Use of Lopinavir/ritonavir (Kaletra) in Infants Less than 6 Months of Age

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There are few data available on the use of antiretroviral drugs in infants. To address this issue, researchers at the Feinberg School of Medicine in Chicago, IL (Northwestern School of Medicine) investigated the pharmacokinetics, safety, and efficacy of lopinavir/ritonavir (Kaletra)-based therapy in HIV positive infants 6 weeks to 6 months of age. Results of the 24-week study appear in the current issue of AIDS (January 11, 2008).

The investigators conducted a prospective, multicenter, open-label trial of 21 infants with HIV RNA > 10,000 copies/mL treated with lopinavir/ritonavir 300/75 mg/m twice daily plus 2 nucleoside reverse transcriptase inhibitors (NRTIs). The median age of the participants was 14.7 weeks.

Intensive pharmacokinetic sampling was performed at 2 weeks and pre-dose concentrations were collected every 8 weeks. Safety and plasma HIV RNA levels were monitored every 4-12 weeks for 24 weeks.

Results

• 19 of 21 infants completed at least 24 weeks of the study.

• Although apparent clearance of lopinavir/ritonavir was slightly higher in infants than in older children, the median area under the concentration-time curve 0-12 hours (67.5 mcg.h/mL) was in the range reported in older children taking the recommended dose of 230/57.5 mg/m.

• Pre-dose concentrations stabilized at a higher level after the first 2 weeks of the study.

• An as-treated analysis at week 24 revealed that 10 of 19 infants (53%) had plasma HIV RNA < 400 copies/mL (median change -3.33 log10 copies/mL).

• Poor adherence contributed to delayed viral suppression, which improved with longer follow-up.

• 3 infants (14%) had transient adverse events of grade 3 or greater that were possibly related to study treatment but did not require permanent discontinuation of therapy.

Conclusion

Based on these results, the study authors concluded, "Despite higher clearance in infants 6 weeks to 6 months of age, a twice daily dose of 300/75 mg/m lopinavir/ritonavir provided similar exposure to that in older children, was well tolerated, and provided favorable virological and clinical efficacy."

Department of Pediatrics, Northwestern University, Feinberg School of Medicine, Chicago, IL.

01/08/08

Reference
EG Chadwick, R Yogev, JA Pinto, and others. Pharmacokinetics, safety and efficacy of lopinavir/ritonavir in infants less than 6 months of age: 24 week results. AIDS 22(2): 249-255. January 11, 2008.

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