Based on 96-week data from the DRIVE-FORWARD study, which was presented at the recent 22nd International AIDS Conference, the U.S. Food and Drug Administration has approved two new antiretroviral medications ahead of schedule. Both drugs contain a new non-nucleoside reverse transcriptase inhibitor (NNRTI), doravirine (Pifeltro). Data from an earlier trial of doravirine, DRIVE-AHEAD, had been presented at the 2017 International AIDS Society Meeting in Paris.
The NNRTI by itself is named Pifeltro, dosed once a day, and it must be taken together with other antiretrovirals. A once-daily fixed-dose combination containing doravirine, lamivudine (3TC, Epivir), and tenofovir disoproxil fumarate (Viread) is named Delstrigo. This combination drug may worsen hepatitis B infection (HBV) after the antiretroviral is no longer taken, drug manufacturer Merck's patient information leaflet warns. The leaflet recommends testing for HBV before starting the drug and close monitoring, including blood work, after stopping the medication.
Participants in both clinical trials were antiretroviral-naive and both drugs have been approved only for people who have never taken HIV medications before. More people in the doravirine-based arms of the two studies were virally suppressed at 48 and 96 weeks than those in the comparator arms. The control groups were based on darunavir (Prezista) or efavirenz (Sustiva, Stocrin). However, in the DRIVE-FORWARD trial, viral suppression rates among those who started out with high viral loads (>100,000 copies/mL) -- 20% of participants -- did not differ between the two arms.
In both studies, lipid profiles were better on the new medication than in the control groups. Since cholesterol levels are linked to cardiovascular problems such as strokes, doravirine could be an option for those with cardiovascular health issues, Kathleen Squires, M.D., Merck's global director of scientific affairs, noted previously. In people living in the U.S. with HIV, strokes are more common among African Americans and women. However, most study participants were white men.
In addition to the resulting paucity of data on doravirine in women, there is also no information on its effect on pregnant or breastfeeding women, the patient information leaflet for Pifeltro notes. The leaflet recommends that women who plan to become pregnant talk to their medical providers before taking the drug and warns against breastfeeding while on it. It also notes interactions with a variety of other medications, including anticonvulsants and tuberculosis drugs, as well as St. John's wort.
Merck anticipates that the two new drugs will be available through wholesalers within a month. Both medications will be covered under the company's Drug Assistance Program. An application for approval by the European Medicines Agency is under review.