Long‐term and concentration‐dependent beneficial effect of efavirenz on HDL‐cholesterol in HIV‐infected patients

Pereira, Sofia A.; Branco, Teresa; Côrte‐Real, Rita; Germano, Isabel; Lampreia, Fátima; Caixas, Umbelina; Monteiro, Emília C.

doi:10.1111/j.1365-2125.2006.02619.x

Cited by 28 publications

(23 citation statements)

References 5 publications

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“…Most of the published studies on this issue concur in showing a negative impact of protease inhibitors (PI) on lipid profile and on cardiovascular risk, particularly with the use of ritonavir as a pharmacological booster, and a better lipid or risk profile associated to use of non-nucleoside reverse transcriptase inhibitors (NNRTIs), particularly nevirapine. 1,3,[6][7][8][9][10][11][12][13][14][15] In recent years, some information became available on the lipid profile of HIV-positive pregnant women receiving antiretroviral treatment. We previously showed, on a background of a progressive increase in plasma triglyceride and cholesterol levels during pregnancy, an additional and independent effect of protease inhibitors in increasing triglyceride levels at all pregnancy trimesters.…”

Section: Introductionmentioning

confidence: 99%

Plasma Lipid Profile in Pregnant Women with HIV Receiving Nevirapine

Floridia

Tamburrini

Anzidei

et al. 2009

AIDS Patient Care and STDs

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Limited information is currently available on the metabolic profile of nevirapine in pregnancy. We used data from a national observational study to evaluate plasma lipid profile in pregnant women receiving nevirapine. Lipid values were collected during routine clinical visits. Midpregnancy (second trimester) lipid values were analyzed according to use of nevirapine, calculating differences and 95% confidence intervals (CI) between women taking and not taking this drug. In order to adjust for possible confounders, multivariable models were constructed using as dependent variables levels of total cholesterol (TC), high-density lipoprotein-cholesterol (HDL-C), low-density lipoprotein-cholesterol (LDL-C), triglyceride (TG) levels and TC/HDL-C ratio, and as independent variables age, body weight, previous treatment history, CD4 count, and presence of any antiretroviral therapy, use or nonuse of protease inhibitors, stavudine, and nevirapine at the time of blood sampling. Overall, 375 women had available data for analysis. Pregnant women on nevirapine, compared to women not taking this drug, had in univariate analyses higher levels of HDL-C (difference: +13.0mg/dL [95%CI 7.4-18.6], p < 0.001), lower values of TC/HDL-C ratio (difference: -0.51 [0.23-0.80], p < 0.001) and a trend for lower levels of triglycerides (difference: -17.6mg/dL [0.7-35.9], p = 0.06). Higher HDL-C levels were also associated with use of protease inhibitors and with no previous antiretroviral experience before pregnancy. The associations with higher HDL-C levels were confirmed in multivariable analyses. Our study indicates in pregnant women an association between nevirapine use and higher HDL-C levels. Further studies should assess whether this effect is due to an intrinsic activity of nevirapine and define the potential mechanisms involved.

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Section: Introductionmentioning

confidence: 99%

Plasma Lipid Profile in Pregnant Women with HIV Receiving Nevirapine

Floridia

Tamburrini

Anzidei

et al. 2009

AIDS Patient Care and STDs

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“…5 Therapy with nonnucleoside reverse transcriptase inhibitor (NNRTI)-based regimens using nevirapine (NVP) or efavirenz (EFV) has been reported to cause modest increases in LDL-C, non-highdensity lipoprotein cholesterol (non-HDL-C), and TG, but also a striking and potentially favorable increase in HDL-C levels. [6][7][8][9] We assessed changes in fasting metabolic (TC, HDL-C, directly measured LDL-C, TG, insulin, glucose, and lactate) parameters and in body circumference indices (waist, hip, midarm, and midthigh) after initiation of PI-sparing regimens within AIDS Clinical Trials Group (ACTG) study 5095, a multicenter ARV trial in treatment-naive subjects conducted by the ACTG. The patients were randomized into 1 of 3 regimens consisting of EFV in combination with zidovudine (ZDV) and lamivudine (3TC) with or without abacavir (ABC) or an all-nucleoside regimen of ZDV/3TC/ABC.…”

mentioning

confidence: 99%

Metabolic Effects of Protease Inhibitor-Sparing Antiretroviral Regimens Given as Initial Treatment of HIV-1 Infection (AIDS Clinical Trials Group Study A5095)

Shikuma

Yang²,

Glesby³

et al. 2007

JAIDS Journal of Acquired Immune Deficiency Syndromes

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“…In addition, it has been shown that alterations in HDL structure and composition can affect PON-1 activity and function [26]. The effect of HIV infection on HDL metabolism is well documented [8], and we have previously shown that EFV is associated with higher values of HDL-c [21]. Thus the alterations of HDL-c caused by EFV could be stabilizing the link of the enzyme to HDL, hence allowing higher enzymatic activity.…”

Section: Discussionmentioning

confidence: 90%

“…The association of PON-1 activity with EFV concentrations is important to distinguish if the effect relies on the response to treatment or on EFV per se. Nevertheless, excluding NNRTI [21,36], the majority of antiretroviral drugs have been described as not affecting HDL-c [2,7].…”

Section: Discussionmentioning

confidence: 99%

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Effect of efavirenz on high‐density lipoprotein antioxidant properties in HIV‐infected patients

Pereira

Batuca

Caixas

et al. 2009

Brit J Clinical Pharma

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WHAT IS ALREADY KNOWN ABOUT THIS SUBJECT• In previous work, we showed a long-term and concentration-dependent beneficial effect of the non-nucleoside reverse transcriptase inhibitor efavirenz (EFV) on high-density lipoproteins (HDL) in human immunodeficiency virus (HIV)-infected patients.• Furthermore, it has been suggested that instead of the current practice of only measuring HDL-chelesterol values, the evaluation of HDL function, namely its antioxidant properties, might be an improved tool for identifying subjects at increased risk for cardiovascular events.• Paraoxonase-1 (PON-1) is an enzyme associated with HDL that is responsible for HDL antioxidant function. WHAT THIS STUDY ADDS• In the present work, we studied the effect of EFV on the activity of PON-1 and showed, for the first time, that EFV-based antiretroviral therapy is associated with a better antioxidant function, i.e. with a higher PON-1 activity. AIMSA long-term and concentration-dependent beneficial effect of efavirenz (EFV) on cholesterol associated with high-density lipoprotein (HDL-c) in human immunodeficiency virus (HIV)-infected patients has been documented. Furthermore, it has been suggested that, instead of the current practice of only measuring HDL-c values, the evaluation of HDL quality might be an improved tool for identifying subjects at increased risk of cardiovascular events. Paraoxonase-1 (PON-1) is an enzyme associated with HDL that is involved in the onset of cardiovascular disease and responsible for HDL antioxidant function. The aim of the present study was to investigate the effect of EFV on the circulating activity of PON-1 in HIV-infected patients. METHODSThe patients included were adults with a documented HIV-1 infection, nontreated or treated with antiretroviral regimens including EFV 600 mg once daily as first therapeutic regimen for at least 3 months. The influence of treatment with EFV, HDL-c and CD4 cell count on PON-1 activity was analysed. RESULTSHIV-infected White patients treated with EFV had higher PON-1 activity [77.35 U l -1 (65.66, 89.04)] (P < 0.05) and higher PON-1 activity : HDL-c ratio [1.88 (1.49, 2.28)] (P < 0.01) than untreated patients. PON-1 activity was higher in Black patients (P < 0.001) and in patients with a CD4 cell count >500 cells ml -1 (P = 0.0120). CONCLUSIONSEFV-based antiretroviral regimens are associated with HDL particles with a better antioxidant function, i.e. with a higher PON-1 activity. The PON-1 activity of Black patients is higher than that found in Whites regardless of treatment. Ethnicity should be taken into consideration when studying drug effects on PON-1 activity.

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Long‐term and concentration‐dependent beneficial effect of efavirenz on HDL‐cholesterol in HIV‐infected patients

Cited by 28 publications

References 5 publications

Plasma Lipid Profile in Pregnant Women with HIV Receiving Nevirapine

Plasma Lipid Profile in Pregnant Women with HIV Receiving Nevirapine

Metabolic Effects of Protease Inhibitor-Sparing Antiretroviral Regimens Given as Initial Treatment of HIV-1 Infection (AIDS Clinical Trials Group Study A5095)

Effect of efavirenz on high‐density lipoprotein antioxidant properties in HIV‐infected patients

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