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

UMMS Affiliation

Department of Pediatrics

Publication Date


Document Type



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

Journal/Book/Conference Title

The Pediatric infectious disease journal

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Link to Article in PubMed

PubMed ID