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To Switch or Not to Switch? That is the ART Question!

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Released: October 07, 2026

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There are many antiretroviral therapy (ART) regimens for HIV that are highly effective, convenient, safe, and well-tolerated, achieving virologic suppression for nearly all people living with HIV. Nevertheless, switching to a more contemporary ART regimen may still be desirable for some people with virologic suppression. Here, I introduce you to a range of common reasons for switching a suppressive ART regimen and some of the available options for each case.

Daniel R. Kuritzkes
Daniel R. Kuritzkes, MD
To Switch or Not to Switch

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Patient-Centered ART Decision Making
With so many antiretroviral therapy (ART) choices available to people living with HIV, I believe it is up to us to regularly assess people’s treatment satisfaction and offer the choice of switching ART through shared decision-making. Some people do well on their current regimen and are perfectly happy to continue it, but it is worth bringing up because in some cases a switch can be worth it.

3 Examples
For people who desire fewer daily pills, a switch to long-acting regimens such as injectable cabotegravir plus rilpivirine (RPV), which can be given every 4 or 8 weeks, is a good option. In the future, once-weekly oral therapy combining lenacapavir (LEN) and islatravir (ISL) may receive FDA approval based on the efficacy and safety results of phase III studies.

For people who have risk factors for cardiovascular disease and are on complex regimens that include a boosted protease inhibitor, there is a concern about an increased risk of myocardial infarction associated with long-term use. These people may benefit from switching to a 2-drug regimen that includes the non-nucleoside reverse transcriptase inhibitor (NNRTI) doravirine plus the nucleoside reverse transcriptase/translocation inhibitor ISL, or the second-generation integrase strand-transfer inhibitor (INSTI) bictegravir (BIC) plus the capsid inhibitor LEN.

People living with HIV who have diminished renal function or decreased bone mineral density who are receiving a tenofovir-containing ART regimen might benefit from a switch to a tenofovir-sparing ART regimen, such as dolutegravir (DTG) plus lamivudine, DTG/RPV, or any of the 2-drug regimens listed above.

Considerations for ART Switch
As a general rule, before making a switch, it is important to assess for a history of resistance to any components of the new regimen. This is particularly important when switching patients to long-acting cabotegravir plus RPV, as preexisting RPV resistance-associated mutations (RAMs) are associated with an increased risk of virologic failure.

By contrast, the presence of nucleoside reverse transcriptase inhibitor RAMs or NNRTI resistance mutations in proviral DNA had no significant impact on the maintenance of viral suppression following a switch to doravirine/ISL. I would expect similar results following a switch to BIC/LEN, though similar analyses have not been presented, so we do not yet know.

Another important consideration is excluding coinfection with hepatitis B virus before switching to a non–tenofovir-containing regimen due to concern for potential hepatitis B virus rebound.

Conversations about switching also need to address what a switch is unlikely to change. One problem faced by people living with HIV is that switching ART regimens will not solve weight gain. Despite earlier concerns that regimens including tenofovir alafenamide and second-generation INSTIs such as BIC and DTG might lead to excessive weight gain in some people, subsequent studies have cast doubt on the role that these drugs have in promoting weight gain (as opposed to effects mediated through viral suppression).

Moreover, several clinical trials have shown no clinically significant effect on weight when switching from a tenofovir alafenamide- and INSTI-containing regimen to a regimen that excludes those drugs. Current HIV and ART guidelines do not recommend an ART switch to reverse weight gain. Rather, they indicate that weight gain is more effectively managed through lifestyle changes or weight-suppressive medication, such as a GLP-1 receptor agonist.

To learn more about switching ART regimens in people living with HIV who are virologically suppressed, I encourage you to register for our upcoming live symposium and simulcast on October 21, 2026. Dr Monica Gandhi, Dr Chloe Orkin, and I will go through case scenarios and explain how we approach switching ART regimens.

Your Thoughts
How often do you discuss treatment satisfaction or ART switch options for people living with HIV? Based on this commentary, do you think you should be doing it more or less often? Why? Leave a comment to join the discussion!

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