Long-term outcomes for HIV-infected infants less than 6 months of age at initiation of lopinavir/ritonavir combination antiretroviral therapy

Abstract

Objective: To investigate the longitudinal pharmacokinetics, safety and efficacy of lopinavir/ritonavir (LPV/r) in HIV-infected infants initiating combination antiretroviral therapy (cART) between 2 weeks and 6 months of age.

Method: A prospective, open-label, multicenter Phase I/II study of LPV/r-based cART at a dose of 300/75 mg/m(2)/dose LPV/r twice daily. Intensive pharmacokinetic sampling at 12 months of age and quarterly predose LPV concentrations were collected and safety, virologic and immunologic responses were monitored every 4-12 weeks up to 252 weeks.

Results: Thirty-one HIV-infected infants enrolled into two age cohorts, 14 days to <6 weeks and 6 weeks to <6 months; 29 completed ≥48 weeks of follow-up (median = 123 weeks, range 4-252). At 12 months of age, median LPV area under the curve was comparable for both age cohorts and similar to older children and adults. At week 48, 22 of 31 patients (71%) had HIV-1 RNA <400 copies/ml and 11 of 15 (73%) had <50 copies/ml; 29 of 31 achieved HIV-1 RNA <400 copies/ml on study treatment and 19 (66%) remained durably suppressed until the end of study; viral suppression correlated with a higher percentage of predose time points exceeding the LPV target of 1 μg/ml (92 vs. 71%, P = 0.002).

Conclusion: LPV/r at 300/75 mg/m(2)/dose as part of a cART regimen resulted in viral suppression through 96 weeks of treatment in >65% of young infants. Due to initially low LPV exposure in infants <6 weeks of age, frequent dose adjustment for weight gain is advisable and consideration should be given to studying a higher dose for very young infants.

Figures

Fig. 1

Median lopinavir (LPV) predose concentrations for patients in each cohort, by age at time of measurement. The solid line represents a nonparametric smooth polynomial through the data; there was a significant positive correlation of LPV trough concentration with age (Spearman r=0.30, P < 0.0001).

Fig. 2

Median nonfasting total cholesterol over time on study, by cohort. The bars represent interquartile range.

Fig. 3

Median weight for age/sex Z score and height-for-age/sex Z score, by cohort over time. The bars represent interquartile range.