Article

Pharmacokinetics, safety and efficacy of lopinavir/ritonavir in infants less than 6 months of age: 24 week results.

Department of Pediatrics, Northwestern University, Feinberg School of Medicine, Chicago, Illinois, USA.
AIDS (London, England) (Impact Factor: 6.56). 01/2008; 22(2):249-55. DOI: 10.1097/QAD.0b013e3282f2be1d
Source: PubMed

ABSTRACT To investigate pharmacokinetics, safety and efficacy of lopinavir/ritonavir (LPV/r)-based therapy in HIV-1-infected infants 6 weeks to 6 months of age.
A prospective, multicenter, open-label trial of 21 infants with HIV-1 RNA > 10 000 copies/ml and treated with LPV/r 300/75 mg/m twice daily plus two nucleoside reverse transcriptase inhibitors. Intensive pharmacokinetic sampling was performed at 2 weeks and predose concentrations were collected every 8 weeks; safety and plasma HIV-1 RNA were monitored every 4-12 weeks for 24 weeks.
Median age at enrollment was 14.7 weeks (range, 6.9-25.7) and 19/21 completed > or= 24 weeks of study. Although LPV/r apparent clearance was slightly higher than in older children, the median area under the concentration-time curve 0-12 h (67.5 mug.h/ml) was in the range reported from older children taking the recommended dose of 230/57.5 mg/m. Predose concentrations stabilized at a higher level after the first 2 weeks of study. In as-treated analysis at week 24, 10/19 (53%) had plasma HIV-1 RNA < 400 copies/ml (median change, -3.33 log10 copies/ml); poor adherence contributed to delayed viral suppression, which improved with longer follow-up. Three infants (14%) had transient adverse events of grade 3 or more that were possibly related to study treatment but did not require permanent treatment discontinuation.
Despite higher clearance in infants 6 weeks to 6 months of age, a twice daily dose of 300/75 mg/m LPV/r provided similar exposure to that in older children, was well tolerated and provided favorable virological and clinical efficacy.

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