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Rapid Screening of HIV Reverse Transcriptase and Integrase Inhibitors
Published on: April 9, 2014
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Genetic barrier to resistance for dolutegravir
Josep M Llibre1, Federico Pulido2, Federico García3
1HIV Unit and "Lluita contra la SIDA Fndn", Univ Hosp Germans Trias i Pujol, Badalona, Spain and Universitat Autònoma de Barcelona, Barcelona, Spain.
AIDS Reviews
|December 5, 2014
Summary
Dolutegravir, an integrase strand-transfer inhibitor, shows a high barrier to resistance in HIV treatment. Studies confirm minimal resistance mutations, preserving future treatment options.
Area of Science:
- Virology
- Pharmacology
- Infectious Diseases
Background:
- Dolutegravir is a novel integrase strand-transfer inhibitor with potent in vitro activity.
- Its pharmacokinetic/pharmacodynamic properties suggest a high barrier to resistance development.
Purpose of the Study:
- To evaluate the resistance profile of dolutegravir in HIV treatment.
- To compare dolutegravir's efficacy and resistance selection against raltegravir in virologically failing patients.
Main Methods:
- Phase III studies of initial HIV therapy.
- Rescue intervention with dolutegravir in integrase-naive subjects with virological failure.
Main Results:
- No resistance-associated mutations were observed in 1,118 individuals on initial dolutegravir therapy.
- Dolutegravir demonstrated higher virological suppression and lower resistance selection compared to raltegravir.
- The R263K mutation, rarely selected, incurs a fitness cost, preventing HIV-1 evasion of drug pressure.
Conclusions:
- Dolutegravir exhibits a high genetic barrier to resistance, leading HIV-1 down an evolutionary pathway with low resistance development potential.
- This characteristic helps preserve future treatment options for patients experiencing treatment failure.
- Dolutegravir's profile is advantageous for both initial therapy and salvage regimens.
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