Русский
Randomized, open-label, controlled, comparative study on switching HIV-infected patients with their antiretroviral therapy experience to a DTG and 3TC regimen: 96-weeks results
DOI: https://dx.doi.org/10.18565/epidem.2021.11.4.45-52
Kanestri V.G., Kravchenko A.V., Pokrovskaya A.V., Kulabukhova E.I., Kuimova U.A., Goliusova M.D., Kozyrina N.V., Shakhgildyan V.I., Yurin O.G.
1) Central Research Institute of Epidemiology, Russian Federal Service for Supervision of Consumer Rights Protection and Human Well-Being, Moscow, Russia; 2) H-Clinic University Clinic, Moscow, Russia; 3) Peoples’ Friendship University of Russia, Moscow, Russia
Subjects and methods. The study enrolled 231 HIV-infected patients with their experience in treatment. The patients were randomized into 2 groups: 1) those, who were switched to the DTG + 3TC regimen and 2) those, who continued to receive the standard triple ART regimen. The groups were equal in terms of sex, age, routes of transmission, stages of HIV infection, baseline immune status, duration of previous ART, and the proportion of patients with concomitant diseases. All the patients had an undetectable baseline viral load (VL).
Results. The DTG + 3TC regimen in patients with their previous stable treatment experience showed a comparable high efficacy of both the standard 3-drug therapy. At week 96, 100% of the patients had an undetectable VL (< 50 copies/ml). During the treatment, there was no virological failure. All the patients who reached the 96-week point showed a high adherence to therapy (> 95%). At the endpoint of the study, clinical adverse events associated with ARV agents were recorded in 2.8% of patients in Group 1 and in 15% in Group 2. In all cases, the side effects were mild and required no drug correction; however, they were the reason for modifying the standard triple therapy regimen in 6.9% of patients. Minor laboratory deviations of the main biochemical parameters were observed in both groups with the same frequency. When switching to the dual ART regimen without TDF, there was no substantial effect on the lipid profile, a significant double decrease in the proportion of patients with a GFR of < 90 ml/min, and alkaline phosphatase normalization in all the patients. During 96-week treatment, the patients’ median weight increased by only 0.9 kg, which was 5 times less than with standard ART.
Conclusion. In the patients with their therapy experience, the simplified DTG + 3TC regimen is as effective as the standard ART regimens, but significantly exceeds them in tolerance and safety.
Literature
1. Cahn P., Andrade-Villanueva J., Arribas J.R., Gatell J.M., Lama J.R., Norton J.R..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): 572–80. doi: 10.1016/S1473-3099(14)70736-4 2. Di Giambenedetto S., Fabbiani M., Quiros Roldan E., Latini А., D’Ettorre G., Antinori А. 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): 1163–71. doi: 10.1093/jac/dkw557 3. Raffi F., Babiker A.G., Richert L., Molina J.-M., George Е.С., Antinori А., Arribas J.R. 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): 1942–51. doi: 10.1016/ S0140-6736(14)61170-3 4. Perez-Molina J.A., Pulido F., Di Giambenedetto S., Ribera Е., Moreno S, Zamora J., Coscia С. et al. Individual patient data meta-analysis of randomized controlled trials of dual therapy with a boosted PI plus lamivudine for maintenance of virological suppression: GeSIDA study 9717. J. Antimicrob Chemother. 2018; 73(11): 2927–35. doi: 10.1093/ jac/dky299 5. Cahn P., Rolón M.J., Figueroa M.I. et al. Dolutegravir-lamivudine as initial therapy in HIV-1 infected, ARV-naive patients, 48-week results of the PADDLE (Pilot Antiretroviral Design with Dolutegravir Lamivudin E) study. J. Int. AIDS Soc. 2017; 20(1): 21678. doi: 10.7448/IAS.20.01.21678 6. Taiwo B.O., Zheng L., Stefanescu A. 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 < 500 000 copies/ml. Clin. Infect. Dis. 2018; 66(11): 1689–97. doi: 10.1093/cid/cix1083 7. Brenner B.G., Wainberg M.A.. Clinical benefit of dolutegravir in HIV-1 management related to the high genetic barrier to drug resistance. Virus Res. 2017; 239: 1–9. doi: 10.1016/j.virusres.2016.07.006 8. Cahn P., Madero J.S., Arribas J.R. et al. Durable Efficacy of Dolutegravir Plus Lamivudine in Antiretroviral Treatment-Naive Adults With HIV-1 Infection: 96-Week Results From the GEMINI-1 and GEMINI-2 Randomized Clinical Trials. J. Acquir. Immune Defic. Syndr, 2020; 83(3): 310–8. doi: 10.1097/QAI.0000000000002275 9. Cahn P., Sierra Madero J., Arribas J.R., Antinori A., Ortiz R., Clarke A.E. et al. Durable Efficacy of Dolutegravir (DTG) Plus Lamivudine (3TC) In Antiretroviral Treatment–Naive Adults With Hiv-1 Infection 3-Year Results From The GEMINI Studies. HIV Drug Therapy Glasgow; 2020; Virtual; Poster P018. 10. Van Wyk J., Ajana F., Bisshop F., De Wit S., Osiyemi O., Sogorb J. P. 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): 1920–9. doi: 10.1093/cid/ciz1243 11. Guidelines for the use of antiretroviral agents in HIV-1-infected adults and adolescents. Developed by the panel on clinical practices for treatment of HIV infection convened by the Department of Health and Human Services (DHHS). AIDS info, 2021. https://clinicalinfo.hiv.gov/en/guidelines 12. EACS Guidelines. Version 10.1. October 2020. http://www.eacsociety.org 13. Antiretroviral Drugs for Treatment and Prevention of HIV Infection in Adults: 2020 Recommendations of the International Antiviral Society-USA Panel. JAMA 2020; 324(16): 1651–69. DOI: 10.1001/jama.2020.17025 14. Покровский В.В., Юрин О.Г., Кравченко А.В., Беляева В.В., Буравцова Е.В., Деулина М.О. и др. Рекомендации по лечению ВИЧ-инфекции и связанных с ней заболеваний, химиопрофилактике заражения ВИЧ. Эпидемиол. инфекц. болезни. Актуал. вопр. 2020; 10 (4, приложение), 92 с. Pokrovsky V.V., Yurin O.G., Kravchenko A.V., Belyaeva V.V., Buravtsova E.E., Deulina M.O. et al. [Recommendations for the treatment of HIV infection and related diseases, chemoprophylaxis of HIV infection]. Epidemiology and infectious diseases. Current items 2020; 10 (4, Suppl.). 92 р. (In Russ.).
About the Autors
Veronika G. Kanestri, MD, Senior Researcher, Central Research Institute of Epidemiology, Russian Federal Service for Supervision of Consumer Rights Protection and Human Well-Being; Infectionist, University Clinic «H-Clinic»; Moscow, Russia; kanestri@yandex.ru; http://orcid.org/0000-0002-2234-7094
Professor Alexey V. Kravchenko, МD, Leading Researcher, Central Research Institute of Epidemiology, Russian Federal Service for Surveillance on Consumer Rights Protection and Human Well-Being, Moscow, Russia; alexey-kravtchenko@yandex.ru; http://orcid.org/0000-0001-7857-3763
Anastasia V. Pokrovskaya, Cand. Med. Sci., Senior Researcher, Central Research Institute of Epidemiology, Russian Federal Service for Supervision of Consumer Rights Protection and Human Well-Being; Associate Professor, Department of Infectious Diseases with Courses of Epidemiology and Phthisiology, Medical Institute, Peoples’ Friendship University; Moscow, Russia; pokrovskaya_av@mail.ru; http://orcid.org/0000-0002-2677-0404
Ekaterina I. Kulabuhova, Cand. Med. Sci., Infectiologist, Central Research Institute of Epidemiology, Russian Federal Service for Surveillance of Consumer Rights Protection and Human Well-Being; Head, Laboratory of the Department of Infectious Diseases with Courses of Epidemiology and Phthisiology, Medical Institute, Peoples’ Friendship University; Moscow, Russia; ekulabukhova@mail.ru; http://orcid.org/0000-0003-3645-7275
Ulyana A. Kuimova, Cand. Med. Sci., Researcher, Central Research Institute of Epidemiology, Russian Federal Service for Supervision of Consumer Rights Protection and Human Well-Being; Moscow, Russia; ulyanakuimova@gmail.com; https://orcid.org/0000-0002-1101-151X
Marina D. Goliusova, Infectiologist, Central Research Institute of Epidemiology, Russian Federal Service for Supervision of Consumer Rights Protection and Human Well-Being; Moscow, Russia; mad2501@yandex.ru; https://orcid.org/0000-0002-5325-6857
Nadezhda V. Kozyrina, Cand. Med. Sci., Senior Researcher, Central Research Institute of Epidemiology, Russian Federal Service for Surveillance oа Consumer Rights Protection and Human Well-Being; Moscow, Russia; nad-kozyrina@yandex.ru; htpp://orcid.org/0000-0001-5134-0054
Vasiliy I. Shakhgildyan, Cand. Med. Sci., Senior Researcher, Central Research Institute of Epidemiology, Russian Federal Service for Surveillance oа Consumer Rights Protection and Human Well-Being; Infectionist, University Clinic «H-Clinic»; Moscow, Russia; vishakh@yandex.ru; htpp://orcid.org/0000-0002-8686-0487
Oleg G. Yurin, МD, Leading Researcher, Central Research Institute of Epidemiology, Russian Federal Service for Surveillance oа Consumer Rights Protection and Human Well-Being; Moscow, Russia; oleg_gerald@mail.ru; htpp://orcid.org/0000-0003-1930-7486
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