Details

Autor(en) / Beteiligte

• Mogalian, Erik
• Stamm, Luisa M
• Osinusi, Anu
• Brainard, Diana M
• Shen, Gong
• Ling, Kah Hiing John
• Mathias, Anita

Titel

Drug-Drug Interaction Studies Between Hepatitis C Virus Antivirals Sofosbuvir/Velpatasvir and Boosted and Unboosted Human Immunodeficiency Virus Antiretroviral Regimens in Healthy Volunteers

Ist Teil von

• Clinical infectious diseases, 2018-08, Vol.67 (6), p.934-940

Ort / Verlag

US: Oxford University Press

Erscheinungsjahr

2018

Quelle

Oxford Journals 2020 Medicine

Beschreibungen/Notizen

• Sofosbuvir/velpatasvir (SOF/VEL) may be administered with atazanavir, cobicistat, darunavir, dolutegravir, efavirenz (EFV), elvitegravir, emtricitabine, lopinavir, raltegravir, rilpivirine, ritonavir, tenofovir alafenamide, or tenofovir disoproxil fumarate without dose adjustment. Use of SOF/VEL with EFV is not recommended. Abstract Background Combining antiviral regimens in the hepatitis C virus (HCV)/human immunodeficiency virus (HIV)-coinfected population can be complex as they share overlapping mechanisms for elimination that may result in drug interactions. The pharmacokinetics, safety, and tolerability of sofosbuvir/velpatasvir (SOF/VEL) with multiple antiretroviral (ARV) regimens were evaluated. Methods Healthy volunteers were enrolled into 2 phase 1, open-label, randomized, multiple-dose, cross-over studies. SOF/VEL and ARV regimens were administered alone and in combination; ARVs (and pharmacokinetic enhancers) included atazanavir (ATV), cobicistat (COBI), darunavir (DRV), dolutegravir (DTG), efavirenz (EFV), elvitegravir (EVG), emtricitabine (FTC), lopinavir (LPV), raltegravir (RAL), rilpivirine (RPV), ritonavir (RTV), tenofovir alafenamide (TAF), and tenofovir disoproxil fumarate (TDF). Geometric least squares means ratios (coadministration:alone) and 90% confidence intervals were constructed for area under the plasma concentration-time curve over the dosing interval, maximum concentration, and trough, for all analytes. Safety and tolerability were also evaluated. Results In total, 237 participants were enrolled. No clinically relevant differences in the pharmacokinetics (PK) of SOF, SOF metabolite GS-331007, or VEL were observed other than an approximate 50% decrease in VEL exposure when administered with EFV/FTC/TDF. No clinically relevant differences in the PK of ARVs were observed when administered with SOF/VEL. Study treatments were well tolerated, including no observed creatinine clearance changes during evaluation of TDF-containing regimens. Conclusions SOF/VEL and ARV regimens including ATV, COBI, DRV, DTG, EVG, FTC, LPV, RAL, RPV, RTV, TAF, or TDF may be coadministered without dose adjustment. Use of SOF/VEL with EFV-containing regimens is not recommended due to an approximate 50% reduction in VEL exposure.