Last reviewed 2026-04-23 · How we verify

MK-8591A

MK-8591A is a nucleoside reverse transcriptase translocation inhibitor (NRTI) that blocks HIV reverse transcriptase by preventing the translocation of the enzyme along the viral RNA template.

MK-8591A is a nucleoside reverse transcriptase translocation inhibitor (NRTI) that blocks HIV reverse transcriptase by preventing the translocation of the enzyme along the viral RNA template. Used for HIV-1 infection (treatment-experienced and treatment-naive patients).

At a glance

Mechanism of action

MK-8591A binds to HIV reverse transcriptase and inhibits its ability to move along the RNA template during viral replication, a mechanism distinct from conventional NRTIs. This translocation inhibition prevents the enzyme from synthesizing viral DNA, thereby suppressing HIV replication. The drug is designed to have activity against both wild-type and drug-resistant HIV strains.

Approved indications

• HIV-1 infection (treatment-experienced and treatment-naive patients)

Common side effects

• Nausea
• Diarrhea
• Headache
• Fatigue

Key clinical trials

• Switch to Doravirine/Islatravir (DOR/ISL) in Human Immunodeficiency Virus 1 (HIV-1) Participants Treated With Bictegravir/Emtricitabine/Tenofovir Alafenamide (BIC/FTC/TAF) (MK-8591A-018) (PHASE3)
• A Study of Doravirine/Islatravir in Healthy Lactating Females (MK-8591A-061) (PHASE1)
• Safety and Efficacy of a Switch to Doravirine/Islatravir in Participants With HIV-1 (MK-8591A-017) (PHASE3)
• Study of Doravirine/Islatravir (DOR/ISL 100 mg/0.75 mg) to Evaluate the Antiretroviral Activity, Safety, and Tolerability in Treatment-Naïve Participants With Human Immunodeficiency Virus Type 1 (HIV-1) Infection (MK-8591A-020) (PHASE3)
• Open-label, Follow-up of Doravirine/Islatravir (DOR/ISL 100 mg/0.75mg) for Participants With Human Immunodeficiency Virus-1 (HIV-1) Infection (MK-8591A-033) (PHASE3)
• A Study of Doravirine/Islatravir (DOR/ISL, MK-8591A) for the Treatment of Human Immunodeficiency Virus 1 (HIV-1) Infection in Participants Who Previously Received DOR/ISL (MK-8591A-054) (PHASE3)
• A Switch to Doravirine/Islatravir (DOR/ISL) in Participants With Human Immunodeficiency Virus Type 1 (HIV-1) Who Are Virologically Suppressed on Antiretroviral Therapy (ART) (MK-8591A-051) (PHASE3)
• A Switch to Doravirine/Islatravir (DOR/ISL) in Participants With Human Immunodeficiency Virus Type 1 (HIV-1) Who Are Virologically Suppressed on Bictegravir/Emtricitabine/Tenofovir Alafenamide (BIC/FTC/TAF) (MK-8591A-052) (PHASE3)

Primary sources

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