Low lopinavir plasma or hair concentrations explain second-line protease inhibitor failures in a resource-limited setting

Gert Uves Van Zyl, Thijs E. Van Mens, Helen McIlleron, Michele Zeier, Jean B. Nachega, Eric Decloedt, Carolina Malavazzi, Peter Smith, Yong Huang, Lize Van Der Merwe, Monica Gandhi, Gary Maartens

Research output: Contribution to journalArticle

Abstract

Background: In resource-limited settings, many patients, with no prior protease inhibitor (PI) treatment on a second-line, high genetic barrier, ritonavir-boosted PI-containing regimen have virologic failure. Methods: We conducted a cross-sectional survey to investigate the aetiology of virologic failure in 2 public health antiretroviral clinics in South Africa documenting the prevalence of virologic failure (HIV RNA load >500 copies/mL) and genotypic antiretroviral resistance; and lopinavir hair and plasma concentrations in a nested case-control study. Results: Ninety-three patients treated with a second-line regimen including lopinavir boosted with ritonavir were included, of whom 50 (25 cases, with virologic failure and 25 controls) were included in a nested case control study. Of 93 patients, 37 (40%) had virological failure, only 2 of them had had major PI mutations. The negative predictive values: probability of failure with lopinavir plasma concentration >1 μg/mL or hair concentrations >3.63 ng/mg for virologic failure were 86% and 89%, and positive predictive values of low concentrations 73% and 79%, respectively, whereas all virologic failures with HIV RNA loads above 1000 copies per milliliter, of patients without PI resistance, could be explained by either having a low lopinavir concentration in plasma or hair. Conclusions: Most patients who fail a lopinavir/ritonavir regimen, in our setting, have poor lopinavir exposure. A threshold plasma lopinavir concentration (indicating recent lopinavir/ritonavir use) and/or hair concentration (indicating longer term lopinavir exposure) are valuable in determining the aetiology of virologic failure and identifying patients in need of adherence counselling or resistance testing.

Original languageEnglish (US)
Pages (from-to)333-339
Number of pages7
JournalJournal of acquired immune deficiency syndromes
Volume56
Issue number4
DOIs
StatePublished - Apr 1 2011

Keywords

  • hair concentration
  • lopinavir
  • medication adherence
  • plasma concentration
  • protease inhibitor resistance mutations
  • resource-limited settings

ASJC Scopus subject areas

  • Infectious Diseases
  • Pharmacology (medical)

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  • Cite this

    Van Zyl, G. U., Van Mens, T. E., McIlleron, H., Zeier, M., Nachega, J. B., Decloedt, E., Malavazzi, C., Smith, P., Huang, Y., Merwe, L. V. D., Gandhi, M., & Maartens, G. (2011). Low lopinavir plasma or hair concentrations explain second-line protease inhibitor failures in a resource-limited setting. Journal of acquired immune deficiency syndromes, 56(4), 333-339. https://doi.org/10.1097/QAI.0b013e31820dc0cc