Protease inhibitor resistance in South African children with virologic failure

Van Zyl G.U. ; Van Der Merwe L. ; Claassen M. ; Cotton M.F. ; Rabie H. ; Prozesky H.W. ; Preiser W. (2009)


Background: In South Africa, first-line antiretroviral therapy for children younger than 3 years of age combines a protease inhibitor (PI) with 2 nucleoside reverse transcription inhibitors. In our study, some pediatric patients received ritonavir (RTV) as single PI (RTV-sPI) and others ritonavir-boosted lopinavir (LPV/r), which has a higher resistance barrier. We explored antiretroviral resistance mutations in pediatric patients failing PI-based antiretroviral therapy and the predictors of major PI resistance mutations (MPIRM) in these patients. MATERIALS AND Methods: We studied pediatric HIV patients at Tygerberg Academic Hospital experiencing virologic failure on a PI regimen. Mixed-effects linear-and mixed-effect logistic regression modeling, were used to explore predictors of MPIRM. Results: MPIRM were found in 12 of 17 patients exposed to RTV-sPI compared with 1 of 13 patients treated with LPV/r. Exposure to RTV-sPI was significantly associated with MPIRM, with both exposure time and estimated failing time on RTV-sPI being significant positive predictors of MPIRM. Neither CD4 count, viral load, age at first visit nor receiving rifampin predicted MPIRM. Conclusions: RTV-sPI in infants and children poses a significant risk of MPIRM which is dependent on the exposure time and time failing while receiving the regimen. © 2009 by Lippincott Williams & Wilkins.

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