[Durgical](https://durgical.com/en/) › [DurgiPedia](https://durgical.com/en/durgipedia/) › [Pharmacology](https://durgical.com/en/pharmacology/) › Nucleoside/nucleotide reverse transcriptase inhibitors (NRTIs)

[Pharmacology](https://durgical.com/en/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)

## Key points

- Abacavir: test for HLA-B*5701 before starting; carriers do not receive it because of the risk of severe hypersensitivity.
- Lamivudine, emtricitabine and tenofovir are also active against hepatitis B virus: stopping them can trigger a severe hepatitis flare.
- Tenofovir disoproxil: watch the kidney (Fanconi syndrome) and bone; tenofovir alafenamide leaves less tenofovir in plasma, so it harms the kidney less.
- Zidovudine: anaemia and neutropenia from bone marrow toxicity; also myopathy.
- Lactic acidosis with hepatic steatosis is a class effect, most typical of older NRTIs.

## Drugs in this class

- [**Abacavir** An NRTI antiretroviral. Before use, patients are tested for HLA-B*5701, which predicts a severe, potentially fatal… HIV-1 reverse transcriptase](https://durgical.com/en/pharmacology/abacavir/)
- [**Lamivudine** A very well tolerated NRTI found in almost every HIV regimen. It also suppresses hepatitis B virus. HIV-1 reverse transcriptase](https://durgical.com/en/pharmacology/lamivudine/)
- [**Tenofovir disoproxil** A prodrug of tenofovir, the most widely used antiretroviral. It treats HIV and hepatitis B and prevents HIV; kidney… HIV-1 reverse transcriptase](https://durgical.com/en/pharmacology/tenofovir-disoproxil/)
- [**Zidovudine** The first antiretroviral (AZT). Little used in adults today because of bone marrow toxicity, but still part of newborn… HIV-1 reverse transcriptase](https://durgical.com/en/pharmacology/zidovudine/)
- [**Emtricitabine** An NRTI almost twin to lamivudine. Usually combined with tenofovir in one tablet, to treat HIV or prevent it (PrEP). HIV-1 reverse transcriptase](https://durgical.com/en/pharmacology/emtricitabine/)
- [**Tenofovir alafenamide** A newer tenofovir prodrug: it enters cells before activation, leaves little tenofovir in blood, and so harms kidney… HIV-1 reverse transcriptase](https://durgical.com/en/pharmacology/tenofovir-alafenamide/)

## 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.

[Add to my cards (4)](https://durgical.app/estudiar/?add=/en/pharmacology/classes/nucleoside-nucleotide-reverse-transcriptase-inhibitors/)

[← All of pharmacology](https://durgical.com/en/pharmacology/)

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](https://atcddd.fhi.no/atc_ddd_index/?code=J05AF) (WHO Collaborating Centre for Drug Statistics Methodology, 2026); [WHO recommends dolutegravir as preferred HIV treatment option in all populations](https://www.who.int/news/item/22-07-2019-who-recommends-dolutegravir-as-preferred-hiv-treatment-option-in-all-populations) (World Health Organization, 2019).

## **Spotted a mistake?** We are always improving for the community. Tell us what is wrong and our team will review it. Report a mistake

Representative model, for educational purposes only.

---
Source: https://durgical.com/en/pharmacology/classes/nucleoside-nucleotide-reverse-transcriptase-inhibitors/
License: CC BY 4.0 (https://creativecommons.org/licenses/by/4.0/). Cite as: DurgiPedia (durgical.com), https://durgical.com/en/pharmacology/classes/nucleoside-nucleotide-reverse-transcriptase-inhibitors/