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Rapid Screening of HIV Reverse Transcriptase and Integrase Inhibitors
Published on: April 9, 2014
HIV-1 resistance to first- and second-generation non-nucleoside reverse transcriptase inhibitors
Jade Ghosn1, Marie-Laure Chaix, Constance Delaugerre
1Université Paris Descartes, EA MRT 3620, Laboratoire de Virologie, AP-HP, CHU Necker-Enfants Malades, Paris, France.
AIDS Reviews
|August 6, 2009
Summary
First-generation non-nucleoside reverse transcriptase inhibitors (NNRTIs) rapidly develop resistance through mutations. Second-generation NNRTIs like etravirine show promise against resistant HIV strains, with high sensitivity observed in most cases.
Area of Science:
- Virology
- Pharmacology
- Infectious Diseases
Background:
- First-generation non-nucleoside reverse transcriptase inhibitors (NNRTIs), such as nevirapine and efavirenz, are prone to rapid resistance development in HIV.
- Mutations in the HIV reverse transcriptase gene confer high-level resistance and cross-resistance, impacting treatment efficacy.
- Transmission of NNRTI-resistant HIV strains is linked to virologic failure in first-line regimens.
Purpose of the Study:
- To evaluate the efficacy of second-generation NNRTIs against NNRTI-resistant HIV strains.
- To assess the genetic barrier to resistance for new NNRTI compounds.
- To determine the prevalence of etravirine sensitivity in NNRTI-experienced patient populations.
Main Methods:
- Analysis of mutations in the HIV reverse transcriptase gene associated with NNRTI resistance.
- In vitro testing of second-generation NNRTIs (etravirine, rilpivirine) against various HIV mutant strains.
- Prevalence studies of NNRTI resistance in patient databases across different geographical regions.
Main Results:
- Single mutations in reverse transcriptase confer high-level resistance to first-generation NNRTIs without affecting viral fitness.
- Second-generation NNRTIs, etravirine and rilpivirine, demonstrate activity against mutant viruses.
- Etravirine requires at least three specific reverse transcriptase mutations to significantly reduce its activity; over 75% of strains from NNRTI-experienced patients remain sensitive.
Conclusions:
- Second-generation NNRTIs represent a significant advancement in combating NNRTI-resistant HIV.
- Etravirine maintains broad activity against prevalent NNRTI resistance mutations, offering a viable treatment option.
- Rilpivirine shows early promise, but further data are needed to fully establish its resistance profile.
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