Last reviewed 2026-04-23 · How we verify

Two NRTIs

Two nucleoside reverse transcriptase inhibitors (NRTIs) work together to block HIV reverse transcriptase, preventing the virus from converting its RNA genome into DNA and integrating into host cells.

Two nucleoside reverse transcriptase inhibitors (NRTIs) work together to block HIV reverse transcriptase, preventing the virus from converting its RNA genome into DNA and integrating into host cells. Used for HIV-1 infection (as part of combination antiretroviral therapy).

At a glance

Mechanism of action

NRTIs are nucleoside analogs that compete with natural nucleotides for incorporation into the growing DNA chain during reverse transcription. When incorporated, they cause chain termination because they lack a 3'-OH group needed for the next phosphodiester bond. Using two NRTIs together provides a backbone regimen that targets the same enzyme through complementary mechanisms, reducing the likelihood of resistance development.

Approved indications

• HIV-1 infection (as part of combination antiretroviral therapy)

Common side effects

• Nausea
• Diarrhea
• Headache
• Fatigue
• Lactic acidosis (rare but serious)
• Hepatotoxicity
• Lipodystrophy

Key clinical trials

• Study to Evaluate the Efficacy, Safety, and Tolerability of Long-acting Intramuscular Cabotegravir and Rilpivirine for Maintenance of Virologic Suppression Following Switch From an Integrase Inhibitor in HIV-1 Infected Therapy Naive Participants (PHASE3)
• Long-Acting Cabotegravir Plus VRC-HIVMAB075-00-AB (VRC07-523LS) for Viral Suppression in Adults Living With HIV-1 (PHASE2)
• Treatment of HIV/HCV Coinfection With Peg-IFN and Ribavirin in Patients Receiving ART Monotherapy With Lopinavir/r (PHASE4)
• Safety and Efficacy of a Switch to Doravirine, Tenofovir, Lamivudine (MK-1439A) in Human Immunodeficiency Virus (HIV-1)-Infected Participants Virologically Suppressed on an Anti-retroviral Regimen in Combination With Two Nucleoside Reverse Transcriptase Inhibitors (MK-1439A-024) (PHASE3)
• Improving HIV-1 Control in Africa with Long Acting Antiretrovirals (PHASE3)
• Regimen Switch to Dolutegravir + Rilpivirine From Current Antiretroviral Regimen in Human Immunodeficiency Virus Type 1 Infected and Virologically Suppressed Adults (SWORD-1) (PHASE3)
• Regimen Switch to Dolutegravir + Rilpivirine From Current Antiretroviral Regimen in Human Immunodeficiency Virus Type 1 Infected and Virologically Suppressed Adults (SWORD-2) (PHASE3)
• ART First-line Treatment Durability in Russia

Primary sources

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