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

Research output: Contribution to journalArticle

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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Rifabutin
Lopinavir
Ritonavir
HIV
Safety
Neutropenia
Therapeutics
Nigeria
Cause of Death
Neutrophils

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., ... 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

Safety and efficacy of rifabutin among HIV/TB-coinfected children on lopinavir/ritonavir-based ART. / Rawizza, Holly E.; Darin, Kristin M.; Oladokun, Regina; Brown, Biobele; Ogunbosi, Babatunde; David, Nkiruka; Akanmu, Sulaimon; Olaitan, Oluremi; Chang, Charlotte; Scarsi, Kimberly K.; Okonkwo, Prosper; Kanki, Phyllis J.

In: Journal of Antimicrobial Chemotherapy, Vol. 74, No. 9, 01.09.2019, p. 2707-2715.

Research output: Contribution to journalArticle

Rawizza, HE, Darin, KM, Oladokun, R, Brown, B, Ogunbosi, B, David, N, Akanmu, S, Olaitan, O, Chang, C, Scarsi, KK, Okonkwo, P & Kanki, PJ 2019, 'Safety and efficacy of rifabutin among HIV/TB-coinfected children on lopinavir/ritonavir-based ART', Journal of Antimicrobial Chemotherapy, vol. 74, no. 9, pp. 2707-2715. https://doi.org/10.1093/jac/dkz219
Rawizza, Holly E. ; Darin, Kristin M. ; Oladokun, Regina ; Brown, Biobele ; Ogunbosi, Babatunde ; David, Nkiruka ; Akanmu, Sulaimon ; Olaitan, Oluremi ; Chang, Charlotte ; Scarsi, Kimberly K. ; Okonkwo, Prosper ; Kanki, Phyllis J. / Safety and efficacy of rifabutin among HIV/TB-coinfected children on lopinavir/ritonavir-based ART. In: Journal of Antimicrobial Chemotherapy. 2019 ; Vol. 74, No. 9. pp. 2707-2715.
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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.",
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AU - Brown, Biobele

AU - Ogunbosi, Babatunde

AU - David, Nkiruka

AU - Akanmu, Sulaimon

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