To the Editor—We appreciated Chang’s and Huang’s comments on our published article entitled “Whole-blood 3-gene signature as a decision aid for rifapentine-based TB preventive therapy” [1] and sharing their experience as well as careful consideration on the predictive power of current 3-gene model on termination of weekly rifapentine plus isoniazid for 12 doses (3HP) treatment due to systemic drug reactions (SDRs).
We, however, want to emphasize the importance of the negative-predictive value (NPV) of the 3-gene model during clinical practice and implementation of a latent tuberculosis infection (LTBI) program. First, do no harm, especially in the setting when the goal of intervention is to prevent, rather than to cure, a disease, which is likely to occur in only 5–10% of the target population [2]. Furthermore, while conducting contact investigation, the occurrence of any adverse reaction in 1 contact might have a butterfly effect, adversely affecting the decision of whether to adhere to the public health policy in others.
Among the 125 cases who were predicted to be safe during 3HP treatment in the training and testing cohorts, only one (0.8%) 52-year-old man developed SDR (NPV for SDR development: 99.2%) after taking 3 doses of 3HP. He presented with fever up to 38.4°C, general malaise, headache, muscle ache, epigastralgia, nausea, and conjunctivitis, yet he completed 3HP treatment without interruption (NPV for SDR-related treatment incompletion: 100%). Furthermore, among the 125 cases, a total of 4 cases terminated 3HP treatment because of flu-like symptoms rather than SDRs, such as flush, dizziness, general malaise, and nausea/vomiting (NPV for treatment incompletion due to flu-like symptoms: 96.8%). This 3-gene model can therefore facilitate safely implementing a 3HP regimen for LTBI intervention.
For those who are predicted to have SDRs, they may receive rifamycin-containing tuberculosis (TB)-preventive regimens other than 3HP, such as 3HR (3 months of daily Isoniazid and Rifampin) and 4R (4 months of daily rifampin) [3]. These regimens are also effective, safe, and convenient [4, 5].
In addition, another short-term rifapentine-based TB-preventive regimen, the 1-month once-daily rifapentine-and-isoniazid regime (1HP), has demonstrated an excellent completion rate up to 90% and also has comparable efficacy and toxicity as 9H in people with human immunodeficiency virus (HIV) [6]. However, the safety of 1HP has never been comprehensively evaluated in non-HIV population. We are currently conducting a randomized controlled trial in a non-HIV population (ClinicalTrials.gov: NCT04094012) to provide a head-to-head comparison between 1HP and 3HP in terms of the completion rate and safety, especially the risk of SDRs. We think this study will provide valuable information to guide individualized TB-preventive therapy. We look forward to sharing the study results in the near future.
Notes
Financial support. The work was supported by grants from Ministry of Science and Technology (MOST109-2314-B-037-085-MY3) and the NYCU-KMU Joint Research Project (NYCU-KMU-111-I003). The funders had no role in the study design, data collection and analysis, decision to publish, or preparation of the manuscript.
Contributor Information
Hung-Ling Huang, Kaohsiung Municipal Ta-Tung Hospital, Kaohsiung, Taiwan; Division of Pulmonary and Critical Care Medicine, Department of Internal Medicine, Kaohsiung Medical University Hospital, Kaohsiung, Taiwan; Department of Internal Medicine, Kaohsiung Medical University Hospital, Kaohsiung, Taiwan; Graduate Institute of Medicine, College of Medicine, Kaohsiung Medical University, Kaohsiung, Taiwan.
Jung-Yu Lee, Institute of Bioinformatics and Systems Biology, National Yang Ming Chiao Tung University, Hsinchu, Taiwan.
Jinn-Moon Yang, Institute of Bioinformatics and Systems Biology, National Yang Ming Chiao Tung University, Hsinchu, Taiwan; Department of Biological Science and Technology, National Yang Ming Chiao Tung University, Hsinchu, Taiwan; Center for Intelligent Drug Systems and Smart Biodevices, National Yang Ming Chiao Tung University, Hsinchu, Taiwan.
Inn-Wen Chong, Division of Pulmonary and Critical Care Medicine, Department of Internal Medicine, Kaohsiung Medical University Hospital, Kaohsiung, Taiwan; Department of Internal Medicine, Kaohsiung Medical University Hospital, Kaohsiung, Taiwan; Graduate Institute of Medicine, College of Medicine, Kaohsiung Medical University, Kaohsiung, Taiwan; Department of Biological Science and Technology, National Yang Ming Chiao Tung University, Hsinchu, Taiwan.
Jann-Yuan Wang, Department of Internal Medicine, National Taiwan University Hospital, National Taiwan University College of Medicine, Taipei, Taiwan.
References
- 1. Huang HL, Lee JY, Lo YS, et al. Whole-blood 3-gene signature as a decision aid for rifapentine-based tuberculosis preventive therapy. Clin Infect Dis 2022; 75:743–52. [DOI] [PMC free article] [PubMed] [Google Scholar]
- 2. World Health Organization . Latent tuberculosis infection: updated and consolidated guidelines for programmatic management. World Health Organization, 2018. Report No: 9241550236. Available at: https://apps.who.int/iris/bitstream/handle/10665/260233/9789241550239-eng.pdf. Accessed 30 June 2022. [PubMed]
- 3. World Health Organization . WHO consolidated guidelines on tuberculosis: tuberculosis preventive treatment. World Health Organization, 2020. Available at: https://apps.who.int/iris/handle/10665/331170. Accessed 30 June 2022.
- 4. Menzies D, Adjobimey M, Ruslami R, et al. Four months of rifampin or nine months of isoniazid for latent tuberculosis in adults. N Engl J Med 2018; 379:440–53. [DOI] [PubMed] [Google Scholar]
- 5. Ena J, Valls V. Short-course therapy with rifampin plus isoniazid, compared with standard therapy with isoniazid, for latent tuberculosis infection: a meta-analysis. Clin Infect Dis 2005; 40:670–6. [DOI] [PubMed] [Google Scholar]
- 6. Swindells S, Ramchandani R, Gupta A, et al. One month of rifapentine plus isoniazid to prevent HIV-related tuberculosis. N Engl J Med 2019; 380:1001–11. [DOI] [PMC free article] [PubMed] [Google Scholar]