doravirine

Doravirine is an antiretroviral medication used to treat HIV-1 infection. It is classified as a non-nucleoside reverse transcriptase inhibitor (NNRTI). Doravirine inhibits HIV-1 replication by binding to the reverse transcriptase enzyme at the NNRTI pocket, blocking the polymerase activity required for viral DNA synthesis.

Doravirine is available as a single-entity tablet (Pifeltro) and in a fixed-dose combination with lamivudine and tenofovir disoproxil fumarate (Delstrigo). The usual dose is 100 mg once daily, taken with or without food, in combination with nucleos(t)ide reverse transcriptase inhibitors as part of combination antiretroviral therapy.

Clinical trials in ART-naive and some experienced patients demonstrated that regimens containing doravirine were noninferior to efavirenz-based regimens in achieving and maintaining virologic suppression, with a lower incidence of central nervous system adverse effects and generally favorable tolerability. Doravirine tends to have a more favorable metabolic and lipid profile than efavirenz.

Common adverse events include nausea, dizziness, and diarrhea. Weight change has been reported but is generally modest. Doravirine is mainly metabolized by hepatic CYP3A4 and has potential for drug interactions with strong CYP3A4 inducers or inhibitors; coadministration with such agents should be managed accordingly.

Resistance to doravirine can arise via mutations in reverse transcriptase, and cross-resistance with other NNRTIs may occur but is not absolute. Virologic failure should prompt resistance testing and regimen change as indicated.