Therapeutic drug monitoring of lopinavir in HIV-infected children on second-line antiretroviral therapy in Asia

Linda Aurpibul, Sirinya Teerananchai, Wasana Prasitsuebsai, Tavitiya Sudjaritruk, Pope Kosalaraksa, Nia Kurniati, Khanh Huu Truong, Viet Chau Do, Lam Van Nguyen, Kulkanya Chokephaibulkit, Thida Singtoroj, Stephen J. Kerr

Research output: Contribution to journalArticlepeer-review

1 Citation (Scopus)

Abstract

Background: Failure rates of second-line boosted protease inhibitor antiretroviral therapy regimens in children rise over time. Therapeutic drug monitoring can contribute to assessments of adherence. The authors assessed the performance characteristics of the US DHHS-recommended lopinavir (LPV) concentration of 1.0 mg/L for predicting virologic failure (VF) and intermediate-to highlevel LPV resistance in Asian children. Methods: LPV concentration, HIV RNA level, and adherence data from study participants in Thailand, Vietnam, and Indonesia receiving second-line LPV-based ART and followed for 24 weeks were analyzed. Results: A total of 223 children at a median age of 10.4 (interquartile range, 7.9-13.4) years were enrolled, and 61% of them were male. Their mean CD4 was 842 6 438 cells per cubic millimeter, and the median LPV duration was 2.5 (interquartile range, 1.3-4.2) years. Five of 84 (6%) and 18 of 139 (13%) children had LPV trough and random concentrations ,1.0 mg/L at study week 24. Using either of these trough or random LPV concentrations, a cutoff at 1.0 mg/L gave an area under the receiver operating characteristics curve of 0.69 in predicting VF with sensitivity of 44% (95% CI 23-66) and specificity of 94% (95% CI 89-97). Seven of 21 with VF and resistance results available had 1 major protease inhibitor mutation. Multivariate logistic regression found LPV concentrations ,1.0 mg/L (odds ratio, 6.47; 95% CI 2.15-19.50, P = 0.001) and CD4 #20% (odds ratio, 2.83; 95% CI 1.01-7.89, P = 0.05) were independently associated with HIV RNA .1000 copies per milliliter. No factors predicted major LPV resistance mutations. Conclusions: The authors support that the DHHS target LPV concentration of ,1.0 mg/L is predictive of VF, but not of the presence of major LPV mutations.

Original languageEnglish
Pages (from-to)791-795
Number of pages5
JournalTherapeutic Drug Monitoring
Volume38
Issue number6
DOIs
Publication statusPublished - 1 Jan 2016

Keywords

  • Antiretroviral treatment
  • Children
  • HIV
  • Lopinavir
  • Pharmacokinetics

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