Correspondence
Rifapentine and Isoniazid for Latent Tuberculosis
N Engl J Med 2012; 366:1447-1448April 12, 2012DOI: 10.1056/NEJMc1200489
- Article
To the Editor:
Sterling et al. (Dec. 8 issue)1 found that discontinuation of therapy for latent tuberculosis infection owing to an adverse event was significantly more frequent among subjects receiving rifapentine plus isoniazid than among those receiving isoniazid alone. However, the corresponding absolute difference between the groups with respect to the frequency of discontinuation was relatively small (1.2 percentage points). In contrast, the overall frequency of discontinuation was much higher among isoniazid-only recipients than among combination-regimen recipients (31.0% vs. 17.9%), for an overall between-group difference of 13.1 percentage points. These data suggest that the isoniazid-only recipients had a much higher frequency of drug discontinuation for reasons other than adverse events (27.3% vs. 13.0%) (see Table 3 of the article). Given the importance of medication adherence for treatment efficacy, it would be useful to know what accounted for the higher frequency of drug discontinuation in the isoniazid-monotherapy group — which is one of the major findings of the study — as compared with the higher frequency of discontinuation owing to adverse events among combination-regimen recipients.
James R. Johnson, M.D.
Veterans Affairs Medical Center, Minneapolis, MN
johns007@umn.edu No potential conflict of interest relevant to this letter was reported.
1 Reference1
Sterling TR ,Villarino ME ,Borisov AS , et al. Three months of rifapentine and isoniazid for latent tuberculosis infection. N Engl J Med 2011;365:2155-2166
Free Full Text | Web of Science | Medline
To the Editor:
One of the exclusion criteria in the study by Sterling et al. was resistance to isoniazid in the index population; this arouses concerns about generalizing these results to immigrants from developing countries, among whom there is a high rate of primary resistance to isoniazid. Isoniazid is not the preferred drug in regimens when the prevalence of isoniazid resistance is greater than 15% (such as in immigrants from Vietnam, Haiti, and the Philippines).1,2 In those immigrants, rifapentine plus isoniazid once a week may be equivalent to the use of monotherapy with rifapentine once a week, which increases the risk of treatment failure and the emergence of selected resistant mutants.3 This caveat may limit the use of rifapentine plus isoniazid in treating latent tuberculosis infection in a considerable number of patients seen in tuberculosis clinics in the United States, and this combination therapy may not be an option in treating immigrants from many developing countries.
Mehdi Mirsaeidi, M.D., M.P.H.
University of Illinois at Chicago, Chicago, IL
golmeh@yahoo.com No potential conflict of interest relevant to this letter was reported.
3 References1
Khan K ,Muennig P ,Behta M ,Zivin JG . Global drug-resistance patterns and the management of latent tuberculosis infection in immigrants to the United States. N Engl J Med 2002;347:1850-1859
Free Full Text | Web of Science | Medline2
Pottie K ,Greenaway C ,Feightner J , et al. Evidence-based clinical guidelines for immigrants and refugees. CMAJ 2011;183:E824-E925
CrossRef | Web of Science | Medline3
Grosset J ,Lounis N ,Truffot-Pernot C ,O'Brien RJ ,Raviglione MC ,Ji B . Once-weekly rifapentine-containing regimens for treatment of tuberculosis in mice. Am J Respir Crit Care Med 1998;157:1436-1440
Web of Science | Medline
Author/Editor Response
In reply to Johnson: after taking into account the subjects who were assigned to treatment but did not receive a study drug, the overall frequency of discontinuation was 27.3% in the isoniazid-only group and 13.0% in the combination-therapy group. The difference between the two groups in permanent drug discontinuation owing to adverse events was small, but this outcome is an important measure of drug tolerability. The reasons for drug discontinuation other than adverse events are shown in Figure 1 in the Supplementary Appendix of our article (available at NEJM.org) and are summarized in Table 1Table 1
Reason for Study-Drug Discontinuation among Subjects in the Modified Intention-to-Treat Population.. The numbers and percentages for many of the reasons for discontinuation are approximately two to three times as high in the isoniazid-only group as in the combination-therapy group; this is consistent with a duration of treatment that was three times as long in the isoniazid-only group as in the combination-therapy group.Our study primarily assessed close contacts of persons with tuberculosis who were susceptible to isoniazid and rifampin; the trial did not provide data relevant to populations with an increased risk of resistance. Drug-resistance rates among immigrants in the United States may be lower than in their country of origin (Centers for Disease Control and Prevention data). Latent Mycobacterium tuberculosis infection is a paucibacillary state, and treatment of latent M. tuberculosis infection has not been associated with increased drug resistance among persons in whom tuberculosis develops despite preventive therapy.1 However, as in our study, it is important that clinicians rule out active tuberculosis before initiating treatment of latent M. tuberculosis infection.
Timothy R. Sterling, M.D.
Vanderbilt University School of Medicine, Nashville, TN
timothy.sterling@vanderbilt. edu Ruth Moro, M.D., M.P.H.
M. Elsa Villarino, M.D., M.P.H.
Centers for Disease Control and Prevention, Atlanta, GADr. Moro reports receiving grant support through the CDC Foundation from Sanofi-Aventis. Since publication of his article, Dr. Sterling reports receiving fees from Otsuka for serving on the data and safety monitoring board for a clinical trial. No other potential conflicts of interest relevant to this letter were reported.
1 Reference1
Van Halsema CL ,Fielding KL ,Chihota VN , et al. Tuberculosis outcomes and drug susceptibility in individuals exposed to isoniazid preventive therapy in high HIV prevalence settings. AIDS 2010;24:1051-1055
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