FDA Approves New Standalone Combo Pill for HIV

The FDA approved islatravir-doravirine (Idvynso) as a standalone, single-tablet regimen for treating HIV in virologically suppressed adults, Merck announcedopens in a new tab or window on Tuesday.

Approval stipulates use of the oral combination in patients with HIV-1 who are virologically suppressed on stable antiretroviral therapy (ART), have no history of virologic treatment failure, and have no known substitutions associated with doravirine resistance. Co-administration with other ART medications is not recommended.

Two- and three-drug regimens with second-generation integrase strand transfer inhibitors (INSTIs), such as bictegravir, are standard in initial HIV therapy. However, some patients face INSTI resistance issues and contraindications.

In two phase III trialsopens in a new tab or window, switching to the INSTI-free single-tablet islatravir-doravirine therapy was just as effective at maintaining viral suppression as bictegravir/emtricitabine/tenofovir alafenamide fumarate (BIC/FTC/TAF; Biktarvy) or a previous ART regimen for virologically suppressed HIV-1 patients.

“Idvynso is the first non-INSTI, tenofovir-free, two-drug regimen to demonstrate noninferior efficacy to standard oral antiretroviral regimens, including Biktarvy,” investigator Amy Colson, MD, director of research at Community Resource Initiative in Boston, said in a statement. “This makes Idvynso a potential alternative for people with virologically suppressed HIV who may need to switch their treatment.”

Islatravir is a nucleoside analog reverse transcriptase inhibitor that blocks HIV-1 replication by multiple mechanisms. Doravirine is a non-nucleoside reverse transcriptase inhibitor that binds to and blocks HIV reverse transcriptase; the drug was first approved in 2018 under the brand name Pifeltro.

In the two trials, 1.4% to 1.5% of patients switching to islatravir-doravirine lost viral suppression (≥50 copies/mL of HIV-1 RNA) at 48 weeks compared with 0.6% and 4.9% of those who took BIC/FTC/TAF or remained on a previous ART regimen, respectively. Islatravir-doravirine users had minimal weight changes from baseline in both trials.

Common adverse events reported in the islatravir-doravirine arms of the trials included diarrhea (1-3%), dizziness (1-2%), fatigue (1-2%), abdominal distension (1-2%), headache (1-2%), and increased weight (<1% to 2%). Merck also noted a single case of severe immune thrombocytopenia that started a month after treatment initiation but resolved after stopping therapy.

Islatravir is the anchor medicine in other investigational two-drug combinationsopens in a new tab or window being developed as potential once-weekly treatmentsopens in a new tab or window for HIV.

Warnings and precautions in the labelingopens in a new tab or window notes severe skin reactions, including Stevens-Johnson syndrome/toxic epidermal necrolysis, and drug rash with eosinophilia and systemic symptoms.

Islatravir-doravirine is contraindicated with strong CYP3A enzyme inducers or the ART drugs lamivudine and emtricitabine.

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