Safety and efficacy of rifabutin among HIV/TB-coinfected children on lopinavir/ritonavir-based ART.
Antibiotics, Antitubercular
/ administration & dosage
Antiretroviral Therapy, Highly Active
Biomarkers
Coinfection
/ drug therapy
Drug Interactions
Drug-Related Side Effects and Adverse Reactions
/ diagnosis
Female
HIV Infections
/ drug therapy
Humans
Lopinavir
/ therapeutic use
Male
Retrospective Studies
Rifabutin
/ administration & dosage
Ritonavir
/ therapeutic use
Treatment Outcome
Tuberculosis
/ drug therapy
Journal
The Journal of antimicrobial chemotherapy
ISSN: 1460-2091
Titre abrégé: J Antimicrob Chemother
Pays: England
ID NLM: 7513617
Informations de publication
Date de publication:
01 09 2019
01 09 2019
Historique:
received:
27
11
2018
revised:
16
04
2019
accepted:
23
04
2019
pubmed:
30
5
2019
medline:
20
8
2020
entrez:
30
5
2019
Statut:
ppublish
Résumé
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. 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. 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. 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.
Sections du résumé
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.
Identifiants
pubmed: 31139825
pii: 5499384
doi: 10.1093/jac/dkz219
pmc: PMC6736350
doi:
Substances chimiques
Antibiotics, Antitubercular
0
Biomarkers
0
Rifabutin
1W306TDA6S
Lopinavir
2494G1JF75
Ritonavir
O3J8G9O825
Types de publication
Journal Article
Research Support, N.I.H., Extramural
Research Support, U.S. Gov't, P.H.S.
Langues
eng
Sous-ensembles de citation
IM
Pagination
2707-2715Subventions
Organisme : NIAID NIH HHS
ID : K23 AI125122
Pays : United States
Organisme : NCATS NIH HHS
ID : UL1 TR002541
Pays : United States
Informations de copyright
© The Author(s) 2019. Published by Oxford University Press on behalf of the British Society for Antimicrobial Chemotherapy. All rights reserved. For permissions, please email: journals.permissions@oup.com.
Références
Am J Health Syst Pharm. 1999 Feb 15;56(4):333-6
pubmed: 10690216
AIDS. 2003 May 2;17(7):987-99
pubmed: 12700448
N Engl J Med. 2003 Sep 18;349(12):1157-67
pubmed: 13679531
Clin Pharmacol Ther. 2003 Dec;74(6):591-2; discussion 592-3
pubmed: 14663461
N Engl J Med. 2004 Apr 29;350(18):1850-61
pubmed: 15115831
J Acquir Immune Defic Syndr. 2008 Apr 15;47(5):566-9
pubmed: 18197120
AIDS. 2008 May 11;22(8):931-5
pubmed: 18453852
J Antimicrob Chemother. 2012 Oct;67(10):2470-3
pubmed: 22678727
N Engl J Med. 2012 Jun 21;366(25):2380-9
pubmed: 22716976
Int J Tuberc Lung Dis. 2013 Nov;17(11):1389-95
pubmed: 24125439
PLoS One. 2013 Nov 08;8(11):e79603
pubmed: 24282510
PLoS One. 2014 Jan 22;9(1):e84866
pubmed: 24465443
J Antimicrob Chemother. 2015 Feb;70(2):543-9
pubmed: 25281400
BMC Pharmacol Toxicol. 2014 Nov 19;15:61
pubmed: 25406657
Antimicrob Agents Chemother. 2015 Feb;59(2):1162-7
pubmed: 25487804
J Pediatr Pharmacol Ther. 2014 Oct-Dec;19(4):262-76
pubmed: 25762871
Lancet HIV. 2015 Oct;2(10):e438-44
pubmed: 26423651
Clin Infect Dis. 2016 Jun 15;62(12):1586-1594
pubmed: 27001796
Int J Tuberc Lung Dis. 2016 Aug;20(8):1046-54
pubmed: 27393538