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Prevalence and risk factors associated with resistance-associated mutations to etravirine in a cohort of perinatally HIV-infected children. | LitMetric

Prevalence and risk factors associated with resistance-associated mutations to etravirine in a cohort of perinatally HIV-infected children.

J Antimicrob Chemother

Division of Paediatric Infectious Diseases, Department of Paediatrics, Medical School, UTHealth, 6431 Fannin Street MSB 3.020, Houston, TX 77030, USA.

Published: October 2013

AI Article Synopsis

  • Etravirine, a second-generation NNRTI, shows reduced resistance compared to first-generation NNRTIs, but many children treated with the latter may have mutations that affect etravirine efficacy.
  • A study from 1998-2009 found that 34.8% of HIV-infected children had resistance-associated mutations (RAMe), with some showing reduced response to etravirine based on their mutation scores.
  • Key risk factors for RAMe included a history of nevirapine use and Hispanic ethnicity, highlighting the need to consider past treatments when planning antiretroviral therapy with etravirine.

Article Abstract

Background: Etravirine is a second-generation non-nucleoside reverse transcriptase inhibitor (NNRTI) with reduced cross-resistance to first-generation NNRTIs. Because many perinatally HIV-infected patients have been treated with first-generation NNRTIs, they may have acquired resistance-associated mutations to etravirine (RAMe).

Methods: We determined for the interval 1998-2009 the prevalence and factors associated with the presence of RAMe.

Results: Twenty-three of 66 (34.8%) children had RAMe; the most common were 181C (19.6%), 190A (7.5%), 98G (6%), 106I (4.5%), 179D (4.5%), 100I (3%), 181I (1.5%), 138A (1.5%) and 179T (1.5%). Eleven children with RAMe (17%) had a mutation score between 2.5 and 3.5 and 1 (1.5%) a score ≥4, indicating an intermediate and reduced response to etravirine. For each 1% increase in CD4% there is a 7% decrease in the odds of RAMe (OR 0.93; 95% CI 0.88-0.97; P < 0.01). History of nevirapine use (OR 8.95; 95% CI 2.31-34.73; P < 0.01) and Hispanic ethnicity (OR 4.76; 95% CI 1.03-21.87; P = 0.04) are significantly associated with risk of RAMe.

Conclusions: RAMe are present and common among antiretroviral-experienced perinatally HIV-infected children without previous exposure to etravirine. This could limit the efficacy of etravirine-based regimens. In addition, our results underscore the importance of taking previous history of nevirapine into account for combined antiretroviral therapy regimens that contain etravirine.

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Source
http://dx.doi.org/10.1093/jac/dkt198DOI Listing

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