Early initiation of lopinavir/ritonavir in infants less than 6 weeks of age: pharmacokinetics and 24-week safety and efficacy
Department of Pediatrics
Area Under Curve; Drug Administration Schedule; Female; HIV Infections; *HIV Protease Inhibitors; effects; HIV-1; Humans; Infant; Male; *Pyrimidinones; effects; RNA, Viral; *Ritonavir; effects; Treatment Outcome; Viral Load
Immunology and Infectious Disease | Pediatrics
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 > or =14 days to /r therapy, and doses were modified to maintain LPV predose concentrations >1 microg/mL and area under the curve (AUC) /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) microg hr/mL; predose concentration = 2.2 (range, 0.99-4.9) microg/mL; maximum concentration = 4.76 (range, 2.84-7.28) microg/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.
DOI of Published Version
Pediatr Infect Dis J. 2009 Mar;28(3):215-9. Link to article on publisher's site
The Pediatric infectious disease journal
Chadwick EG, Pinto J, Yogev R, Alvero CG, Hughes MD, Palumbo P, Robbins B, Hazra R, Serchuck L, Heckman BE, Purdue L, Browning R, Luzuriaga K, Rodman J, Capparelli EV. (2009). Early initiation of lopinavir/ritonavir in infants less than 6 weeks of age: pharmacokinetics and 24-week safety and efficacy. Immunology/Infectious Disease. https://doi.org/10.1097/INF.0b013e31818cc053. Retrieved from https://escholarship.umassmed.edu/peds_immunology/62