Doravirine HIV treatment resulted in fewer adverse events

The use of once-daily oral doravirine plus tenofovir/emtricitabine resulted in fewer adverse events in patients with HIV-1 compared with efavirenz plus tenofovir/emtricitabine, according to data presented at the International Congress on HIV Drug Therapy in HIV Infection in Glasgow, Scotland.

Merck researchers randomly assigned 25 mg, 50 mg, 100 mg or 200 mg of the investigational non-nucleoside reverse-transcriptase inhibitor doravirine (n=166) or 600 mg efavirenz (n=42) to previously untreated patients with HIV-1 in combination with tenofovir/emtricitabine (TDF/FTC). After 24 weeks of the phase 2b trial, safety and efficacy data from doravirine-treated patients was used to determine optimal dosage for an expansion phase. Patients were enrolled in the extension and assigned either 100 mg doravirine plus TDF/FTC or efavirenz plus TDF/FTC for a planned duration of 96 weeks.

By week 8 of the expansion, fewer central nervous system adverse events were seen (22.2% vs. 43.5%) in the 100-mg doravirine group (n=108) than the efavirenz group (n=108). The most common events were dizziness (9.3% vs. 27.8%), insomnia (6.5% vs. 2.8%), abnormal dreams (5.6% vs. 16.7%) and nightmares (5.6% vs. 8.3%).

Within the earlier dose-ranging part of the study, patients assigned doravirine also had lower overall incidence of drug-related adverse events (36.7%) than those assigned efavirenz (57.1%) after 48 weeks. The most common drug-related adverse events were abnormal dreams (10.2% vs. 9.5%), nausea (7.8% vs. 2.4%), fatigue (7.2% vs. 4.8%), diarrhea (4.8% vs. 9.5%) and dizziness (3% vs. 23.8%).

Also at 48 weeks, patients who received doravirine at any dosage showed a 76% overall virologic response rate (<40 copies/mL) compared with the 71% reported for patients who received efavirenz. All treatment groups and dosages had increased CD4 cell counts relative to baseline, findings consistent with those reported after 24 weeks at CROI 2014.

“This program underscores Merck’s ongoing commitment to the research and development of new therapeutic options for patients with HIV,” Hedy Teppler, MD, executive director of infectious diseases at Merck Research Laboratories, said in a press release. “We are encouraged by the antiviral activity and the overall tolerability profile of doravirine, and look forward to initiating phase 3 studies [before the end of the year].”

For more information:

Gatell J.M. Abstract 0434. Presented at: International Congress on Drug Therapy in HIV Infection. Nov. 2-6; Glasgow, Scotland.

Disclosure: One of the researchers reports grants or honoraria for lectures or for advisory boards from Abbvie, Bristol-Myers Squibb, Gilead, Janssen, Merck and ViiV.