Effectiveness, Safety, and Cost-Effectiveness of the Tenofovir/Lamivudine/Dolutegravir (TLD) Regimen Compared to Tenofovir/Lamivudine/Efavirenz (TLE) in HIV Patients: A Narrative Review
DOI:
https://doi.org/10.55927/modern.v5i4.53Keywords:
HIV, TLD, TLE, Dolutegravir, Efavirenz, Antiretroviral Therapy, Cost-EffectivenessAbstract
Human Immunodeficiency Virus (HIV) infection is a chronic disease that requires long-term antiretroviral therapy to suppress viral replication and improve immune function. This study is a narrative review aimed at comparing the effectiveness, safety, and cost-effectiveness of the Tenofovir/Lamivudine/Dolutegravir (TLD) regimen with the Tenofovir/Lamivudine/Efavirenz (TLE) regimen. The literature was retrieved from PubMed, PubMed Central, ScienceDirect, and Google Scholar, covering publications from 2021 to 2026, with a total of 50 articles included in the review. The findings indicate that TLD provides superior viral load suppression, greater CD4 cell count improvement, and higher treatment success rates compared with TLE. In terms of safety, TLD demonstrates better tolerability with a lower incidence of neuropsychiatric adverse effects, although it may be associated with weight gain and metabolic changes. Pharmacoeconomic analyses further indicate that TLD is cost-effective over the long term. Overall, TLD is more effective, safer, and more cost-effective than TLE, supporting its recommendation as the preferred first-line antiretroviral regimen for HIV treatment
References
Anil, A. C., Gedam, S., Sethi, G., Parashar, N., Barmaiya, N., & Aryasree, L. (2024). A retrospective cohort study on the potential link between dolutegravir-based anti-retroviral therapy and weight gain compared to efavirenz-based anti-retroviral therapy in a tertiary care center in Jabalpur, Madhya Pradesh. National Journal of Physiology, Pharmacy and Pharmacology, 14(7), 1454–1459. https://doi.org/10.5455/njppp.2024.14.05215202429052024
Ayal, M. A., & Berha, A. B. (2023). Comparative safety and changes in immunologic and virologic parameters of dolutegravir versus efavirenz-based antiretroviral therapies among HIV patients. HIV/AIDS - Research and Palliative Care, 15, 173–190.
Belay, Y. B., Ali, E. E., Chung, K. Y., Gebretekle, G. B., & Sander, B. (2021). Cost-utility analysis of dolutegravir- versus efavirenz-based regimens as a first-line treatment in adult HIV/AIDS patients in Ethiopia. PharmacoEconomics Open, 5, 655–664.
Brites, C., Lacerda, M., Sprinz, E., Bay, M., Pinto, G., & Azevedo, P. (2024). Outcomes of severely ill patients with AIDS treated with efavirenz or dolutegravir: A multicenter, observational study. Frontiers in Medicine, 11, 1302710. https://doi.org/10.3389/fmed.2024.1302710
Chan, P., Yoon, B., Colby, D., Kroon, E., Sacdalan, C., & Sriplienchan, S. (2023). Immunological, cognitive, and psychiatric outcomes after initiating efavirenz- and dolutegravir-based antiretroviral therapy during acute human immunodeficiency virus infection. Clinical Infectious Diseases, 76(7), e1207–e1215.
Chiabi, A., Nykam, S., Kan, K., Fomenky, C., Tanlaka, L. M., & Ngueiwoh, F. N. (2025). Efficacy of dolutegravir-based regimen in HIV-infected children in a treatment center in a regional health facility in Cameroon. International Journal of Infectious Diseases, 153, 107550.
Chongyangyuenvong, P., & Kiertiburanakul, S. (2026). Changes in metabolic parameters after switching from efavirenz to dolutegravir-based regimen: A cohort study in Thai people living with HIV. AIDS Research and Human Retroviruses, 42(4), 315–323.
Doke, N., Hajgude, S., Dhande, A., Tole, S., Gunjegaonkar, S., & Joshi, A. (2024). The clinical efficacy of integrating dolutegravir into the conventional therapeutic regimen for HIV management. International Journal of Pharmaceutical Sciences and Drug Research, 16(6), 940–948. https://doi.org/10.25004/IJPSDR.2024.160603
Dumchev, K., Kiriazova, T., Riabokon, S., Shost, A., Parrish, C., & Shapoval, A. (2022). Comparative clinical outcomes with scale-up of dolutegravir as first-line antiretroviral therapy in Ukraine. Journal of Acquired Immune Deficiency Syndromes, 91(2), 197–209. https://doi.org/10.1097/QAI.0000000000003038
Eifa, A., & Ketema, W. (2022). Could a dolutegravir-based antiretroviral therapy lead to clinical obesity? A retrospective cohort study conducted at Hawassa University Comprehensive Specialized Hospital in Hawassa, Sidama, Ethiopia. Journal of Obesity, 2022, 1234567.
Facha, W., Tadesse, T., Wolka, E., & Astatkie, A. (2024). Viral load non-suppression status among women exposed to dolutegravir-based versus efavirenz-based regimens in Ethiopia: A before-and-after study. PLOS ONE, 19(6), e0305331. https://doi.org/10.1371/journal.pone.0305331
Hickey, M. D., Wafula, E., Ogachi, S. M., Ojwando, H., Orori, G., & Adede, R. O. (2024). Weight change following switch to dolutegravir for HIV treatment in rural Kenya during country roll-out. Journal of Acquired Immune Deficiency Syndromes, 95(2), e45–e53.
Isah, A., Chukwu, P. O., Abba, A., Igboeli, N. U., Ebere, A., & Omotola, O. F. (2023). Cost-effectiveness of dolutegravir vs. efavirenz-based combined antiretroviral therapies in HIV-infected treatment-naive patients in a Nigerian treatment centre. African Health Sciences, 23(1), 157–169. https://doi.org/10.4314/ahs.v23i1.18
Jamieson, L., Serenata, C., Makhubele, L., Sokhela, S., Mashabane, N., & Akpomiemie, G. (2021). Cost and cost-effectiveness of dolutegravir-based antiretroviral regimens: An economic evaluation of a clinical trial. AIDS, 35(Suppl 2), S173–S182. https://doi.org/10.1097/QAD.0000000000003068
Jaya, D. J., Mudi, Y. J., Sani, A., Leonita, Aprilio, F. A., Lestari, S. V, Kemala, G., Jannah, S. M., Nandes, Y. N., Sahra, Djami, M. K., Wanja, F. H. W., Wulandari, I., Marfuah, L., Khaldun, Y., & Sihura, C. (2026). Aksi donor darah “Berani Donor, Berani Peduli” sebagai media edukasi dan peningkatan partisipasi donor di Yogyakarta. Welfare: Jurnal Pengabdian Masyarakat, 4(1), 1–7.
Jemal, M., Adugna, A., Getinet, M., Baylie, T., & Waritu, N. C. (2024). Overweight and obesity among people living with HIV on dolutegravir- and efavirenz-based therapies: A comparative cross-sectional study. International Journal of Endocrinology, 9958452.
Jemal, M., Molla, T. S., Medhin, M. T. G., Abebe, E. C., & Dejenie, T. A. (2023). Blood glucose level and serum lipid profiles among people living with HIV on dolutegravir-based versus efavirenz-based cART: A comparative cross-sectional study. Annals of Medicine, 55(2), 2295435.
Kashyap, M., Verma, A., Pathak, D., Gautam, S., & Gupta, M. (2026). Comparative analysis of effectiveness of dolutegravir-based regimen (TLD) vs efavirenz-based regimen (TLE) to prevent mother-to-child transmission of HIV. Cureus, 18(1), e100824. https://doi.org/10.7759/cureus.100824
Khemla, S., Meesing, A., Sribenjalux, W., & Chetchotisakd, P. (2023). Lipid profiles of people with human immunodeficiency virus with dyslipidemia after switching from efavirenz to dolutegravir. Drug Target Insights, 17, 45–53. https://doi.org/10.33393/dti.2023.2529
Li, M., Cao, Y., Huang, H., Qin, G., Chu, M., & Zou, M. (2023). Cost-effectiveness analysis of antiretroviral drugs for treatment-naive HIV infection in China. BMC Public Health, 23, 2228. https://doi.org/10.1186/s12889-023-17052-1
Majula, J., & Mweya, C. N. (2024). Long-term virologic outcomes and safety after transition from efavirenz-based to dolutegravir-based antiretroviral therapy among adults living with HIV in Tanzania. AIDS Research and Therapy, 21, 98. https://doi.org/10.1186/s12981-024-00662-z
Malaba, T. R., Nakatudde, I., Kintu, K., Colbers, A., Chen, T., & Reynolds, H. (2022). 72 weeks post-partum follow-up of dolutegravir versus efavirenz initiated in late pregnancy (DolPHIN-2): An open-label, randomised controlled study. Lancet HIV, 9(8), e534–e543.
Mengistu, E. F., Malik, T., Molla, M. D., Adugna, A., & Jemal, M. (2024). Liver function tests, CD4+ counts, and viral load among people living with HIV on dolutegravir compared to efavirenz-based cART: A comparative cross-sectional study. Heliyon, 10, e33054.
Mukti, Y. A. (2023). Komunikasi lintas budaya dalam channel YouTube Dale Philips “Bule makan rujak di jalanan Jakarta.” Jurnal Ilmu Sosial Dan Humaniora, 1(1), 73–83.
Mukuna, D. M. (2024). Excessive weight gain among adults receiving dolutegravir-based versus efavirenz-based antiretroviral therapy in Eswatini. AIDS Research and Therapy, 21, 4. https://doi.org/10.1186/s12981-023-00591-3
Nabila, N. A., Karim, M. A., & Akhmad, A. D. (2025). Characteristics and evaluation of potential drug interactions among HIV/AIDS outpatients: A retrospective study at primary health center in a North Lampung regency, Indonesia. Pharmacy Reports, 5(1), 102. https://doi.org/10.51511/pr.102
Njuguna, C., Maluleke, C., Davies, N., Hans, L., Mutasa, B., & Rees, K. (2025). Viral suppression in adults on efavirenz- or dolutegravir-based antiretroviral therapy in Mopani District, South Africa. South African Journal of HIV Medicine, 26(1), a1718. https://doi.org/10.4102/sajhivmed.v26i1.1718
Nuwamanya, E., Nassiwa, S. C., Kuznik, A., Waitt, C., Malaba, T., & Myer, L. (2024). Cost-effectiveness of dolutegravir compared with efavirenz for prevention of perinatal transmission in women presenting with HIV in late pregnancy in Uganda. Value in Health Regional Issues, 44, 101017.
Nwachukwu, C. C., Njelita, I. A., Eyisi, G. I., Ezenyeaku, C. A., Nwachukwu, A. C., & Okechi, O. (2023). Treatment outcomes for HIV patients on three HAART regimens in South East Nigeria: A comparative study. American Journal of Public Health Research, 11(2), 75–83. https://doi.org/10.12691/ajphr-11-2-6
Phillips, A. N., Bansi-Matharu, L., Shahmanesh, M., Hargreaves, J. R., Smith, J., Revill, P., Sibanda, E., Ehrenkranz, P., Sikwese, K., Rodger, A., Lundgren, J. D., Gilks, C. F., Godfrey, C., Cowan, F., & Cambiano, V. (2023). Potential cost-effectiveness of community availability of tenofovir, lamivudine, and dolutegravir for HIV prevention and treatment in east, central, southern, and west Africa: A modelling analysis. The Lancet Global Health, 11(10), e1648–e1657. https://doi.org/10.1016/S2214-109X(23)00383-2
Putri, O. S., Nugraheni, E., Erlinawati, N. D., Sundari, M., & Rizqoh, D. (2024). Relationship between viral load levels and malnutrition screening and nutritional status in HIV patients at RSUD Dr. M. Yunus Bengkulu. Proceedings International Conference on Innovation in Science, Technology and Health Education, 4(1), 88–104.
Rafindra, M. K., Andriani, M., & Dewi, R. (2024). Cost-effective analysis (AEB) of antiretroviral (ARV) use of TLD and TLE in outpatient HIV patients. Jambura Journal of Health Sciences Research, 6(1), 156–165.
Ram, R., Subramanian, A., & Rajeshwari, K. (2025). Metabolic dysfunction-associated steatotic liver disease (MASLD) in people living with HIV attending centre of excellence in HIV care at a tertiary hospital in North India: A pilot study. Ochsner Journal, 25(1), 1–10.
Ramesh, P., & Swathi, S. (2025). Clinical outcomes of dolutegravir-based antiretroviral therapy. BioClinix Journal of Medical and Pharmaceutical Sciences, 1(1), 63–74.
Rosandy, M. G., Candradikusuma, D., & Yudha, N. S. D. (2025). Association of antiretroviral regimens and CD4 counts with dyslipidemia in HIV patients: Implications for metabolic management. Indonesian Journal of Medicine, 10(1), 73–80. https://doi.org/10.26911/theijmed.2025.10.01.07
Sari, P. A. K., Widiastuti, R., & Azmi, N. A. (2025). Analisis efektivitas regimen terapi antiretroviral terhadap status viral load pada pasien HIV di Puskesmas Umbulharjo 1 dan Gedongtengen. Indonesian Journal of Pharmaceutical and Natural Products, 8(1), 70–78.
Sawry, S., Ayalew, K., Maimela, G., Briggs-Hagen, M., van Wyk-Heath, M., & Mthethwa, S. (2024). Assessment of weight gain in adult patients living with HIV receiving first-line dolutegravir-based or efavirenz-based ART regimens in routine care clinics in Tshwane district, South Africa: An observational study. HIV Medicine, 25(7), 826–839. https://doi.org/10.1111/hiv.13638
Setpakdee, R., & Kiertiburanakul, S. (2025). Effect of dolutegravir on weight changes and lipid profile compared with efavirenz in people living with HIV: A retrospective cohort study. Journal of Infection and Public Health, 18(2), 102456.
Sihombing, I. U. A., Sudaryo, M. K., Helda, H., Umniyati, H., & Hasyim, I. Z. (2025). Determinants of success of antiretroviral therapy in HIV/AIDS patients: A viral load-based study in Bekasi Regency, 2023–2024. Jurnal Ilmiah Kesehatan Masyarakat, 17(2), 87–101. https://doi.org/10.52022/jikm.v17i2.805
Silva, G. J., Mendicino, C. C. P., Menezes de Pádua, C. A., & Tupinambás, U. (2023). Suppression of HIV in the first 12 months of antiretroviral therapy: A comparative analysis of dolutegravir- and efavirenz-based regimens. Einstein (São Paulo), 21, eAO0156. https://doi.org/10.31744/einstein_journal/2023AO0156
Simeo, J., Silabi, E., Kikwale, M., Mahamudu, H., Mateso, C., & Baraka, O. (2022). The role of impact approach in minimizing wastage during TLE-TLD transition: A case of Geita Region. International Journal of Health Economics and Policy, 7(4), 78–83. https://doi.org/10.11648/j.hep.20220704.11
Slot, M., Rasmussen, T. B., Nørgaard, M., Larsen, C. S., & Ehlers, L. H. (2024). Evaluating cost-effectiveness of antiretroviral therapy over time: A cohort and cost-effectiveness study. PharmacoEconomics Open, 8, 847–856. https://doi.org/10.1007/s41669-024-00513-7
Tiendrebeogo, T., Malateste, K., Poda, A., Minga, A., Lahiri, C. D., & Ezechi, O. (2024). Impact of switching to a dolutegravir-based regimen on body weight changes: Insights from West African adult HIV cohorts. Journal of the International AIDS Society, 27, e26371. https://doi.org/10.1002/jia2.26371
Van der Wekken-Pas, L., Nassiwab, S., Malaba, T., Lamorde, M., Myer, L., & Waitt, C. (2024). Comparison of dolutegravir and efavirenz on depression, anxiety, and sleep disorders in pregnant and postpartum women living with HIV. AIDS, 38(7), 975–981.
Vu, T. T., Rupasinghe, D., Nguyen, D. T. H., Choi, J. Y., Kiertiburanakul, S., & Kumarasamy, N. (2026). Kidney dysfunction in adults living with HIV and HBV: A 10-year retrospective cohort study across seven Asia-Pacific countries. AIDS Research and Therapy, 23, 14. https://doi.org/10.1186/s12981-025-00831-8
Weisser, M., Mapesi, H., Vanobberghen, F., Okuma, J., Eichenberger, A., & Wilson, H. I. (2025). Body weight changes in people with HIV starting dolutegravir versus efavirenz-based regimens in a large cohort in rural Tanzania. AIDS, 39(3), 362–372. https://doi.org/10.1097/QAD.0000000000004085
Zheng, A., Fox, M. P., Greener, R., Kileel, E. M., Bor, J., & Venter, W. D. F. (2026). Initiation of dolutegravir vs efavirenz on 12- and 24-month weight, body mass index, blood pressure, and incident hypertension: A target trial emulation. Annals of Epidemiology, 117, 110074. https://doi.org/10.1016/j.annepidem.2026.110074
Zhong, M., Li, M., Qi, M., Su, Y., Yu, N., & Lv, R. (2023). A retrospective clinical study of dolutegravir- versus efavirenz-based regimen in treatment-naïve patients with advanced HIV infection in Nanjing, China. Frontiers in Immunology, 13, 1033098. https://doi.org/10.3389/fimmu.2022.1033098
Zuhdi, M. N., Halim, R., Alimuddin, S., Bakri, S., Iskandar, H., & Zainuddin, A. (2026). Comparison of clinical stadium changes and immunologic parameter of adult HIV patients with dolutegraviral and efavirenz based antiretroviral therapy. F1000Research, 15, 582. https://doi.org/10.12688/f1000research.179310.1
