Safety and efficacy of rifabutin among HIV/TB-coinfected children on lopinavir/ritonavir-based ART

Holly E. Rawizza, Kristin M. Darin, Regina Oladokun, Biobele Brown, Babatunde Ogunbosi, Nkiruka David, Sulaimon Akanmu, Oluremi Olaitan, Charlotte Chang, Kimberly K. Scarsi, Prosper Okonkwo, Phyllis J. Kanki

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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 6 month rifabutin course with resolution of TB symptoms and 79% were retained in care at 12 months. 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.

Original languageEnglish (US)
Pages (from-to)2707-2715
Number of pages9
JournalJournal of Antimicrobial Chemotherapy
Volume74
Issue number9
DOIs
StatePublished - Sep 1 2019

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ASJC Scopus subject areas

  • Pharmacology
  • Microbiology (medical)
  • Infectious Diseases
  • Pharmacology (medical)

Cite this

Rawizza, H. E., Darin, K. M., Oladokun, R., Brown, B., Ogunbosi, B., David, N., Akanmu, S., Olaitan, O., Chang, C., Scarsi, K. K., Okonkwo, P., & Kanki, P. J. (2019). Safety and efficacy of rifabutin among HIV/TB-coinfected children on lopinavir/ritonavir-based ART. Journal of Antimicrobial Chemotherapy, 74(9), 2707-2715. https://doi.org/10.1093/jac/dkz219