Risk of Metabolic Abnormalities in Patients Infected with HIV Receiving Antiretroviral Therapy that Contains Lopinavir‐Ritonavir

Martínez, Estebán; Domingo, Peré; Galindo, Marı́a José; Milinkovic, Ana; Arroyo, Juan Antonio; Baldovi, F; Larrousse, María; León, Agathe; Lazzari, Elisa de; Gatell, José M.

doi:10.1086/382531

Cited by 75 publications

(61 citation statements)

References 23 publications

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“…Despite the clinic significance of PIs, accumulating clinical evidence indicates that the incorporation of HIV PIs into HAART is associated with various adverse effects, such as metabolic syndrome characterized by dyslipidemia, insulin resistance, and lipodystrophy [2,3] . 20(S)-Ginsenoside Rh2 (Rh2), a component isolated from red ginseng [4] , is one of the most studied ginsenosides due to its various pharmacological activities, such as anti-cancer effects, anti-hyperglycemic effects, and anti-obesity effects [5][6][7][8] .…”

Section: Introductionmentioning

confidence: 99%

Pharmacokinetic interactions between 20(S)-ginsenoside Rh2 and the HIV protease inhibitor ritonavir in vitro and in vivo

et al. 2013

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Aim: 20(S)-Ginsenoside Rh2 (Rh2) has shown potent inhibition on P-glycoprotein (P-gp), while most HIV protease inhibitors are both substrates and inhibitors of P-gp and CYP3A4. The aim of this study was to investigate the potential pharmacokinetic interactions between Rh2 and the HIV protease inhibitor ritonavir. Methods: The effects of Rh2 on the cellular accumulation and transepithelial transport of ritonavir were studied in Caco-2 and MDCK-MDR1 cells. Male rats were administered Rh2 (25 or 60 mg/kg, po) or Rh2 (5 mg/kg, iv), followed by ritonavir (25 mg/kg, po). The P-gp inhibitors verapamil (20 mg/kg, po) or GF120918 (5 mg/kg, po) were used as positive controls. The concentrations of ritonavir in plasma, bile, urine, feces and tissue homogenates were analyzed using LC-MS. Results: Rh2 (10 μmol/L) significantly increased the accumulation and inhibited the efflux of ritonavir in Caco-2 and MDCK-MDR1 cells, as verapamil did. But Rh2 did not significantly alter ritonavir accumulation or transport in MDCK-WT cells. Intravenous Rh2 significantly increased the plasma exposure of ritonavir while reducing its excretion in the bile, and oral verapamil or GF120918 also increased plasma exposure of ritonavir but without changing its excretion in the bile. Interestingly, oral Rh2 at both doses did not significantly change the plasma profile of ritonavir. Moreover, oral Rh2 (25 mg/kg) significantly elevated the ritonavir concentration in the hepatic portal vein, and markedly increased its urinary excretion and tissue distribution, which might counteract the elevated absorption of ritonavir. Conclusion: Rh2 inhibits the efflux of ritonavir through P-gp in vitro. The effects of Rh2 on ritonavir exposure in vivo depend on the administration route of Rh2: intravenous, but not oral, administration of Rh2 significantly increased the plasma exposure of ritonavir.

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Section: Introductionmentioning

confidence: 99%

Pharmacokinetic interactions between 20(S)-ginsenoside Rh2 and the HIV protease inhibitor ritonavir in vitro and in vivo

et al. 2013

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“…Dyslipidemia in HIV-infected patients using HAART includes, elevated level of total cholesterol (TC), LDL cholesterol (LDL-c), triglycerides (TG), and decreased HDLcholesterol (HDL-c), and severe hypertriglyceridemia in several patients (El-Sadr et al, 2005). Stavudine (d4T) from nucleoside reverse transcriptase inhibitors (NRTIs) regimens is the most commonly mentioned antiretroviral agent that is being associated with metabolic syndrome (MS) and HIV related fat accumulation (Matinez et al, 2004;Jemsek et al, 2006). Lipoatrophy and lipohypertrophy are associated with multiple metabolic derangements in the setting of HIV infection and antiretroviral therapy (ART).…”

Section: Introductionmentioning

confidence: 99%

Change in serum lipid profiles and glucose after switching from stavudine/lamivudine to zidovudine/lamivudine in non-nucleoside reverse transcriptase inhibitors based anti-retroviral regimens in Southern Ethiopia

Tadewos¹,

Fenta²

2015

J. AIDS HIV Res.

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Data concerning any difference in serum lipid profiles and glucose level after patients switched from stavudine to zidovudine in Ethiopia is very limited. Seventy eight adults receiving antiretroviral therapy (ART) that included stavudine/lamivudine with either of efavirenz or nevirapine during ART initiation were enrolled. Of these patients, 53 were switched to zidovudine/lamivudine/nevirapine (NVP-group) and the rest 25 were switched to zidovudine/lamivudine/efavirenz (EFV-group). Serum lipid profiles and glucose were determined after overnight fasting. Dyslipidemia and dysglycaemia were assessed according to the United State National Cholesterol Education program-III guideline. Statistical analysis was done using Statistical Package for Social Sciences (SPSS) Version 20. Of the 78 patients, 39.7% were males and 60.3% were females. At the end of the study follow-up, the prevalence of TC ≥ 200 mg/dl, LDL-c ≥ 130 mg/dl, TG ≥ 150 mg/dl, HDL-c < 40 mg/dl and glucose ≥ 110 mg/dl were higher in EFV group when compared with NVP. About 74.4% patients had at least two laboratory abnormities which is compatible with a diagnosis of dyslipidemia at 12 month of post switch. Four lipid profiles abnormal within a single individual was 16% in EFV and 3.8% in NVP group, p = 0.08. Raised HDL-c concentration was observed in NVP group in both periods when compared with EFV. In addition, patients that switched from d4T/3TC/NVP to AZT/3TC/NVP had a significant change in TC and TG (p = 0.001 for both). Also TC ≥ 200 mg/dl was decreased from 49 to 16% (p = 0.04). Furthermore, sex was significantly and negatively associated with raised TC and TGs among patients using NVP based regimen. Raised HDL-c concentration, decreased proportion of abnormal lipid profiles and abnormal glucose was observed in the NVP group. Based on these findings, NVP may be expected to reduce the risk of cardiovascular diseases.

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“…Grade 3 or higher hypercholesterolaemia and hypertriglyceridaemia have been reported in around 10% of antiretroviral therapy-naive patients and in up to 30% of patients with prevous PI-experience [1][2][3][4]. Patients with initially high lipid levels are at higher risk of developing (severe) hyperlipidaemia.…”

Section: Introductionmentioning

confidence: 99%

Lopinavir Plasma Concentrations and Serum Lipids in Therapy Naïve HIV-Patients: A Sub Analysis of the FREE Study

Hofstede¹,

Koopmans²,

Burger³

et al. 2012

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Antiretroviral therapy in HIV patients is known for its negative effect on the cardiovascular system. One of the major adverse events in patients on lopinavir is increasing lipids. Hyperlipidaemia together with chronic inflammation by HIV-infection itself makes these patients prone for cardiovascular diseases.The purpose of this study (a sub study within the FREE-study) was to determine if higher plasma lopinavir (LPV) concentrations lead to increase of serum lipids. Plasma drug concentrations were analysed up to week 24 in a prospective cohort of HIV antiretroviral therapy naive patients who started on a regimen of zidovudine, lamivudine and ritonavir-boosted lopinavir (FREE study). Prospectively we measured plasma lopinavir concentrations from baseline to week 24 in 72 naive HIV-patients starting on lopinavir (59 males and 13 females). A total of 210 samples were analysed, with at least 2 samples in every patient. Mean LPV trough concentration was 4.3 mg/L (± 2.1). The median intra-subject variation in LPV level was 38% (range 4% -111%). Serum lipids were not correlated to LPV plasma concentrations possibly due to the wide intra-individual variability in LPV trough levels. Monitoring of plasma lopinavir and subsequent dose adjustment of LPV will not be useful to prevent hyperlipidaemia in HIV-patients treated with lopinavir.

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Risk of Metabolic Abnormalities in Patients Infected with HIV Receiving Antiretroviral Therapy that Contains Lopinavir‐Ritonavir

Cited by 75 publications

References 23 publications

Pharmacokinetic interactions between 20(S)-ginsenoside Rh2 and the HIV protease inhibitor ritonavir in vitro and in vivo

Pharmacokinetic interactions between 20(S)-ginsenoside Rh2 and the HIV protease inhibitor ritonavir in vitro and in vivo

Change in serum lipid profiles and glucose after switching from stavudine/lamivudine to zidovudine/lamivudine in non-nucleoside reverse transcriptase inhibitors based anti-retroviral regimens in Southern Ethiopia

Lopinavir Plasma Concentrations and Serum Lipids in Therapy Naïve HIV-Patients: A Sub Analysis of the FREE Study

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Risk of Metabolic Abnormalities in Patients Infected with HIV Receiving Antiretroviral Therapy that Contains Lopinavir‐Ritonavir

Cited by 75 publications

References 23 publications

Pharmacokinetic interactions between 20(S)-ginsenoside Rh2 and the HIV protease inhibitor ritonavir in vitro and in vivo

Pharmacokinetic interactions between 20(S)-ginsenoside Rh2 and the HIV protease inhibitor ritonavir in vitro and in vivo

Change in serum lipid profiles and glucose after switching from stavudine/lamivudine to zidovudine/lamivudine in non-nucleoside reverse transcriptase inhibitors based anti-retroviral regimens in Southern Ethiopia

Lopinavir Plasma Concentrations and Serum Lipids in Therapy Na&#239;ve HIV-Patients: A Sub Analysis of the FREE Study

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Lopinavir Plasma Concentrations and Serum Lipids in Therapy Naïve HIV-Patients: A Sub Analysis of the FREE Study