Novel HIV Drug Doravirine Non-Inferior to Darunavir

As the market for HIV drugs widens, individuals living with the condition must work with their health care providers to carefully consider all of the options and choose the ones likely to be the most efficient and least toxic.

Thanks to an ongoing clinical trial, HIV-positive individuals hopefully soon will have yet another option for fighting HIV: doravirine. This non-nucleoside reverse transcriptase inhibitor (NNRTI) has been found to be non-inferior to ritonavir-boosted darunavir, a protease inhibitor, based on results from phase 3 of the international DRIVE-FORWARD trial.

In a recent article in The Lancet, the researchers—who are based in the United States, Europe, Latin America, and South Africa—described their findings. Over a period of nearly a year between 2014 and 2015, they screened more than 1,000 adult HIV-positive subjects at 125 locations in 15 countries. Eventually, 769 subjects were chosen to enroll in the trial; none had ever taken HIV medication before, and all had a plasma RNA level of at least 1,000 copies/mL.

The subjects were randomly divided into 2 groups. One group was given doravirine and the other was assigned to take ritonavir-boosted darunavir. A handful of subjects dropped out, but the trial ended up with 766 subjects who were followed for at least 48 weeks. In-person visits were as frequent as every 2 weeks at first, then were spaced out to every 12 weeks toward the end of the first year; blood was drawn at every visit. The primary endpoint of the study was the percentage of subjects who had achieved a plasma RNA level of less than 50 copies/mL by week 48, indicative of virological suppression.

The researchers found that doravirine was non-inferior to darunavir boosted with ritonavir, with the overwhelming majority of subjects in both groups achieving viral suppression by week 48: 84% of the doravirine group achieved suppression, compared with 80% of those taking boosted darunavir, and both groups reached a plateau around week 24. In the subgroup of participants who began the trial with plasma RNA levels of 100,000 copies/mL of higher, 81% of the doravirine group and 76% of those taking darunavir achieved viral suppression. Even in the tiny cohort of subjects who had plasma RNA levels of at least 500,000 copies/mL at the study’s start, doravirine was effective—14 out of 17 subjects (82%) achieved viral suppression 48 weeks out compared with 6 out of 12 in the darunavir group.

“The expectation was that doravirine would be non-inferior to ritonavir-boosted darunavir with a superior lipid profile at week 48, which was confirmed in the trial,” Carey Hwang, MD, PhD, executive director of clinical research at Merck, the pharmaceutical company that introduced doravirine, and the lead author of the study, told Contagion^®.

“The profile of doravirine allows it to be a good option for people living with HIV, since it has demonstrated strong efficacy and good tolerability with a favorable lipid profile in a drug class that clinicians are familiar with. Doravirine addresses many of the issues with existing NNRTIs (these include central nervous system issues, rash and hyperlipidemia, drug-drug interactions, and convenience factors such as food effect and dosing frequency) and may be a good option for patients with elevated lipids, those taking proton pump inhibitors or cation supplements, and those on multiple concomitant medications,” he said.

One subgroup of patients who should not take doravirine: those with HIV who are also infected with tuberculosis and are taking rifampin, as that drug has a significant negative impact on doravirine levels.

Although both doravirine and darunavir are effective against HIV, they, unfortunately, serve up side effects as well. Eighty percent of the doravirine takers experienced adverse effects along with 78% on darunavir, mainly diarrhea, nausea, and headache. But according to Dr. Hwang, these side effects should be considered within the bigger picture.

“Overall, doravirine was generally well-tolerated in DRIVE-FORWARD,” he said. “Only 4 participants (1%) in the doravirine arm discontinued from the trial due to a treatment-related adverse event. Diarrhea is a well-established side effect with ritonavir-boosted darunavir, and doravirine had less than half the reports of [treatment-related] diarrhea compared to ritonavir-boosted darunavir (5% vs 13%).”

As with all HIV drugs, no one drug is right for everyone. “Based on the profile of doravirine, it may provide another strong treatment option for people with HIV,” said Dr. Hwang. “Clinicians should choose the best available regimen for each patient.”

Laurie Saloman, MS, is a health writer with more than 20 years of experience working for both consumer- and physician-focused publications. She is a graduate of Brandeis University and the Medill School of Journalism at Northwestern University. She lives in New Jersey with her family.