Efficacy and Safety of 4-Month Rifapentine-Based Tuberculosis Treatments in Persons with Diabetes. A previous study demonstrated noninferior efficacy of 4-month rifapentine/moxifloxacin regimen for tuberculosis (TB) treatment compared with the standard regimen. We explored results among study participants with diabetes. Among 2,516 randomized participants, 181 (7.2%) had diabetes. Of 166 participants with diabetes in the microbiologically eligible analysis group, 26.3% (15/57) had unfavorable outcomes in the control regimen, 13.8% (8/58) in the rifapentine/moxifloxacin regimen, and 29.4% (15/51) in the rifapentine regimen. The difference in proportion of unfavorable outcomes between the control and rifapentine/moxifloxacin arms in the microbiologically eligible analysis group was -12.5% (95
Completion, Safety and Tolerability of Once-Weekly Isoniazid and Rifapentine for Tuberculosis Infection by Children and Adolescents. Treating patients for tuberculosis (TB) infection prevents future cases and transmission. Long treatment regimens have been associated with low completion rates. We describe a 1-decade experience with treating children and adolescents for TB infection (TBI) with 3 months of once-weekly doses of isoniazid and rifapentine (3HP). This was a retrospective review (2014-2024) of 2 to <21 year olds who received 3HP under directly observed therapy for TBI. We abstracted demographic data, testing methods and treatment course information. Our primary outcome was treatment completion; our secondary outcome was adverse events (AEs). Eight hundred two patients met inclusion
Pharmacokinetics and safety of rifapentine in children: dosing for latent tuberculosis infection. To assess the safety of 4-week daily rifapentine-isoniazid regimen in latent tuberculosis for Chinese children, and to provide paediatric-specific evidence for extrapolating adult dosing strategies to children. An open-label, prospective, single-arm clinical trial was conducted among eligible patients (aged <10 years old). Rifapentine concentrations and laboratory safety biomarker (total bilirubin) were analysed and used for population pharmacokinetic-toxicity model development. Simulations were performed to compare efficacy and safety of weight-based and flat-dosing strategy. Once-daily rifapentine treatment was well tolerated: 310 samples (rifapentine n = 139; total bilirubin n = 171) from
Single-Dose Rifapentine in Household Contacts of Patients with Leprosy. Previous studies have suggested that a single dose of rifampin has protective effects against leprosy in close contacts of patients with the disease. Rifapentine was shown to have greater bactericidal activity against than rifampin in murine models of leprosy, but data regarding its effectiveness in preventing leprosy are lacking. We conducted a cluster-randomized, controlled trial to investigate whether single-dose rifapentine is effective in preventing leprosy in household contacts of patients with leprosy. The clusters (counties or districts in Southwest China) were assigned to one of three trial groups: single-dose rifapentine, single-dose rifampin, or control (no intervention). The primary outcome was the 4-year
Assessment for Antibodies to Rifapentine and Isoniazid in Persons Developing Flu-like Reactions During Treatment of Latent Tuberculosis Infection. Flu-like reactions can occur after exposure to rifampin, rifapentine, or isoniazid. Prior studies have reported the presence of antibodies to rifampin, but associations with underlying pathogenesis are unclear. We evaluated PREVENT TB study participants who received weekly isoniazid + rifapentine for 3 months (3HP) or daily isoniazid for 9 months (9H) as treatment for M. tuberculosis infection. Flu-like reaction was defined as a grade ≥2 of any of flu-like symptoms. Controls (3HP or 9H) did not report flu-like reactions. We developed a competitive enzyme-linked immunosorbent assays (ELISA) to detect antibodies against rifapentine, isoniazid
Genetic and clinical predictors of rifapentine and isoniazid pharmacokinetics in paediatrics with tuberculosis infection. Twelve weekly doses of rifapentine and isoniazid (3HP regimen) are recommended for TB preventive therapy in children with TB infection. However, they present with variability in the pharmacokinetic profiles. The current study aimed to develop a pharmacokinetic model of rifapentine and isoniazid in 12 children with TB infection using NONMEM. Ninety plasma and 41 urine samples were collected at Week 4 of treatment. Drug concentrations were measured using a validated HPLC-UV method. MassARRAY® SNP genotyping was used to investigate genetic factors, including P-glycoprotein (ABCB1), solute carrier organic anion transporter B1 (SLCO1B1), arylacetamide deacetylase (AADAC) and N
Twice-Daily Dolutegravir Based Antiretroviral Therapy with One Month of Daily Rifapentine and Isoniazid (1HP) for TB Prevention. One month of daily rifapentine + isoniazid (1HP) is an effective, ultrashort option for TB prevention in people with HIV (PWH). However, rifapentine may decrease antiretroviral drug concentrations and increase the risk of virologic failure. ACTG A5372 evaluated the effect of 1HP on the pharmacokinetics of twice daily dolutegravir. A5372 was a multicenter, pharmacokinetic study in PWH (≥18 years) already on dolutegravir-containing antiretroviral therapy with HIV RNA < 50 copies/mL. Participants received daily rifapentine/isoniazid (600mg/300mg) for 28 days as part of 1HP. Dolutegravir was increased to 50mg twice daily during 1HP and intensive pharmacokinetic
Comparison of 3 optimized delivery strategies for completion of isoniazid-rifapentine (3HP) for tuberculosis prevention among people living with HIV in Uganda: A single-center randomized trial. Expanding access to shorter regimens for tuberculosis (TB) prevention, such as once-weekly isoniazid and rifapentine taken for 3 months (3HP), is critical for reducing global TB burden among people living
One-month daily and three-month weekly rifapentine plus isoniazid are comparable in completion rate and safety for latent tuberculosis infection in non-HIV Population: A randomized controlled trial. The 3HP regimen, consisting of 12 doses of weekly rifapentine plus isoniazid, improves completion rate of latent tuberculosis infection (LTBI) treatment, but flu-like symptoms are common. The novel 1HP regimen, involving daily rifapentine plus isoniazid for 28 days, has demonstrated low toxicity in Human Immunodeficiency Virus (HIV)-infected populations. We aimed to investigate whether 1HP has a lower incidence rate of systemic drug reaction (SDR) compared with 3HP during treatment in non-HIV populations. This randomised, multicentre trial compared the completion rate and risks of SDRs of 1HP
Drug monitoring was conducted for rifapentine among people with HIV receiving dolutegravir containing antiretroviral therapy and latent tuberculosis treatment. The proportion of trough plasma concentration of dolutegravir (DTG) above protein adjusted 90 % inhibition concentration (IC90) (0.064 mg/L) was 98.1 % across all visits during the twelve doses of once-weekly rifapentine and isoniazid (3HP
Use of rifapentine in the treatment of latent tuberculosis infection Use of rifapentine in the treatment of latent tuberculosis infection Summary DECEMBER 2019 Une production de l’Institut national d’excellence en santé et en services sociaux (INESSS) Direction du médicament 1 SUMMARY Use of rifapentine in the treatment of latent tuberculosis infection Introduction Tuberculosis (TB [WHO, 2015]. In Quebec, TB outbreaks have occurred among Inuit populations living in remote and isolated regions in Nunavik, persons in a situation of marginalisation in urban settings, prison inmates and new immigrants and refugees. Rifapentine is used in combination with isoniazid to treat LTBI in some countries, including the United States. However, rifapentine is not marketed in Canada
Pharmacokinetics, Safety, and Tolerability of Once-Daily Darunavir With Cobicistat and Weekly Isoniazid/Rifapentine. Once-weekly isoniazid with rifapentine (HP) for 3 months is a recommended treatment for latent tuberculosis infection in persons with HIV. HP reduces exposures of certain antiretroviral medications, resulting in limited options for the concomitant use of these therapies. Here, we
Scale up of rifapentine-isoniazid (3HP) for tuberculosis prevention amongst household contacts in two urban centers: An effectiveness assessment. Scaling up a shorter preventive regimen such as weekly isoniazid-rifapentine (3HP) for three months is a priority for tuberculosis (TB) prevention treatment (TPT). However, there are limited data on 3HP acceptability and completion from high-burden TB
Symptoms and Systemic Drug Reactions in Persons Receiving Weekly Rifapentine Plus Isoniazid (3HP) Treatment for Latent Tuberculosis Infection. Three months of weekly rifapentine plus isoniazid (3HP) therapy for latent tuberculosis infections (LTBI) is recommended worldwide. The development of symptoms and systemic drug reactions (SDR) on 3HP have not been fully characterized. We aimed
Optimizing (O) rifapentine-based (RI) regimen and shortening (EN) the treatment of drug-susceptible tuberculosis (T) (ORIENT) using an adaptive seamless design: study protocol of a multicenter randomized controlled trial. Standard treatment for drug-susceptible tuberculosis (DS-TB) includes a multidrug regimen requiring at least 6 months of treatment, and this lengthy treatment easily leads regimen. In stage 1, corresponding to a phase II trial, a total of 400 patients are randomly divided into four arms, stratified by site and the presence of lung cavitation. Investigational arms include 3 short-term regimens with rifapentine 10 mg/kg, 15 mg/kg, and 20 mg/kg, while the control arm uses the standardized six-month treatment regimen. A combination of rifapentine, isoniazid, pyrazinamide
Using Dynamic Oral Dosing of Rifapentine and Rifabutin to Simulate Exposure Profiles of Long-Acting Formulations in a Mouse Model of Tuberculosis Preventive Therapy. Administration of tuberculosis preventive therapy (TPT) to individuals with latent tuberculosis infection is an important facet of global tuberculosis control. The use of long-acting injectable (LAI) drug formulations may simplify and shorten regimens for this indication. Rifapentine and rifabutin have antituberculosis activity and physiochemical properties suitable for LAI formulation, but there are limited data available for determining the target exposure profiles required for efficacy in TPT regimens. The objective of this study was to determine exposure-activity profiles of rifapentine and rifabutin to inform development of LAI
Treatment responses to integrase strand-transfer inhibitor-containing antiretroviral regimens in combination with short-course rifapentine-based regimens for latent tuberculosis infection among people with HIV. Real-world experience with combinations of short-course rifapentine-based regimens and integrase strand-transfer inhibitor (InSTI)-containing antiretroviral therapy (ART) in management of latent tuberculous infection (LTBI) is limited among people with HIV (PWH). From August 2019 to October 2022, PWH receiving 3 months of weekly rifapentine plus isoniazid (3HP) or 1 month of daily rifapentine plus isoniazid (1HP) in combination with ART were included. The primary outcome was virologic response within 12 months after LTBI treatment, and the secondary outcomes included treatment
High Isoniazid Exposures When Administered with Rifapentine Once Weekly for Latent Tuberculosis in Individuals with Human Immunodeficiency Virus. Isoniazid pharmacokinetics are not yet well-described during once weekly, high-dose administrations with rifapentine (3HP) for latent tuberculosis infection (LTBI). Fewer data describe 3HP with dolutegravir-based antiretroviral therapy were compared to previously reported data describing 3HP with dolutegravir, 3HP alone, and isoniazid with neither dolutegravir nor rifapentine. The isoniazid concentrations were adequately described by a one compartment model with a transit compartment absorption process. The isoniazid clearance for slow (8.33 L/h) and intermediate (12 L/h) acetylators were similar to previously reported values
Rifapentine With and Without Moxifloxacin for Pulmonary Tuberculosis in People With Human Immunodeficiency Virus (S31/A5349). Tuberculosis (TB) Trials Consortium Study 31/AIDS Clinical Trials Group A5349, an international randomized open-label phase 3 noninferiority trial showed that a 4-month daily regimen substituting rifapentine for rifampin and moxifloxacin for ethambutol had noninferior -free survival 12 months after randomization (efficacy) and ≥ grade 3 adverse events (AEs) on treatment (safety) were compared, using a 6.6% noninferiority margin for efficacy. Randomization was stratified by site, pulmonary cavitation, and HIV status. PWH were enrolled in a staged fashion to support cautious evaluation of drug-drug interactions between rifapentine and efavirenz. A total of 2516
Using a medication event monitoring system to evaluate self-report and pill count for determining treatment completion with self-administered, once-weekly isoniazid and rifapentine. Treatment completion is essential for the effectiveness of any latent tuberculosis infection (LTBI) regimen. The Tuberculosis Trials Consortium (TBTC) Study 33 (iAdhere) combined self-report and pill counts - standard of care (SOC) with a medication event monitoring system (MEMS) to determine treatment completion for 12-dose once-weekly isoniazid and rifapentine (3HP). Understanding the performance of SOC relative to MEMS can inform providers and suggest when interventions may be applied to optimize LTBI treatment completion. iAdhere randomized participants to directly observed therapy (DOT), SAT, or SAT