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Direct-acting antivirals (DAAs) are not widely used for patients with chronic hepatitis C virus (HCV) infection and multidrug- or rifampicin-resistant TB (MDR/RR-TB). We describe the implementation aspects of a new integrated model of care in Armenia and the perceptions of the healthcare staff and patients.We used qualitative methods, including a desktop review and semi-structured individual interviews with healthcare staff and with patients receiving HCV and MDR/RR-TB treatment.The new integrated model resulted in simplified management of HCV and MDR/RR-TB at public TB facilities. Training on HCV was provided for TB clinic staff. All MDR/RR-TB patients were systematically offered HCV testing and those diagnosed with HCV, offered treatment with DAAs. Treatment monitoring was performed by TB staff in coordination with a hepatologist. The staff interviewed had a positive opinion of the new model. They suggested that additional training should be provided. Most patients were fully satisfied with the care received. Some were concerned about the increased pill burden.Integrating HCV treatment into MDR/ RR-TB care was feasible and appreciated by patients and staff. This new model facilitated HCV diagnosis and treatment among people with MDR/RR-TB. Our results encourage piloting this model in other settings.Les antiviraux à action directe (DAA) sont peu prescrits aux patients atteints d’hépatite C (HCV) chronique et de TB multirésistante ou résistante à la rifampicine (MDR/RR-TB). Nous décrivons la mise en place d’un nouveau modèle de soins intégrés en Arménie, ainsi que l’opinion du personnel soignant et des patients.Nous avons utilisé des méthodes qualitatives, comprenant un examen électronique de la documentation et des entretiens individuels semi-structurés avec le personnel soignant et les patients sous traitement pour HCV et MDR/RR-TB.Le nouveau modèle intégré a permis de simplifier la prise en charge du HCV et de la MDR/RR-TB dans les centres de soins publics de la TB. Une formation sur le HCV a été dispensée au personnel des centres antituberculeux. Tous les patients atteints de MDR/RR-TB se sont vu systématiquement proposer un test de dépistage du HCV, et un traitement par DAA a été proposé à ceux dont le résultat était positif. Le suivi du traitement a été réalisé par le personnel des centres antituberculeux, conjointement à un hépatologue. Les membres du personnel interrogés avaient une opinion positive du nouveau modèle et suggéraient de dispenser d’autres formations. La plupart des patients étaient pleinement satisfaits des soins reçus, mais certains étaient inquiets au vu du nombre accru de comprimés à prendre.L’intégration du traitement du HCV aux soins de la MDR/RR-TB s’est avérée possible et a été appréciée par les patients et le personnel soignant. Ce nouveau modèle a facilité le diagnostic et le traitement du HCV chez les patients atteints de MDR/RR-TB. Ce modèle devrait être testé dans d’autres contextes.

BACKGROUND AND SETTING Bedaquiline (BDQ) was initially only available through compassionate use programmes. OBJECTIVE To assess the effectiveness and safety of multidrug-resistant tuberculosis (MDR-TB) treatment containing BDQ. METHOD Retrospective analysis of data from patients receiving BDQ through compassionate use in Armenia and Georgia from April 2013 to April 2015. Logistic regression was used to assess the risk factors associated with unsuccessful treatment outcomes. RESULTS Of 82 patients included, 84.2% (69/82) had fluoroquinolone-resistant MDR-TB and 43.4% (23/53) were seropositive for the hepatitis C virus (HCV). The culture conversion rate was 84.4% (54/64), and 18.5% (10/54) reverted back to positive. In total, 79.3% (65/82) of the patients reported at least one adverse event. Serious adverse events were reported in 14 patients, with 10/14 patients experiencing fatal outcomes-6/10 related to advanced TB and 2/10 assessed as possibly related to BDQ. Treatment outcomes were as follows: 58.5% treatment success, 12.2% deaths, 7.3% failures and 21.9% lost to follow-up. HCV coinfection was associated with unsuccessful outcomes (adjusted OR 4.45, 95%CI 1.23-16.13). CONCLUSION BDQ through compassionate use showed relatively good success rates and safety profiles in a cohort with difficult-to-treat MDR-TB. High rates of reversion may indicate that >24 weeks of BDQ is necessary in some cases. HCV coinfection should be diagnosed and treatment considered in MDR-TB patients.

The emergence of multidrug-resistant tuberculosis (MDR-TB; defined as resistance to at least rifampicin and isoniazid) represents a growing threat to public health and economic growth. Never before in the history of mankind have more patients been affected by MDR-TB than is the case today. The World Health Organization reports that MDR-TB outcomes are poor despite staggeringly high management costs. Moreover, treatment is prolonged, adverse events are common, and the majority of affected patients do not receive adequate treatment. As MDR-TB strains are often resistant to one or more second-line anti-TB drugs, in-depth genotypic and phenotypic drug susceptibility testing is needed to construct personalised treatment regimens to improve treatment outcomes. For the first time in decades, the availability of novel drugs such as bedaquiline allow us to design potent and well-tolerated personalised MDR-TB treatment regimens based solely on oral drugs. In this article, we present management guidance to optimise the diagnosis, algorithm-based treatment, drug dosing and therapeutic drug monitoring, and the management of adverse events and comorbidities, associated with MDR-TB. We also discuss the role of surgery, physiotherapy, rehabilitation, palliative care and smoking cessation in patients with MDR-TB. We hope that incorporating these recommendations into patient care will be helpful in optimising treatment outcomes, and lead to more MDR-TB patients achieving a relapse-free cure.

Rationale: Treatment outcomes may be compromised among patients with multidrug- or rifampicin-resistant tuberculosis with additional fluoroquinolone resistance. Evidence is needed to inform optimal treatment for these patients., Objectives: We compared the effectiveness of longer individualized regimens comprised of bedaquiline for 5 to 8 months, linezolid, and clofazimine to those reinforced with at least 1 third-tier drug and/or longer duration of bedaquiline., Methods: We emulated a target trial to compare the effectiveness of initiating and remaining on the core regimen to one of five regimens reinforced with (1) bedaquiline for ≥9 months, (2) bedaquiline for ≥9 months and delamanid, (3) imipenem, (4) a second-line injectable, or (5) delamanid and imipenem. We included patients in whom a fluoroquinolone was unlikely to be effective based on drug susceptibility testing and/or prior exposure. Our analysis consisted of cloning, censoring, and inverse-probability weighting to estimate the probability of successful treatment., Measurements and Main Results: Adjusted probabilities of successful treatment were high across regimens, ranging from 0.75 (95%CI:0.61, 0.89) to 0.84 (95%CI:0.76, 0.91). We found no substantial evidence that any of the reinforced regimens improved effectiveness of the core regimen, with ratios of treatment success ranging from 1.01 for regimens reinforced with bedaquiline ≥9 months (95%CI:0.79, 1.28) and bedaquiline ≥9 months plus delamanid (95%CI:0.81, 1.31) to 1.11 for regimens reinforced by a second-line injectable (95%CI:0.92, 1.39) and delamanid and imipenem (95%CI:0.90, 1.41)., Conclusions: High treatment success underscores the effectiveness of regimens comprised of bedaquiline, linezolid, and clofazimine, highlighting the need for expanded access to these drugs.