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ART Switch: How to Personalize

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Released: August 11, 2026

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There are many ART switch options available for people living with virologically suppressed HIV who desire regimen simplification, decreased pill burden, or modernization. However, the specifics of patients’ treatment history, resistance profile, and comorbidities will affect which switch regimens are available to them, and these must be considered to determine available switch regimens before incorporating individual goals. Read on to learn what options are available and how to select among them.

Daniel Moring-Parris
Daniel Moring-Parris, MD, AAHIVS
Personalizing ART Switch

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Once you and your patient have made a shared decision to switch antiretroviral therapy (ART) regimens, work truly begins. Before even beginning to discuss specific switch regimens, it is crucial to do a thorough review of patients’ ART history, to determine any available genotype information, followed by an in-depth review of all their comorbidities, including hepatitis B infection, chronic kidney disease, cardiovascular disease, and any comedications they are currently receiving. These are all key factors that will affect the drugs you choose.

The specifics of patients’ treatment history, resistance profile, and comorbidities will affect which switch regimens are available to them. Once the available regimens are identified, it is important to gain an understanding of patients’ goals: Do they want to decrease their pill burden, modernize their regimen, or switch to an injectable regimen?

Single-Tablet 2-Drug ART Switch Options
Often, regimen simplification is the goal for an ART switch in the context of a person living with virologically suppressed HIV who is adherent to their ART. In this scenario, single-tablet 2-drug regimens are a compelling, modern option.

There are several existing drugs that are good options for these switches. Dolutegravir (DTG)/rilpivirine (RPV) is a single-tablet 2-drug regimen that is not only tenofovir sparing but also highly tolerable, with a high barrier to resistance. DTG/lamivudine (3TC) is another agent that can be considered, which is also tenofovir sparing, although it is not recommended for people with advanced chronic kidney disease.

Doravirine (DOR)/islatravir (ISL) is a single-tablet 2-drug option that was just recently approved. DOR, which was approved in 2018, is already widely used. It is highly tolerable and has a reasonably high barrier to resistance. ISL is a novel nucleoside reverse transcriptase translocation inhibitor that was approved in April 2026 and is both tenofovir and protease inhibitor sparing.

One important consideration is that 2-drug regimens have some limitations. First, these regimens are specifically approved for people whose HIV has been virologically suppressed for at least 3-6 months and who do not have concomitant hepatitis B infection. Because 2-drug regimens, by definition, have fewer active drugs, it is even more important to ensure that your patient does not have resistance to any of the drug components in the regimen. In addition, these regimens are also not typically recommended for people with prior virologic failure.

Other Single-Tablet or Injectable ART Switch Options
In addition to 2-drug regimens, there are many other single-tablet options for people who are switching.

For example, single-tablet 3-drug regimens include the protease inhibitor–based regimen containing cobicistat (COB)-boosted darunavir (DRV)/emtricitabine (FTC)/tenofovir alafenamide (TAF). There is also the widely used single-tablet regimen consisting of bictegravir (BIC)/FTC/TAF. For those with cardiovascular disease risk factors, an appealing single-tablet option is the combination of doravirine (DOR)/(3TC)/tenofovir disoproxil fumarate (TDF). It is important to note that this regimen is not recommended for those with concerns for kidney disease or decreased bone mineral density because of the TDF component.

Finally, long-acting (LA) injectable cabotegravir (CAB) plus rilpivirine (RPV) is a great option for people who are experiencing pill fatigue, who have concerns about HIV-related stigma and being seen with pills, or whose living situations make it difficult to maintain adherence to oral ART. Similar to the oral 2-drug regimens, LA CAB + RPV is not recommended for patients living with hepatitis B infection.

There are also multiple off-label options for individuals with drug resistance on complex regimens, who are looking to decrease pill burden but still maintain 3 active drug classes. For example, DTG/COBI/FTC/TDF with an added integrase inhibitor or nonnucleoside reverse transcriptase inhibitor could be considered. Similarly, BIC/FTC/TAF with a boosted protease inhibitor is another option. Finally, if the goal is to decrease pill burden while avoiding tenofovir for an individual who may also have nucleos(t)ide reverse transcriptase inhibitor resistance, adding boosted DRV/COBI to DTG or adding DOR to DTG are great options.

An Anticipated ART Switch Option
One regimen that is highly anticipated, but not yet approved, is the oral combination of BIC/lenacapavir (LEN), both modern agents with high barriers to resistance.

This regimen was studied in both the ARTISTRY 1 and ARTISTRY 2 trials. ARTISTRY 1 enrolled people switching from a complex ART regimen to BIC/LEN, and ARTISTRY 2 enrolled people switching from standard BIC/FTC/TAF to BIC/LEN. In both studies, BIC/LEN was safe and effective in maintaining viral suppression at 48 weeks. I am optimistic that, once approved, this will be a useful option for people who want a tenofovir-sparing regimen but have significant drug resistance. Like other 2-drug regimens such as DTG/3TC, DTG/RPV, and DOR/ISL, BIC/LEN will potentially also be an attractive, modern 2-drug regimen for people who are receiving BIC/FTC/TAF but are interested in less medication exposure.

Your Thoughts
What questions would you ask a person living with virologically suppressed HIV who expresses an interest in switching their ART? Leave a comment to join the discussion and sign up for the live webinar for more!

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