title: Therapeutic Drug Monitoring of Lopinavir in HIV-Infected Children on Second-Line Antiretroviral Therapy in Asia.
abstract: 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 high-level LPV resistance in Asian children.
  
  
  
  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.
  
  
  
  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 ± 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.
  
  
  
  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.
authors.affiliation: *Research Institute for Health Sciences, Chiang Mai University, Chiang Mai, Thailand; †The HIV Netherlands Australia Thailand Research Collaboration (HIV-NAT), The Thai Red Cross AIDS Research Centre, Bangkok, Thailand; ‡Department of Pediatrics, Faculty of Medicine, Chiang Mai University, Chiang Mai, Thailand; §Srinagarind Hospital, Khon Kaen University, Khon Kaen, Thailand; ¶Cipto Mangunkusumo General Hospital, Jakarta, Indonesia; ‖Children's Hospital 1, Ho Chi Minh City, Vietnam; **Children's Hospital 2, Ho Chi Minh City, Vietnam; ††National Hospital of Pediatrics, Hanoi, Vietnam; ‡‡Faculty of Medicine Siriraj Hospital, Mahidol University, Bangkok, Thailand; §§TREAT Asia/amfAR-The Foundation for AIDS Research, Bangkok, Thailand; ¶¶The Kirby Institute, UNSW Australia, Sydney, Australia; and ‖‖Department of Global Health, Academic Medical Center, University of Amsterdam, Amsterdam Institute for Global Health and Development, Amsterdam, the Netherlands.
authors.forename: Linda
authors.initials: L
authors.lastname: Aurpibul
authors.forename: Sirinya
authors.initials: S
authors.lastname: Teerananchai
authors.forename: Wasana
authors.initials: W
authors.lastname: Prasitsuebsai
authors.forename: Tavitiya
authors.initials: T
authors.lastname: Sudjaritruk
authors.forename: Pope
authors.initials: P
authors.lastname: Kosalaraksa
authors.forename: Nia
authors.initials: N
authors.lastname: Kurniati
authors.forename: Khanh Huu
authors.initials: KH
authors.lastname: Truong
authors.forename: Viet Chau
authors.initials: VC
authors.lastname: Do
authors.forename: Lam Van
authors.initials: LV
authors.lastname: Nguyen
authors.forename: Kulkanya
authors.initials: K
authors.lastname: Chokephaibulkit
authors.forename: Thida
authors.initials: T
authors.lastname: Singtoroj
authors.forename: Stephen J
authors.initials: SJ
authors.lastname: Kerr
mesh_terms: D000293:Adolescent; D044966:Anti-Retroviral Agents / Q000627:therapeutic use*; D001208:Asia; D002648:Child; D016903:Drug Monitoring / Q000379:methods; D005260:Female; D015658:HIV Infections / Q000188:drug therapy*; D015497:HIV-1 / Q000187:drug effects; D006801:Humans; D061466:Lopinavir / Q000627:therapeutic use*; D008297:Male; D019562:Viral Load / Q000187:drug effects
chemical_list: D044966:Anti-Retroviral Agents; D061466:Lopinavir