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Protease inhibitor resistance in South African children with virologic failure

Gert U van Zyl1, Lize van der Merwe, Mathilda Claassen

  • 1Centre for Infectious Diseases, Division of Medical Virology, Tygerberg and Stellenbosch University, Cape Town, South Africa. guvz@sun.ac.za

The Pediatric Infectious Disease Journal
|September 26, 2009
PubMed

Insights

Ritonavir-single protease inhibitor (RTV-sPI) regimens in children carry a high risk of major protease inhibitor resistance mutations (MPIRM). Longer exposure and failure times on RTV-sPI significantly predict MPIRM development in pediatric HIV patients.

Area of Science:

  • Pediatric infectious diseases
  • HIV/AIDS research
  • Pharmacogenetics

Background:

  • First-line antiretroviral therapy (ART) in South African children under 3 combines a protease inhibitor (PI) with two nucleoside reverse transcription inhibitors.
  • This study compared ritonavir (RTV) as a single PI (RTV-sPI) versus ritonavir-boosted lopinavir (LPV/r), which has a higher resistance barrier.
  • The research focused on identifying antiretroviral resistance mutations in pediatric patients experiencing virologic failure on PI-based ART.

Purpose of the Study:

  • To investigate antiretroviral resistance mutations in pediatric patients failing PI-based ART.
  • To identify predictors of major PI resistance mutations (MPIRM) in this patient group.

Main Methods:

  • A study was conducted on pediatric HIV patients at Tygerberg Academic Hospital who experienced virologic failure on a PI regimen.
  • Mixed-effects linear and logistic regression models were employed to analyze predictors of MPIRM.

Main Results:

  • Major PI resistance mutations (MPIRM) were detected in 12 out of 17 patients who received RTV-sPI, compared to only 1 out of 13 patients on LPV/r.
  • Exposure to RTV-sPI was significantly associated with MPIRM.
  • Both the duration of exposure and the time to treatment failure while on RTV-sPI were significant positive predictors of MPIRM. CD4 count, viral load, age at first visit, and rifampin co-administration did not predict MPIRM.

Conclusions:

  • The use of RTV-sPI in infants and children presents a substantial risk for developing MPIRM.
  • The development of MPIRM is directly related to the duration of exposure and the time to virologic failure while on the RTV-sPI regimen.
Abstract

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