Trial reportClinical infectious diseases : an official publication of the Infectious Diseases Society of America2018
Cytokine-Mediated Systemic Adverse Drug Reactions in a Drug-Drug Interaction Study of Dolutegravir With Once-Weekly Isoniazid and Rifapentine.
Trial report in Clinical infectious diseases : an official publication of the Infectious Diseases Society of America, 2018. The graph could read no effect estimate from its abstract, so it casts no vote on the map. It is linked to trial NCT02771249 (Impact of Once-Weekly Rifapentine and Isoniazid on the Steady State Pharmacokinetics of Dolutegravir and Darunavir Boosted With Cobicistat in Healthy Volunteers), which is not on this map. Cited by 35 papers, 2 of them syntheses that pooled it.
What it found
Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.
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.
Impact of Once-Weekly Rifapentine and Isoniazid on the Steady State Pharmacokinetics of Dolutegravir and Darunavir Boosted With Cobicistat in Healthy Volunteers
Who cites it
35 citing papers in PubMed, 2 syntheses or guidelines pooled it, 58 citations in OpenAlex.
- Tuberculosis preventive therapy for people living with HIV: A systematic review and network meta-analysis.PLoS medicine · 2021Pooled it
- Guideline
- Trial
- Assessment for Antibodies to Rifapentine and Isoniazid in Persons Developing Flu-Like Reactions During Treatment of Latent Tuberculosis Infection.The Journal of infectious diseases · 2024Trial
- Twice-Daily Dolutegravir-Based Antiretroviral Therapy With 1 Month of Daily Rifapentine and Isoniazid for Tuberculosis Prevention.Clinical infectious diseases : an official publication of the Infectious Diseases Society of America · 2024Trial
- High Isoniazid Exposures When Administered with Rifapentine Once Weekly for Latent Tuberculosis in Individuals with Human Immunodeficiency Virus.Antimicrobial agents and chemotherapy · 2023Trial
- Trial
- Pharmacokinetics and Safety of 3 Months of Weekly Rifapentine and Isoniazid for Tuberculosis Prevention in Pregnant Women.Clinical infectious diseases : an official publication of the Infectious Diseases Society of America · 2022Trial
- Pharmacokinetic profile and safety of adjusted doses of darunavir/ritonavir with rifampicin in people living with HIV.The Journal of antimicrobial chemotherapy · 2020Trial
- One Month of Rifapentine plus Isoniazid to Prevent HIV-Related Tuberculosis.The New England journal of medicine · 2019Trial
- Towards ending tuberculosis in South Africa: an uncertainty analysis of the programmes and factors most critical to future declines.Global health action · 2026Article
- Adverse Drug Reactions Related to Isoniazid Preventive Therapy Among Persons Living With HIV on Dolutegravir-Based Regimens in Uganda Between July 2019 and March 2020.Journal of acquired immune deficiency syndromes (1999) · 2026Article
- Dolutegravir concentrations in children receiving 3-month weekly isoniazid and rifapentine (3HP) for tuberculosis prevention.Microbiology spectrum · 2026Observational
- Drug-Drug Interactions Between HIV Antivirals and Concomitant Drugs in HIV Patients: What We Know and What We Need to Know.Pharmaceutics · 2024Review
- Pharmacokinetics, Safety, and Tolerability of Once-Daily Darunavir With Cobicistat and Weekly Isoniazid/Rifapentine.Journal of acquired immune deficiency syndromes (1999) · 2023Article
- Article
- Review
- Whole-Blood 3-Gene Signature as a Decision Aid for Rifapentine-based Tuberculosis Preventive Therapy.Clinical infectious diseases : an official publication of the Infectious Diseases Society of America · 2022Article
- Prevalence and factors associated with adverse drug events among patients on dolutegravir-based regimen at the Immune Suppression Syndrome Clinic of Mbarara Regional Referral Hospital, Uganda: a mixed design study.AIDS research and therapy · 2022Article
- TIMP-2 regulates 5-Fu resistance via the ERK/MAPK signaling pathway in colorectal cancer.Aging · 2022Article
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
14 authors at 5 institutions in 1 country.
Funding
Abstract
Background: Once-weekly isoniazid and rifapentine for 3 months is a treatment option in persons with human immunodeficiency virus and latent tuberculosis infection. This study aimed to examine pharmacokinetic drug-drug interactions between this regimen and dolutegravir, a first-line antiretroviral medication. Methods: This was a single-center, open-label, fixed-sequence, drug-drug interaction study in healthy volunteers. Subjects received oral dolutegravir 50 mg once daily alone (days 1-4) and concomitantly with once-weekly isoniazid 900 mg, rifapentine 900 mg, and pyridoxine 50 mg (days 5-19). Dolutegravir concentrations were measured on days 4, 14, and 19, and rifapentine, 25-desacetyl-rifapentine, and isoniazid concentrations were measured on day 19. Cytokines and antidrug antibodies to isoniazid and rifapentine were examined at select time points. Results: The study was terminated following the development of flu-like syndrome and elevated aminotransferase levels in 2 of 4 subjects after the third isoniazid-rifapentine dose. Markedly elevated levels of interferon-γ, CXCL10, C-reactive protein, and other cytokines were temporally associated with symptoms. Antidrug antibodies were infrequently detected. Dolutegravir area under the curve (AUC) was decreased by 46% (90% confidence interval, 27-110%; P = .13) on day 14. Rifapentine and 25-desacetyl rifapentine levels on day 19 were comparable to reference data, whereas isoniazid AUCs were approximately 67%-92% higher in the subjects who developed toxicities. Conclusions: The combined use of dolutegravir with once-weekly isoniazid-rifapentine resulted in unexpected and serious toxicities that were mediated by endogenous cytokine release. Additional investigations are necessary to examine the safety and efficacy of coadministering these medications. Clinical Trials Registration: NCT02771249.
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Registered trials
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.