Last reviewed 2026-04-22 · How we verify

nucleoside reverse transcriptase inhibitors

Nucleoside reverse transcriptase inhibitors block the reverse transcriptase enzyme that HIV uses to convert its RNA genome into DNA, preventing viral replication.

Nucleoside reverse transcriptase inhibitors block the reverse transcriptase enzyme that HIV uses to convert its RNA genome into DNA, preventing viral replication. Used for HIV-1 infection (as part of combination antiretroviral therapy).

At a glance

Mechanism of action

These drugs are nucleoside analogs that compete with natural nucleosides for incorporation into the growing DNA chain during reverse transcription. Once incorporated, they cause chain termination because they lack a 3'-OH group needed for the next phosphodiester bond. This prevents HIV from converting its RNA genome into DNA, which is essential for the virus to integrate into the host cell genome and replicate.

Approved indications

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

Common side effects

• Mitochondrial toxicity / lactic acidosis
• Lipodystrophy
• Peripheral neuropathy
• Pancreatitis
• Hepatotoxicity
• Gastrointestinal disturbances

Key clinical trials

• A Trial of 2 Options for Second Line Combination Antiretroviral Therapy Following Virological Failure of a Standard Non-nucleoside Reverse Transcriptase Inhibitor (NNRTI)+2N(t)RTI First Line Regimen (PHASE4)
• 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)
• A Study to Provide Continued Access to Study Drug to Children and Adolescents Who Have Completed Clinical Studies Involving Gilead HIV Treatments (PHASE4)
• DTG/3TC Fixed Dose Formulations for the Maintenance of Virological Suppression in Children With HIV Infection Aged 2 to <15 Years Old (PHASE2, PHASE3)
• Doravirine (DOR) in Human Immunodeficiency Virus (HIV)-Infected Children Aged 4 Weeks to <12 Years and <45 kg (MK-1439-066) (PHASE2)
• Safety and Efficacy of a Switch to Doravirine/Islatravir in Participants With HIV-1 (MK-8591A-017) (PHASE3)
• Trial to Evaluate the Interest of a Reductive Anti Retroviral Strategy Using Dual Therapy Inspite of Triple Therapy (PHASE3)
• Therapeutic Drug Monitoring to oPtimize ANtiretroviral regimeNs in HIV-infected Women Who wAnt to Breastfeed

Primary sources

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