Population trends in the prevalence and patterns of protease resistance related to exposure to unboosted and boosted protease inhibitors.
BACKGROUND
In recent years, several new drugs from the protease inhibitor (PI) class designed to treat HIV infection have become available and the use of ritonavir-boosting has increased in popularity. These changes might be expected to affect the prevalence and patterns of protease resistance in the population of patients who experience treatment failure.


METHODS
The UK HIV Drug Resistance Database aims to capture the results of all genotypic resistance tests conducted nationally. Tests on antiretroviral therapy-experienced patients were identified through linkage with the UK Collaborative HIV Cohort Study, from which detailed clinical information on these patients, including a full antiretroviral therapy history, was obtained.


RESULTS
Analyses were on the basis of 8,553 genotypic resistance tests carried out between 1998 and 2005, during which time the overall prevalence of protease resistance halved from 35% to 16%. Substantial declines were observed regardless of whether the patient had been exposed to unboosted PIs and/or boosted PIs. The frequency of protease resistance among patients who had received boosted PIs fell sharply until 2002 with a weaker trend thereafter, falling to 12% in 2005. Individual mutations L33F, M461/L, V82A/F/T/S/L and 184V became relatively more frequent over the period of study.


CONCLUSIONS
The decline in protease resistance was partly due to increasing use of ritonavir-boosting. Nonetheless, the prevalence of resistance was higher than suggested by clinical trials, indicating that prolonged exposure to a boosted PI could ultimately select for major protease mutations.
Dunn
David
D
MRC Clinical Trials Unit, London, UK.
Geretti
Anna Maria
AM
Green
Hannah
H
Fearnhill
Esther
E
Pozniak
Anton
A
Churchill
Duncan
D
Pillay
Deenan
D
Sabin
Caroline
C
Phillips
Andrew
A
D015331:Cohort Studies; D003430:Cross-Sectional Studies; D016208:Databases, Factual; D024882:Drug Resistance, Viral / Q000235:genetics*; D005820:Genetic Testing; D006678:HIV / Q000187:drug effects* / Q000201:enzymology / Q000235:genetics; D015658:HIV Infections / Q000188:drug therapy* / Q000821:virology; D016333:HIV Protease / Q000187:drug effects / Q000235:genetics*; D017320:HIV Protease Inhibitors / Q000008:administration & dosage*; D006801:Humans; D009154:Mutation; D015995:Prevalence; D019438:Ritonavir / Q000008:administration & dosage*; D016896:Treatment Outcome; D006113:United Kingdom / Q000453:epidemiology
D017320:HIV Protease Inhibitors; D016333:HIV Protease; D019438:Ritonavir