title: Effect of Lopinavir and Nevirapine Concentrations on Viral Outcomes in Protease Inhibitor-experienced HIV-infected Children.
abstract: Adequate exposure to antiretroviral drugs is necessary to achieve and sustain viral suppression. However, the target antiretroviral concentrations associated with long-term viral suppression have not been adequately defined in children. We assessed the relationship between plasma lopinavir or nevirapine concentrations and the risk of subsequent viremia in children initially suppressed on antiretroviral therapy.
  
  
  
  After an induction phase of antiretroviral treatment, 195 children with viral suppression (viral load ≤400 copies/mL) were randomized to continue a lopinavir/ritonavir-based regimen or to switch to a nevirapine-based regimen (together with lamivudine and stavudine). Viral load and lopinavir or nevirapine concentrations were measured at clinic visits 4, 8, 12, 16, 20, 24, 36, 52, 64 and 76 weeks post randomization. Cox multiple failure event models were used to estimate the effects of drug concentrations on the hazard of viremia (viral load >50 copies/mL) RESULTS:: At randomization, the median (interquartile range) age, CD4 T-Lymphocyte percentage, weight-for-age and weight-for-height z scores were 19 (16-24) months, 29% (23-37), -0.6 (-1.3 to 0.2) and -3.2 (-4.1 to -2.1), respectively. The proportion of children with viral load 51-400 copies/mL at randomization was 43%. The hazard of subsequent viremia during follow-up was increased for lopinavir concentrations <1 versus ≥1 mg/L [adjusted hazard ratio 0.62 (95% confidence interval, 0.40-0.94)] and for children with viral loads 51-400 copies/mL at randomization. Nevirapine concentrations were not significantly associated with subsequent viremia.
  
  
  
  Plasma lopinavir concentrations predicted viral outcomes in children receiving lopinavir-based antiretroviral therapy. Our findings support a minimum target concentration of ≥1 mg/L of lopinavir to ensure sustained viral suppression.
authors: From the *Division of Clinical Pharmacology, Department of Medicine, University of Cape Town, Cape Town, South Africa; †Centre for Infectious Diseases Epidemiology and Research, School of Public Health and Family Medicine, University of Cape Town, Cape Town, South Africa; ‡Gertrude H Sergievsky Center, College of Physicians and Surgeons, and Department of Epidemiology, Mailman School of Public Health, Columbia University, New York, NY; §Empilweni Services and Research Unit, Rahima Moosa Mother and Child Hospital, Faculty of Health Sciences, University of Witwatersrand, Johannesburg, South Africa; ¶ICAP, Mailman School of Public Health, and College of Physicians & Surgeons, Columbia University, New York, NY; and ‖Institute of Infectious Diseases and Molecular 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: Castel
authors: Lubbe
authors: L
authors: Wiesner
authors: Ashraf
authors: A
authors: Coovadia
authors: Renate
authors: R
authors: Strehlau
authors: Faeezah
authors: F
authors: Patel
authors: Francoise
authors: F
authors: Pinillos
authors: Elaine J
authors: EJ
authors: Abrams
authors: Gary
authors: G
authors: Maartens
authors: Helen
authors: H
authors: McIlleron
mesh_terms: D002675:Child, Preschool; D016903:Drug Monitoring; D015658:HIV Infections / Q000188:drug therapy* / Q000821:virology; D017320:HIV Protease Inhibitors / Q000097:blood* / Q000493:pharmacokinetics / Q000627:therapeutic use; D006801:Humans; D007223:Infant; D061466:Lopinavir / Q000097:blood* / Q000493:pharmacokinetics / Q000627:therapeutic use; D019829:Nevirapine / Q000097:blood* / Q000493:pharmacokinetics / Q000627:therapeutic use; D016896:Treatment Outcome; D019562:Viral Load; D014766:Viremia / Q000188:drug therapy* / Q000821:virology
chemical_list: D017320:HIV Protease Inhibitors; D061466:Lopinavir; D019829:Nevirapine