Dual antiretroviral regimens: A new challenging issue of HIV-infected patient treatment

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Ratchayut Harichtee
Nattabhum Kunathikom
Kittiya Jantarathaneewat


Triple antiretroviral (ARV) regimens are recommended as first-line treatment for HIV infection in various guidelines. However, there are limitations in some HIV-infected patients who have adverse drug reactions or drug interaction with other medication resulting in inability to use these triple regimens. Dual antiretroviral regimens with high efficacy are considered as an alternative choice for both treatment-naïve and treatment-experienced patients. Dolutegravir and lamivudine are one of dual ARV regimens which have been widely studied and mostly recommended by several guidelines. However, there are some important factors to consider prior to prescribing dual ARV regimen such as viral load, comorbidity, and history of hepatitis B infection. In addition, there have been recent studies about other dual ARV regimens which could be used as alternatives in the near future. This review article aimed to review studies about currently available dual ARV regimens in terms of benefits, disadvantages, efficacy, and safety precaution.


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Achhra AC, Mwasakifwa G, Amin J, Boyd MA. Efficacy and safety of contemporary dual-drug antiretroviral regimens as first-line treatment or as a simplification strategy: a systematic review and meta-analysis. Lancet HIV. 2016;3(8):e351-e360.

Agarwal D, Chakravarty J, Chaube L, Rai M, Agrawal NR, Sundar S. High incidence of zidovudine induced anaemia in HIV infected patients in eastern India. Indian J Med Res. 2010 Oct;132:386-9.

AIDS Surveillance System. Prevalence of HIV infection in Thailand 2018 [Online]. 2019 [cited 2021 June 23]. Available from: http://aidsboe.moph.go.th/app/homeup/uploads/2020-07-30354372811.pdf.

Arribas JR, Girard PM, Landman R, Pich J, Mallolas J, Martínez-Rebollar M, et al. Dual treatment with lopinavir-ritonavir plus lamivudine versus triple treatment with lopinavir-ritonavir plus lamivudine or emtricitabine and a second nucleos(t)ide reverse transcriptase inhibitor for maintenance of HIV-1 viral suppression (OLE): a randomised, open-label, non-inferiority trial. Lancet Infect Dis. 2015; 15(7): 785-792.

Baril JG, Angel JB, Gill MJ, Gathe J, Cahn P, van Wyk J, Walmsley S. Dual Therapy Treatment Strategies for the Management of Patients Infected with HIV: A Systematic Review of Current Evidence in ARV-Naive or ARV-Experienced, Virologically Suppressed Patients. PLoS One. 2016;11(2):e0148231.

Cahn P, Andrade-Villanueva J, Arribas JR, Gatell JM, Lama JR, Norton M, et al. Dual therapy with lopinavir and ritonavir plus lamivudine versus triple therapy with lopinavir and ritonavir plus two nucleoside reverse transcriptase inhibitors in antiretroviral-therapy-naive adults with HIV-1 infection: 48 week results of the randomised, open label, non-inferiority GARDEL trial. Lancet Infect Dis. 2014; 14(7): 572-580.

Cahn P, Madero JS, Arribas JR, Antinori A, Ortiz R, Clarke AE, et al. Dolutegravir plus lamivudine versus dolutegravir plus tenofovir disoproxil fumarate and emtricitabine in antiretroviral-naive adults with HIV-1 infection (GEMINI-1 and GEMINI-2): week 48 results from two multicentre, double-blind, randomised, non-inferiority, phase 3 trials. Lancet. 2019; 393(10167): 143-155.

Cahn P, Rolón MJ, Figueroa MI, Gun A, Patterson P, Sued O. Dolutegravir-lamivudine as initial therapy in HIV-1 infected, ARV-naive patients, 48-week results of the PADDLE (Pilot Antiretroviral Design with Dolutegravir LamivudinE) study. J. Int. AIDS Soc. 2017; 20(1): 21678.

Davis W, Mantsios A, Karver T, Murray M, Punekar Y, Ward D, et al. "It made me more confident that I have it under control": Patient and provider perspectives on moving to a two-drug ART regimen in the United States and Spain. PLoS One. 2020; 15(5): e0232473.

Department of Disease Control. Thai national guidelines on HIV/AIDS Diagnosis, Treatment and Prevention 2020 [Internet]. Bangkok: Aksorn Graphic and Design; 2020 [Access on 2020 Apr 14]. Available from: http://www.thaiaidssociety.org/images/PDF/thai_aids_guidelines_2563.pdf.

Di Giambenedetto S, Fabbiani M, Quiros Roldan E, Latini A, D'Ettorre G, Antinori A, et al. Treatment simplification to atazanavir/ritonavir + lamivudine versus maintenance of atazanavir/ritonavir + two NRTIs in virologically suppressed HIV-1-infected patients: 48 week results from a randomized trial (ATLAS-M). J Antimicrob Chemother. 2017; 72(4): 1163-1171.

Figueroa MI, Sued OG, Gun AM, Belloso W, Cecchini DM, Lopardo G, Pryluka D, Rolon MJ, Fink VI, Lloret SP, Cahn P. DRV/R/3TC FDC for HIV-1 treament naïve patients: week 48 results of the ANDES Study. Conference on Retroviruses and Opportunistic Infections; Boston, MA, USA 2018.

Food and Drug Administration. FDA Approves First Extended-Release, Injectable Drug Regimen for Adults Living with HIV [press release] (2021 Jan 21).

Food and Drug Administration. FDA approves first two-drug complete regimen for HIV-infected patients who have never received antiretroviral treatment [press release] (2019 Apr 4).

Healthcare ViiV. Highlight of prescribing information: Cabenuva 2021 [Internet]. [Access on 2021 June 23]. Available from: https://gskpro.com/content/dam/global/hcpportal/en_US/Prescribing_Information/Cabenuva/pdf/CABENUVA-PI-PIL-IFU2-IFU3.PDF.

Healthcare ViiV. Highlight of prescribing information: Juluca 2020 [Internet]. [Access on 2020 Apr 14]. Available from: https://www.accessdata.fda.gov/drugsatfda_docs/label/2020/210192s007lbl.pdf.

Healthcare ViiV. Highlights of prescribing information: Dovato [Internet]. 2021 [Access on 2020 Apr 14]. Available from:https://gskpro.com/content/dam/global/hcpportal/en_US/Prescribing_Information/Dovato/pdf/DOVATO-PI-PIL.PDF

HIV Info HUB. Estimate HIV infections Thailand. [Online]. 2019 [cited 2021 June 23]. Available from: https://hivhub.ddc.moph.go.th/epidemic.php

Huang Y, Huang X, Chen H, Wu H, Chen Y. Efficacy and Safety of Raltegravir-Based Dual Therapy in AIDS Patients: A Meta-Analysis of Randomized Controlled Trials. Front Pharmacol. 2019;10:1225.

Kanters S, Socias ME, Paton NI, Vitoria M, Doherty M, Ayers D, Popoff E, Chan K, Cooper DA, Wiens MO, Calmy A, Ford N, Nsanzimana S, Mills EJ. Comparative efficacy and safety of second-line antiretroviral therapy for treatment of HIV/AIDS: a systematic review and network meta-analysis. Lancet HIV. 2017 ;4(10):e433-e441.

Lambert-Niclot S, George EC, Pozniak A, White E, Schwimmer C, Jessen H, et al. Antiretroviral resistance at virological failure in the NEAT 001/ANRS 143 trial: raltegravir plus darunavir/ritonavir or tenofovir/emtricitabine plus darunavir/ritonavir as first-line ART. J Antimicrob Chemother. 2016;71(4):1056-62.

Llibre JM, Hung CC, Brinson C, Castelli F, Girard PM, Kahl LP, et al. Efficacy, safety, and tolerability of dolutegravir-rilpivirine for the maintenance of virological suppression in adults with HIV-1: phase 3, randomised, non-inferiority SWORD-1 and SWORD-2 studies. Lancet. 2018; 391(10123): 839-849.

Maeda K, Das D, Kobayakawa T, Tamamura H, Takeuchi H. Discovery and Development of Anti-HIV Therapeutic Agents: Progress Towards Improved HIV Medication. Curr Top Med Chem. 2019;19(18):1621-1649.

Maggiolo F, Di Filippo E, Valenti D, Serna Ortega PA, Callegaro A. NRTI Sparing Therapy in Virologically Controlled HIV-1 Infected Subjects: Results of a Controlled, Randomized Trial (Probe). J Acquir Immune Defic Syndr. 2016; 72(1): 46-51.

Margolis DA, Brinson CC, Smith GHR, de Vente J, Hagins DP, Eron JJ, et al. Cabotegravir plus rilpivirine, once a day, after induction with cabotegravir plus nucleoside reverse transcriptase inhibitors in antiretroviral-naive adults with HIV-1 infection (LATTE): a randomised, phase 2b, dose-ranging trial. Lancet Infect Dis. 2015; 15(10): 1145-1155.

Margolis DA, Gonzalez-Garcia J, Stellbrink HJ, Eron JJ, Yazdanpanah Y, Podzamczer D, et al. Long-acting intramuscular cabotegravir and rilpivirine in adults with HIV-1 infection (LATTE-2): 96-week results of a randomised, open-label, phase 2b, non-inferiority trial. Lancet. 2017; 390(10101): 1499-1510.

Mocroft A, Lundgren JD, Ross M, Fux CA, Reiss P, Moranne O, et al. Cumulative and current exposure to potentially nephrotoxic antiretrovirals and development of chronic kidney disease in HIV-positive individuals with a normal baseline estimated glomerular filtration rate: a prospective international cohort study. Lancet HIV. 2016 ;3(1):e23-32.

National Drug Information. dolutegravir and rilpivirine [Internet]. 2021 [Access on 2020 Apr 14]. Available from: http://ndi.fda.moph.go.th/drug_detail/index/?ndrug=1&rctype=2C&rcno=6200008&lpvncd=10&lcntpcd=%E0%B8%99%E0%B8%A21&lcnno=2600375&licensee_no=375/2526.

Ofotokun I, Sheth AN, Sanford SE, Easley KA, Shenvi N, White K, et al. A switch in therapy to a reverse transcriptase inhibitor sparing combination of lopinavir/ritonavir and raltegravir in virologically suppressed HIV-infected patients: a pilot randomized trial to assess efficacy and safety profile: the KITE study. AIDS Res Hum Retroviruses. 2012; 28(10): 1196-1206.

Panel on Antiretroviral Guidelines for Adults and Adolescents. Guidelines for the Use of Antiretroviral Agents in Adults and Adolescents with HIV: Department of Health and Human Services; [Internet]. 2019 [Access on 2020 Apr 14]. Available from: https://clinicalinfo.hiv.gov/sites/default/files/inline-files/AdultandAdolescentGL.pdf.

Perez-Molina JA, Rubio R, Rivero A, Pasquau J, Suárez-Lozano I, Riera M, et al. Dual treatment with atazanavir-ritonavir plus lamivudine versus triple treatment with atazanavir-ritonavir plus two nucleos(t)ides in virologically stable patients with HIV-1 (SALT): 48 week results from a randomised, open-label, non-inferiority trial. Lancet Infect Dis. 2015; 15(7): 775-784.

Pett SL, Amin J, Horban A, Andrade-Villanueva J, Losso M, Porteiro N, et al. Maraviroc, as a Switch Option, in HIV-1-infected Individuals With Stable, Well-controlled HIV Replication and R5-tropic Virus on Their First Nucleoside/Nucleotide Reverse Transcriptase Inhibitor Plus Ritonavir-boosted Protease Inhibitor Regimen: Week 48 Results of the Randomized, Multicenter MARCH Study. Clin Infect Dis. 2016; 63(1): 122-132.

Pinola M, Lazzarin A, Antinori A, Carosi G, Perri GD, Moroni M, Vullo V, Pastore G, Norton M, Paparatt UL. Lopinavir/ritonavir + tenofovir Dual Therapy versus Lopinavir/ritonavir-Based Triple Therapy in HIV-Infected Antiretroviral Naïve Subjects: The Kalead Study. J Antivir Antiretrovir. 2010; 2(4): 56-62.

Pisaturo M, Onorato L, Russo A, Martini S, Chiodini P, Signoriello S, et al. Risk of failure in dual therapy versus triple therapy in naïve HIV patients: a systematic review and meta-analysis. Clin Microbiol Infect. 2021 ;27(1):28-35.

Pulido F, Ribera E, Lagarde M, Pérez-Valero I, Palacios R, Iribarren JA, et al. Dual Therapy With Darunavir and Ritonavir Plus Lamivudine vs Triple Therapy With Darunavir and Ritonavir Plus Tenofovir Disoproxil Fumarate and Emtricitabine or Abacavir and Lamivudine for Maintenance of Human Immunodeficiency Virus Type 1 Viral Suppression: Randomized, Open-Label, Noninferiority DUAL-GESIDA 8014-RIS-EST45 Trial. Clin Infect Dis. 2017; 65(12): 2112-2118.

Raffi F, Babiker AG, Richert L, Molina JM, George EC, Antinori A, et al. Ritonavir-boosted darunavir combined with raltegravir or tenofovir-emtricitabine in antiretroviral-naive adults infected with HIV-1: 96 week results from the NEAT001/ANRS143 randomised non-inferiority trial. Lancet. 2014; 384(9958): 1942-1951.

Reynes J, Trinh R, Pulido F, Soto-Malave R, Gathe J, Qaqish R, et al. Lopinavir/ritonavir combined with raltegravir or tenofovir/emtricitabine in antiretroviral-naive subjects: 96-week results of the PROGRESS study. AIDS Res Hum Retroviruses. 2013; 29(2): 256-265.

Riddler SA, Haubrich R, DiRienzo AG, Peeples L, Powderly WG, Klingman KL, et al. Class-sparing regimens for initial treatment of HIV-1 infection. N Engl J Med. 2008; 358(20): 2095-2106.

Rutherford GW, Sangani PR, Kennedy GE. Three- or four- versus two-drug antiretroviral maintenance regimens for HIV infection. Cochrane Database Syst Rev. 2003(4): Cd002037.

Ryom L, Cotter A, De Miguel R, Béguelin C, Podlekareva D, Arribas JR, et al. 2019 update of the European AIDS Clinical Society Guidelines for treatment of people living with HIV version 10.0. HIV medicine. 2020; 21(10): 617-624.

Ryom L, Lundgren JD, El-Sadr W, Reiss P, Kirk O, Law M, et al. Cardiovascular disease and use of contemporary protease inhibitors: the D:A:D international prospective multicohort study. Lancet HIV. 2018; 5(6): e291-e300.

Saag MS, Gandhi RT, Hoy JF, Landovitz RJ, Thompson MA, Sax PE, et al. Antiretroviral Drugs for Treatment and Prevention of HIV Infection in Adults: 2020 Recommendations of the International Antiviral Society-USA Panel. JAMA. 2020; 324(16): 1651-1669.

Sabin CA, Reiss P, Ryom L, Phillips AN, Weber R, Law M, et al.Is there continued evidence for an association between abacavir usage and myocardial infarction risk in individuals with HIV? A cohort collaboration. BMC Med. 2016 ;14:61.

Shu Y, Qiu C, Tu X, Deng Z, Deng Y, Wang H, et al. Efficacy and Safety of Triple versus Dolutegravir-based Dual Therapy in Patients with HIV-1 Infection: A Meta-analysis of Randomized Controlled Trials. AIDS Rev. 2021. doi: 10.24875/AIDSRev.20000103. Epub ahead of print.

Spinner CD, Kümmerle T, Schneider J, Cordes C, Heiken H, Stellbrink HJ, et al. Efficacy and Safety of Switching to Dolutegravir With Boosted Darunavir in Virologically Suppressed Adults With HIV-1: A Randomized, Open-Label, Multicenter, Phase 3, Noninferiority Trial: The DUALIS Study. Open Forum Infect Dis. 2020; 7(9): ofaa356.

Stellbrink HJ, Le Fevre E, Carr A, Saag MS, Mukwaya G, Nozza S, et al. Once-daily maraviroc versus tenofovir/emtricitabine each combined with darunavir/ritonavir for initial HIV-1 treatment. AIDS. 2016; 30(8): 1229-1238.

Taiwo BO, Marconi VC, Berzins B, Moser CB, Nyaku AN, Fichtenbaum CJ, et al. Dolutegravir Plus Lamivudine Maintains Human Immunodeficiency Virus-1 Suppression Through Week 48 in a Pilot Randomized Trial. Clin Infect Dis. 2018; 66(11): 1794-1797.

Taiwo BO, Zheng L, Stefanescu A, Nyaku A, Bezins B, Wallis CL, et al. ACTG A5353: A Pilot Study of Dolutegravir Plus Lamivudine for Initial Treatment of Human Immunodeficiency Virus-1 (HIV-1)-infected Participants With HIV-1 RNA <500000 Copies/mL. Clin Infect Dis. 2018; 66(11): 1689-1697.

van Lunzen J, Pozniak A, Gatell JM, Antinori A, Klauck I, Serrano O, et al. Brief Report: Switch to Ritonavir-Boosted Atazanavir Plus Raltegravir in Virologically Suppressed Patients With HIV-1 Infection: A Randomized Pilot Study. J Acquir Immune Defic Syndr. 2016; 71(5): 538-543.

van Wyk J, Ajana F, Bisshop F, De Wit S, Osiyemi O, Portilla Sogorb J, 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. Clin Infect Dis. 2020; 71(8): 1920-1929.

Waters L, Church H. Two drugs regimens for HIV. Curr Opin Infect Dis. 2020; 33(1): 28-33.

World Health Organization. Update of recommendations on first- and second-line antiretroviral regimens 2019 [Internet]. [Access on 2020 Apr 14]. Available from: https://apps.who.int/iris/bitstream/handle/10665/325892/WHO-CDS-HIV-19.15-eng.pdf?ua=1.