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
JournalThe Journal 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)
  • Pharmacology (medical)
  • Infectious Diseases

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. The 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: The 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', The 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: The 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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