Investigational once-weekly ART combo maintained viral suppression in HIV

Ogbuagu pointed to several favorable characteristics of ulonivirine, including its ability to retain activity against most variants resistant to other first- and second-generation non-nucleoside reverse transcriptase inhibitors (NNRTIs) in its class. “This is important because transmitted drug-resistant variants commonly include NNRTI mutations,” he said.

He also highlighted its once-weekly dosing, allowing it to be paired well with other antivirals in development with similar once-weekly pharmacokinetic profiles. Though the weekly combination of islatravir with lenacapavir (Sunlenca) is further along in development, “thus offering a potential competitive landscape for weekly-dosed oral regimens … ulonivirine may have the advantage of less drug-drug interaction potential relative to lenacapavir,” he added.

“With future concerns for integrase inhibitor resistance rising, I see a role for ulonivirine in the treatment of [these] individuals … but this group is not being studied yet,” Ogbuagu said.

He also noted that “weekly regimens hold promise to address pill fatigue and adherence issues, but real-world uptake and adherence to this unusual dosing frequency are yet to be evaluated.”

The trial randomly assigned 161 adults with HIV-1 to receive the nucleoside reverse transcriptase translocation inhibitor islatravir 20 mg with 100 mg, 200 mg, or 400 mg of ulonivirine or to BIC/FTC/TAF. No participants had a history of treatment failure on any regimen, any known virologic resistance to NNRTIs, or active hepatitis B or C co-infection.

Median age was 45 years, 80.7% were men, 65% were white, a quarter to a third were Black, and 15% to 20% were Hispanic/Latino. CD4 counts at baseline were an average 748 cells/mm³, and at least 93% of participants in each group had a CD4 count above 350 cells/mm³. Participants had been on ART a median 64.7 to 116.8 months across groups, and prior BIC/FTC/TAF duration was a median 21-23 months.

At 24 weeks, the patients with all data available included 34 receiving BIC/FTC/TAF, 28 receiving islatravir plus ulonivirine 400 mg, 28 receiving islatravir plus ulonivirine 200 mg, and 26 receiving islatravir plus ulonivirine 100 mg. Following the trial’s end at 24 weeks, participants transitioned to a different ART with continued safety monitoring follow-up.

Overall adverse events occurred in 76.9% across the islatravir/ulonivirine groups and 67.5% in the BIC/FTC/TAF group. However, none receiving BIC/FTC/TAF experienced serious adverse events compared with 2.5% in the islatravir/ulonivirine 400 mg group, 7.3% in the islatravir/ulonivirine 200 mg group, and 5% in the islatravir/ulonivirine 100 mg group. The most commonly reported adverse events with islatravir/ulonivirine included fatigue, diarrhea, headache, and nausea.

Drug-related adverse events occurred in 17.4% receiving islatravir/ulonivirine and 10% receiving BIC/FTC/TAF, with 2.5% receiving islatravir/ulonivirine and no patients receiving BIC/FTC/TAF discontinuing due to adverse events.

Infection rates were similar with both drug combinations. Adverse events with a toxicity grade of 3-4 occurred in 2.5% of BIC/FTC/TAF participants, 7.5% of the islatravir/ulonivirine 400 mg group, 14.6% of the islatravir/ulonivirine 200 mg group, and 5% of the islatravir/ulonivirine 100 mg group.

By Tara Haelle