Trial reportThe Journal of antimicrobial chemotherapy2015
Pharmacokinetics and safety of rifabutin in young HIV-infected children receiving rifabutin and lopinavir/ritonavir.
Trial report in The Journal of antimicrobial chemotherapy, 2015. The graph could read no effect estimate from its abstract, so it casts no vote on the map. It is linked to trial NCT01259219 (Dosing, Safety and Pharmacokinetic Profile of Rifabutin in Children Receiving Concomitant Treatment With Kaletra), which is not on this map. Cited by 20 papers, 1 of them a synthesis that pooled it.
What it found
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The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.
The trial behind it
Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.
Dosing, Safety and Pharmacokinetic Profile of Rifabutin in Children Receiving Concomitant Treatment With Kaletra
Who cites it
20 citing papers in PubMed, 1 synthesis or guideline pooled it, 42 citations in OpenAlex.
- Pharmacokinetics of antiretroviral and tuberculosis drugs in children with HIV/TB co-infection: a systematic review.The Journal of antimicrobial chemotherapy · 2020Pooled it
- Effect of SLCO1B1 Polymorphisms on Rifabutin Pharmacokinetics in African HIV-Infected Patients with Tuberculosis.Antimicrobial agents and chemotherapy · 2016Trial
- Randomized pharmacokinetic evaluation of different rifabutin doses in African HIV- infected tuberculosis patients on lopinavir/ritonavir-based antiretroviral therapy.BMC pharmacology & toxicology · 2014Trial
- Population pharmacokinetics of rifabutin among HIV/TB co-infected children on lopinavir/ritonavir-based antiretroviral therapy.Antimicrobial agents and chemotherapy · 2024Article
- HIV-Associated Tuberculosis in Children and Adolescents: Evolving Epidemiology, Screening, Prevention and Management Strategies.Pathogens (Basel, Switzerland) · 2021Review
- Rifabutin pharmacokinetics and safety among TB/HIV-coinfected children receiving lopinavir/ritonavir-containing second-line ART.The Journal of antimicrobial chemotherapy · 2021Article
- Prediction of Clearance in Children from Adults Following Drug-Drug Interaction Studies: Application of Age-Dependent Exponent Model.Drugs in R&D · 2020Article
- Pharmacokinetics of plasma lopinavir and ritonavir in tuberculosis-HIV co-infected African adult patients also receiving rifabutin 150 or 300 mg three times per week.Annals of clinical microbiology and antimicrobials · 2020Article
- Efavirenz and Lopinavir/Ritonavir Alter Cell Cycle Regulation in Lung Cancer.Frontiers in oncology · 2020Article
- Safety and efficacy of rifabutin among HIV/TB-coinfected children on lopinavir/ritonavir-based ART.The Journal of antimicrobial chemotherapy · 2019Article
- Drug-Drug Interactions of Infectious Disease Treatments in Low-Income Countries: A Neglected Topic?Clinical pharmacology and therapeutics · 2019Review
- Current research toward optimizing dosing of first-line antituberculosis treatment.Expert review of anti-infective therapy · 2019Review
- Revisiting the mutant prevention concentration to guide dosing in childhood tuberculosis.The Journal of antimicrobial chemotherapy · 2017Review
- Impact of Drug Treatment at Neonatal Ages on Variability of Drug Metabolism and Drug-drug Interactions in Adult Life.Current pharmacology reports · 2017Article
- Population pharmacokinetic drug-drug interaction pooled analysis of existing data for rifabutin and HIV PIs.The Journal of antimicrobial chemotherapy · 2016Article
- Successful Treatment of Disseminated Bacillus Calmette-Guérin Disease in an HIV-Infected Child with a Linezolid-Containing Regimen.Case reports in infectious diseases · 2016Article
- Special populations and pharmacogenetic issues in tuberculosis drug development and clinical research.The Journal of infectious diseases · 2015Review
- Tuberculosis: opportunities and challenges for the 90-90-90 targets in HIV-infected children.Journal of the International AIDS Society · 2015Review
- Getting to 90-90-90 in paediatric HIV: What is needed?Journal of the International AIDS Society · 2015Article
- Article
Corrections and comments
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Authors and funding
8 authors at 3 institutions in 2 countries.
Funding
Abstract
objectivesCo-treatment of HIV and TB in young children is complicated by limited treatment options and complex drug-drug interactions. Rifabutin is an alternative to rifampicin for adults receiving a ritonavir-boosted PI. We aimed to evaluate the short-term safety and pharmacokinetics of rifabutin when given with lopinavir/ritonavir in children. PATIENTS AND
methodsWe conducted an open-label study of rifabutin dosed at 5 mg/kg three times a week in HIV-infected children≤5 years of age receiving lopinavir/ritonavir. Intensive steady-state pharmacokinetic sampling was conducted after six doses. The Division of AIDS 2004, clarification 2009, table for grading severity of adverse events was used to classify drug toxicities. The study was registered with ClinicalTrials.gov, number NCT01259219.
resultsSix children completed the study prior to closure by institutional review boards. The median (range) AUC0-48 of rifabutin was 6.91 (3.52-8.67) μg · h/mL, the median (range) Cmax of rifabutin was 0.39 (0.19-0.46) μg/mL, the median (range) AUC0-48 of 25-O-desacetyl rifabutin was 5.73 (2.85-9.13) μg · h/mL and the median (range) Cmax of 25-O-desacetyl rifabutin was 0.17 (0.08-0.32) μg/mL. The neutrophil count declined in all children; two children experienced grade 4 neutropenia, which resolved rapidly without complications. There was strong correlation between AUC0-48 measures and neutrophil counts.
conclusionsRifabutin dosed at 5 mg/kg three times per week resulted in lower AUC0-48, AUC0-24 and Cmax values for rifabutin and 25-O-desacetyl rifabutin compared with adults receiving 150 mg of rifabutin daily, the current recommended dose. We observed high rates of severe transient neutropenia, possibly due to immaturity of CYP3A4 in young children. It remains unclear whether a safe and effective rifabutin dose exists for treatment of TB in children receiving lopinavir/ritonavir.
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Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.