Pharmacology · Class
Nucleoside/nucleotide reverse transcriptase inhibitors (NRTIs) !
Fake DNA building blocks: HIV reverse transcriptase adds them and the viral DNA chain stops. They form the backbone of almost every HIV regimen.
Updated 2026-11-01
What they are
Nucleoside analogues (abacavir, lamivudine, emtricitabine, zidovudine) or nucleotide analogues (tenofovir), usually given as a pair forming the regimen's backbone, together with a third drug from another class (today usually an integrase inhibitor).
Mechanism of action
They are prodrugs: cellular kinases phosphorylate them to the triphosphate form (diphosphate for tenofovir). Reverse transcriptase mistakes them for natural nucleotides and adds them to viral DNA; lacking a 3'-hydroxyl group, no further nucleotide can be joined and the chain terminates. Some also inhibit human mitochondrial DNA polymerase γ, the source of the mitochondrial toxicity of older agents.
Target: HIV reverse transcriptase (polymerase active site)
Drugs in this class
- AbacavirAn NRTI antiretroviral. Before use, patients are tested for HLA-B*5701, which predicts a severe, potentially fatal…HIV-1 reverse transcriptase
- LamivudineA very well tolerated NRTI found in almost every HIV regimen. It also suppresses hepatitis B virus.HIV-1 reverse transcriptase
- Tenofovir disoproxilA prodrug of tenofovir, the most widely used antiretroviral. It treats HIV and hepatitis B and prevents HIV; kidney…HIV-1 reverse transcriptase
- ZidovudineThe first antiretroviral (AZT). Little used in adults today because of bone marrow toxicity, but still part of newborn…HIV-1 reverse transcriptase
- EmtricitabineAn NRTI almost twin to lamivudine. Usually combined with tenofovir in one tablet, to treat HIV or prevent it (PrEP).HIV-1 reverse transcriptase
- Tenofovir alafenamideA newer tenofovir prodrug: it enters cells before activation, leaves little tenofovir in blood, and so harms kidney…HIV-1 reverse transcriptase
Others in the class
- Stavudine (withdrawn in many countries)
- Didanosine (withdrawn in many countries)
Test yourself
Think of the answer, then tap the question to see it.
Why do NRTIs stop viral DNA synthesis?
Once phosphorylated, reverse transcriptase incorporates them into DNA, but they lack the 3'-hydroxyl needed to join the next nucleotide, so the chain terminates.
Which NRTI requires a genetic test before starting, and which test?
Abacavir: testing for the HLA-B*5701 allele, which predicts a severe hypersensitivity reaction.
What risk do lamivudine, emtricitabine and tenofovir share in a person with hepatitis B?
A severe acute flare of hepatitis B when they are stopped, because they also suppress that virus.
Which human enzyme explains NRTI mitochondrial toxicity?
Mitochondrial DNA polymerase γ, which some NRTIs also inhibit; it shows up as lactic acidosis, steatosis or myopathy.
Educational content on how drugs work; not a prescribing guide and no substitute for a health professional's advice. No doses are given.
Sources: Goodman & Gilman's The Pharmacological Basis of Therapeutics, 14th ed., ch. 64 (McGraw Hill, 2023); ATCDDD - ATC/DDD Index (WHO Collaborating Centre for Drug Statistics Methodology, 2026); WHO recommends dolutegravir as preferred HIV treatment option in all populations (World Health Organization, 2019).
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Representative model, for educational purposes only.