Pharmacology · Class
Non-nucleoside reverse transcriptase inhibitors (NNRTIs) !
Drugs that wedge into a pocket of HIV-1 reverse transcriptase, away from the active site, and bend the enzyme so it stops copying the virus.
Updated 2026-11-01
What they are
Allosteric inhibitors of HIV-1 reverse transcriptase: efavirenz, nevirapine, rilpivirine and doravirine. They need no intracellular activation and are inactive against HIV-2. Because resistance has risen, WHO no longer prefers them for first-line treatment.
Mechanism of action
They bind a hydrophobic pocket in the p66 subunit of reverse transcriptase, near but outside the catalytic site. The shape change slows the enzyme non-competitively. Because the pocket is specific to HIV-1, a single mutation (for example K103N) can be enough to lose the older agents.
Target: Allosteric pocket of HIV-1 reverse transcriptase
Drugs in this class
- EfavirenzA once-daily NNRTI used for years as first-line treatment. Typical effects are dizziness, vivid dreams and psychiatric…HIV-1 reverse transcriptase (NNRTI pocket)
- NevirapineAn old, cheap NNRTI. It can cause hepatitis and severe skin reactions in the first weeks, more often in people with…HIV-1 reverse transcriptase (NNRTI pocket)
- RilpivirineA second-generation NNRTI. It is absorbed only with food and stomach acid; there is also a long-acting injectable form.HIV-1 reverse transcriptase (NNRTI pocket)
- DoravirineA newer NNRTI: taken with or without food, independent of stomach acid, with fewer nervous system and lipid effects…HIV-1 reverse transcriptase (NNRTI pocket)
Others in the class
- Etravirine
Test yourself
Think of the answer, then tap the question to see it.
How does the binding site of an NNRTI differ from that of an NRTI?
The NRTI enters the active site as a fake nucleotide; the NNRTI binds a nearby allosteric pocket and distorts the enzyme, with no need for phosphorylation.
Why are NNRTIs useless against HIV-2?
The allosteric pocket they bind is specific to HIV-1 reverse transcriptase.
What does a low genetic barrier mean for older NNRTIs?
That a single viral mutation (such as K103N) is enough to lose activity, often across the older class.
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.