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[Non-nucleoside reverse transcriptase inhibitors]
Annales De Medecine Interne
|August 3, 2000
Summary
Non-nucleoside reverse transcriptase inhibitors (NNRTIs) are crucial for HIV-1 treatment, but their low genetic barrier necessitates combination therapy. Careful monitoring is essential due to potential drug interactions and resistance development.
Area of Science:
- Pharmacology and Virology
- Antiretroviral Therapy Research
Context:
- Non-nucleoside reverse transcriptase inhibitors (NNRTIs) are a class of drugs used to treat HIV-1 infection.
- These drugs inhibit the HIV-1 reverse transcriptase (RT) enzyme.
- Available NNRTIs include nevirapine, delavirdine, and efavirenz, with others in development.
Purpose:
- To review the efficacy, pharmacokinetic interactions, resistance patterns, and side effects of non-nucleoside reverse transcriptase inhibitors (NNRTIs).
- To discuss the role of NNRTIs in various antiretroviral therapy regimens.
- To highlight the importance of using NNRTIs as part of a potent combination therapy to prevent resistance.
Summary:
- NNRTIs bind non-competitively to HIV-1 RT, but have a low genetic barrier to resistance, often requiring only a single mutation.
- They undergo hepatic metabolism via cytochrome P450, leading to potential pharmacokinetic interactions, especially with protease inhibitors (PIs).
- Common side effects include rash (nevirapine, delavirdine) and central nervous system complaints (efavirenz).
Impact:
- NNRTIs are valuable in treatment-naive patients when combined with nucleosides and/or PIs.
- Their use in second-line therapy shows promise in small studies.
- Due to rapid resistance development, NNRTIs should not be added to failing antiretroviral regimens to avoid cross-resistance.