Positive results have been announced from a pivotal phase 3 trial evaluating the safety and efficacy of doravirine (Merck), an investigational non-nucleoside reverse transcriptase inhibitor (NNRTI). The study met its primary efficacy endpoint of the proportion of participants achieving levels of human immunodeficiency virus-1 (HIV-1) RNA of less than 50 copies/mL after 48 weeks of treatment, demonstrating the noninferiority of once-daily doravirine compared with once-daily ritonavir-boosted darunavir (DRV+r), each administered with tenofovir disoproxil fumarate/emtricitabine (TDF/FTC) or abacavir/lamivudine (ABC/3TC), in treatment-naïve adults with HIV-1 infection.
In addition, a secondary endpoint showed that the doravirine-treated group had significantly lower levels of fasting low-density lipoprotein cholesterol (LDL-C) compared with the DRV+r group.
The DRIVE-FORWARD trial was a multicenter, double-blind, randomized, noninferiority study in which 769 treatment-naïve adults with HIV-1 infection received either doravirine 100 mg or darunavir 800 mg plus ritonavir 100 mg, both administered orally once-daily in combination with either TDF/FTC or ABC/3TC. After 48 weeks of treatment, the proportions of subjects achieving levels of HIV-1 RNA of less than 50 copies/mL after once-daily doravirine or once-daily DRV+r, each in combination with either TDF/FTC or ABC/3TC, were 84% (321/383) and 80% (306/383), respectively. Increases in mean CD4+ T-cell counts from baseline were similar for the doravirine and DRV+r treatment groups: 193 and 186 cells/mm3, respectively.
In addition, comparable efficacy was observed in subjects with baseline levels of HIV-1 RNA of greater than 100,000 copies/mL: 81% (64/79) for doravirine and 76% (55/72) for DRV+r. One out of 383 subjects developed phenotypic and genotypic resistance in the doravirine arm; this patient was omitted from the study at week 24 because of nonadherence. None of the 383 participants receiving DRV+r developed phenotypic or genotypic resistance.
The rates of reported adverse events were 31% (117/383) for doravirine and 32% (123/383) for DRV+r. Discontinuations due to adverse events for the doravirine and DRV+r groups were 2% (6/383) and 3% (12/383), respectively. The most common adverse events associated with doravirine and DRV+r included diarrhea (14% vs. 22%, respectively), headache (14% vs. 11%), nausea (11% vs. 12%), and nasopharyngitis (8% vs. 10 %).
An analysis of fasting serum blood lipids for the doravirine and DRV+r groups showed a statistically significant difference (P < 0.0001) in mean changes from baseline in the levels of LDL-C (–4.5 mg/dL vs. +9.9 mg/dL, respectively) and in levels of non–high-density lipoprotein cholesterol (non–HDL-C) (–5.3 mg/dL vs. +13.8 mg/dL). Mean changes from baseline in total cholesterol, HDL-C, and triglycerides were –1.4 mg/dL, +3.9 mg/dL, and –3.1 mg/dL for the doravirine group compared with +17.9 mg/dL, +4.2 mg/dL, and +22 mg/dL for the DRV+r group.
Source: Merck; February 15, 2017.