Perrine Courlet1, Françoise Livio1, Susana Alves Saldanha1, Alexandra Scherrer2,3, Manuel Battegay4,5, Matthias Cavassini6, Marcel Stoeckle4,5, Laurent Arthur Decosterd1, Catia Marzolini4,5,7. 1. Service of Clinical Pharmacology, University Hospital of Lausanne and University of Lausanne, Lausanne, Switzerland. 2. Division of Infectious Diseases and Hospital Epidemiology, University Hospital of Zurich, University of Zurich, Zurich, Switzerland. 3. Institute of Medical Virology, University of Zurich, Zurich, Switzerland. 4. University of Basel, Basel, Switzerland. 5. Division of Infectious Diseases and Hospital Epidemiology, Departments of Medicine and Clinical Research, University Hospital of Basel, Basel, Switzerland. 6. Service of Infectious Diseases, University Hospital of Lausanne and University of Lausanne, Lausanne, Switzerland. 7. Department of Molecular and Clinical Pharmacology, Institute of Translational Medicine, University of Liverpool, Liverpool, UK.
Abstract
BACKGROUND: PIs cause drug-drug interactions (DDIs) with most statins due to inhibition of drug-metabolizing enzymes and/or the hepatic uptake transporter OATP1B1, which may alter the pharmacodynamic (PD) effect of statins. OBJECTIVES: To assess the management of DDIs between antiretrovirals (ARVs) and statins in people living with HIV (PLWH) considering statin plasma concentrations, compliance with dosing recommendations and achievement of lipid targets. METHODS: PLWH of the Swiss HIV Cohort Study were eligible if they received a statin concomitantly with ARVs. HDL, total cholesterol (TC) and statin plasma concentration were measured during follow-up visits. Individual non-HDL and TC target values were set using the Framingham score and the 2018 European AIDS Clinical Society recommendations. RESULTS: Data were analysed for rosuvastatin (n = 99), atorvastatin (n = 92), pravastatin (n = 46) and pitavastatin (n = 21). Rosuvastatin and atorvastatin underdosing frequently led to suboptimal PD response. Insufficient lipid control was observed with PIs despite high atorvastatin concentrations, likely explained by inhibition of OATP1B1 resulting in less statin uptake in the liver. Target lipid values were more often achieved with unboosted integrase inhibitors due to both their favourable DDI profiles and neutral effect on lipids. Insufficient lipid control was common with pravastatin and pitavastatin regardless of co-administered ARVs and despite using maximal recommended statin doses. The latter suggests lower efficacy compared with rosuvastatin or atorvastatin. CONCLUSIONS: Suboptimal management of DDIs with statin underdosing was observed in 29% of prescriptions. Integrase inhibitor-based regimens and/or treatment with rosuvastatin or atorvastatin should be favoured in patients with refractory dyslipidaemia.
BACKGROUND:PIs cause drug-drug interactions (DDIs) with most statins due to inhibition of drug-metabolizing enzymes and/or the hepatic uptake transporter OATP1B1, which may alter the pharmacodynamic (PD) effect of statins. OBJECTIVES: To assess the management of DDIs between antiretrovirals (ARVs) and statins in people living with HIV (PLWH) considering statin plasma concentrations, compliance with dosing recommendations and achievement of lipid targets. METHODS: PLWH of the Swiss HIV Cohort Study were eligible if they received a statin concomitantly with ARVs. HDL, total cholesterol (TC) and statin plasma concentration were measured during follow-up visits. Individual non-HDL and TC target values were set using the Framingham score and the 2018 European AIDS Clinical Society recommendations. RESULTS: Data were analysed for rosuvastatin (n = 99), atorvastatin (n = 92), pravastatin (n = 46) and pitavastatin (n = 21). Rosuvastatin and atorvastatin underdosing frequently led to suboptimal PD response. Insufficient lipid control was observed with PIs despite high atorvastatin concentrations, likely explained by inhibition of OATP1B1 resulting in less statin uptake in the liver. Target lipid values were more often achieved with unboosted integrase inhibitors due to both their favourable DDI profiles and neutral effect on lipids. Insufficient lipid control was common with pravastatin and pitavastatin regardless of co-administered ARVs and despite using maximal recommended statin doses. The latter suggests lower efficacy compared with rosuvastatin or atorvastatin. CONCLUSIONS: Suboptimal management of DDIs with statin underdosing was observed in 29% of prescriptions. Integrase inhibitor-based regimens and/or treatment with rosuvastatin or atorvastatin should be favoured in patients with refractory dyslipidaemia.
Authors: Triin Umbleja; Todd T Brown; Edgar T Overton; Heather J Ribaudo; Jennifer A Schrack; Kathleen V Fitch; Pamela S Douglas; Steven K Grinspoon; Sarah Henn; Roberto C Arduino; Benigno Rodriguez; Constance A Benson; Kristine M Erlandson Journal: J Infect Dis Date: 2020-07-09 Impact factor: 5.226
Authors: Chi-Hua Lu; Edward M Bednarczyk; Linda M Catanzaro; Alyssa Shon; Jia-Chen Xu; Qing Ma Journal: Curr Res Pharmacol Drug Discov Date: 2021-08-08