Rifampin and Pyrazinamide vs Isoniazid for Prevention of Tuberculosis in HIV-Infected Persons&lt;SUBTITLE&gt;An International Randomized Trial&lt;/SUBTITLE&gt;

Gordin, Fred M.; Chaisson, Richard E.; Matts, John P.; Miller, Carol A.; García, María de Lourdes García; Hafner, Richard; Valdespino, Jósé Luis; Coberly, Jacqueline S.; Schechter, Mauro; Klukowicz, Alan; Barry, Mazin; O’Brien, Richard

doi:10.1001/jama.283.11.1445

Cited by 249 publications

(123 citation statements)

References 23 publications

(18 reference statements)

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“…This rate of rifampin and pyrazinamide toxicity is comparable to rates reported in recent years from several observational studies and two clinical trials in individuals without HIV infection (23)(24)(25)(26)(27)(28)(29), but is substantially higher than rates reported in clinical trials of patients with HIV infection (7)(8)(9).…”

Section: Discussionsupporting

confidence: 79%

“…Several studies of rifampin-based short-course regimens for latent TB have shown similar or superior efficacy to longer courses of INH (6)(7)(8)(9). Rifapentine is a long-acting rifamycin with activity comparable to rifampin but with a prolonged half-life that permits weekly dosing (10).…”

mentioning

confidence: 99%

“…We therefore conducted a phase 2 trial comparing the safety and efficacy of a weekly dosing regimen of rifapentine and INH to daily rifampin and pyrazinamide, a regimen shown to be equivalent to INH alone in HIV-infected patients with latent TB infection (7)(8)(9). Rifampin and pyrazinamide were selected as the control regimen because of their known efficacy, and because we believed that recruitment of patients would be facilitated by having two relatively similar short courses of therapy rather than one short and one long regimen.…”

mentioning

confidence: 99%

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Weekly Rifapentine/Isoniazid or Daily Rifampin/Pyrazinamide for Latent Tuberculosis in Household Contacts

Schechter

Zajdenverg

Falco

et al. 2006

Am J Respir Crit Care Med

129

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Rationale: Treatment of latent tuberculosis (TB) infection with weekly rifapentine and isoniazid is a potentially effective alternative to current therapies. Objectives: To compare the efficacy of weekly rifapentine/isoniazid to daily rifampin/pyrazinamide in preventing TB in household contacts of patients with pulmonary TB in Brazil. Methods: Contacts of patients with TB were randomized to rifapentine 900 mg/isoniazid 900 mg once weekly for 12 wk or rifampin 450-600 mg/pyrazinamide 750-1,500 mg daily for 8 wk and followed for at least 2 yr. Measurements: TB rates, adverse events, and adherence to therapy. Main Results: A total of 399 household contacts were enrolled, 206 in the rifapentine/isoniazid arm and 193 in the rifampin/pyrazinamide arm. The median age was 34 yr, median weight was 63 kg, 60% of participants were female, and only one patient was HIV infected. Rifapentine/isoniazid was well tolerated, but the trial was halted by the investigators before completion because of unanticipated hepatotoxicity in the rifampin/pyrazinamide arm. Twenty of 193 participants (10%) receiving rifampin/pyrazinamide experienced grade 3 or 4 hepatotoxicity, compared with 2 of 206 participants (1%) on rifapentine/isoniazid (p Ͻ 0.001). There were no hospitalizations or deaths due to hepatotoxicity, and all participants' liver enzyme levels returned to normal during follow-up. During followup, four cases of active TB developed, three in the rifapentine/ isoniazid group and one in the rifampin/pyrazinamide group (1.46 vs. 0.52%; difference, 0.94%; 95% confidence interval, Ϫ1.6 to 3.7%). Conclusions: Rifapentine/isoniazid was better tolerated than rifampin/ pyrazinamide and was associated with good protection against TB. Rifapentine/isoniazid weekly for 12 wk is likely a promising therapy for latent TB infection.Keywords: controlled clinical trial; latent tuberculosis; pyrazinamide; rifampin; rifapentine Treatment of latent Mycobacterium tuberculosis infection is an important component of tuberculosis (TB) control (1, 2) In Western countries, targeted testing and treatment of latently infected individuals is recommended for those at increased risk of developing active TB, including contacts of infectious cases, individuals with HIV infection and other conditions that reduce host resistance to TB, and immigrants from endemic areas, among others (1). Chemoprophylaxis of high-risk patients using isonia- zid (INH) reduces the risk of developing active disease by 60 to 90%, and is the standard of care throughout the world (3). Although INH preventive therapy is highly efficacious and inexpensive, its use may be limited by toxicity and poor adherence with the long duration of treatment required for patients with no symptoms. Consequently, the development of alternative, shorter regimens to treat latent TB infection has become a priority (4).Rifamycin antibiotics have greater potency against the dormant and semidormant organisms that characterize latent TB infection than INH alone, and may be effective when given for shorter duration...

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Section: Discussionsupporting

confidence: 79%

mentioning

confidence: 99%

mentioning

confidence: 99%

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Weekly Rifapentine/Isoniazid or Daily Rifampin/Pyrazinamide for Latent Tuberculosis in Household Contacts

Schechter

Zajdenverg

Falco

et al. 2006

Am J Respir Crit Care Med

129

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“…17 Studies have documented that LTBI treatment given to HIV-positive persons will reduce the risk of developing active TB by 62-80%, and preventive LTBI treatment among HIV-infected persons is an important part of the TB control strategy worldwide. [18][19][20][21][22] In recognition of the risk of starting LTBI treatment in a person with active TB, there is a need for clear recommendations about how to rule out active disease ahead of treatment. In our study, sputum samples for culture were collected from 70% of the participants before treatment, of whom 63% were culture-negative at…”

Section: Public Health Action Ltbi In Norway 169mentioning

confidence: 99%

Management of latent tuberculous infection in Norway in 2009: a descriptive cross-sectional study

Olsen

Andersen

Aßmus

et al. 2013

public health action

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“…In this setting, BCG-immunized mice are better able to restrict the growth of M. tuberculosis infection, leading to smaller bacterial populations that are more representative of LTBI in humans (33)(34)(35). This model proved its utility when it was used to demonstrate the superior activity of short-course RIF plus PZA over that of INH (33), a finding that prompted the clinical development of the former highly efficacious combination regimen (4)(5)(6).…”

mentioning

confidence: 99%

Rifapentine, Moxifloxacin, or DNA Vaccine Improves Treatment of Latent Tuberculosis in a Mouse Model

Nuermberger

Tyagi

Williams

et al. 2005

Am J Respir Crit Care Med

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Rationale: Priorities for developing improved regimens for treatment of latent tuberculosis (TB) infection include (1 ) developing shorter and/or more intermittently administered regimens that are easier to supervise and (2 ) developing and evaluating regimens that are active against multidrug-resistant organisms. Objectives and Methods: By using a previously validated murine model that involves immunizing mice with Mycobacterium bovis bacillus Calmette-Guérin to augment host immunity before infection with virulent Mycobacterium tuberculosis, we evaluated new treatment regimens including rifapentine and moxifloxacin, and assessed the potential of the Mycobacterium leprae heat shock protein-65 DNA vaccine to augment the activity of moxifloxacin. Measurements: Quantitative spleen colony-forming unit counts, and the proportion of mice with culture-positive relapse after treatment, were determined. Main Results: Three-month, once-weekly regimens of rifapentine combined with either isoniazid or moxifloxacin were as active as daily isoniazid for 6-9 mo. Six-month daily combinations of moxifloxacin with pyrazinamide, ethionamide, or ethambutol were more active than pyrazinamide plus ethambutol, a regimen recommended for latent TB infection after exposure to multidrug-resistant TB. The combination of moxifloxacin with the experimental nitroimidazopyran PA-824 was especially active. Finally, the heat shock protein-65 DNA vaccine had no effect on colony-forming unit counts when given alone, but augmented the bactericidal activity of moxifloxacin. Conclusions: Together, these findings suggest that rifapentine, moxifloxacin, and, perhaps, therapeutic DNA vaccination have the potential to improve on the current treatment of latent TB infection.Keywords: DNA vaccine; latency; moxifloxacin; rifapentine; tuberculosisThe objective of treatment for latent tuberculosis infection (LTBI) is to prevent the development of overt tuberculosis (TB) disease in infected, but asymptomatic, individuals. At present, a 9-mo course of daily isoniazid (INH) is recommended as firstline therapy for LTBI (1). Alternative regimens include a shorter 6-mo course of INH, which is likely inferior to a 9-mo course (2), or a 4-mo course of daily rifampin (RIF), which is largely untested (1, 3). Although it is comparable in efficacy to 6 or 12 mo of INH (4-6), a 2-mo course of RIF plus pyrazinamide (PZA) is no longer recommended for use because of concerns over excessive hepatotoxicity (7). Priorities for developing improved regimens for treatment of LTBI include (1 ) developing shorter and/or more intermittently administered regimens that are easier to supervise and (2 ) developing and evaluating regimens that are active against multidrug-resistant organisms (8).(Received in original form July 6, 2005; accepted in final form September 7, 2005) Supported by the National Institutes of Health (grant AI58993 and supplement to grant AI43846), the Global Alliance for TB Drug Development, and the Potts Memorial Foundation. Regarding the first objective, the l...

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Rifampin and Pyrazinamide vs Isoniazid for Prevention of Tuberculosis in HIV-Infected Persons<SUBTITLE>An International Randomized Trial</SUBTITLE>

Cited by 249 publications

References 23 publications

Weekly Rifapentine/Isoniazid or Daily Rifampin/Pyrazinamide for Latent Tuberculosis in Household Contacts

Weekly Rifapentine/Isoniazid or Daily Rifampin/Pyrazinamide for Latent Tuberculosis in Household Contacts

Management of latent tuberculous infection in Norway in 2009: a descriptive cross-sectional study

Rifapentine, Moxifloxacin, or DNA Vaccine Improves Treatment of Latent Tuberculosis in a Mouse Model

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