Symptoms and Systemic Drug Reactions in Persons Receiving Weekly Rifapentine Plus Isoniazid (3HP) Treatment for Latent Tuberculosis Infection

Sadowski, Claire; Belknap, Robert; Holland, David P.; Moro, Ruth N.; Chen, Michael P.; Wright, Alicia; Millet, Joan Pau; Caylà, Joan A.; Scott, Nigel A.; Borisov, Andrey; Gandhi, Neel R.

doi:10.1093/cid/ciad083

Symptoms and Systemic Drug Reactions in Persons Receiving Weekly Rifapentine Plus Isoniazid (3HP) Treatment for Latent Tuberculosis Infection

Journal Article · 23 February 2023 · Clinical Infectious Diseases

DOI:https://doi.org/10.1093/cid/ciad083· OSTI ID:2425813

; Belknap, Robert; Holland, David P.; Moro, Ruth N.; Chen, Michael P.; Wright, Alicia; Millet, Joan Pau; Caylà, Joan A.; Scott, Nigel A.; Borisov, Andrey; Gandhi, Neel R.

Abstract Background

Three months of weekly rifapentine plus isoniazid (3HP) therapy for latent tuberculosis infection (LTBI) is recommended worldwide. The development of symptoms and systemic drug reactions (SDRs) on 3HP have not been fully characterized. We aimed to determine the patterns of symptom development and identify SDRs and associated factors in patients taking 3HP.

Methods

We analyzed symptoms data in participants receiving 3HP in the Tuberculosis Trials Consortium's iAdhere study (Study 33). We examined the patterns of symptom reporting across participants from baseline and 4 monthly visits. Bivariate analyses and multivariable regression models were used to identify factors associated with SDRs. Risk ratios (RRs) and 95% confidence intervals (CIs) were calculated.

Results

Among 1002 participants receiving 3HP, 768 (77%) reported at least 1 symptom; 97% of these symptoms were grade 1 (79%) or grade 2 (18%). Most symptoms developed in the first month and resolved. A total of 111 (11%) participants had symptoms that met criteria for SDRs; however, 53 (48%) of these participants completed therapy. Factors associated with SDRs and discontinuation included female sex (RR: 2.05; 95% CI: 1.19–3.54), age ≥45 years (RR: 1.99; 95% CI: 1.19–3.31), and use of concomitant medications (RR: 2.26; 95% CI: 1.15–4.42).

Conclusions

Although most patients receiving 3HP reported symptoms, most were mild, occurred early, and resolved without stopping treatment. Among patients experiencing SDRs, nearly half were able to complete therapy. Patient and provider education should focus on differentiating severe reactions where 3HP should be stopped from minor symptoms that will resolve.

Clinical Trials Registration. NCT01582711.

Research Organization:: Oak Ridge Institute for Science and Education (ORISE), Oak Ridge, TN (United States)

Sponsoring Organization:: USDOE Office of Science (SC)

DOE Contract Number:: SC0014664

OSTI ID:: 2425813

Journal Information:: Clinical Infectious Diseases, Journal Name: Clinical Infectious Diseases Journal Issue: 12 Vol. 76; ISSN 1058-4838

Publisher:: Oxford University Press

Country of Publication:: United States

Language:: English

References (22)

Modelling tuberculosis trends in the USA Hill, A. N.; Becerra, J. E.; Castro, K. G. Epidemiology and Infection, Vol. 140, Issue 10 https://doi.org/10.1017/S095026881100286X	journal	January 2012
Self-administered Versus Directly Observed Once-Weekly Isoniazid and Rifapentine Treatment of Latent Tuberculosis Infection Belknap, Robert; Holland, David; Feng, Pei-Jean Annals of Internal Medicine, Vol. 167, Issue 10 https://doi.org/10.7326/M17-1150	journal	November 2017
Incidence and risk factors for drug intolerance and association with incomplete treatment for tuberculosis: analysis of national case registers for England, Wales and Northern Ireland, 2001–2010: Table 1 Smith, Catherine; Abubakar, Ibrahim; Thomas, H. Lucy Thorax, Vol. 69, Issue 10 https://doi.org/10.1136/thoraxjnl-2013-204503	journal	December 2013
Potentially serious side-effects of high-dose twice-weekly rifampicin Poole, Graham; Stradling, Peter; Worlledge, Sheila Postgraduate Medical Journal, Vol. 47, Issue 553 https://doi.org/10.1136/pgmj.47.553.742	journal	November 1971
Immediate Hypersensitivity to Rifampicin in 3 Patients: Diagnostic Procedures and Induction of Clinical Tolerance Buergin, Stephan; Scherer, Kathrin; Häusermann, Peter International Archives of Allergy and Immunology, Vol. 140, Issue 1 https://doi.org/10.1159/000091839	journal	January 2006
High Rate of Treatment Completion in Program Settings With 12-Dose Weekly Isoniazid and Rifapentine for Latent Mycobacterium tuberculosis Infection Sandul, Amy L.; Nwana, Nwabunie; Holcombe, J. Mike Clinical Infectious Diseases, Vol. 65, Issue 7 https://doi.org/10.1093/cid/cix505	journal	May 2017
Detecting Alcoholism Ewing, John A. JAMA, Vol. 252, Issue 14 https://doi.org/10.1001/jama.1984.03350140051025	journal	October 1984
Efficacy and safety of weekly rifapentine and isoniazid for tuberculosis prevention in Chinese silicosis patients: a randomized controlled trial Ruan, Qiao-ling; Huang, Xi-tian; Yang, Qing-luan Clinical Microbiology and Infection, Vol. 27, Issue 4 https://doi.org/10.1016/j.cmi.2020.06.008	journal	April 2021
Prospects for Tuberculosis Elimination in the United States: Results of a Transmission Dynamic Model Menzies, Nicolas A.; Cohen, Ted; Hill, Andrew N. American Journal of Epidemiology, Vol. 187, Issue 9 https://doi.org/10.1093/aje/kwy094	journal	May 2018
Controlling latent TB tuberculosis infection in high-burden countries: A neglected strategy to end TB Churchyard, Gavin J.; Swindells, Sue PLOS Medicine, Vol. 16, Issue 4 https://doi.org/10.1371/journal.pmed.1002787	journal	April 2019
Guidelines for the Treatment of Latent Tuberculosis Infection: Recommendations from the National Tuberculosis Controllers Association and CDC, 2020 Sterling, Timothy R.; Njie, Gibril; Zenner, Dominik MMWR. Recommendations and Reports, Vol. 69, Issue 1 https://doi.org/10.15585/mmwr.rr6901a1	journal	February 2020
Update of Recommendations for Use of Once-Weekly Isoniazid-Rifapentine Regimen to Treat LatentMycobacterium tuberculosisInfection Borisov, Andrey S.; Bamrah Morris, Sapna; Njie, Gibril J. MMWR. Morbidity and Mortality Weekly Report, Vol. 67, Issue 25 https://doi.org/10.15585/mmwr.mm6725a5	journal	June 2018
Higher Completion Rates With Self-administered Once-weekly Isoniazid-rifapentine Versus Daily Rifampin in Adults With Latent Tuberculosis Haas, Michelle K.; Aiona, Kaylynn; Erlandson, Kristine M. Clinical Infectious Diseases, Vol. 73, Issue 9 https://doi.org/10.1093/cid/ciaa1364	journal	September 2020
Three Months of Rifapentine and Isoniazid for Latent Tuberculosis Infection Sterling, Timothy R.; Villarino, M. Elsa; Borisov, Andrey S. New England Journal of Medicine, Vol. 365, Issue 23 https://doi.org/10.1056/NEJMoa1104875	journal	December 2011
Sensitivity to Rifampicin: Incidence, Mechanism, and Prevention Pujet, J. -C.; Homberg, J. -C.; Decroix, G. BMJ, Vol. 2, Issue 5916 https://doi.org/10.1136/bmj.2.5916.415	journal	May 1974
Interventions to improve medication adherence in tuberculosis patients: a systematic review of randomized controlled studies Pradipta, Ivan S.; Houtsma, Daphne; van Boven, Job F. M. npj Primary Care Respiratory Medicine, Vol. 30, Issue 1 https://doi.org/10.1038/s41533-020-0179-x	journal	May 2020
Serum rifampicin concentration related to dose size and to the incidence of the ‘flu’ syndrome during intermittent rifampicin administration Dickinson, J. M.; Mitchison, D. A.; Lee, S. K. Journal of Antimicrobial Chemotherapy, Vol. 3, Issue 5 https://doi.org/10.1093/jac/3.5.445	journal	January 1977
Flu-like and Other Systemic Drug Reactions Among Persons Receiving Weekly Rifapentine Plus Isoniazid or Daily Isoniazid for Treatment of Latent Tuberculosis Infection in the PREVENT Tuberculosis Study Sterling, Timothy R.; Moro, Ruth N.; Borisov, Andrey S. Clinical Infectious Diseases, Vol. 61, Issue 4 https://doi.org/10.1093/cid/civ323	journal	April 2015
What's the Relative Risk? Zhang, Jun; Yu, Kai F. JAMA, Vol. 280, Issue 19 https://doi.org/10.1001/jama.280.19.1690	journal	November 1998
Three months of weekly rifapentine and isoniazid for treatment of Mycobacterium tuberculosis infection in HIV-coinfected persons Sterling, Timothy R.; Scott, Nigel A.; Miro, Jose M. AIDS, Vol. 30, Issue 10 https://doi.org/10.1097/QAD.0000000000001098	journal	June 2016
Psychological and Educational Intervention to Improve Tuberculosis Treatment Adherence in Ethiopia Based on Health Belief Model: A Cluster Randomized Control Trial Tola, Habteyes Hailu; Shojaeizadeh, Davoud; Tol, Azar PLOS ONE, Vol. 11, Issue 5 https://doi.org/10.1371/journal.pone.0155147	journal	May 2016
The influence of age and sex on the incidence of the ‘flu’ syndrome and rifampicin dependent antibodies in patients on intermittent rifampicin for tuberculosis No authors listed Tubercle, Vol. 56, Issue 3 https://doi.org/10.1016/0041-3879(75)90049-5	journal	September 1975

Similar Records

COVID ‐19 outcomes in patients with cancer: Findings from the University of California health system database

Journal Article · 2022 · Cancer medicine · OSTI ID:1854047

The Efficacy and Safety of Mesalamine and Probiotics in Mild‐to‐Moderate Ulcerative Colitis: A Systematic Review and Meta‐Analysis

Journal Article · 2020 · Evidence-Based Complementary and Alternative Medicine · OSTI ID:1607584

Related Subjects

Immunology
Infectious Diseases
Microbiology

Symptoms and Systemic Drug Reactions in Persons Receiving Weekly Rifapentine Plus Isoniazid (3HP) Treatment for Latent Tuberculosis Infection

Citation Formats

References (22)

Similar Records

Related Subjects