General Information

Pifeltro (doravirine) is a non-nucleoside reverse transcriptase inhibitor.

Pifeltro is specifically indicated for use in combination with other antiretroviral agents for the treatment of HIV-1 infection in adult patients with no prior antiretroviral treatment history. FDA approval was subsequently expanded to include adult patients with HIV-1 infection who are virologically suppressed (HIV-1 RNA less than 50 copies per mL) on a stable antiretroviral regimen with no history of treatment failure and no known substitutions associated with resistance to Pifeltro.

Pifeltro is supplied as a tablet for oral administration. The recommended dosage regimen in adults is one 100 mg tablet taken orally once daily with or without food.

Mechanism of Action

Pifeltro (doravirine) is a pyridinone non-nucleoside reverse transcriptase inhibitor of HIV-1 and inhibits HIV-1 replication by non-competitive inhibition of HIV-1 reverse transcriptase (RT). Doravirine does not inhibit the human cellular DNA polymerases α, ß, and mitochondrial DNA polymerase γ.

Side Effects

Adverse reactions associated with he use of Pifeltro may include, but are not limited to, the following:

• nausea
• dizziness
• headache
• fatigue
• diarrhea
• abdominal pain
• abnormal dreams

Clinical Trial Results

The FDA approval of Pifeltro was based on 48-week data from a randomized, multicenter, double-blind, active controlled Phase III trial, DRIVE-FORWARD, in HIV-1 infected subjects with no antiretroviral treatment history. In DRIVE-FORWARD, 766 subjects were randomized and received at least 1 dose of either Pifeltro (doravirine [DOR]) once daily or darunavir 800 mg + ritonavir 100 mg (DRV+r) once daily each in combination with emtricitabine/tenofovir DF (FTC/TDF) or abacavir/lamivudine (ABC/3TC) selected by the investigator. In this trial, after 96 weeks of treatment, the proportion of subjects achieving HIV-1 RNA less than 50 copies/mL was 73.1% in the DOR group and 66% in the DRV+r group (treatment difference: 7.1%). Results for subjects with high baseline viral load (HIV-1 RNA greater than 100,000 copies/mL) were 65.4% for DOR and 65.2% for DRV+r (treatment difference: -1.1%). In addition, the mean change from baseline in CD4+ T-cell count at 96 weeks was 224 cells/mm3 for DOR and 207 cells/mm3 for DRV+r (treatment difference: 17.4 cells/mm3).