梁雪蕾;李群;肖晴;劳晓洁;张福杰;

• 1:首都医科大学附属北京地坛医院
• 2:首都医科大学艾滋病临床诊疗与研究中心

摘要(Abstract)：

联合抗反转录病毒治疗（cART）已经使艾滋病成为一种慢性可控性传染病。cART虽然可以使病毒得到抑制，但需终身服药。治疗前耐药率的增加、药物不良反应、每日口服药物的依从性等仍是治疗HIV的主要挑战。基于此，新的抗病毒药物的不断研发，ART方案不断优化，抗病毒药物的有效性、安全性、简便性和耐药屏障也不断提高。复方片剂、新治疗靶点药物和长效药物是目前研发的主要趋势。本文概述了ART的最新进展，以期为临床提供参考。

关键词(KeyWords)： 艾滋病;抗反转录病毒治疗;药物

Abstract:

Keywords:

基金项目(Foundation): “十三五”国家科技重大专项（2018ZX10302-102）;; 北京市医管中心项目（DFL20191802）;; 北京市医院管理局临床医学发展专项（ZYLX202126）;; 首都卫生发展科研专项（2020-2-2174）~~

作者(Authors): 梁雪蕾;李群;肖晴;劳晓洁;张福杰;

DOI: 10.13419/j.cnki.aids.2022.11.25

参考文献(References)：

• [1]World Health Organization.HIV/AIDS[EB/OL].(2022-07-17)[2022-10-25].https：//www.who.int/news-room/fact-sheets/detail/hiv-aids.
• [2]SERUMULA W,FERNANDEZ G,GONZALEZ VM,et al.Anti-HIV aptamers:challenges and prospects[J].Curr HIVRes,2022,20(1):7-19.DOI:10.2174/1570162X19666210908114825.
• [3]BERTRAND L,VELICHKOVSKA M,TOBOREK M.Cerebral vascular toxicity of antiretroviral therapy[J].JNeuroimmune Pharmacol,2021,16(1):74-89.DOI:10.1007/s11481-019-09858-x.
• [4]BLASSEL L,TOSTEVIN A,VILLABONA-ARENAS CJ,et al.Using machine learning and big data to explore the drug resistance landscape in HIV[J].PLo S Comput Biol,2021,17(8):e1008873.DOI:10.1371/journal.pcbi.1008873.
• [5]HINES DM,DING Y,WADE RL,et al.Treatment adherence and persistence among HIV-1 patients newly starting treatment[J].Patient Prefer Adherence,2019(13):1927-1939.DOI:10.2147/PPA.S207908.
• [6]FDA.FDA approves first two-drug complete regimen for HIV-infected patients who have never received antiretroviral treatment[EB/OL].(2019-04-08)[2022-10-25].https：//www.fda.gov/newsevents/press-announcements/fda-approves-first-two-drug-completeregimen-hiv-infected-patients-who-have-never-received.
• [7]中华医学会感染病学分会艾滋病丙型肝炎学组，中国疾病预防控制中心.中国艾滋病诊疗指南（2021年版）[J].中国艾滋病性病.2021,27(11):1182-1201.
• [8]CAHN P,SIERRA MADERO J,ARRIBAS JR,et al.Threeyear durable efficacy of dolutegravir plus lamivudine in antiretroviral therapy-naive adults with HIV-1 infection[J].AIDS,2022,36(1):39-48.DOI:10.1097/QAD.0000000000003070.
• [9]VAN WYK J,AJANA F,BISSHOP F,et al.Efficacy and safety of switching to dolutegravir/lamivudine fixed-dose 2-drug regimen vs continuing a tenofovir alafenamide-based 3-or 4-drug regimen for maintenance of virologic suppression in adults living with human immunodeficiency virus type 1:phase 3,randomized,noninferiority TANGO study[J].Clin Infect Dis,2020,71(8):1920-1929.DOI:10.1093/cid/ciz1243.
• [10]LLIBRE JM,BRITES C,CHENG CY,et al.Efficacy and safety of switching to the 2-drug regimen dolutegravir/lamivudine versus continuing a 3-or 4-drug regimen for maintaining virologic suppression in adults living with HIV-1:week 48 results from the phase 3,non-inferiority SALSArandomized trial[J].Clin Infect Dis,2022:ciac130.(Epub ahead of Print).DOI:10.1093/cid/ciac130.
• [11]SAX P,JOSE A,CHLOE O,et al.Long-term Integrated Analysis of B/F/TAF in Treatment-Na?ve Adults With HIVThrough Five Years of Follow-up[C].AIDS 2022,Poster EPB150.
• [12]AVIHINGSANON A.,Lu H.,LEONG C.L.,et al.Week 48results of a Phase 3 randomized controlled trial of bictegravir/emtricitabine/tenofovir alafenamide (B/F/TAF) vs dolutegravir+emtricitabine/tenofovir Disoproxil Fumarate (DTG+F/TDF)as initial treatment in HIV/HBV-coinfected adults(ALLIANCE)[C].AIDS 2022,Oral abstract OALBX0105.
• [13]BARES SH,SCARSI KK.A new paradigm for antiretroviral delivery:long-acting cabotegravir and rilpivirine for the treatment and prevention of HIV[J].Curr Opin HIV AIDS,2022,17(1):22-31.DOI:10.1097/COH.0000000000000708.
• [14]SWINDELLS S,ANDRADE-VILLANUEVA JF,RICHMONDGJ,et al.Long-acting cabotegravir and rilpivirine for maintenance of HIV-1 suppression[J].N Engl J Med,2020,382(12):1112-1123.DOI:10.1056/NEJMoa1904398.
• [15]RIZZARDINI G,OVERTON ET,ORKIN C,et al.Longacting injectable cabotegravir+rilpivirine for HIV maintenance therapy:week 48 pooled analysis of phase 3 ATLAS and FLAIRtrials[J].J Acquir Immune Defic Syndr,2020,85(4):498-506.DOI:10.1097/QAI.0000000000002466.
• [16]OVERTON ET,RICHMOND G,RIZZARDINI G,et al.Longacting cabotegravir and rilpivirine dosed every 2 months in adults with HIV-1 infection(ATLAS-2M),48-week results:a randomised,multicentre,open-label,phase 3b,non-inferiority study[J].Lancet,2021,396(10267):1994-2005.DOI:10.1016/S0140-6736(20)32666-0.
• [17]JAEGER H,OVERTON ET,RICHMOND G,et al.Longacting cabotegravir and rilpivirine dosed every 2 months in adults with HIV-1 infection(ATLAS-2M),96-week results:a randomised,multicentre,open-label,phase 3b,non-inferiority study[J].Lancet HIV,2021,8(11):e679-e689.DOI:10.1016/S2352-3018(21)00185-5.
• [18]FDA.CABENUVA (cabotegravir extended-release injectable suspension;rilpivirine extended-release injectale suspension),co-packaged for intramuscular use[EB/OL].(2022-03-29)[2022-10-25].https：//www.accessdata.fda.gov/drugsatfda_docs/label/2022/212888 s005 s006lbl.pdf.
• [19]RAEL CT,MARTINEZ M,GIGUERE R,et al.Barriers and facilitators to oral Pr EP use among transgender women in New York City[J].AIDS Behav,2018,22(11):3627-3636.DOI:10.1007/s10461-018-2102-9.
• [20]OGUNBAJO A,STORHOLM ED,OBER AJ,et al.Multilevel barriers to HIV Pr EP uptake and adherence among black and hispanic/latinx transgender women in southern California[J].AIDS Behav,2021,25(7):2301-2315.DOI:10.1007/s10461-021-03159-2.
• [21]MAYER KH,AGWU A,MALEBRANCHE D.Barriers to the wider use of pre-exposure prophylaxis in the United States:a narrative review[J].Adv Ther,2020,37(5):1778-1811.DOI:10.1007/s12325-020-01295-0.
• [22]LANDOVITZ RJ,DONNELL D,CLEMENT ME,et al.Cabotegravir for HIV prevention in cisgender men and transgender women[J].N Engl J Med,2021,385(7):595-608.DOI:10.1056/NEJMoa2101016.
• [23]DELANY-MORETLWE S,HUGHES JP,BOCK P,et al.Cabotegravir for the prevention of HIV-1 in women:results from HPTN 084,a phase 3,randomised clinical trial[J].Lancet,2022,399(10337):1779-1789.DOI:10.1016/S0140-6736(22)00538-4.
• [24]FDA.FDA Approves First Injectable Treatment for HIV PreExposure Prevention[EB/OL].(2021-12-20)[2022-10-25].https：//www.fda.gov/news-events/press-announcements/fdaapproves-first-injectable-treatment-hiv-pre-exposure-prevention.
• [25]GAUTAM N,MCMILLAN JM,KUMAR D,et al.Lipophilic nanocrystal prodrug-release defines the extended pharmacokinetic profiles of a year-long cabotegravir[J].Nat Commun,2021,12(1):3453.DOI:10.1038/s41467-021-23668-x.
• [26]SEGAL-MAURER S,DEJESUS E,STELLBRINK HJ,et al.Capsid inhibition with lenacapavir in multidrug-resistant HIV-1infection[J].N Engl J Med,2022,386(19):1793-1803.DOI:10.1056/NEJMoa2115542.
• [27]GUPTA SK,JAMES S,CYNTHIA B,et al.LENACAPAVIRAS PART OF A COMBINATION REGIMEN IN TREATMENTNA?VE PWH:WEEK 54 RESULTS[C].CROI 2022,Oral 138.
• [28]MOLINA JM,YAZDANPANAH Y,AFANI SAUD A,et al.Islatravir in combination with doravirine for treatment-naive adults with HIV-1 infection receiving initial treatment with islatravir,doravirine,and lamivudine:a phase 2b,randomised,double-blind,dose-ranging trial[J].Lancet HIV,2021,8(6):e324-e333.DOI:10.1016/S2352-3018(21)00021-7.
• [29]MATTHEWS RP,PATEL M,BARRETT SE,et al.Safety and pharmacokinetics of islatravir subdermal implant for HIV-1 preexposure prophylaxis:a randomized,placebo-controlled phase1 trial[J].Nat Med,2021,27(10):1712-1717.DOI:10.1038/s41591-021-01479-3.
• [30]MERCK.Merck Announces Clinical Holds on Studies Evaluating Islatravir for the Treatment and Prevention of HIV-1Infection[EB/OL].(2021-12-13)[2022-10-25].https：//www.merck.com/news/merck-announces-clinical-holds-on-studiesevaluating-islatravir-for-the-treatment-and-prevention-of-hiv-1-infection/.
• [31]MERCK.Merck to Initiate New Phase 3 Clinical Program with Lower Dose of Daily Oral Islatravir in Combination with Doravirine for Treatment of People with HIV-1 Infection[EB/OL].(2022-9-20)[2022-10-25].https：//www.merck.com/news/merck-to-initiate-new-phase-3-clinical-program-with-lower-doseof-daily-oral-islatravir-in-combination-with-doravirine-for-treatmentof-people-with-hiv-1-infection/.
• [32]GRANT PM,KOZAL MJ.Fostemsavir:a first-in-class HIV-1attachment inhibitor[J].Curr Opin HIV AIDS,2022,17(1):32-35.DOI:10.1097/COH.0000000000000712.
• [33]LATAILLADE M,LALEZARI JP,KOZAL M,et al.Safety and efficacy of the HIV-1 attachment inhibitor prodrug fostemsavir in heavily treatment-experienced individuals:week96 results of the phase 3 BRIGHTE study[J].Lancet HIV,2020,7 (11):e740-e751.DOI:10.1016/S2352-3018 (20)30240-X.
• [34]JOSHI SR,FERNANDO D,IGWE S,et al.Phase I evaluation of the safety,tolerability,and pharmacokinetics of GSK3640254,a next-generation HIV-1 maturation inhibitor[J].Pharmacol Res Perspect,2020,8(6):e00671.DOI:10.1002/prp2.671.
• [35]SPINNER CD,FELIZARTA F,RIZZARDINI G,et al.Phase IIa proof-of-concept evaluation of the antiviral efficacy,safety,tolerability,and pharmacokinetics of the next-generation maturation inhibitor GSK3640254[J].Clin Infect Dis,2022,75(5):786-794.DOI:10.1093/cid/ciab1065.
• [36]MAHOMED S,GARRETT N,BAXTER C,et al.Clinical trials of broadly neutralizing monoclonal antibodies for human immunodeficiency virus prevention:a review[J].J Infect Dis,2021,223(3):370-380.DOI:10.1093/infdis/jiaa377.
• [37]MIN S,SLOAN L,DEJESUS E,et al.Antiviral activity,safety,and pharmacokinetics/pharmacodynamics of dolutegravir as 10-day monotherapy in HIV-1-infected adults[J].AIDS,2011,25(14):1737-45.DOI:10.1097/QAD.0b013e32834a1 dd9.
• [38]GALLANT JE,THOMPSON M,DEJESUS E,et al.Antiviral Activity,Safety,and Pharmacokinetics of Bictegravir as 10-Day Monotherapy in HIV-1-Infected Adults[J].J Acquir Immune Defic Syndr,2017,75(1):61-66.DOI:10.1097/QAI.0000000000001306.
• [39]Developed by the HHS Panel on Antiretroviral Guidelines for Adults and Adolescents-A Working Group of the Office of AIDS Research Advisory Council(OARAC).Guidelines for the Use of Antiretroviral Agents in Adults and Adolescents with HIV[EB/OL].(2022-09-21)[2022-10-25].https：//clinicalinfo.hiv.gov/sites/default/files/guidelines/documents/adult-adolescent-arv/guidelines-adult-adolescent-arv.pdf.
• [40]SAAG MS,GANDHI RT,HOY JF,et al.Antiretroviral Drugs for Treatment and Prevention of HIV Infection in Adults:2020Recommendations of the International Antiviral Society-USAPanel[J].JAMA,2020,324(16):1651-1669.DOI:10.1001/jama.2020.17025.
• [41]European AIDS Clinical Society.EACS Guidelines 2022(Version 11.1)[EB/OL].(2022-10)[2022-10-25].https：//www.eacsociety.org/media/guidelines-11.1_final_09-10.pdf.
• [42]World Health Organization.Consolidated Guidelines on HIVPrevention,Testing,Treatment,Service Delivery and Monitoring:Recommendations for a Public Health Approach[Internet][R].Geneva:World Health Organization,2021.
• [43]KOETHE JR,LAGATHU C,LAKE JE,et al.HIV and antiretroviral therapy-related fat alterations[J].Nat Rev Dis Primers,2020,6(1):48.DOI:10.1038/s41572-020-0181-1.
• [44]MARGOLIS DM,ARCHIN NM,COHEN MS,et al.Curing HIV:seeking to target and clear persistent infection[J].Cell,2020,181(1):189-206.DOI:10.1016/j.cell.2020.03.005.
• [45]SPIVAK AM,PLANELLES V.Novel latency reversal agents for HIV-1 cure[J].Annu Rev Med,2018(69):421-436.DOI:10.1146/annurev-med-052716-031710.
• [46]HENDERSON LJ,REOMA LB,KOVACS JA,et al.Advances toward Curing HIV-1 Infection in Tissue Reservoirs[J].J Virol,2020,94(3):e00375-19.DOI:10.1128/JVI.00375-19.
• [47]DEEKS SG,ARCHIN N,CANNON P,et al.Research priorities for an HIV cure:International AIDS Society Global Scientific Strategy 2021[J].Nat Med,2021,27(12):2085-2098.DOI:10.1038/s41591-021-01590-5.