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Drug resistance mutations during structured treatment interruptions
Sabine Yerly1, Catherine Fagard, Huldrych F Günthard
1Laboratory of Virology, Geneva University Hospital, Switzerland.
Antiviral Therapy
|December 3, 2003
Summary
Repeatedly interrupting highly active antiretroviral therapy (HAART) frequently selects for drug resistance mutations, particularly the M184V/I mutation, increasing the risk of virologic failure.
Area of Science:
- Virology
- Immunology
- Pharmacology
Background:
- The Swiss-Spanish Intermittent Treatment Trial (SSITT) investigated drug resistance mutations during treatment interruptions in patients on HAART.
- Patients had undetectable viral load for at least six months before the study began.
Purpose of the Study:
- To determine if intermittent treatment interruptions select for mutations associated with drug resistance.
- To assess the impact of these mutations on virologic failure.
Main Methods:
- Genotypic resistance testing was performed on samples from patients experiencing virologic failure or viral rebound.
- Testing was conducted at specific time points during and after treatment interruptions.
Main Results:
- Drug resistance mutations were detected in 17% of patients, with the M184V/I mutation being the most common.
- Patients with the M184V/I mutation had a 2.55-fold higher risk of virologic failure.
- The M184V/I mutation was frequently selected during repeated treatment interruptions.
Conclusions:
- Repeated treatment interruptions are associated with the selection of drug resistance mutations.
- The M184V/I mutation is a key resistance marker selected during intermittent HAART regimens.