Outcomes of a nine-month regimen for rifampicin-resistant tuberculosis up to 24 months after treatment completion in nine African countries

Abstract

Background: Treatment outcomes of the shorter regimen for rifampicin-resistant tuberculosis are not completely established. We report on these outcomes two years after treatment completion among patients enrolled in an observational cohort study in nine African countries. Methods: 1,006 patients treated with the nine-month regimen were followed every six months with sputum cultures up to 24 months after treatment completion. The risk of any unfavourable outcome, of failure and relapse, and of death during and after treatment was analysed according to patient's characteristics and initial drug susceptibility by Cox proportional hazard models. Findings: Respectively 67.8% and 57.2% patients had >=1 culture result six months and 12 months after treatment completion. Fourteen relapses were diagnosed. The probability of relapse-free success was 79.3% (95% confidence interval [CI] 76.6À82.0%) overall, 80.9% (95% CI 78.0À84.0%) among HIV-negative and 72.5% (95% CI 66.5À78.9%) among HIV-infected patients. Initial fluoroquinolone (adjusted hazard ratio [aHR] 6.7 [95% CI 3.4À13.1]) and isoniazid resistance (aHR 9.4 [95% CI 1.3À68.0]) were significantly associated with increased risk of failure/relapse and of any unfavourable outcome. Interpretation: The close to 80% relapse-free success indicates the good outcome of the regimen in low-and middle-income settings. Results confirm the lesser effectiveness of the regimen in patients with initial resistance to fluoroquinolones and support the use of high-dose isoniazid, but do not support exclusion of patients for resistance to drugs other than fluoroquinolones.

Course of Adverse Events during Short Treatment Regimen in Patients with Rifampicin-Resistant Tuberculosis in Burundi

“…Gastro-intestinal events were more common in other studies (54.6–57.1%) compared to Burundi, where light meals prior to drug administration during the intensive phase may have prevented disturbances [ 6 , 11 , 12 ]. The most debilitating AE were hearing loss and tinnitus, occurring in one in ten patients, less frequent than in other studies on STR (25.3–44.3% [ 3 , 4 ]) and 36% in other cohorts with >20% HIV-positive patients [ 12 ]. Regular audiograms were taken at the same frequency compared to the nine-country study (at initiation and month four), but less frequent than in Niger (also at month two) [ 6 , 11 ].…”

“…We had a very high coverage of post-treatment follow-up; 94.7% had at least one follow-up visit, and 83.8% were followed a year or more after treatment ended. This is much higher compared to the African nine-country study, where only 57.2% of patients were followed until a year after completion [ 3 ]. Any missing data, inconsistencies or doubts were verified by checking the original patient files.…”

“…Globally, RR-TB treatment success was 56% [ 1 ]. Short treatment regimens (STR), based on the so-called “Bangladesh regimen”, showed over 80% treatment success [ 2 , 3 ], compared to 75% of patients treated with longer individualised regimens [ 4 ].…”

Case Report: Dynamics of Acquired Fluoroquinolone Resistance under Standardized Short-Course Treatment of Multidrug-Resistant Tuberculosis

“…She was started on the STR 1 day after the diagnosis of rifampicin-resistant TB, as per routine practice in Rwanda. As per national guidelines adapted from a previous survey protocol, 6 based on the patient’s weight, the initiated STR comprised moxifloxacin (200 mg), kanamycin (500 mg), protionamide (500 mg), ethambutol (600 mg), clofazimine (100 mg), isoniazid (300 mg), and pyrazinamide (800 mg).…”

Initial resistance to companion drugs should not be considered an exclusion criterion for the shorter multidrug-resistant tuberculosis treatment regimen

“…A study on the implementation of the shorter MDR-TB treatment regimen in nine African countries found that isoniazid susceptibility was associated with a significantly lower risk of bacteriological failure. Since testing for isoniazid resistance is still difficult and often not done, this is another reason to use isoniazid indiscriminately for all rifampicin-resistant TB (RR-TB; Schwœbel et al, 2020 , Trébucq et al, 2018 ). Resistance also to isoniazid (MDR-TB) is highly prevalent in RR-TB isolates ( WHO, 2019a ), but the frequency of the highest level of resistance, conferred by double mutations in katG and inhA ( Ghodousi et al, 2019 , Lempens et al, 2018 ), is low (<5% in most settings) ( Seifert et al, 2015 ), and the association between different levels of resistance to the drug and treatment outcome remains unclear.…”