FDA Expands Indications for Pifeltro and Delstrigo for HIV

Troy Brown, RN

September 20, 2019

The US Food and Drug Administration (FDA) expanded the indications for two HIV drugs to include appropriate patients with HIV-1 who are virologically suppressed, according to a company news release.

The indications were expanded for doravirine (Pifeltro, Merck) in combination with other antiretroviral agents and for doravirine/lamivudine/tenofovir disoproxil fumarate (Delstrigo, Merck) as a complete regimen.

"Thanks to developments in HIV science, more treatment options are becoming available to address the medical needs of people living with HIV," Princy Kumar, MD, chief, Division of Infectious Diseases and Tropical Medicine at MedStar Georgetown University Hospital and professor of Medicine and Microbiology, Georgetown University School of Medicine, Washington, DC, said in the news release.

"The expanded indications offer certain people with HIV-1 infection, and their doctors, the choice to switch their current antiretroviral therapy to Delstrigo or Pifeltro in combination with other antiretroviral agents," he added.

Doravirine is a non-nucleoside reverse transcriptase inhibitor (NNRTI). It is given by mouth as a 100-mg tablet together with other antiretroviral agents. The three-drug combo of doravirine/lamivudine/tenofovir disoproxil fumarate will be available as a fixed-dose, once-daily tablet containing doravirine 100 mg, lamivudine (3TC, 300 mg), and tenofovir disoproxil fumarate (TDF, 300 mg).

The FDA approved both drugs for patients with HIV-1 with no prior exposure to antiretroviral therapy on August 30, 2018. The expanded indications are for adults "with HIV-1 who are virologically suppressed (HIV-1 RNA < 50 copies/mL) on a stable antiretroviral regimen with no history of treatment failure and no known substitutions associated with resistance to Pifeltro or the individual components of Delstrigo," according to the news release.

Clinical Trials

The approvals follow consideration of safety and efficacy data from the phase 3 DRIVE-SHIFT Trial Evaluating a Switch to Delstrigo. That trial was a randomized, international, multicenter, open-label study among patients with viral suppression who had been on a baseline antiretroviral regimen (consisting of two NRTIs in combination with a protease inhibitor plus either ritonavir or cobicistat, or elvitegravir plus cobicistat) or an NNRTI for at least 6 months before trial entry.

The study randomly assigned 670 patients to begin treatment with the three-drug combo immediately on the first day (immediate switch group, ISG; n = 447) or after 24 weeks (delayed switch group, DSG; n = 223).

The trial compared the efficacy between the ISG at week 48 and the baseline regimen DSG at week 24. Of those in the Delstrigo ISG, 2% had HIV-1 RNA ≥ 50 copies/mL at week 48 compared with 1% in the baseline regimen DSG at Week 24 (treatment difference, 0.7%; 95% CI, -1.3 to 2.6).

Ninety-one percent of patients in the ISG had HIV-1 RNA < 50 copies/mL at week 48 compared with 95% of patients in the DSG at week 24.

The safety profile was similar for patients in both groups.

Two phase 3 studies evaluated safety in patients with HIV-1 and no prior antiretroviral treatment: DRIVE-AHEAD in patients taking the three-drug combo and DRIVE FORWARD in patients taking doravirine.

In DRIVE-AHEAD, the rate of treatment discontinuation as a result of adverse events was lower in those receiving the drug combo compared with those treated with efavirenz (EFV)/emtricitabine (FTC)/TDF (3% vs 6%). Clinical adverse events of all grades seen in at least 5% of patients in the drug combo group included dizziness (7%), nausea (5%), and abnormal dreams (5%). At least 2% of patients in the drug combo group had no moderate or severe adverse events.

In DRIVE-FORWARD, 2% of patients in the doravirine group discontinued therapy compared with 3% in the group that received darunavir plus ritonavir, each together with FTC/TDF or abacavir/3TC. Clinical adverse events of all grades that occurred in at least 5% of those in the doravirine group included nausea (7%), headache (6%), fatigue (6%), diarrhea (5%), and abdominal pain (5%). At least 2% of those in the doravirine group experienced no moderate or severe adverse reactions.

Box Warning, Contraindications

Delstrigo has a boxed warning about post-treatment acute exacerbation of hepatitis B virus infection.

Neither drug cures HIV-1 infection or AIDS.

Strong cytochrome P450 (CYP)3A enzyme inducers can cause "significant decreases in doravirine plasma concentrations," which may lessen the effectiveness of both drugs. The three-drug combo is contraindicated in those with a history of hypersensitivity reaction to 3TC.

Delstrigo should not be given to patients who are currently using, or who have recently used, a nephrotoxic agent.

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