Follow-up results of dolutegravir/lamiıvudine switch therapy

Abstract

Aim: Observing and revealing the switch reasons to dolutegravir/lamivudine (DTG/3TC) dual therapy, virological supression ratio, side effects, and monitoring of renal function during follow-up after switch in people living with HIV (PLWH) were aimed. Method: Thirty-eight adult PLWH who were followed by a single physician and switched to dual therapy between 2015-2021 were retrospectively analyzed. Results: The most common reason for switching to dual therapy was the prevention of potential renal toxicities, recorded as 44.7% (17/38), the median age was 51.5 years, and the median follow-up period was 54 months. Virological failure was not observed in any PLWH, including three PLWH that had Nucleoside Reverse Transcriptase Inhibitor (NRTI) mutation (K65R, M41L, K70T/S). There was a significant increase in CD4+ T lymphocyte number. Glomerular filtration rate (GFR) improvement and regression of proteinuria were recorded especially in the early period. The discontinuation rate due to side effects was 5.3% (2/38). The death rate was observed to be 18.4% (7/38), and the most common cause was myocardial infarction (4/7). Conclusion: DTG/3TC, which is observed to be a regimen with high virological suppression success and low side effect rate, can be considered as an ideal treatment alternative in PLWH.

Keywords

• HIV
• Dolutegravir
• Lamivudine

Dolutegravir/lamivudin geçiş tedavisi izlem sonuçları

Abstract

Amaç: Dolutegravir/lamivudin (DTG/3TC) ikili tedavisine geçiş yapılan HIV ile yaşayan bireylerdeki (HYB) ikili tedaviye geçiş sebepleri, ikili tedaviye geçişten sonra elde edilen virolojik baskılama başarısı, yan etkiler, takip sırasında böbrek fonksiyon seyrinin ortaya konulması amaçlanmıştır. Yöntem: Tek hekimden takipli olup 2015-2021 yılları arasında ikili tedaviye geçiş yapılan 38 erişkin HYB retrospektif olarak incelenmiştir. Bulgular: İkili tedaviye geçişte en sık sebep, potansiyel renal toksisistelerin önlenmesi %44,7(17/38) olarak kaydedildi, median yaş 51.5, median takip süresi 54 ay olarak saptandı. Nukleozid Reverse Transkriptaz İnhibitörü (NRTI) mutasyonu (K65R, M41L, K70T/S) izlenen üç HYB de dahil olmak üzere virolojik başarısızlık hiçbir HYB’de izlenmedi. CD4+ T lenfosit sayısında anlamlı artış izlendi. Glomerüler filtrasyon hızında (GFR) erken dönemde düzelme ve proteinüride gerileme kaydedildi. Yan etki nedeniyle kesilme oranı %5,3 (2/38) olarak izlendi. Ölüm oranı %18.4 (7/38) oranında izlendi, en sık sebebin myokard enfarktüsü (4/7) olduğu görüldü. Sonuç: Virolojik baskılama başarısı yüksek, yanetki oranı düşük bir rejim olduğu izlenen DTG/3TC , tedavi uyumu iyi olan HYB’ lerde ideal bir tedavi alternatifi olarak kabul edilebilir.

Keywords

• HIV
• Dolutegravir
• Lamivudin

References

1. Erdinc FS, Dokuzoguz B, Unal S, et al. Temporal Trends in the Epidemiology of HIV in Turkey. Curr HIV Res. 2020;18(4):258-266.
2. European AIDS Clinical Society. https://www.eacsociety.org/guidelines/eacs-guidelines/ Ekim 2023’te basıldı. 6 Şubat 2025’te erişildi.
3. European AIDS Clinical Society (EACS). EACS Guidelines for the Management of People Living with HIV (PLWH) in Europe. Version 10.1. Published 2020. 25 Nisan 2025’te erişildi. https://www.eacsociety.org/files/guidelines-10.1_5.pdf
4. Rossetti B, Montagnani F, De Luca A. Current and emerging two-drug approaches for HIV-1 therapy in ART-naïve and ART-experienced, virologically suppressed patients. Expert Opin Pharmacother. 2018;19(7):713-738.
5. Ciccullo A, Borghi V, Giacomelli A, et al. Five Years With Dolutegravir Plus Lamivudine as a Switch Strategy: Much More Than a Positive Finding. J Acquir Immune Defic Syndr. 2021;88(3):234-237.
6. Baldin, G., Ciccullo, A., Rusconi, S., Capetti, A., Sterrantino, G., Colafigli, M., et al. Long-term data on the efficacy and tolerability of lamivudine plus dolutegravir as a switch strategy in a multi-centre cohort of HIV-1-infected, virologically suppressed patients. Int J Antimicrob Agents. 2019;54(6):728-734.
7. Borghetti A, Lombardi F, Gagliardini R, Baldin G, Ciccullo A, Moschese D, et al. Efficacy and tolerability of lamivudine plus dolutegravir compared with lamivudine plus boosted PIs in HIV-1 positive individuals with virologic suppression: a retrospective study from the clinical practice. BMC Infect Dis. 2019;19:1-9.
8. Hidalgo-Tenorio C, Cortés LL, Gutiérrez A, Santos J, Omar M, Gálvez C, et al. DOLAMA study: effectiveness, safety and pharmacoeconomic analysis of dual therapy with dolutegravir and lamivudine in virologically suppressed HIV-1 patients. Medicine (Baltimore). 2019;98(32):e16813.

9. 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. Year. Available at https://clinicalinfo.hiv.gov/en/guidelines/adult-and-adolescent-arv. 12 Eylül 2024’te basıldı. 6 Şubat 2025’te erişildi.
10. Cossarizza A, Cozzi-Lepri A, Mattioli M, et al. Evaluating immunological and inflammatory changes of treatment-experienced people living with HIV switching from first-line triple cART regimens to DTG/3TC vs. B/F/TAF: the DEBATE trial. Front Immunol. 2023;14:1279390. Published 2023 Oct 16.
11. 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. Clin Infect Dis. 2020;71(8):1920-1929.
12. Türkiye İlaç ve Tıbbi Cihaz Kurumu. https://titck.gov.tr/kubkt. 11.02.2025’te erişildi.
13. Inker LA, Eneanya ND, Coresh J, et al. New creatinine- and cystatin C–based equations to estimate GFR without race. N Engl J Med. 2021;385:1737-1749.
14. Ergen P, Bektas B, Aydın Ö, et al. Evaluation of treatment efficacy after switching to dolutegravir-lamivudine dual therapy in people living with HIV. Afr Health Sci. 2022;22(3):426-435.
15. Maggiolo F, Gulminetti R, Pagnucco L, Digaetano M, Cervo A, Valenti D, et al. Long-term outcome of lamivudine/dolutegravir dual therapy in HIV-infected, virologically suppressed patients. BMC Infect Dis. 2022;22(1):782.
16. Martínez-Serra A, De Lazzari E, Berrocal L, Foncillas A, De La Mora L, Inciarte A, et al. Clinical use and effectiveness of dolutegravir and lamivudine: a long-term, real-world, retrospective study. J Antimicrob Chemother. 2023;78(8):1955-1962.
17. Maggiolo F, Gulminetti R, Pagnucco L, Digaetano M, Benatti S, Valenti D, et al. Lamivudine/dolutegravir dual therapy in HIV-infected, virologically suppressed patients. BMC Infect Dis. 2017;17:1-7.
18. Santoro MM, Armenia D, Teyssou E, Santos JR, Charpentier C, Lambert-Niclot S, et al. Virological efficacy of switch to DTG plus 3TC in a retrospective observational cohort of suppressed HIV-1 patients with or without past M184V: the LAMRES study. J Glob Antimicrob Resist. 2022;31:52-62.
19. Çağlayık DY, Arıkan H, Çeçen S. HIV ile enfekte olan obez bireylerde Sistatin- C. Turk Hij Den Biyol Derg. December 2019;76(4):461-468.
20. Cecen S, Caglayik DY, Ilgin C. Use of HCRP and Cystatin-c as Inflammation Markers in the Follow-up of Kidney Functions in Obesity. Acta Physiologica. February 2022;234:51
21. Brunet L, Wyatt C, Hsu R, Mounzer K, Fusco J, Fusco G. Assessing bias introduced in estimated glomerular filtration rate by the inhibition of creatinine tubular secretion from common antiretrovirals. Antivir Ther. 2020;25(5):287-292.
22. Campbell L, Ibrahim F, Barbini B, Samarawickrama A, Orkin C, Fox J, et al. Bone mineral density, kidney function and participant-reported outcome measures in women who switch from tenofovir disoproxil emtricitabine and a non-nucleoside reverse transcriptase inhibitor to abacavir, lamivudine and dolutegravir. HIV Med. 2022;23(4):362-370.