Abstract:
Background: TB is the leading cause of death among HIV-infected children, yet treatment options for those who
require PI-based ART are suboptimal. Rifabutin is the preferred rifamycin for adults on PI-based ART; only one
study has evaluated its use among children on PIs and two of six children developed treatment-limiting
neutropenia.
Methods: Since 2009, rifabutin has been available for HIV/TB-coinfected children requiring PI-based ART in the
Harvard/APIN programme in Nigeria. We retrospectively analysed laboratory and clinical toxicities at baseline
and during rifabutin therapy, and examined HIV/TB outcomes.
Results: Between 2009 and 2015, 48 children received rifabutin-containing TB therapy with PI (lopinavir/ritonavir)-
based ART: 50% were female with a median (IQR) baseline age of 1.7 (0.9–5.0) years and a median (IQR)
CD4! cell percentage of 15% (9%–25%); 52% were ART experienced. Eighty-five percent completed the
6month rifabutin course with resolution of TB symptoms and 79% were retained in care at 12months. Adverse
events (grade 1–4) were more common at baseline (27%) than during rifabutin treatment (15%) (P"0.006).
Absolute neutrophil count was lower during rifabutin compared with baseline (median"1762 versus 2976 cells/
mm3, respectively), but only one instance (2%) of grade 3 neutropenia occurred during rifabutin treatment.
Conclusions: With clinical and laboratory monitoring, our data suggest that rifabutin is a safe option for TB therapy
among children on PI-based ART. By contrast with the only other study of this combination in children,
severe neutropenia was rare. Furthermore, outcomes from this cohort suggest that rifabutin is effective, and a
novel option for children who require PI-based ART. Additional study of rifabutin plus PIs in children is urgently needed.
