Title | Population trends in the prevalence and patterns of protease resistance related to exposure to unboosted and boosted protease inhibitors |
Publication Type | Journal Article |
Year of Publication | 2008 |
Authors | Dunn DT, Geretti AM, Green H, Fearnhill E, Pozniak A, Churchill D, Pillay D, Sabin CA, Phillips AN |
Journal | Antivir Ther |
Volume | 13 |
Pagination | 771-7 |
ISBN Number | 1359-6535 (Print)<br/>1359-6535 |
Accession Number | 18839778 |
Keywords | Cohort Studies, Cross-Sectional Studies, Databases, Factual, Drug Resistance, Viral/*genetics, Genetic Testing, Great Britain/epidemiology, HIV Infections/*drug therapy/virology, HIV Protease Inhibitors/*administration & dosage, HIV Protease/drug effects/*genetics, HIV/*drug effects/enzymology/genetics, Humans, Mutation, Prevalence, Ritonavir/*administration & dosage, Treatment Outcome |
Abstract | 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. |
Short Title | Antiviral therapy |
Alternate Journal | Antiviral therapy |