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Drug-Drug Interactions of Glecaprevir and Pibrentasvir Coadministered With Human Immunodeficiency Virus Antiretrovirals.
The Journal of Infectious Diseases ( IF 6.4 ) Pub Date : 2020-01-02 , DOI: 10.1093/infdis/jiz439
Matthew P Kosloski 1 , Rajneet Oberoi 1 , Stanley Wang 1 , Rolando M Viani 1 , Armen Asatryan 1 , Beibei Hu 1 , Bifeng Ding 1 , Xin Qi 1 , Elaine J Kim 1 , Federico Mensa 1 , Jens Kort 1 , Wei Liu 1
Affiliation  

BACKGROUND Treatment of patients coinfected with hepatitis C and human immunodeficiency viruses (HCV; HIV) requires careful consideration of potential drug-drug interactions between HCV direct-acting antiviral agents (DAA) and HIV antiretrovirals. Glecaprevir/pibrentasvir is a fixed-dose combination of an NS3/4A protease inhibitor and an NS5A inhibitor approved for the treatment of chronic HCV genotype 1-6 infection, including patients with HIV coinfection. METHODS A series of phase 1 studies was conducted to evaluate potential interactions of glecaprevir and pibrentasvir with elvitegravir/cobicistat/emtricitabine/tenofovir alafenamide, abacavir/dolutegravir/lamivudine, raltegravir, rilpivirine, atazanavir/ritonavir, darunavir/ritonavir, lopinavir/ritonavir, or efavirenz/emtricitabine/tenofovir disoproxil fumarate. Pharmacokinetics of the antiretrovirals and DAAs were characterized when administered alone and in combination to quantify changes in systemic drug exposure. RESULTS Glecaprevir area under the curve increased >4-fold in the presence of ritonavir-boosted HIV protease inhibitors, while pibrentasvir concentrations were not significantly affected; elevations in alanine transaminase occurred in combination with atazanavir/ritonavir only. Exposures of glecaprevir and pibrentasvir may be significantly decreased by efavirenz. Coadministration with glecaprevir and pibrentasvir did not result in clinically significant changes in the exposure of any antiretroviral agents. CONCLUSIONS Atazanavir is contraindicated with glecaprevir/pibrentasvir and use of boosted protease inhibitors or efavirenz is not recommended. No clinically significant interactions were observed with other studied antiretrovirals.

中文翻译:

Glecaprevir和Pibrentasvir与人类免疫缺陷病毒抗逆转录病毒药物共同给药的药物相互作用。

背景技术对合并感染丙型肝炎和人类免疫缺陷病毒(HCV; HIV)的患者的治疗需要仔细考虑HCV直接作用抗病毒药(DAA)和HIV抗逆转录病毒药之间的潜在药物相互作用。Glecaprevir / pibrentasvir是NS3 / 4A蛋白酶抑制剂和NS5A抑制剂的固定剂量组合,已批准用于治疗HCV 1-6型慢性感染,包括HIV合并感染的患者。方法进行了一系列的第一阶段研究,以评估格列卡韦和匹布那韦与elvitegravir / cobicistat / emtricitabine / tenofovir alafenamide,abacavir / dolutegravir / lamivudine,raltegravir,rilpivirine,atazanavir / ritonavir / darunavir / ritona,darunavir / ritona的潜在相互作用依非韦伦/恩曲他滨/替诺福韦富马酸替索非尔。抗逆转录病毒药物和DAA的药代动力学可以单独或组合给药以定量全身性药物暴露的变化。结果在存在利托那韦增强的HIV蛋白酶抑制剂的情况下,曲线下的Glecaprevir面积增加了4倍以上,而pibrentasvir的浓度未受到明显影响。仅与阿扎那韦/利托那韦联合使用时,丙氨酸转氨酶升高。依法韦仑可能会显着降低格列卡韦和比布那他韦的暴露。与glecaprevir和pibrentasvir并用不会导致任何抗逆转录病毒药物暴露的临床显着变化。结论Atazanavir与glecaprevir / pibrentasvir禁忌使用,不建议使用加强型蛋白酶抑制剂或依非韦伦。
更新日期:2019-12-30
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