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  • HIV Nucleoside and Nucleotide Reverse Transcriptase Inhibitors (NRTIs) are a class of structurally-related drugs which mimic nucleosides and nucleotides and specifically inhibit viral Reverse Transcriptase. They were one of the first classes of HIV antiviral therapy developed and are a mainstay of treatment today. Importantly, these drugs are only effective in preventing infection of new cells and have no efficacy for cell already infected with HIV.
Mechanism of Action
  • NRTIs are nucleoside analogs which are tri-phosphorylated by host enzymes as part of the nucleotide synthetic pathway. While host polymerases can easily distinguish NRTI tri-phosphates, viral Reverse Transcriptase cannot and incorporates the NRTIs during reverse transcription of the ssRNA HIV genome (See: Replicative Cycle section of HIV page). Importantly, NRTIs lack the critical Ribose 3' hydroxyl-group required for further addition of nucleotides and thus their incorporation results in chain termination.
Member Drugs and Adverse Effects
  • Overview
    • The following NRTIs mimic a variety of different nucleosides but ultimately result in chain termination during reverse transcription. All these drugs can produce a variety of nonspecific adverse effects including headache, nausea, insomnia, and malaise.
  • Member Drugs
    • Zidovudine (AZT): At high doses can cause bone marrow suppression, resulting in anemia or leukopenia
    • Didanosine: Peripheral neuropathy and chronic pancreatitis
    • Stavudine: Peripheral neuropathy
    • Lamivudine: Generally well-tolerated (see page)
    • Zalcitabine: Peripheral neuropathy and stomatitis
    • Abacavir: In roughly 5% of patients a serious hypersensitivity syndrome can develop which manifests as fever, abdominal pain, and GI complaints. If hypersensitivity develops the drug must be discontinued and never administered again