Early initiation of lopinavir/ritonavir in infants less than 6 weeks of age: Pharmacokinetics and 24-week safety and efficacy

Ellen Gould Chadwick, Jorge Pinto, Ram Yogev, Carmelita G. Alvero, Michael D. Hughes, Paul Palumbo, Brian Robbins, Rohan Hazra, Leslie Serchuck, Barbara E. Heckman, Lynette Purdue, Renee Browning, Katherine Luzuriaga, John Rodman, Edmund Capparelli

Research output: Contribution to journalArticlepeer-review

47 Scopus citations


BACKGROUND:: With increasing recognition of the benefits of early antiretroviral therapy initiation in perinatally HIV-infected infants, data are needed regarding the pharmacokinetics (PK), safety, and efficacy of recommended first-line protease inhibitors such as lopinavir/ritonavir (LPV/r). METHODS:: A prospective, phase I/II, open-label, dose-finding trial evaluated LPV/r at a dose of 300/75 mg/m twice daily plus 2 nucleoside analogs in HIV-1-infected infants ≥14 days to <6 weeks of age. Intensive 12-hour PK evaluations were performed after 2 weeks of LPV/r therapy, and doses were modified to maintain LPV predose concentrations >1 μg/mL and area under the curve (AUC) <170 μg hr/mL. RESULTS:: Ten infants enrolled [median age 5.7 (range, 3.6-5.9) weeks] with median HIV-1 RNA of 6.0 (range, 4.7-7.2) log10 copies/mL; all completed 24 weeks of follow-up. Nine completed the intensive PK evaluation at a median LPV dose of 267 (range, 246-305) mg/m q12 hours; median measures were AUC ≤ 36.6 (range, 27.9-62.6) μg hr/mL; predose concentration ≤ 2.2 (range, 0.99-4.9) μg/mL; maximum concentration ≤ 4.76 (range, 2.84-7.28) μg/mL and apparent clearance (L/h/m) ≤ 6.75 (range, 2.79-12.83). Adverse events were limited to transient grade 3 neutropenia in 3 subjects. By week 24, 2 of 10 subjects had experienced a protocol-defined virologic failure. CONCLUSIONS:: Although the LPV AUC in this population was significantly lower than that observed in infants ages 6 weeks to 6 months, LPV/r-based antiretroviral therapy in doses of 300/75 mg/m BID was well tolerated and resulted in virologic control in 8 of 10 infants by 24 weeks. Additional investigation is needed to understand the long-term implications of the lower LPV exposure in this age group.

Original languageEnglish (US)
Pages (from-to)215-219
Number of pages5
JournalPediatric Infectious Disease Journal
Issue number3
StatePublished - Mar 2009


  • Infants, HIV-1
  • Lopinavir/ritonavir
  • Pharmacokinetics

ASJC Scopus subject areas

  • Pediatrics, Perinatology, and Child Health
  • Microbiology (medical)
  • Infectious Diseases


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