The investigational non-nucleoside reverse transcriptase inhibitor doravirine, in combination with other ART drugs, was well-tolerated and associated with higher rates of viral suppression compared with ritonavir-boosted darunavir in treatment-naive patients with HIV, according to 96-week data from the phase 3 DRIVE-FORWARD trial.
The findings are consistent with 48-week data that were previously presented at CROI 2017.
“All in all, we are very pleased with the 96-week data,” George Hanna, MD, vice president and therapeutic area head of infectious diseases, global clinical development at Merck Research Laboratories, told Infectious Disease News. “It confirms that the efficacy, tolerability and safety of doravirine that we saw at 48 weeks continue to be durable through essentially 2 years of therapy.”
For the trial, Hanna and colleagues randomly assigned 766 treatment-naive participants to receive doravirine (DOR; 100 mg) or ritonavir-boosted darunavir (DRV+r; 800 mg and 100 mg, respectively) taken once daily in combination with emtricitabine/tenofovir disoproxil fumarate (FTC/TDF) or abacavir/lamivudine (ABC/3TC).
At 96 weeks, 73.1% of patients in the DOR group (n = 383) achieved viral suppression, defined as less than 50 copies/mL of HIV-1 RNA, vs. 66% in the DRV+r group (n = 383). The difference in treatment was 7.1% (95% CI/ 0.5-13.7).
Adverse events (AEs) were similar among patients in both treatment groups. The most common AEs in the DOR and DRV+r groups included diarrhea (17% vs. 23.8%), nausea (11.7% vs. 13.6%), headache (14.9% vs. 12%), upper respiratory tract infection (13.3% vs. 7.8%) and viral respiratory tract infection (11.5% vs. 13.1%). Overall, 1.6% of patients in the DOR group and 3.4% in the DRV+r group discontinued therapy due to AEs. Two patients who received DOR developed genotypic and phenotypic resistance by 96 weeks.
According to Hanna, DOR had a more favorable lipid profile compared with DRV+r.
“As expected for DRV+r, there is an increase in [low-density lipoprotein (LDL)] cholesterol, but we don’t see that with doravirine,” he said. “LDL is important for anybody because high LDL levels are often a risk factor for coronary artery disease. We know that people with HIV are at even greater risk for coronary artery disease than the HIV-negative population, so it is all the more important to ensure that we keep the risk manageable for people who have HIV.”
Doravirine was also examined in the phase 3 DRIVE-AHEAD trial, which compared the drug with efavirenz (EFV) in ART-naive adult patients with HIV. In this trial, 84.3% of patients receiving DOR/3TC/TDF achieved viral suppression at 48 weeks compared with 80.8% of patients in the EFV/FTC/TDF study arm, according to findings presented last year at the International AIDS Society conference. The study also met its primary safety endpoint, with fewer patients reporting neuropsychiatric AEs, including dizziness, sleep disorders and disturbances and inability to think clearly or concentrate.
“This is an example of how doravirine has a distinguishing property compared to another drug in that same class, such as efavirenz,” Hanna said.
In January, Merck submitted two new drug applications for doravirine as a once-daily tablet for use with other ART agents, as well as for use as a once-daily fixed-dose combination regimen with 3TC/TDF. The target action date is set for Oct. 23.
“It is important to have different treatment options so that people living with HIV can have a regimen that is targeted to their individual needs,” Hanna said. “We feel doravirine has a lot of promise to meet the unmet needs of HIV-infected individuals.” – by Stephanie Viguers
Molina JM, et al. Abstract LBPEB017. Presented at: Presented at: International AIDS Conference; July 23-27, 2018; Amsterdam.
Disclosures: Hanna is an employee of Merck.