (0.02 vs. 0.02 g/L) compared with ATZ/r treatment. ATZ/r use was associated with higher mean TG increases (27.80 vs. 0.02 mg/dL; P 5 0.0001). Significantly greater mean decreases in TC:HDL-c and ApoB/ApoA ratios were observed with NVP vs. ATZ/r (P 5 0.0001 and P 5 0.008, respectively). Framingham CR scores were low and comparable between the arms, with only a slight mean increase from baseline to week 48 of 0.70 for NVP and 0.80 for ATZ/r [difference À 0.069; 95% confidence interval (CI) À 0.61 to 0.46; P 5 0.80]. ConclusionsIn ARV-naïve patients with low CR at the outset, NVP showed a potentially less atherogenic lipid profile compared with ATZ/r. DOI: 10.1111/j.1468-1293.00917.x HIV Medicine (2011 r 2011 British HIV Association 374 IntroductionCombination antiretroviral (ARV) therapy for patients with HIV-1 infection has resulted in increased life expectancy as a consequence of marked reductions in morbidity and mortality rates, which has elevated the importance of both improvements in antiviral activity and minimization of ARV-related adverse events (AEs) [1]. Serum lipid levels can be adversely affected by ARV drugs and may contribute to insulin resistance and morphological changes, including visceral, breast and local fat accumulation, as well as subcutaneous fat loss [2]. However, these changes are the result of a complex multifactorial interplay which is yet to be fully understood. These dyslipidaemic effects may potentially lead to an increased risk of cardiovascular disease (CVD) among patients infected with HIV-1 [2-4]. The incidence of myocardial infarction (MI) has been shown to increase by 26% per year of exposure to combination ARV treatment [5,6]. Furthermore, a prospectiv...

show abstract

mentioning

confidence: 71%

Lipid profiles for nevirapine vs. atazanavir/ritonavir, both combined with tenofovir disoproxil fumarate and emtricitabine over 48 weeks, in treatment-naïve HIV-1-infected patients (the ARTEN study)

et al. 2011

View full text Add to dashboard Cite

show abstract

“…Even if the ability of individual molecules to induce these alterations varies according to the molecule, PIs were collectively found to increase total and LDL cholesterol and also TG (17)(18)(19). However, among PIs, some of them affect mainly lipid metabolism (e.g., lopinavir [LPV], ritonavir [RTV], and, to a lesser extent, nelfi navir [NFV]), while others, such as atazanavir (ATV), appear to be lipid-friendly ( 17,18,(20)(21)(22). Additionally, some PIs were shown to directly affect adipose tissue lipid metabolism, even in the absence of an abnormal fat distribution.…”

mentioning

confidence: 99%

Glyceroneogenesis is inhibited through HIV protease inhibitor-induced inflammation in human subcutaneous but not visceral adipose tissue

Leroyer

Vatier

Kadiri

et al. 2011

Journal of Lipid Research

View full text Add to dashboard Cite

Adipose tissue exerts two important functions involved in the regulation of lipid metabolism and insulin sensitivity: 1 ) storage of FFA as triglycerides (TG) into adipocytes and their disposal by lipolysis, and 2 ) secretion of adipokines and cytokines that could promote either insulin sensitivity or resistance in target tissues. Type 2 diabetes has been shown to be associated with disturbances in glucose and lipid metabolism, with modifi cations in systemic levels of adipokines, cytokines, and FFAs, partly as a consequence of adipose tissue dysfunction and infl ammation. In particular, dysregulation of FFA metabolism would be an essential cause of metabolic anomalies because a defect in their storage into adipocytes could lead to their ectopic depot in the liver, muscles, heart, and pancreas, where they play an important role in dyslipidemia, insulin resistance, and altered glucose tolerance ( 1 ). Recently, the antiretroviral drugs given to patients to control human immunodeficiency virus (HIV) infection were recognized as responsible for metabolic alterations and abnormal adipose tissue distribution, together with modifi cations in adipokines, cytokines, and FFAs, and with ectopic depots of lipids in nonfat tissues, arguing for mechanisms common to those reported in diabetes ( 2, 3 ).We recently highlighted, in human adipose tissue, the importance of the metabolic pathway, glyceroneogenesis (GNG), which is able to limit FFA release to blood under physiological fasting situations and which is a new target of thiazolidinedione action ( 4-6 ). FFA re-esterifi cation via GNG was fi rst described by Ballard et al. ( 7 )

show abstract

“…Amprenavir administered for 48 weeks increased LDL cholesterol levels by 28% [13]. Nelfinavir increased LDL cholesterol levels by 16% to 31% [14,61,62].…”

Section: Effects Of Protease Inhibitors On Low-density Lipoprotein Chmentioning

confidence: 96%

“…Amprenavir administered for 48 weeks increased fasting triglyceride levels by 90% [13]. Studies report nelfinavir increasing fasting triglyceride levels by 42% to 50%, but one study reported no increase in fasting triglyceride levels with nelfinavir [14,61,62].…”

Section: Effects Of Protease Inhibitors On Triglycerides and Very Lowmentioning

confidence: 98%

“…A prospective study of 14 patients starting amprenavir therapy found that insulin resistance by minimal model analysis did not significantly increase in the first 24 weeks, but there was a trend toward a 39% increase after 48 weeks (P = 0.06) [13]. In 20 patients prospectively followed after starting nelfinavir with zidovudine and lamivudine, there was no significant change in HOMA insulin resistance index after 6 to 12 months of therapy [14].…”

Section: Prospective Studies Of Protease Inhibitor-induced Insulin Rementioning

confidence: 99%

See 1 more Smart Citation

The effects of HIV protease inhibitors on carbohydrate and lipid metabolism

Lee

Rao²,

Grünfeld³

2004

Curr Infect Dis Rep

View full text Add to dashboard Cite

Since the introduction of HIV protease inhibitors (PIs), disorders of glucose and lipid metabolism have emerged. In dissecting out the direct effect on lipid and glucose metabolism, it has become apparent that individual PIs have different effects on metabolism. Some PIs such as indinavir acutely induce insulin resistance. PIs have also been shown to cause other disorders of glucose metabolism, including impairment of insulin secretion and increased endogenous glucose production. Individual PIs also have different effects on lipid metabolism. Ritonavir predominantly increases triglyceride and very low-density lipoprotein cholesterol levels. Limited studies in HIV-negative volunteers suggest that several of the PIs do not increase low-density lipoprotein cholesterol levels. This review examines the direct effects of PIs on glucose and lipid metabolism by assessing prospective studies of HIV-infected and healthy normal volunteers, and in vitro studies.

show abstract

A Comparison of the Effects of Nevirapine and Nelfinavir on Metabolism and Body Habitus in Antiretroviral-Naive Human Immunodeficiency Virus-Infected Patients: A Randomized Controlled Study

Cited by 49 publications

References 46 publications

Lipid profiles for nevirapine vs. atazanavir/ritonavir, both combined with tenofovir disoproxil fumarate and emtricitabine over 48 weeks, in treatment-naïve HIV-1-infected patients (the ARTEN study)

Lipid profiles for nevirapine vs. atazanavir/ritonavir, both combined with tenofovir disoproxil fumarate and emtricitabine over 48 weeks, in treatment-naïve HIV-1-infected patients (the ARTEN study)

Glyceroneogenesis is inhibited through HIV protease inhibitor-induced inflammation in human subcutaneous but not visceral adipose tissue

The effects of HIV protease inhibitors on carbohydrate and lipid metabolism

Contact Info

Product

Resources

About