Fixed-Dose Doravirine Combination Non-Inferior in Treatment-Experienced Patients

Doravirine/Lamivudine/Tenofovir Disoproxil Fumarate (Delstrigo)

A fixed-dose combination regimen containing the newly approved antiretroviral doravirine (Pifeltro) was non-inferior to other triple combination therapies in participants who switched from their current regimen to the new drug, announced Merck, doravirine’s manufacturer, at IDWeek 2018 in San Francisco. The once-daily pill Delstrigo contains doravirine, lamivudine (3TC, Epivir) and tenofovir disoproxil fumarate (Viread). Principal investigator Princy Kumar, M.D., of Medstar Georgetown University Hospital, Washington, D.C., presented the data.

All 670 study participants were durably virally suppressed (viral load less than 40 copies/mL for at least six months) on a stable regimen of two nucleoside reverse transcriptase inhibitors plus a boosted protease inhibitor, a boosted elvitegravir (Vitekta), or a non-nucleoside reverse transcriptase inhibitor. They were randomized 1:2 to immediately switch to Delstrigo or continue for 24 weeks on their current regimen and then switch to the study drug. The entire study ran for 48 weeks.

At week 24, viral suppression rates (less than 50 copies/mL) were similar between the immediate-switch arm (93.7% of participants in that arm) and the deferred-switch arm (94.6%). By week 48, 90.8% of those who had immediately changed regimens were still virally suppressed. That result was compared with the 94.6% who were virally suppressed at week 24 on their baseline regimens (i.e., before participants in that arm switched to the new drug). The difference of -3.8% fell within the pre-defined -8% non-inferiority margin. Forty-eight-week data on viral suppression in the delayed-switch arm were not reported in the abstract or press release.

Lipid levels were significantly better among the immediate-switch arm compared with those in the deferred-switch arm who took a ritonavir (Norvir)-boosted protease inhibitor (PI). Fasting low-density lipoprotein dropped by 16.5 mg/dL in the study drug group compared with 1.9 mg/dL in the PI group. Similarly, non-high-density lipoprotein fell by 24.7 mg/dL on Delstrigo versus 1.3 mg/dL on the PI. Tenofovir disoproxil fumarate, one of the study drug’s components, is known to reduce lipid levels.

After 24 weeks, more participants on Delstrigo had dropped out of the study due to adverse events (2.5%) than had those still on their baseline regimens (0.4%). The most common complaints in both arms and at both 24 and 48 weeks were nasopharyngitis and headache. Drug-related headaches occurred in 0.4% of participants on their baseline regimen, 1.6% of those who immediately switched to the new drug, and 2.4% of those who switched later.

The non-inferiority shown in this trial means that Delstrigo is an option for people who need to switch their HIV regimen, concluded George Hanna, M.D., of Merck in a company press release.