Antiretroviral Regimen–associated Immunometabolic Alterations and Liver Outcomes in People Living with HIV
Abstract
People living with HIV (PLWH) may experience metabolic and hepatic complications during long-term antiretroviral therapy (ART).
This single-center retrospective study compared lipid profile changes and liver-related outcomes among PLWH receiving bictegravir/emtricitabine/tenofovir alafenamide (B/F/TAF), NNRTI-based regimens, or boosted protease inhibitor (PI)-based regimens, emphasizing metabolic and hepatic safety in routine clinical care.
Between January 2024 and December 2025, 120 PLWH on ART were included and grouped by primary regimen: B/F/TAF (n=60), NNRTI-based regimens (n=30), and boosted PI-based regimens (n=30). Demographic and clinical variables, including HIV RNA, CD4+ T-cell counts, lipid parameters, and liver function indices, were collected. Outcomes included dyslipidemia, lipid changes, liver enzyme abnormalities, and liver-related adverse events. Between-group comparisons and exploratory multivariable logistic regression were performed. Baseline characteristics were similar across groups. During follow-up, dyslipidemia prevalence differed significantly (20.0%, 30.0%, and 50.0%, respectively), with hypertriglyceridemia occurring in 8.3%, 13.3%, and 30.0% of patients. Boosted PI users demonstrated greater increases in atherogenic lipid measures. Multivariable analysis indicated that boosted PI use, higher BMI, and baseline dyslipidemia were associated with higher dyslipidemia risk. Liver laboratory indices remained largely stable, and severe hepatotoxicity was uncommon. Liver enzyme abnormalities appeared more related to underlying conditions (e.g., fatty liver and viral hepatitis coinfection) than to ART regimen type.
Overall, B/F/TAF showed relatively mild lipid changes, whereas boosted PI-based regimens were linked to higher dyslipidemia risk. Limitations include lack of systematic immune-recovery and inflammatory biomarker data; prospective studies incorporating these markers are needed.
2. Deeks ED. Bictegravir/Emtricitabine/Tenofovir Alafenamide: A Review in HIV-1 Infection. Drugs. 2018;78(17):1817-1828. doi:10.1007/s40265-018-1010-7.
3. Smith RA, Raugi DN, Wu VH, et al. Comparison of the Antiviral Activity of Bictegravir against HIV-1 and HIV-2 Isolates and Integrase Inhibitor-Resistant HIV-2 Mutants. Antimicrob Agents Chemother. 2019;63(5):e00014-19. Published 2019 Apr 25. doi:10.1128/AAC.00014-19
4. Beavers C, Pau AK, Glidden D, Hyle E, Kuriakose S, Martin SS, et al. Statin Therapy as Primary Prevention for Persons With HIV: A Synopsis of Recommendations From the U.S. Department of Health and Human Services Antiretroviral Treatment Guidelines Panel. Ann Intern Med. 2025;178(6):847-57.
5. Gallant J, Lazzarin A, Mills A, Orkin C, Podzamczer D, Tebas P, et al. Bictegravir, emtricitabine, and tenofovir alafenamide versus dolutegravir, abacavir, and lamivudine for initial treatment of HIV-1 infection (GS-US-380-1489): a double-blind, multicentre, phase 3, randomised controlled non-inferiority trial. Lancet. 2017;390(10107):2063-72.
6. Sax PE, Pozniak A, Montes ML, Koenig E, DeJesus E, Stellbrink HJ, et al. Coformulated bictegravir, emtricitabine, and tenofovir alafenamide versus dolutegravir with emtricitabine and tenofovir alafenamide, for initial treatment of HIV-1 infection (GS-US-380-1490): a randomised, double-blind, multicentre, phase 3, non-inferiority trial. Lancet. 2017;390(10107):2073-82.
7. Orkin C, DeJesus E, Sax PE, Arribas JR, Gupta SK, Martorell C, et al. Fixed-dose combination bictegravir, emtricitabine, and tenofovir alafenamide versus dolutegravir-containing regimens for initial treatment of HIV-1 infection: week 144 results from two randomised, double-blind, multicentre, phase 3, non-inferiority trials. Lancet HIV. 2020;7(6):e389-e400.
8. Squillace N, Ricci E, Maggi P, Taramasso L, Menzaghi B, De Socio GV, et al. Real-life safety of Emtricitabine/Tenofovir Alafenamide/Bictegravir. PLoS One. 2023;18(8):e0289132.
9. Kalra DK, Vorla M, Michos ED, Agarwala A, Virani S, Duell PB, et al. Dyslipidemia in Human Immunodeficiency Virus Disease: JACC Review Topic of the Week. J Am Coll Cardiol. 2023;82(2):171-81.
10. Ofotokun I, Na LH, Landovitz RJ, Ribaudo HJ, McComsey GA, Godfrey C, et al. Comparison of the metabolic effects of ritonavir-boosted darunavir or atazanavir versus raltegravir, and the impact of ritonavir plasma exposure: ACTG 5257. Clin Infect Dis. 2015;60(12):1842-51.
11. Mallon PWG, Brunet L, Fusco JS, Prajapati G, Beyer A, Fusco GP, et al. Lipid Changes After Switch From TDF to TAF in the OPERA Cohort: LDL Cholesterol and Triglycerides. Open Forum Infect Dis. 2021;9(1):ofab621.
12. Grinspoon SK, Fitch KV, Zanni MV, Fichtenbaum CJ, Umbleja T, Aberg JA, et al. Pitavastatin to Prevent Cardiovascular Disease in HIV Infection. N Engl J Med. 2023;389(8):687-99.
13. Kalligeros M, Vassilopoulos A, Shehadeh F, Vassilopoulos S, Lazaridou I, Mylonakis E, et al. Prevalence and Characteristics of Nonalcoholic Fatty Liver Disease and Fibrosis in People Living With HIV Monoinfection: A Systematic Review and Meta-analysis. Clin Gastroenterol Hepatol. 2023;21(7):1708-22.
14. Sterling RK, Lissen E, Clumeck N, Sola R, Correa MC, Montaner J, et al. Development of a simple noninvasive index to predict significant fibrosis in patients with HIV/HCV coinfection. Hepatology. 2006;43(6):1317-25.
15. Roen AO, Peters L, Wandeler G, van der Valk M, Zangerle R, Günthard HF, et al. Chronic Liver Enzyme Elevation and Use of Contemporary ARVs Among People With HIV. Open Forum Infect Dis. 2024;11(6):ofae308.
16. von Elm E, Altman DG, Egger M, Pocock SJ, Gøtzsche PC, Vandenbroucke JP, et al. The Strengthening the Reporting of Observational Studies in Epidemiology (STROBE) statement: guidelines for reporting observational studies. Ann Intern Med. 2007;147(8):573-7.
17. Joint Committee on the Chinese Guidelines for Lipid Management. Chinese guideline for lipid management (primary care version 2024)]. Zhonghua Xin Xue Guan Bing Za Zhi. 2024;52(4):330-7.
18. Moro RN, Johnson JL, Martinson N, et al. Differences in Neutrophil Counts Between African and Non-African Countries in 2 International Clinical Trials. J Infect Dis. 2025;232(5):1128-1138. doi:10.1093/infdis/jiaf291
19. Deeks ED. Bictegravir/Emtricitabine/Tenofovir Alafenamide: A Review in HIV-1 Infection. Drugs. 2018;78(17):1817-28.
20. Hsu JY, Sun HY, Chen LY, Chang SY, Chuang YC, Huang YS, et al. Weight and metabolic changes among virally suppressed people with HIV who switched to co-formulated bictegravir/emtricitabine/tenofovir alafenamide. J Glob Antimicrob Resist. 2024;36:426-35
21. Feinstein MJ, Hsue PY, Benjamin LA, Bloomfield GS, Currier JS, Freiberg MS, et al. Characteristics, Prevention, and Management of Cardiovascular Disease in People Living With HIV: A Scientific Statement From the American Heart Association. Circulation. 2019;140(2):e98-e124.
22. Orkin C, Squires KE, Molina JM, Sax PE, Wong WW, Sussmann O, et al. Doravirine/Lamivudine/Tenofovir Disoproxil Fumarate is Non-inferior to Efavirenz/Emtricitabine/Tenofovir Disoproxil Fumarate in Treatment-naive Adults With Human Immunodeficiency Virus-1 Infection: Week 48 Results of the DRIVE-AHEAD Trial. Clin Infect Dis. 2019;68(4):535-44.
23. Johnson M, Kumar P, Molina JM, Rizzardini G, Cahn P, Bickel M, et al. Switching to Doravirine/Lamivudine/Tenofovir Disoproxil Fumarate (DOR/3TC/TDF) Maintains HIV-1 Virologic Suppression Through 48 Weeks: Results of the DRIVE-SHIFT Trial. J Acquir Immune Defic Syndr. 2019;81(4):463-72.
24. Ambrosioni J, Levi LI, Alagaratnam J, Sempere A, Mastrangelo A, Paioni P, et al. Major revision version 13.0 of the European AIDS Clinical Society guidelines 2025. HIV Med. 2026;27(1):18-32.
25. Blackard JT, Welge JA, Taylor LE, Mayer KH, Klein RS, Celentano DD, et al. HIV mono-infection is associated with FIB-4 - A noninvasive index of liver fibrosis - in women. Clin Infect Dis. 2011;52(5):674-80.
26. Resino S, Micheloud D, Miralles P, Bellón JM, Vargas A, Catalán P, et al. Diagnosis of advanced fibrosis in HIV and hepatitis C virus-coinfected patients via a new noninvasive index: the HGM-3 index. HIV Med. 2010;11(1):64-73.
| Files | ||
| Issue | Articles in Press | |
| Section | Original Article(s) | |
| Keywords | ||
| Antiretroviral therapy Boosted protease inhibitor B/F/TAF Dyslipidemia HIV Liver function | ||
| Rights and permissions | |
|
This work is licensed under a Creative Commons Attribution-NonCommercial 4.0 International License. |
