As HIV care extends across decades for most patients, treatment durability has emerged as a central consideration in clinical decision-making. Durability includes sustained virologic suppression, long-term tolerability, minimal drug-drug interactions, and preservation of future treatment options.1 Together, these factors collectively shape long-term treatment success, making it essential for providers to understand the evolving landscape of durable regimens to optimize patient outcomes.1,2
Current guidelines emphasize integrase strand transfer inhibitor (INSTI)-based regimens as preferred initial therapy, with agents that demonstrate sustained virologic suppression across diverse patient populations and favorable tolerability profiles.1 Three-drug fixed-dose combinations containing bictegravir, emtricitabine, and tenofovir alafenamide exemplify this approach, offering once-daily dosing with minimal food requirements and low discontinuation rates.3-5 These characteristics support adherence, the foundation of treatment durability.
However, durability extends beyond initial viral suppression. Emerging data highlight the importance of bone and renal health monitoring, particularly in aging populations with HIV.6 Similarly, managing metabolic complications and cardiovascular risk factors requires ongoing attention as patients with HIV achieve near-normal life expectancy.7
Long-acting injectable regimens, such as cabotegravir plus rilpivirine administered monthly or every two months, now provide an alternative dosing option for patients.8 Additionally, lenacapavir, a capsid inhibitor with twice-yearly dosing, introduces a novel approach for treatment and prevention.9
Treatment simplification should not compromise resistance monitoring. Routine viral load surveillance enables early detection of virologic failure, preserving therapeutic options and preventing resistance accumulation. Providers should also remain informed about drug interaction profiles, particularly as patients age and comorbidity management becomes increasingly complex.
By prioritizing regimens that balance efficacy, safety, and convenience, clinicians can support sustained viral suppression across the HIV care continuum, ultimately improving quality of life and reducing transmission risk.
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[1] Gandhi RT, Landovitz RJ, Sax PE, et al. Antiretroviral Drugs for Treatment and Prevention of HIV in Adults: 2024 Recommendations of the International Antiviral Society–USA Panel. 2025;333(7):609–628. doi:10.1001/jama.2024.24543
[2] Department of Health and Human Services. Panel on Antiretroviral Guidelines for Adults and Adolescents. Guidelines for the Use of Antiretroviral Agents in Adults and Adolescents With HIV 2024 [Available from: https://clinicalinfo.hiv.gov/en/guidelines/hiv-clinical-guidelines-adult-and-adolescent-arv/whats-new
[3] Orkin C, DeJesus E, Sax PE, 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. doi:10.1016/S2352-3018(20)30099-0
[4] Taguchi N, Piao Y, Rubino A, Lee K, Chen M, Harada K, Tanikawa T, Naito T. Relationship between adherence to bictegravir/emtricitabine/tenofovir alafenamide fumarate and clinical outcomes in people with HIV in Japan: a claims database analysis. Sci Rep. 2024 Jul 22;14(1):16785. doi: 10.1038/s41598-024-67837-6. PMID: 39039129; PMCID: PMC11263482.
[5] Iván Chivite, Leire Berrocal, Elisa de Lazzari, Soodabeh Navadeh, Carla Lluis-Ganella, Alexy Inciarte, Lorena de la Mora, Ana González-Cordón, Maria Martínez-Rebollar, Montserrat Laguno, Berta Torres, José Luis Blanco, Esteban Martínez, Josep Mallolas, Juan Ambrosioni, Effectiveness, safety and discontinuation rates of bictegravir/emtricitabine/tenofovir alafenamide (BIC/FTC/TAF) in people with HIV using real-world data: a systematic review and meta-analysis, Journal of Antimicrobial Chemotherapy, Volume 79, Issue 8, August 2024, Pages 1775–1783, https://doi.org/10.1093/jac/dkae138
[6] Dumitrescu F, Dragonu L, Marcu EA, Pădureanu V, Stoian AC, Rădoi-Troacă CL, Pădureanu R, Duduveche A, Georgescu IA, Giubelan L. Bone Mineral Density in HIV-Infected People-the Experience of Craiova Regional Center. Biomedicines. 2025 Sep 20;13(9):2305. doi: 10.3390/biomedicines13092305. PMID: 41007865; PMCID: PMC12467255.
[7] Yeh SJ, Li CW, Lo CL, et al. Cardiometabolic multimorbidity in aging adults with HIV: Real-world evidence from a care cohort in Taiwan. J Microbiol Immunol Infect. 2026;59(1):21-27. doi:10.1016/j.jmii.2025.06.011
[8] National Institutes of Health. “Cabotegravir.” ClinicalInfo HIV.gov, June 27, 2024. https://clinicalinfo.hiv.gov/en/guidelines/pediatric-arv/cabotegravir.
[9] Canales E, Tse W, Schroeder SD, Chou CH, Liu Q, Zhang J, Lazerwith SE, Morganelli P, Saito RD, Brizgys G, Li J, Wu Q, Graupe M, Halcomb RL, Desai M, Cannizzaro C, Hu E, Perry JK, Villaseñor AG, Somoza JR, Ferrao RD, Swaminathan S, Zheng J, Lu B, Mwangi J, Wang K, Subramanian R, Smith BJ, Rhodes G, Rowe W, Sauer D, Lad L, Papalia GA, Clancy S, Stepan GJ, Yu H, Sakowicz R, Shi B, Carr G, Bam RA, Tsai LK, Singer E, Hansen D, Mulato A, Yant SR, Cihlar T, Link JO. Discovery of Lenacapavir: First-in-Class Twice-Yearly Capsid Inhibitor for HIV-1 Treatment and Pre-exposure Prophylaxis. J Med Chem. 2025 Oct 23;68(20):21072-21094. doi: 10.1021/acs.jmedchem.5c01625. Epub 2025 Oct 1. PMID: 41032707; PMCID: PMC12557389.
