FDA Approves Doravirine (Pifeltro) and New FDC With TDF/3TC (Delstrigo) in the U.S.

On 30 August 2018, the U.S. FDA approved doravirine as a separate formulation for use with ART and in a fixed-dose combination (FDC) with generic tenofovir DF and lamivudine (3TC).1

Doravirine is a once daily NNRTI that was initially developed as MK-1439. The standard adult dose is 100 mg once-daily, with or without food.

Approval is based on results from two large international randomised phase 3 studies in treatment-naive participants with control arms using darunavir (in DRIVE-FORWARD) and efavirenz (in DRIVE-AHEAD).

Each study reported primary endpoint results of viral suppression <50 copies/mL at 48 weeks in 84% vs approximately 81% (doravirine vs control respectively), with 95% confidence intervals that confirmed non-inferiority.

Although discontinuation rates were low in all study arms, tolerability advantages favoured doravirine from fewer darunavir/ritonavir-associated or efavirenz-associated side effects.

Doravirine is marketed in the U.S. with the trade name Pifeltro and the FDC is marketed as Delstrigo. Both formulations were developed by Merck (MSD).


Although most treatment guidelines now recommend integrase inhibitor-based first line treatment, drug-pricing is also increasingly important.

Doravirine has a better tolerability profile compared to efavirenz (which is still widely-used despite the guidelines).

The FDA indication is only for people who are treatment-naive. However, in vitro, doravirine retains sensitivity to common NNRTI resistance mutations (K103N, Y181C, G190A, E101K, E138K, and K103N/Y181C), with a profile that suggests limited cross-resistance to rilpivirine and etravirine. In vivo, doravirine selects for distinct mutations (V106A and F227L) that remain sensitive to rilpivirine and efavirenz (with possible increased sensitivity to the NRTI MK-8591).

Several studies in treatment-experienced participants are ongoing, but only as switch options in people with current viral suppression.

Development of a paediatric granule formulation has been delayed by a waiver on the grounds that doravirine does not represent a significant therapeutic benefit over existing treatments. The timeline for completing the paediatric plan is 2024.

Doravirine is also included in an FDC with 3TC plus the investigational NRTI EFdA (MK-8591), with phase 2 results expected in mid-2019.2


  1. Merck (MSD) press release. FDA approves Merck's Delstrigo (doravirine/lamivudine/tenofovir disoproxil fumarate), a once-daily fixed-dose combination tablet as a complete regimen and Pifeltrotm (doravirine), an NNRTI, both for the treatment of HIV-1 in appropriate patients. (30 August 2018).
  2. ClinicalTrials.gov. MK-8591 with doravirine and lamivudine in participants infected with HIV type 1 (MK-8591-011) (DRIVE2Simplify). NCT03272347.

[Note from TheBodyPRO: This article was originally published by HIV i-Base on Aug. 31, 2018. We have cross-posted it with their permission.]