Clinical Application of Genvoya? in Adult HIV/AIDS Patients

doi:10.12114/j.issn.1007-9572.2020.00.131.

Abstract

Abstract: With the advent and widespread application of antiretroviral therapy（ART），AIDS has become a chronic controllable disease.AIDS is still a incurable disease and patients need to take their drugs for life.With the continuous updating of ART drugs，ensuring the antiviral effect and choosing drugs that are easy to take，have small adverse reactions，are safe and well tolerated is crucial to improving the quality of life of patients.Genvoya?，namely elvitegravir（EVG） / cobicistat（COBI） / emtricitabine（FTC） / tenofovir alafenamide（TAF），a combination of four drugs in a single tablet，abbreviated as E / C / F / TAF，has been approved by the US，EU and China Food and Drug Administration for AIDS treatment.This article focused on Genvoya?'s metabolic mechanism，clinical research，drug interactions and adverse reactions，and research on drug resistance in order to improve the comprehensive understanding of the drug by clinicians and patients.

Key words: AIDS, Antiretroviral therapy, Genvoya?, Elvitegravir（EVG）, cobicistat（COBI）, emtricitabine（FTC）, tenofovir alafenamide（TAF）

摘要： 随着抗逆转录病毒治疗的出现和广泛应用，获得性免疫缺陷综合征（AIDS）成为了一种慢性可控性疾病。目前AIDS仍不可治愈，患者仍需终生服药，但随着抗逆转录病毒药物不断更新，在保证抗病毒疗效的同时，选择服用方便、不良反应小、安全性和耐受性好的药物对提高患者生存质量至关重要。艾考恩，丙替（Genvoya?），即艾维雷韦（EVG）、科比司他（COBI）、恩曲他滨（FTC）、替诺福韦艾拉酚胺（TAF），四药合一的复方单片制剂，简写为E/C/F/TAF，先后获得美国、欧盟以及中国食品药品监督管理局批准用于AIDS治疗。本文重点对Genvoya?的代谢作用机制、临床研究、药物相互作用及不良反应、耐药性相关的研究进行概述，以提高临床医师和患者对该药物的综合认识。

关键词: 获得性免疫缺陷综合征, 抗逆转录病毒治疗, 艾考恩, 丙替, 艾维雷韦, 科比司他, 恩曲他滨, 替诺福韦艾拉酚胺

TAN Qing1,2,ZHOU Zhonghui2, et al. Clinical Application of Genvoya? in Adult HIV/AIDS Patients[J]. Chinese General Practice, 2020, 23(23): 2964-2968. DOI: 10.12114/j.issn.1007-9572.2020.00.131..
谭清1,2,周仲辉2等. 艾考恩，丙替在成年获得性免疫缺陷综合征患者的临床应用[J]. 中国全科医学, 2020, 23(23): 2964-2968. DOI: 10.12114/j.issn.1007-9572.2020.00.131..

References

［1］吴尊友.我国艾滋病经性传播新特征与防治面临的挑战［J］．中华流行病学杂志，2018，39（6）：707-709．DOI：10.3760/cma.j.issn.0254-6450.2018.06.002.
WU Z Y.Characteristics of HIV sexually transmission and challenges for controlling the epidemic in China［J］．Chinese Journal of Epidemiology，2018，39（6）：707-709．DOI：10.3760/cma.j.issn.0254-6450.2018.06.002.
［2］KEARNEY B P，FLAHERTY J F，SHAH J.Tenofovir disoproxil fumarate：clinical pharmacology and pharmacokinetics［J］．Clin Pharmacokinet，2004，43（9）：595-612．DOI：10.2165/00003088-200443090-00003.
［3］DE CLERCQ E.Tenofovir alafenamide（TAF） as the successor of tenofovir disoproxil fumarate（TDF）［J］．Biochem Pharmacol，2016，119：1-7．DOI：10.1016/j.bcp.2016.04.015.
［4］GIBSON A K，SHAH B M，NAMBIAR P H，et al．Tenofovir alafenamide［J］．Ann Pharmacother，2016，50（11）：942-952．DOI：10.1177/1060028016660812.
［5］GIACOMET V，COSSU M V，CAPETTI A F，et al．An evaluation of elvitegravir plus cobicistat plus tenofovir alafenamide plus emtricitabine as a single-tablet regimen for the treatment of HIV in children and adolescents［J］．Expert Opin Pharmacother，2019，20（3）：269-276．DOI：10.1080/14656566.2018.1559299.
［6］IRKUS G，WANG R，LIU X H，et al．Cathepsin A is the major hydrolase catalyzing the intracellular hydrolysis of the antiretroviral nucleotide phosphonoamidate prodrugs GS-7340 and GS-9131［J］．Antimicrob Agents Chemother，2007，51（2）：543-550．DOI：10.1128/AAC.00968-06.
［7］RAY A S，CIHLAR T，ROBINSON K L，et al．Mechanism of active renal tubular efflux of tenofovir［J］．Antimicrob Agents Chemother，2006，50（10）：3297-3304．DOI：10.1128/AAC.00251-06.
［8］BAM R A，YANT S R，CIHLAR T.Tenofovir alafenamide is not a substrate for renal organic anion transporters（OATs） and does not exhibit OAT-dependent cytotoxicity［J］．Antivir Ther，2014，19（7）：687-692．DOI：10.3851/imp2770.
［9］SAX P E，WOHL D，YIN M T，et al．Tenofovir alafenamide versus tenofovir disoproxil fumarate，coformulated with elvitegravir，cobicistat，and emtricitabine，for initial treatment of HIV-1 infection：two randomised，double-blind，phase 3，non-inferiority trials［J］．Lancet，2015，385（9987）：2606-2615．DOI：10.1016/S0140-6736（15）60616-X.
［10］RAMANATHAN S，MATHIAS A A，GERMAN P，et al．Clinical pharmacokinetic and pharmacodynamic profile of the HIV integrase inhibitor elvitegravir［J］．Clin Pharmacokinet，2011，50（4）：229-244．DOI：10.2165/11584570-000000000-00000.
［11］ROQUEBERT B，DAMOND F，COLLIN G，et al．HIV-2 integrase gene polymorphism and phenotypic susceptibility of HIV-2 clinical isolates to the integrase inhibitors raltegravir and elvitegravir in vitro［J］．J Antimicrob Chemother，2008，62（5）：914-920．DOI：10.1093/jac/dkn335.
［12］IMAZ A，PODZAMCZER D.Tenofovir alafenamide，emtricitabine，elvitegravir，and cobicistat combination therapy for the treatment of HIV［J］．Expert Rev Anti Infect Ther，2017，15（3）：195-209．DOI：10.1080/14787210.2017.1286736.
［13］LAMPIRIS H W.Elvitegravir：a once-daily，boosted，HIV-1 integrase inhibitor［J］．Expert Rev Anti Infect Ther，2012，10（1）：13-20．DOI：10.1586/eri.11.157.
［14］HAZUDA D，IWAMOTO M，WENNING L.Emerging pharmacology：inhibitors of human immunodeficiency virus integration［J］．Annu Rev Pharmacol Toxicol，2009，49：377-394．DOI：10.1146/annurev.pharmtox.011008.145553.
［15］CHAUVIN B，DROUOT S，BARRAIL-TRAN A，et al．Drug-drug interactions between HMG-CoA reductase inhibitors（statins） and antiviral protease inhibitors［J］．Clin Pharmacokinet，2013，52（10）：815-831．DOI：10.1007/s40262-013-0075-4.
［16］LEPIST E I，ZHANG X X，HAO J，et al．Contribution of the organic anion transporter OAT2 to the renal active tubular secretion of creatinine and mechanism for serum creatinine elevations caused by cobicistat［J］．Kidney Int，2014，86（2）：350-357．DOI：10.1038/ki.2014.66.
［17］TSENG A，HUGHES C A，WU J，et al．Cobicistat versus ritonavir：similar pharmacokinetic enhancers but some important differences［J］．Ann Pharmacother，2017，51（11）：1008-1022．DOI：10.1177/1060028017717018.
［18］SCH?LLER-GYüRE M，KAKUDA T N，RAOOF A，et al．Clinical pharmacokinetics and pharmacodynamics of etravirine［J］．Clin Pharmacokinet，2009，48（9）：561-574．DOI：10.2165/10895940-000000000-00000.
［19］KANG-BIRKEN S L，EL-SAYED D，PRICHARD J.HIV viral rebound due to a possible drug-drug interaction between elvitegravir/cobicistat/emtricitabine/tenofovir alafenamide and calcium-containing products：report of 2 cases［J］．J Int Assoc Provid AIDS Care，2019，18：2325958218821653．DOI：10.1177/2325958218821653.
［20］GERMAN P，LIU H C，SZWARCBERG J，et al．Effect of cobicistat on glomerular filtration rate in subjects with normal and impaired renal function［J］．J Acquir Immune Defic Syndr，2012，61（1）：32-40．DOI：10.1097/QAI.0b013e3182645648.
［21］ARRIBAS J R，THOMPSON M，SAX P E，et al．Brief report：randomized，double-blind comparison of tenofovir alafenamide（TAF） vs tenofovir disoproxil fumarate（TDF），each coformulated with elvitegravir，cobicistat，and emtricitabine（E/C/F） for initial HIV-1 treatment：week 144 results［J］．J Acquir Immune Defic Syndr，2017，75（2）：211-218．DOI：10.1097/QAI.0000000000001350.
［22］MILLS A，ARRIBAS J R，ANDRADE-VILLANUEVA J，et al．Switching from tenofovir disoproxil fumarate to tenofovir alafenamide in antiretroviral regimens for virologically suppressed adults with HIV-1 infection：a randomised，active-controlled，multicentre，open-label，phase 3，non-inferiority study［J］．Lancet Infect Dis，2016，16（1）：43-52．DOI：10.1016/S1473-3099（15）00348-5.
［23］GANTNER P，HESSAMFAR M，SOUALA F，et al．E/C/F/TAF single tablet regimen for HIV postexposure prophylaxis［C］//Conference on Retroviruses and Opportunistic Infections：Abstract eBook，2019：386.
［24］FORD N，IRVINE C，SHUBBER Z，et al．Adherence to HIV postexposure prophylaxis：a systematic review and meta-analysis［J］．AIDS，2014，28（18）：2721-2727．DOI：10.1097/QAD.0000000000000505.
［25］GALLANT J，BRUNETTA J，CROFOOT G，et al．Brief report：efficacy and safety of switching to a single-tablet regimen of elvitegravir/cobicistat/emtricitabine/tenofovir alafenamide in HIV-1/hepatitis B-coinfected adults［J］．J Acquir Immune Defic Syndr，2016，73（3）：294-298．DOI：10.1097/QAI.0000000000001069.
［26］GODINHO R，BUGNON S，GRACIN T，et al．Severe rhabdomyolysis-induced acute kidney injury following concomitant use of Genvoya?（EVG/COBI/FTC/TAF） and simvastatin；a case report［J］．BMC Nephrol，2019，20（1）：69．DOI：10.1186/s12882-019-1257-6.
［27］KANG-BIRKEN S L，EL-SAYED D，PRICHARD J.HIV viral rebound due to a possible drug-drug interaction between elvitegravir/cobicistat/emtricitabine/tenofovir alafenamide and calcium-containing products：report of 2 cases［J］．J Int Assoc Provid AIDS Care，2019，18：2325958218821653．DOI：10.1177/2325958218821653.
［28］SAX P E，WOHL D，YIN M T，et al．Tenofovir alafenamide versus tenofovir disoproxil fumarate，coformulated with elvitegravir，cobicistat，and emtricitabine，for initial treatment of HIV-1 infection：two randomised，double-blind，phase 3，non-inferiority trials［J］．Lancet，2015，385（9987）：2606-2615．DOI：10.1016/S0140-6736（15）60616-X.
［29］MARGOT N，COX S，DAS M，et al．Rare emergence of drug resistance in HIV-1 treatment-na?ve patients receiving elvitegravir/cobicistat/emtricitabine/tenofovir alafenamide for 144 weeks［J］．J Clin Virol，2018，103：37-42．DOI：10.1016/j.jcv.2018.03.012.

[1]	DUAN Yuxia, LI Zhen, ZHANG Siqi, FANG Zhixue, QIN Yuelan. Effect of Patient Decision Aids in the Diagnosis and Treatment of Colorectal Cancer: a Systematic Review [J]. Chinese General Practice, 2023, 26(25): 3194-3201.
[2]	Dongli WANG, Yanke AI, Jun YUAN, Xiuxia MA, Huijun GUO, Qianlei XU, Yantao JIN. Prevalence and Influencing Factors of Immunological Non-response in HIV/AIDS Patients with Second-line Antiretroviral Therapy [J]. Chinese General Practice, 2022, 25(30): 3789-3795.
[3]	Peng ZHANG, Yanping HUANG, Mingjia LIN, Wenjuan JING, Zhongsheng JIANG. Development and Application Assessment of a Clinical Diagnostic Scoring System for Tuberculous Meningitis [J]. Chinese General Practice, 2022, 25(24): 3043-3048.
[4]	Jun YANG, Pengyu LI, Yantao JIN, Jinyan PEI, Jingyu ZANG, Yanan LIU, Huangchao JIA, Zhihui WU, Zhenkui ZHANG, Yueyuan WANG, Huijun GUO. Quality of Life and Influencing Factors in Henan Rural People Living with HIV/AIDS [J]. Chinese General Practice, 2022, 25(21): 2646-2650.
[5]	GAO Chuan, GAO Ying, ZHOU Yuyu, GUO Xufang, HE Zhong. Effect of Patient Decision Aids in the Diagnosis and Treatment of Coronary Artery Disease：a Systematic Review [J]. Chinese General Practice, 2022, 25(05): 530-534.
[6]	LIU Jiamin，ZHAO Yasha，WANG Jingrui，LIU Peixuan，XI Ruihan，HAN Lin，DAI Fumin. Advances in the Use of Hearing Aids Improving Hearing Impairment in Older People with Community-based Home Care　 [J]. Chinese General Practice, 2021, 24(34): 4415-4420.
[7]	JIANG Zhongsheng，CHEN Tao，HU Jiaguang，ZHANG Peng，LI Minji. Effect of HAART on the Progression of Liver Fibrosis in Patients with both HIV and HBV Infection [J]. Chinese General Practice, 2019, 22(8): 925-930.