Rifabutin dosed 2.5 mg/kg daily with lopinavir/r in children achieves comparable exposure to adults

In children, rifabutin 2.5 mg/kg daily with lopinavir/ritonavir co-treatment achieved AUC0–24 comparable to adults. Serious adverse events were rare and HIV and TB outcomes were favourable. Neutropenia was rare, mild, and improved with ongoing rifabutin treatment.

These findings from an interim analysis of a pharmacokinetic (PK) study conducted in coinfected Nigerian children were presented at the 19th International Workshop on Clinical Pharmacology.

Treatment options are lacking for HIV/TB coinfected children needing protease inhibitor (PI)-based ART. Rifabutin (RBT) is the preferred rifamycins for adults receiving PIs.

Only one previous study looked at RBT PK in children on PIs. It was stopped early after two of six children developed grade 4 neutropenia.

The Nigerian study evaluated PK of RBT in children aged 3–15 years receiving lopinavir/ritonavir (LPV/r)-based ART and RBT 2.5 mg/kg daily-containing TB treatment over 48 weeks. Intensive 24-hour PK sampling was performed at 2, 4, and 8 weeks after starting RBT.

At interim analysis, 8 children (75% male), median age 13.5 years (IQR 12.8–14.3) and weight 28.5 kg (IQR 24.1–32.1) had 20 PK visits.

The median RBT AUC0-24 was 4.77 ug*h/mL (IQR 3.84-6.75). Three participants had an AUC0-24 less than 3.2 ug*h/mL at week 2; but all were above 3.8 ug*h/mL (comparator: adults receiving RBT 300 mg daily without ART) at the 4 and 8 week visits.

Serious adverse events were uncommon: of 407 follow-up laboratory results, grade 3 and 4 abnormalities were reported in 11 (3%) and 2 (0.5%) cases, respectively.

Grade 3 neutropenia occurred on 3 occasions, and resolved without stopping RBT in all cases. Anaemia was the most common adverse event. No discontinuations due to ART or TB treatment were reported.

The investigators reported that the children are doing well clinically with six of seven achieving viral load suppression to less than 1000 copies/mL and resolution of TB symptoms at six months.

Enrollment into this study (n=15) is now complete and an additional study is now underway in young children aged 12–36 months.