Lopinavir/ritonavir for young infants

Lopinavir/ritonavir is increasingly recommended for treating young infants but in the absence of published data. Ellen Chadwick and colleagues from the PACTG 1030 study group evaluated dose requirements for babies <6 months that provide systemic exposure similar to that which has been shown to be safe and effective in older children and adults.

Results were available for 12 infants (5 boys, 7 girls) and stratified by age: 14days to 6 weeks and 6 weeks to 6 months. A dose of 300 mg/m2 lopinavir/ 75mg/m2 ritonavir was studied in combination with two nucleosides.

Intensive PK studies were performed at two weeks with a dose adjustment if LPV/r 12-hour post-dose concentration (C12) was < 1 mg/L; C12 was measured every 12 weeks and intensive pharmacokinetic studies were repeated if there was dose adjustment at one year of age.

The study defined virologic success as viral load < 400 copies/mL at week 16; failure as never achieving < 400 copies/mL and late suppressors as achieving < 400 copies/mL after week 16. CD4 percentage was measured every 12 weeks.

Median follow-up at analysis was 50 weeks (range 19 to 112 weeks). At entry, median age was 9.4 weeks (range 3.6 to 25.7 weeks), log10 HIV-1 RNA 5.6 (3.77 to 6.88) and CD4 percentage 37% (19 to 59%). Six of the 12 infants (50%) had virologic success, 2 (17%) virologic failure, and 4 (34%) were defined as late suppressors (< 400 copies/mL at week 32 to 48). The authors noted that poorer adherence contributed to poorer response.

In 6 infants studied through week 36, CD4 percentage showed a median increase of 8% (–9 to +20%) from baseline.

One infant required dose adjustment. Infants with virologic success vs virologic failure/late suppressors were significantly younger (median 5.6 vs 15.9 weeks, p = 0.004).

The authors found that the dose of 300 mg/m2 LPV/r twice daily was well tolerated in young infants and produced encouraging results in those infants adherent to therapy. At week 2 lower plasma concentrations were reported than found in adults despite a surface area adjusted dose approximately 35% higher than recommended for adults.

To better define age-related differences in pharmacokinetics and response to LPV/r, this group will study a second cohort of 12 infants.