[Comment] Managing complex antiretroviral regimens

Managing complex antiretroviral regimens
Affiliations & Notes
Department of Medicine, Division of Infectious Diseases, University of Alabama at Birmingham, Birmingham, AL 35294, USA
Article Info
Publication History:
Published February 25, 2026
DOI: 10.1016/S0140-6736(26)00364-8 External LinkAlso available on ScienceDirect External Link
Copyright: © 2026 Elsevier Ltd. All rights are reserved, including those for text and data mining, AI training, and similar technologies.
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OkThe practice of switching antiretroviral therapy (ART) in people with HIV who have reached and maintained virological suppression is an important component of contemporary HIV care. Advances in ART pharmacology, tolerability, and the expanding availability of simplified, single-tablet regimens have shifted treatment goals beyond viral suppression alone towards long-term safety, durability, adherence optimisation, and improved quality of life.1,2
References
1.
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
https://clinicalinfo.hiv.gov/sites/default/files/guidelines/documents/adult-adolescent-arv/guidelines-adult-adolescent-arv.pdf
Date accessed: February 16, 2026
2.
Gandhi, RT ∙ Landovitz, RJ ∙ Sax, PE ∙ et al.
Antiretroviral drugs for treatment and prevention of HIV infection in adults: 2024 recommendations of the International Antiviral Society–USA Panel
JAMA. 2025; 333:609-628
3.
Orkin, C ∙ Ruane, PJ ∙ Hedgcock, M ∙ et al.
Switch to single-tablet bictegravir–lenacapavir from a complex HIV regimen (ARTISTRY-1): a randomised, open-label, phase 3 clinical trial
Lancet. 2026;
published online Feb 25. https://doi.org/10.1016/S0140-6736(26)00307-7
4.
Llibre, JM ∙ Hung, CC ∙ Brinson, C ∙ et al.
Phase III SWORD 1 & 2: switch to dolutegravir plus rilpivirine maintains virologic suppression
Lancet. 2018; 391:839-849
5.
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; 71:1920-1929
6.
Overton, ET ∙ Richmond, G ∙ Rizzardini, G ∙ et al.
Long-acting cabotegravir and rilpivirine dosed every 2 months in adults with HIV-1 infection (ATLAS-2M), 48-week results: a randomised, multicentre, open-label, phase 3b, non-inferiority study
Lancet. 2021; 396:1994-2005
7.
Sax, PE ∙ Rockstroh, JK ∙ Luetkemeyer, AF ∙ et al., the GS-US-380–4030 Investigators
Switching to bictegravir, emtricitabine, and tenofovir alafenamide in virologically suppressed adults with human immunodeficiency virus
Clin Infect Dis. 2021; 73:e485-e493
8.
Daar, ES ∙ DeJesus, E ∙ Ruane, P ∙ et al.
Efficacy and safety of switching to fixed-dose bictegravir, emtricitabine, and tenofovir alafenamide from boosted protease inhibitor-based regimens in virologically suppressed adults with HIV-1: 48 week results of a randomised, open-label, multicentre, phase 3, non-inferiority trial
Lancet HIV. 2018; 5:e347-e356
9.
Colson, AE ∙ Mills, AM ∙ Ramgopal, MN ∙ et al.
Switch to fixed-dose doravirine (100 mg) and islatravir (0·25 mg) once daily in virologically suppressed adults with HIV-1 on bictegravir, emtricitabine, and tenofovir alafenamide: 48-week results of a phase 3, multicentre, randomised, controlled, double-blind, non-inferiority trial
Lancet. 2026; 407:611-621
10.
Orkin, C ∙ Arasteh, K ∙ Górgolas Hernández-Mora, M ∙ et al.
Long-acting cabotegravir and rilpivirine after oral induction for HIV-1 infection
N Engl J Med. 2020; 382:1124-1135

Facts Only

Department of Medicine, Division of Infectious Diseases, University of Alabama at Birmingham
Advances in ART pharmacology, tolerability, and the expanding availability of simplified, single-tablet regimens
Shift in treatment goals towards long-term safety, durability, adherence optimization, and improved quality of life
Switching antiretroviral therapy (ART) in people with HIV who have reached and maintained virological suppression
Single-tablet bictegravir–lenacapavir from a complex HIV regimen (ARTISTRY-1)
Dolutegravir plus rilpivirine maintains virologic suppression (SWORD 1 & 2)
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 (TANGO study)
Long-acting cabotegravir and rilpivirine dosed every 2 months in adults with HIV-1 infection (ATLAS-2M), 48-week results
Switching to bictegravir, emtricitabine, and tenofovir alafenamide in virologically suppressed adults with human immunodeficiency virus
Efficacy and safety of switching to fixed-dose bictegravir, emtricitabine, and tenofovir alafenamide from boosted protease inhibitor-based regimens in virologically suppressed adults with HIV-1
Switch to fixed-dose doravirine (100 mg) and islatravir (0·25 mg) once daily in virologically suppressed adults with HIV-1 on bictegravir, emtricitabine, and tenofovir alafenamide

Executive Summary

Managing complex antiretroviral regimens is a crucial aspect of contemporary HIV care, with the primary goal shifting towards long-term safety, durability, adherence optimization, and improved quality of life for patients. The article highlights several studies that demonstrate the benefits of switching to simplified antiretroviral therapy (ART) regimens, such as single-tablet regimens or fixed-dose combinations, in maintaining viral suppression while improving tolerability and adherence. These studies compare various treatment options, including bictegravir–lenacapavir, dolutegravir plus rilpivirine, doravirine, and long-acting cabotegravir and rilpivirine, among others. The goal is to provide safer, more durable, and easier-to-administer treatment options for patients living with HIV.

Full Take

As the practice of managing complex antiretroviral regimens evolves, it is essential to recognize patterns in the presentation and discussion of treatment options. Manipulation may occur through the use of ambiguity (ARC-0024) or forced binary choices (False framing), as some treatments are presented as superior while others are omitted or downplayed. It is crucial for patients, healthcare providers, and researchers to critically evaluate the evidence supporting various ART options, considering their safety, efficacy, durability, and ease of administration.
Root cause: The drive behind managing complex antiretroviral regimens stems from a desire to improve treatment outcomes for people living with HIV while addressing challenges related to adherence, tolerability, and long-term health impacts.
Implications: The advancements in ART will have significant implications for the overall health and wellbeing of individuals living with HIV. Improved treatment options may lead to better outcomes, increased longevity, and enhanced quality of life. However, accessibility and affordability remain key concerns, as not all patients may have equal access to these new treatments.
Bridge questions: What factors contribute to the unequal distribution of advanced ART treatments? How can healthcare systems ensure equitable access to these life-saving interventions for all individuals living with HIV? What additional research is needed to further optimize ART regimens and improve treatment outcomes?