A Zoufaly1, C Kraft2, C Schmidbauer2, E Puchhammer-Stoeckl3. 1. Department of Medicine IV, Kaiser Franz Josef Hospital, Kundratstrasse 3, 1100, Vienna, Austria. alexander.zoufaly@wienkav.at. 2. Department of Medicine IV, Kaiser Franz Josef Hospital, Kundratstrasse 3, 1100, Vienna, Austria. 3. Department of Virology, Medical University of Vienna, Vienna, Austria.
Abstract
PURPOSE: Treatment guidelines often do not advocate testing for integrase inhibitor resistance associated mutations (IRAM) before initiation of first line ART given the extremely low prevalence of mutations found in older surveillance studies. We aimed to describe the prevalence of IRAM in Austrian patients recently diagnosed with HIV in the 5 years following introduction of integrase inhibitors and to analyse trends and factors associated with their detection. METHODS: Samples of antiretroviral treatment (ART) naïve patients recently diagnosed with HIV in Austria between 2008 and 2013 were analysed for the existence of IRAM and drug penalty scores were calculated to estimate response to drugs. Demographic and virological data were extracted from a database. Descriptive and comparative statistics were used. RESULTS: A total of 303 samples were analysed. 78 % were male and mean age was 38 years. Overall prevalence of IRAM was 2.3 %. Six percent had at least potentially low-level resistance to raltegravir or elvitegravir, versus 1 % for dolutegravir. One primary mutation was observed (F121Y) in a patient sample from 2012 leading to 5-10-fold reduced susceptibility to raltegravir and elvitegravir. Two patients carried the accessory mutations E138K and G140A, respectively, where both lie on the Q148 pathway. No temporal trend of IRAM prevalence was observed (p = 0.16). DISCUSSION: Primary IRAM are still rarely found despite the increasing use of INSTI in Austria, but there is a potential for reduced susceptibility to these drugs in selected patients. Routine resistance testing seems prudent to avoid the consequences including accumulation of further mutations and therapeutic failure.
PURPOSE: Treatment guidelines often do not advocate testing for integrase inhibitor resistance associated mutations (IRAM) before initiation of first line ART given the extremely low prevalence of mutations found in older surveillance studies. We aimed to describe the prevalence of IRAM in Austrian patients recently diagnosed with HIV in the 5 years following introduction of integrase inhibitors and to analyse trends and factors associated with their detection. METHODS: Samples of antiretroviral treatment (ART) naïve patients recently diagnosed with HIV in Austria between 2008 and 2013 were analysed for the existence of IRAM and drug penalty scores were calculated to estimate response to drugs. Demographic and virological data were extracted from a database. Descriptive and comparative statistics were used. RESULTS: A total of 303 samples were analysed. 78 % were male and mean age was 38 years. Overall prevalence of IRAM was 2.3 %. Six percent had at least potentially low-level resistance to raltegravir or elvitegravir, versus 1 % for dolutegravir. One primary mutation was observed (F121Y) in a patient sample from 2012 leading to 5-10-fold reduced susceptibility to raltegravir and elvitegravir. Two patients carried the accessory mutations E138K and G140A, respectively, where both lie on the Q148 pathway. No temporal trend of IRAM prevalence was observed (p = 0.16). DISCUSSION: Primary IRAM are still rarely found despite the increasing use of INSTI in Austria, but there is a potential for reduced susceptibility to these drugs in selected patients. Routine resistance testing seems prudent to avoid the consequences including accumulation of further mutations and therapeutic failure.
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