Medicine & USMLE


  1. Oseltamivir, Zanamivir
  2. Acyclovir (Famciclovir, Valacyclovir)
  3. Ganciclovir
  4. Foscarnet
  5. Cidofovir
  6. NRTIs
  7. NNRTIs
  8. Integrase Inhibitors
  9. Protease Inhibitors
  10. Entry Inhibitors (Enfuvirtide, Maraviroc)
  11. NS5A Inhibitors
  12. NS5B Inhibitors
  13. NS3/4A Inhibitors


Nucleoside Reverse Transcriptase Inhibitors, also known as the NRTIs for short, are drugs used to treat HIV. There are seven NRTIs that you should know for the exam: Abacavir, Zidovudine, Emtricitabine, Lamivudine, Didanosine, Stavudine, and Tenofovir. These drugs function as  nucleoside analogs and inhibit the enzyme reverse transcriptase at its active site.  Since NRTIs lack the terminating 3-prime hydroxyl group that is needed to continue building the DNA strand, reverse transcriptase is blocked, thereby, preventing viral DNA synthesis. Note that all of the NRTIs require the addition of a phosphate group in order to function, except for Tenofovir which is already in a triphosphate nucleotide form! Side effects of all NRTIs include bone marrow suppression, lipoatrophy, lactic acidosis, and neuropathy. Specific side effects associated with a single NRTI drug include hypersensitivity to abacavir, which is seen specifically in patients expressing the HLA B*57:01 allele.  Didanosine is associated with pancreatitis, and zidovudine is highly associated with bone marrow suppression in the form of anemia.

Key Points

  • Nucleoside Reverse Transcriptase Inhibitors (NRTIs)
    • Drug Names
      • Abacavir (ABC)
      • Zidovudine (ZDV)
      • Emtricitabine (FTC)
      • Lamivudine (3TC)
      • Didanosine (ddI)
      • Stavudine (d4T)
      • Tenofovir (TDF)
        • Only nucleoTide; other NRTIs are nucleoSides
    • Mechanism
      • Inhibit retroviral reverse transcriptase
        • Compete with nucleotides to bind reverse transcriptase but cause DNA chain termination due to the lack of a 3′ OH group
        • This prevents synthesis of DNA from a viral RNA template
      • Require phosphorylation to be activated into a triphosphate nucleotide analog (except tenofovir)
        • Conversion from nucleoSide form to nucleoTide by a cellular thymidine kinase
        • Contrast vs. NNRTIs, which do not require phosphorylation
    • Clinical Use
      • HIV
        • Highly active against both HIV-1 and HIV-2
        • Component of highly-active antiretroviral therapy (HAART)
          • Usually 3 drugs: 2 NRTIs and integrase or protease inhibitor
        • ZDV can be used for general prophylaxis and during pregnancy to reduce risk of fetal transmission
    • Adverse Effects
      • Abacavir: Hypersensitivity
        • Strongly associated with HLA B*57:01 allele
        • Characterized by Type 4 HSR with fever, nausea, vomiting, rash
      • Bone marrow suppression
        • Can be reversed with granulocyte colony-stimulating factor (G-CSF) and erythropoietin
        • Anemia is especially common with zidovudine
      • Pancreatitis (didanosine)
      • Lipoatrophy
        • May also be occur with hepatic steatosis
        • Wasting of subcutaneous fat
      • Peripheral neuropathy
      • Lactic acidosis
        • Rare side effect of older NRTIs
        • Occurs due to mitochondrial toxicity