title: Plasma lopinavir concentrations predict virological failure in a cohort of South African children initiating a protease-inhibitor-based regimen.
abstract: BACKGROUND
  Poor adherence to antiretroviral therapy contributes to pharmacokinetic variability and is the major determinant of virological failure. However, measuring treatment adherence is difficult, especially in children. We investigated the relationship between plasma lopinavir concentrations, pretreatment characteristics and viral load >400 copies/ml.
  
  
  METHODS
  A total of 237 HIV-infected children aged 4-42 months on lopinavir/ritonavir oral solution were studied prospectively and followed for up to 52 weeks. Viral load and lopinavir concentration were measured at clinic visits 12, 24, 36 and 52 weeks after starting treatment. Cox multiple failure events models were used to estimate the crude and adjusted effect of lopinavir concentrations on the hazard of viral load >400 copies/ml.
  
  
  RESULTS
  The median (IQR) pretreatment CD4(+) T-lymphocyte percentage was 18.80% (12.70-25.35) and 53% of children had a pretreatment viral load >750,000 copies/ml. The median (IQR) weight-for-age and height-for-age z-scores were -2.17 (-3.35--2.84) and -3.34 (-4.57--3.41), respectively. Median (IQR) lopinavir concentrations were 8.00 mg/l (4.11-12.42) at median (IQR) 3.50 h (2.67-4.25) after the dose. The hazard of viral load >400 copies/ml was increased with lopinavir concentrations <1 mg/l versus ≥1 mg/l (adjusted hazard ratio 2.3 [95% CI 1.63, 3.26]) and lower height-for-age z-scores.
  
  
  CONCLUSIONS
  Low lopinavir concentrations (<1 mg/l) are associated with viraemia in children. This measure could be used as a proxy for adherence and to determine which children are more likely to fail.
authors: Division of Clinical Pharmacology, Department of Medicine, University of Cape Town, Cape Town, South Africa.
authors: Retsilisitsoe R
authors: RR
authors: Moholisa
authors: Michael
authors: M
authors: Schomaker
authors: Louise
authors: L
authors: Kuhn
authors: Sandra
authors: S
authors: Meredith
authors: Lubbe
authors: L
authors: Wiesner
authors: Ashraf
authors: A
authors: Coovadia
authors: Renate
authors: R
authors: Strehlau
authors: Leigh
authors: L
authors: Martens
authors: Elaine J
authors: EJ
authors: Abrams
authors: Gary
authors: G
authors: Maartens
authors: Helen
authors: H
authors: McIlleron
mesh_terms: D019380:Anti-HIV Agents / Q000493:pharmacokinetics* / Q000627:therapeutic use*; D023241:Antiretroviral Therapy, Highly Active; D002675:Child, Preschool; D016903:Drug Monitoring; D005260:Female; D015658:HIV Infections / Q000188:drug therapy* / Q000821:virology*; D017320:HIV Protease Inhibitors / Q000493:pharmacokinetics* / Q000627:therapeutic use*; D015497:HIV-1; D006801:Humans; D007223:Infant; D008297:Male; D012189:Retrospective Studies; D017211:Treatment Failure; D016896:Treatment Outcome; D019562:Viral Load; D014766:Viremia
chemical_list: D019380:Anti-HIV Agents; D017320:HIV Protease Inhibitors