Doravirine/Islatravir: Clinical Considerations for Newly Approved HIV Treatment

This week, the FDA approved doravirine/islatravir (Idvynso), a single-tablet, once-daily regimen combining doravirine and islatravir, for adults living with HIV who have virologic suppression and have no history of treatment failure or resistance to doravirine. The therapy was developed by Merck, and designed to replace existing antiretroviral regimens in eligible patients. Doravirine/islatravir stands out as the first and only non–integrase strand transfer inhibitor (INSTI), tenofovir-free, complete 2-drug regimen to demonstrate noninferior efficacy in a head-to-head phase 3 trial against the widely used 3-drug regimen bictegravir/emtricitabine/tenofovir alafenamide (Biktarvy).

The therapy is being positioned as a viable option alongside existing regimens. Its availability reflects a broader shift toward personalized HIV care, where treatment decisions are increasingly guided by individual patient preferences, comorbidities, and long-term medication burden.

Contagion spoke with Amy Colson, MD, MPH, medical director of the Zinberg Clinic at Cambridge Health Alliance and research director at Community Resource Initiative, about the clinical trial, including it efficacy and safety profiles, as well as the potential patient candidates for the treatment.

Contagion: I wanted to begin by discussing the new HIV therapeutic, Idvynso, which is described as the first non-INSTI, tenofovir-free, two-drug regimen to demonstrate noninferiority efficacy. How might this shift current HIV treatment strategies for virologically suppressed patients?

Colson: Yeah, so the availability of a simple two-drug regimen that does not contain an INSTI or tenofovir provides another treatment option for virologically suppressed adults living with HIV. As clinicians, we now have an effective alternative to offer patients who have difficulty tolerating an INSTI-based regimen due to symptomatic side effects, or who simply wish to simplify their regimen or reduce the number of HIV medications they are taking, given that the current paradigm for HIV treatment is lifelong, continuous therapy. Tailoring therapy to a person’s individual preferences and medical profile is really important.

Contagion: In thinking about this newly approved therapeutic, what patient populations or clinical scenarios make someone an ideal candidate for switching to it?

Colson: Generally speaking, this regimen should only be used in people who are virologically suppressed, with no history of treatment failure and no known resistance-associated mutations. Ideal candidates are individuals experiencing symptoms that may be related to their current treatment regimen, or those who wish to reduce polypharmacy. It is also a safe and simple two-drug option for people managing multimorbidity and polypharmacy as they age. In the clinical trials, 11% of participants were over the age of 65 and 1% were over the age of 75. What we saw was that efficacy, tolerability, and safety in older participants were quite similar to those observed in younger participants.

Contagion: In thinking about the phase 3 trials, which showed strong efficacy and comparable safety, what should clinicians keep in mind when weighing the benefits against potential risks, such as drug interactions or rare skin reactions?

Colson: Overall, the safety of this regimen was demonstrated by week 48 data from two large, randomized, active-controlled trials. Serious adverse events and discontinuations due to adverse events occurred at comparable rates in the treatment arm and the comparator arms. This trial data makes me confident in its safety.

Rare but serious cutaneous reactions are a risk with many drugs, and this small risk would not dissuade me from using this regimen. However, I would counsel patients to stop therapy and seek immediate care in the case of a severe or progressive skin rash, especially if there is mucosal involvement or systemic symptoms.

Additionally, many drugs are affected by coadministration with strong and moderate CYP3A inhibitors, which can make treating HIV particularly challenging. For my patients on strong CYP3A inhibitors, I am careful to check drug interaction resources to ensure I am selecting an antiviral therapy that is compatible with their other medications.

Contagion: How does simplifying treatment to a single-tablet, two-drug regimen impact long-term adherence and quality of life for people aging with HIV?

Colson: In my own clinical population, I’ve noticed that as people age, their medical profile and medication preferences may shift. As we discussed, this is a very safe and simple two-drug option for individuals managing multimorbidity and polypharmacy as they age, which reflects many of the patients in my practice.