Cardiovascular risk factors in patients on long-term treatment with nevirapine- or efavirenz-based regimens

Maggi, Paolo; Bellacosa, Chiara; Carito, Valentina; Perilli, Francesco; Lillo, Antonio; Volpe, Anna; Trillo, Giovanna; Angiletta, Domenico; Regina, Guido; Angarano, Gioacchino

doi:10.1093/jac/dkq507

Cited by 28 publications

(27 citation statements)

References 20 publications

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“…These increases in blood pressure persisted after adjusting for baseline blood pressure, age, CD4+ T-cell count, and HIV-1 RNA. Maggi and colleagues observed in a limited retrospective study of NVP-based ART a significant increase in hypertension at 5 years of follow-up, which was not observed in those receiving EFV [35]. Of note, no significant changes in pathology were observed in color-Doppler ultrasonography of the peri-aortic vasculature in the NVP group in that report [35].…”

Section: Discussionmentioning

confidence: 98%

“…We found mean increases in all CVD risk factors at nearly all follow-up visits with the exception of TGs, which decreased in the NVP group by 48 weeks and remained below the value at time of ART initiation thereafter. Decreases in TGs have been described in patients with advanced HIV who received zidovudine monotherapy early in the epidemic and more recently in patients on long-term NVP-based ART [6, 34, 35]. However, NVP-based ART has also been associated with increases in TGs, although to a lesser extent compared with efavirenz (EFV) [36, 37].…”

Section: Discussionmentioning

confidence: 99%

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Cardiovascular Disease Risk Factors in HIV-Infected Women After Initiation of Lopinavir/Ritonavir- and Nevirapine-Based Antiretroviral Therapy in Sub-Saharan Africa

Shaffer

Hughes

Sawe

et al. 2014

JAIDS Journal of Acquired Immune Deficiency Syndromes

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Background Limited comparative, prospective data exist regarding cardiovascular risk factors in HIV-infected women starting antiretroviral therapy (ART) in Africa. Methods In 7 African countries, 741 women with CD4<200 cells/mm3 were randomized to tenofovir/emtricitabine (TDF/FTC) plus either nevirapine (NVP, n=370) or lopinavir/ritonavir (LPV/r, n=371). Lipids and blood pressure (BP) were evaluated at entry, 48, 96, and 144 weeks. Multivariable linear and logistic regression models were used to evaluate mean risk factor changes and clinically relevant risk factor changes. Results At entry, both NVP and LPV/r groups were similar regarding age (mean=33.5 [SD=7.1] yrs), CD4 (129 [67] cells/mm3), and HIV-1 RNA (5.1 [0.6] log10 copies/ml). Nearly all women had normal lipids and BP except for HDL. Over 144 weeks, the LPV/r compared to NVP group had significantly greater mean lipid increases (e.g. non-HDL: +29 vs. +13 mg/dL) and smaller HDL increases (+12 vs. +21 mg/dL). In contrast, the NVP compared to LPV/r group had greater mean increases in BP (e.g. diastolic BP: +5 vs. −0.5 mmHg). Significantly more women assigned LPV/r had week 144 “abnormal” lipid levels (e.g. HDL 29.7% vs. 14.8% and triglycerides 28.6% vs. 8.2%), and significantly more women assigned NVP had “abnormal” BP (e.g. diastolic BP 22.7% vs. 6.5%). Most differences remained significant when adjusted for baseline risk factor, age, CD4, and HIV-1 RNA. Conclusions In HIV-infected women initiating ART in Africa, LPV/r+TDF/FTC was associated with less favorable changes in lipids, and use of NVP+TDF/FTC was associated with less favorable changes in BP.

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Section: Discussionmentioning

confidence: 98%

Section: Discussionmentioning

confidence: 99%

Cardiovascular Disease Risk Factors in HIV-Infected Women After Initiation of Lopinavir/Ritonavir- and Nevirapine-Based Antiretroviral Therapy in Sub-Saharan Africa

Shaffer

Hughes

Sawe

et al. 2014

JAIDS Journal of Acquired Immune Deficiency Syndromes

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“…Several studies also suggest that efavirenz could trigger endothelial dysfunction and increase the cardiovascular risk in HIV‐infected patients (Maggi et al. 2011; Gupta et al. 2012).…”

Section: Introductionmentioning

confidence: 99%

Role of endoplasmic reticulum stress in drug‐induced toxicity

Foufelle

Fromenty

2016

Pharmacology Res & Perspec

181

161

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Drug‐induced toxicity is a key issue for public health because some side effects can be severe and life‐threatening. These adverse effects can also be a major concern for the pharmaceutical companies since significant toxicity can lead to the interruption of clinical trials, or the withdrawal of the incriminated drugs from the market. Recent studies suggested that endoplasmic reticulum (ER) stress could be an important event involved in drug liability, in addition to other key mechanisms such as mitochondrial dysfunction and oxidative stress. Indeed, drug‐induced ER stress could lead to several deleterious effects within cells and tissues including accumulation of lipids, cell death, cytolysis, and inflammation. After recalling important information regarding drug‐induced adverse reactions and ER stress in diverse pathophysiological situations, this review summarizes the main data pertaining to drug‐induced ER stress and its potential involvement in different adverse effects. Drugs presented in this review are for instance acetaminophen (APAP), arsenic trioxide and other anticancer drugs, diclofenac, and different antiretroviral compounds. We also included data on tunicamycin (an antibiotic not used in human medicine because of its toxicity) and thapsigargin (a toxic compound of the Mediterranean plant Thapsia garganica) since both molecules are commonly used as prototypical toxins to induce ER stress in cellular and animal models.

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“…This effect is probably related to the impact of NNRTIs on metabolism of HDL-cholesterol and triglycerides, and to the absence of protease inhibitors (PI) in the combination. Other studies have documented a late improve of HDL-cholesterol and of Total-Cholesterol/HDLCholesterol ratio in association with a long run use of NVP [1,29,30].…”

Section: Discussionmentioning

confidence: 95%

Long-term efficacy and safety of treatment with nevirapine plus nucleoside reverse transcriptase inhibitors for HIV-1 infection: An eight-years follow-up

et al. 2012

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a b s t r a c tBackground: The aim of this retrospective study is to evaluate long-term efficacy and safety of highly active antiretroviral therapy (HAART) regimens based on nevirapine (NVP) plus nucleoside reverse transcriptase inhibitors (NRTIs), with particular regard to NVP's effect on liver function and lipid profile, in both HAARTexperienced patients and naϊve. Material and methods: We have continuously treated with NVP for at least 8 years a total of 197 HIV-1 positive patients (126 males, 71 females) and we have followed-up them over a eight-years period: 54.7% of them were HAART-experienced patients and have switched to NVP for simplification, intolerance or dyslipidemia, while 45.3% were naïve to antiretroviral drugs. Co-infection with hepatitis C viruses was detected in 20% of patients. Viral load, CD4+ cell count, liver enzymes and lipid profile were investigated on 2, 4, 6 and 8 years follow-up controls, retrospectively. Results: The initial positive anti-viral answer obtained with NVP have been lasting in time in all patients. The patients which were continuously treated with NVP kept undetectable viral load from 2 to 8 years follow-up controls. None of these patients developed liver toxicity. An increased in of ␥-GT levels occurred in the first two years of treatment, then they remained stable; AST and ALT levels showed no significant variations. Lipid levels remained in normal range, with a significant improvement of HDL-cholesterol in naïve patients. Conclusion: Long-term treatment with NVP is safe and effective, and it do not require use of statins in both experienced and naïve patients.

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Cardiovascular risk factors in patients on long-term treatment with nevirapine- or efavirenz-based regimens

Abstract: Patients treated with nevirapine demonstrated a better lipid and glucose profile and a lower tendency to develop subclinical atherosclerotic lesions.

Cited by 28 publications

References 20 publications

Cardiovascular Disease Risk Factors in HIV-Infected Women After Initiation of Lopinavir/Ritonavir- and Nevirapine-Based Antiretroviral Therapy in Sub-Saharan Africa

Cardiovascular Disease Risk Factors in HIV-Infected Women After Initiation of Lopinavir/Ritonavir- and Nevirapine-Based Antiretroviral Therapy in Sub-Saharan Africa

Role of endoplasmic reticulum stress in drug‐induced toxicity

Long-term efficacy and safety of treatment with nevirapine plus nucleoside reverse transcriptase inhibitors for HIV-1 infection: An eight-years follow-up

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