title: Using Lopinavir Concentrations in Hair Samples to Assess Treatment Outcomes on Second-Line Regimens Among Asian Children.
abstract: We conducted a prospective monitoring study to determine whether antiretroviral (ARV) levels in hair of Asian children on second-line protease inhibitor-based ARV therapy (ART) are associated with virologic failure (VF), compared to plasma drug levels and self-reported adherence. HIV-infected Asian children on second-line ART regimens were enrolled into a longitudinal cohort. Traditional adherence measures, plasma, and hair samples were collected 24 weeks after study enrollment. Hair ARV levels were determined via liquid chromatography/tandem mass spectrometry. Among 149 children on lopinavir/ritonavir-based regimens, 47% were female; the median [interquartile range (IQR)] age was 10.3 (7.9-13.3) years. The median CD4% was 26% (IQR 21.7-32.1%) and the median CD4 cell count 754 (IQR 596-1,013) cells/mm(3). The median duration of lopinavir-based ART prior to week 24 of the study was 2.9 (IQR 1.6-4.2) years. Adherence was >95% in 91% (135/148) by visual analogue scale and 89% (129/145) by pill count. The median lopinavir hair concentrations were 5.43 (IQR 3.21-9.01) ng/mg in children with HIV RNA >1,000 copies/ml and 9.96 (IQR 6.51-12.31) ng/mg in children with HIV RNA <1,000 copies/ml (p = 0.003). Plasma trough and lopinavir hair concentrations were not statistically significantly correlated (Pearson's correlation coefficient 0.20; p = 0.13). Increasing lopinavir hair concentrations in quartiles were strongly associated with virologic success (odds ratios ≥4.0, overall p = 0.02), while self-reported adherence, pill count, and plasma lopinavir levels were not. Based on this first report of hair ARV concentrations and virologic outcomes in children, ARV hair concentrations, representing longer-term adherence, may be useful to identify children at risk for VF.
authors.affiliation: 1 The HIV Netherlands Australia Thailand Research Collaboration (HIV-NAT), The Thai Red Cross AIDS Research Centre , Bangkok, Thailand .
authors.forename: Wasana
authors.initials: W
authors.lastname: Prasitsuebsai
authors.affiliation: 1 The HIV Netherlands Australia Thailand Research Collaboration (HIV-NAT), The Thai Red Cross AIDS Research Centre , Bangkok, Thailand .
authors.forename: Stephen J
authors.initials: SJ
authors.lastname: Kerr
authors.affiliation: 2 Children's Hospital 1 , Ho Chi Minh City, Vietnam .
authors.forename: Khanh Huu
authors.initials: KH
authors.lastname: Truong
authors.affiliation: 3 U.S. Military HIV Research Program, Walter Reed Army Institute of Research , Silver Spring, Maryland and the Henry M. Jackson Foundation for the Advancement of Military Medicine, Bethesda, Maryland.
authors.forename: Jintanat
authors.initials: J
authors.lastname: Ananworanich
authors.affiliation: 4 Children's Hospital 2 , Ho Chi Minh City, Vietnam .
authors.forename: Viet Chau
authors.initials: VC
authors.lastname: Do
authors.affiliation: 5 National Hospital of Pediatrics , Hanoi, Vietnam .
authors.forename: Lam Van
authors.initials: LV
authors.lastname: Nguyen
authors.affiliation: 6 Cipto Mangunkusumo General Hospital , Jakarta, Indonesia .
authors.forename: Nia
authors.initials: N
authors.lastname: Kurniati
authors.affiliation: 7 Division of Infectious Diseases, Department of Pediatrics, Khon Kaen University , Khon Kaen, Thailand .
authors.forename: Pope
authors.initials: P
authors.lastname: Kosalaraksa
authors.affiliation: 8 Research Institute for Health Sciences and Faculty of Medicine, Chiang Mai University , Chiang Mai, Thailand .
authors.forename: Tavitiya
authors.initials: T
authors.lastname: Sudjaritruk
authors.affiliation: 9 Faculty of Medicine Siriraj Hospital, Mahidol University , Bangkok, Thailand .
authors.forename: Kulkanya
authors.initials: K
authors.lastname: Chokephaibulkit
authors.affiliation: 1 The HIV Netherlands Australia Thailand Research Collaboration (HIV-NAT), The Thai Red Cross AIDS Research Centre , Bangkok, Thailand .
authors.forename: Narukjaporn
authors.initials: N
authors.lastname: Thammajaruk
authors.affiliation: 10 TREAT Asia/amfAR-The Foundation for AIDS Research , Bangkok, Thailand .
authors.forename: Thida
authors.initials: T
authors.lastname: Singtoroj
authors.affiliation: 1 The HIV Netherlands Australia Thailand Research Collaboration (HIV-NAT), The Thai Red Cross AIDS Research Centre , Bangkok, Thailand .
authors.forename: Sirinya
authors.initials: S
authors.lastname: Teeraananchai
authors.affiliation: 11 Department of Bioengineering and Therapeutic Sciences, University of California , San Francisco, San Francisco, California.
authors.forename: Howard
authors.initials: H
authors.lastname: Horng
authors.affiliation: 12 Department of Epidemiology and Biostatistics, University of California , San Francisco, San Francisco, California.
authors.forename: Peter
authors.initials: P
authors.lastname: Bacchetti
authors.affiliation: 13 Department of Medicine, University of California , San Francisco, San Francisco, California.
authors.forename: Monica
authors.initials: M
authors.lastname: Gandhi
authors.affiliation: 10 TREAT Asia/amfAR-The Foundation for AIDS Research , Bangkok, Thailand .
authors.forename: Annette H
authors.initials: AH
authors.lastname: Sohn
mesh_terms: D000293:Adolescent; D019380:Anti-HIV Agents / Q000008:administration & dosage / Q000032:analysis* / Q000493:pharmacokinetics*; D044466:Asian People; D002648:Child; D002853:Chromatography, Liquid; D016903:Drug Monitoring / Q000379:methods*; D005260:Female; D015658:HIV Infections / Q000188:drug therapy*; D006197:Hair / Q000737:chemistry*; D006801:Humans; D008137:Longitudinal Studies; D061466:Lopinavir / Q000008:administration & dosage / Q000032:analysis* / Q000493:pharmacokinetics*; D008297:Male; D055118:Medication Adherence; D010949:Plasma / Q000737:chemistry; D011446:Prospective Studies; D053719:Tandem Mass Spectrometry; D016896:Treatment Outcome
chemical_list: D019380:Anti-HIV Agents; D061466:Lopinavir