Treatment outcomes and predictive factors for multidrug-resistant TB and HIV coinfection in Rio de Janeiro State, Brazil

BACKGROUND: Brazil ranks 14th worldwide in the number of TB cases and 19th in terms of TB-HIV co-infected cases. This study aims at identifying clinical and demographic factors associated with unsuccessful treatment outcomes (loss to follow-up, treatment failure and death) of HIV-positive patients with multidrug-resistant TB (MDR-TB) in Rio de Janeiro State, Brazil.METHODS: This was a retrospective cohort study of MDR-TB cases notified from 2000 to 2016 in RJ. Cox proportional hazard regression models were used to assess risk factors associated with unsuccessful treatment in HIV-positive patients with MDR-TB.RESULTS: Among 2,269 patients, 156 (6.9%) were HIV-positive and had a higher proportion of unsuccessful treatment outcomes (52.6%) than HIV-negative cases (43.7%). All HIV-positive cases with extensively drug-resistant TB (XDR-TB) had unsuccessful treatment outcomes. Multivariate analysis shows that previous MDR-TB treatment (HR 1.97, 95% CI 1.22–3.18) and illicit drugs use (HR 1.68, 95% CI 1.01–2.78) were associated with a greater hazard of unsuccessful treatment outcomes, while 6-month culture conversion (HR 0.48, 95% CI 0.27–0.84) and use of antiretroviral therapy (ART) (HR 0.51, 95% CI 0.32–0.80) were predictors of reduced risk.CONCLUSIONS: Unsuccessful treatment was higher among HIV patients with MDR-TB than among HIV-negative patients. Prompt initiation of ART and effective interventions are necessary to improve treatment adherence and prevent retreatment cases.

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Treatment Outcomes and Predictive Factors for Multidrug-Resistant TB and HIV Coinfection in Rio De Janeiro State, Brazil

10.21203/rs.3.rs-54252/v1 ◽

2020 ◽

Author(s):

Marcela Lopes Bhering ◽

Raquel Duarte ◽

Afrânio Kritski

Keyword(s):

Treatment Outcomes ◽

Rio De Janeiro ◽

Protective Factor ◽

Multidrug Resistant ◽

Hiv Positive ◽

Loss To Follow Up ◽

Factors Associated ◽

Hiv Coinfection ◽

Mdr Tb

Abstract Background: This study aims to identify and compare factors associated with the unfavorable treatment of MDR-TB patients with HIV coinfection in the State of Rio de Janeiro (RJ), Brazil.Methods: A retrospective cohort study with data from TB-MDR patients notified between 2000 and 2016 in RJ. Clinical and epidemiological characteristics and treatment outcomes of patients with HIV positive, negative, and unknown were compared. Bivariate and multivariate Cox hazard regression analysis was conducted to identify factors associated with unfavorable treatment results in patients MDR-TB / HIV positive. Results: Of 2,269 cases, 1,999 (88.1%) had a negative result for HIV, 156 (6.9%) positive and 114 (5.0%) unknown. The proportion of unfavourable outcomes was 43.7% among HIV negative, 52.6% among HIV positive and 43.9% among HIV unknown. Regarding MDR-TB / HIV positive cases, the unfavorable outcomes more prevalent were loss to follow up (24.4%) and death (23.1%). Previous MDR-TB treatment was associated with unsuccess and death. Illicit drugs use was a risk factor for unsuccess and loss to follow up. The six-month culture conversion was a protective factor for unsuccess and death. Administration of antiretroviral therapy was a protective factor for unsuccess, death and failure. The risk of XDR-TB cases for failure was six times higher than that of MDR-TB patients. All XDR-TB / HIV positive cases had unfavorable outcomes.Conclusions: Early identification and immediate initiation of appropriate treatment are key to reducing unfavorable outcomes among MDR-TB / HIV positive. The high proportions of loss to follow-up and death may reflect difficulties in monitoring treatment, due to poor integration between the TB and HIV programs. In addition, none of XDR-TB / HIV positive patient had therapeutic success, highlighting the urgency to incorporate new drugs for the treatment of multidrug-resistant TB by Brazil's Ministry of Health.

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Treatment outcomes among multidrug-resistant TB patients in Bahawal Victoria Hospital, Bahawalpur, Pakistan: a retrospective record review

Transactions of the Royal Society of Tropical Medicine and Hygiene ◽

10.1093/trstmh/traa040 ◽

2020 ◽

Vol 114 (10) ◽

pp. 733-741

Author(s):

Muhammad Atif ◽

Wajiha Ahmad ◽

Nafees Ahmad ◽

Iram Malik ◽

Sajjad Sarwar

Keyword(s):

Success Rate ◽

Treatment Outcomes ◽

Treatment Success ◽

Binary Logistic Regression ◽

Multidrug Resistant ◽

Treatment Success Rate ◽

Binary Logistic Regression Analysis ◽

Factors Associated ◽

Unsuccessful Treatment ◽

Mdr Tb

Abstract Background This study aims to evaluate the treatment outcomes and factors associated with unsuccessful treatment outcomes among multidrug-resistant TB (MDR-TB) patients. Method This was a retrospective observational study conducted at the Bahawal Victoria Hospital, Bahawalpur, Pakistan. The sociodemographic, clinical and treatment-related data of MDR-TB patients registered at the study site between June 2014 and December 2016 were retrospectively collected. Patients’ treatment outcomes were categorized on the basis of WHO-recommended criteria. Multivariate binary logistic regression analysis was used to find the independent factors associated with unsuccessful treatment outcomes. Results Out of 179 MDR-TB patients, 106 (59.2%) completed their treatment successfully. The remaining 73 patients (40.8%) had unsuccessful treatment outcomes, among whom 45 (25.1%) died, while 18 (10.1%) were lost to follow-up. Factors associated with unsuccessful treatment outcomes included age ≥40 y (AOR 4.310; p = 0.006), unsuccessful interim treatment outcomes (AOR 5.810; p = 0.032), occurrence of adverse events (AOR 0.290; p = 0.029) and ofloxacin resistance (AOR 2.952; p = 0.042). Conclusion The treatment success rate among the selected cohort of MDR-TB patients was less than the target of ≥75% set by the WHO in the End TB Strategy. The lower treatment success rate at the study site requires urgent attention from clinicians and program managers.

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Predictive factors for unfavourable treatment in MDR-TB and XDR-TB patients in Rio de Janeiro State, Brazil, 2000-2016

10.1101/656884 ◽

2019 ◽

Author(s):

Marcela Bhering ◽

Raquel Duarte ◽

Afrânio Kritski

Keyword(s):

Rio De Janeiro ◽

Treatment Options ◽

New Drugs ◽

Hiv Positive ◽

Unfavourable Outcome ◽

Factors Associated ◽

Mdr Tb ◽

Logistic Regressions ◽

Primary Transmission ◽

Janeiro State

AbstractSettingThe State of Rio de Janeiro stands out as having the second highest incidence and the highest mortality rate due to TB in Brazil. This study aims at identifying the factors associated with the unfavourable treatment of MDR/XDR-TB patients in that State.MethodData on 2269 MDR-TB cases reported in 2000-2016 in Rio de Janeiro State were collected from the Tuberculosis Surveillance System. Bivariate and multivariate logistic regressions were run to estimate the factors associated with unfavourable outcomes (failure, default, and death) and, specifically, default and death.ResultsThe proportion of unfavourable outcomes was 41.9% among MDR-TB and 81.5% among XDR-TB. Having less than 8 years of schooling, and being an Afro-Brazilian, under 40 years old and drug user were associated with unfavourable outcome and default. Bilateral disease, HIV positive, and comorbidities were associated with death. XDR-TB cases had a 4.7-fold higher odds of an unfavourable outcome, with 29.3% of such cases being in the first treatment for multidrug resistance.ConclusionAbout 30% of XDR-TB cases may have occurred by primary transmission. The high rates of failure and death in this category reflect the limitation of treatment options. This highlights the urgency to incorporate new drugs in the treatment.

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Brazilian cohort study of risk factors associated with unsuccessful outcomes of drug resistant tuberculosis

BMC Infectious Diseases ◽

10.1186/s12879-021-06756-7 ◽

2021 ◽

Vol 21 (1) ◽

Author(s):

Patricia Bartholomay ◽

Rejane Sobrino Pinheiro ◽

Fernanda Dockhorn ◽

Daniele Maria Pelissari ◽

Wildo Navegantes de Araújo

Keyword(s):

Treatment Outcomes ◽

Illicit Drugs ◽

Multinomial Logistic Regression ◽

Multidrug Resistant ◽

Individual Characteristics ◽

Drug Resistant ◽

Factors Associated ◽

Four Blocks ◽

Lost To Follow Up

Abstract Background Treatment outcomes were evaluated of a cohort of new pulmonary tuberculosis (TB) cases that were rifampicin resistant, multidrug-resistant, or extensively resistant during 2013 and 2014 in Brazil. The objective of this study is to identify factors associated with unfavorable treatment outcomes for drug-resistant TB cases. Methods The Brazilian Special Tuberculosis Treatment Information System (SITE-TB) was the main data source. The independent variables were classified into four blocks (block I: individual characteristics; block II: clinical characteristics and proposed treatment; block III: treatment follow-up characteristics; and block IV: TB history). The category of successful therapeutic outcome was compared with lost to follow-up, failure, and death. Considering the multiple outcomes as the dependent variable, the odds ratios (OR) and its respective 95% confidence interval (95% CI) were estimated by multinomial logistic regression. Results After applying the exclusion criteria, 980 (98.8%) individuals were included in the study. Of these, 621 (63.4%) had successful treatment, 163 (16.6%) lost to follow-up, 76 (7.8%) failed, and 120 (12.2%) died. Important factors associated with lost to follow-up in the final model included use of illicit drugs (OR = 2.5 95% CI: 1.57–3.82). Outcome failure was associated with having disease in both lungs (OR = 2.0; 95% CI: 1.09–3.62) and using more than one or not using injectable medication (OR = 2.8; 95% CI: 1.05–7.69). Major factors for the death outcome were at least 60 years old (OR = 3.4; 95% CI: 1.90–6.03) and HIV positive (OR = 2.7; 95% CI: 1.45–4.83). Conclusions The factors associated with unfavorable treatment outcomes were different. Some of these factors are specific to each outcome, which reflects the complexity of providing care to these individuals.

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Treatment outcomes and antiretroviral uptake in Multidrug-Resistant Tuberculosis and HIV coinfected Patients in Sub Saharan Africa. A Systematic Review and Meta-Analysis

10.21203/rs.2.10131/v1 ◽

2019 ◽

Author(s):

Elvis Dzelamonyuy Chem ◽

Marie Claire Van Hout ◽

Vivian Hope

Keyword(s):

Treatment Outcomes ◽

Meta Analysis ◽

Multidrug Resistant ◽

Pooled Analysis ◽

Sub Saharan Africa ◽

Resistant Tuberculosis ◽

Multidrug Resistant Tuberculosis ◽

Mdr Tb ◽

Sub Saharan ◽

Hiv Negative

Abstract Background Multidrug-resistant tuberculosis (MDR-TB) in HIV endemic settings is a major threat to public health. MDR-TB is a substantial and underreported problem in Sub-Saharan Africa (SSA), with recognised cases projected to increase with advancement in diagnostic technology. There is paucity of review evidence on treatment outcomes and antiretroviral (ART) uptake among MDR-TB patients with HIV in SSA. To address this gap a review of treatment outcomes in HIV patients co-infected with MDR-TB in the SSA region was undertaken. Methods Three databases (Medline, Web of Science, CINHAL), Union on Lung Heath conference proceedings and grey literature were searched for publications between January 2004 and May 2018. Records were assessed for eligibility and data extracted. Random effect meta-analysis was conducted using STATA and Cochrane’s review manager. Results A total of 271 publications were identified of which nine fulfilled the inclusion criteria. Data was collected from 3,368 MDR-TB and HIV co-infected patients from four SSA countries; South Africa (6), Lesotho (1), Botswana (1) and Ethiopia (1). The most common outcome was cure (34.9% cured in the pooled analysis), this was followed by death (18.1% in pooled analysis). ART uptake was high, at 83% in the pooled analysis. Cure ranged from 22.2% to 57.7% among patients on ART and from 28.6% to 54.7% among those not on ART medication. MDR-TB and HIV coinfected patients were less likely to be successfully treated than HIV negative MDR-TB patients (Risk Ratio = 0.87, 95% CI 0.97, 0.96). Conclusion Treatment outcomes for MDR-TB and HIV coinfected patients do not vary widely from those reported globally. However, treatment success was lower among HIV positive MDR-TB patients compared to HIV negative MDR-TB patients. Prompt antiretroviral initiation and interventions to improve treatment adherence are necessary.

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Effect of reliance on Xpert MTB/RIF on time to treatment and multidrug-resistant tuberculosis treatment outcomes in Tanzania: a retrospective cohort study

International Health ◽

10.1093/inthealth/ihz005 ◽

2019 ◽

Vol 11 (6) ◽

pp. 520-527 ◽

Cited By ~ 3

Author(s):

Edson Mollel ◽

Isack Lekule ◽

Lutgarde Lynen ◽

Tom Decroo

Keyword(s):

Cohort Study ◽

Treatment Outcome ◽

Treatment Outcomes ◽

Retrospective Cohort Study ◽

Retrospective Cohort ◽

Multidrug Resistant ◽

Tb Treatment ◽

Resistant Tuberculosis ◽

Unsuccessful Treatment ◽

Mdr Tb

Abstract Background During 2009–2013, Xpert MTB/RIF testing was decentralized in Tanzania. Standardized treatment of multidrug-resistant/rifampicin-resistant tuberculosis (MDR/RR-TB) was centralized at the Kibong’oto Infectious Diseases Hospital. Initially, Xpert MTB/RIF results were confirmed and complemented with phenotypic drug susceptibility testing before MDR-TB treatment was started. Since 2013, the decision to start MDR-TB treatment in patients with RR-TB relied on Xpert MTB/RIF results. Methods A retrospective cohort study of predictors of unsuccessful treatment outcomes (including death, lost to follow-up and treatment failure) was carried out. Results During the study period, 201 patients started MDR-TB treatment. The number of patients starting MDR-TB treatment increased over time. Out of 201 patients, 48 (23.9%) had an unsuccessful treatment outcome. The median time between sample collection and MDR-TB treatment initiation was reduced from 155 d (IQR 40–228) in the 2009–2012 period to 26 d (IQR 13–64) in 2013. Patients who started MDR-TB treatment in 2013 were more likely (adjusted OR 2.3; 95% CI 1.1–4.7; p=0.02) to have an unsuccessful treatment outcome. Conclusions Xpert MTB/RIF testing increased enrolment on MDR-TB treatment. Reliance on Xpert MTB/RIF results to start MDR-TB treatment reduced time to treatment. However, treatment outcomes did not improve.

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High rate of successful treatment outcomes among childhood rifampicin/multidrug-resistant tuberculosis in Pakistan: a multicentre retrospective observational analysis

BMC Infectious Diseases ◽

10.1186/s12879-021-06935-6 ◽

2021 ◽

Vol 21 (1) ◽

Author(s):

Farah Naz ◽

Nafees Ahmad ◽

Abdul Wahid ◽

Izaz Ahmad ◽

Asad Khan ◽

...

Keyword(s):

Treatment Failure ◽

Treatment Outcomes ◽

Successful Treatment ◽

Multidrug Resistant ◽

P Value ◽

Factors Associated ◽

Tb Treatment ◽

Mdr Tb ◽

History Of

Abstract Background There was a complete lack of information about the treatment outcomes of rifampicin/multidrug resistant (RR/MDR) childhood TB patients (age ≤ 14 years) from Pakistan, an MDR-TB 5th high burden country. Therefore, this study evaluated the socio-demographic characteristics, drug resistance pattern, treatment outcomes and factors associated with unsuccessful outcomes among childhood RR/MDR-TB patients in Pakistan. Methods This was a multicentre retrospective record review of all microbiologically confirmed childhood RR/MDR-TB patients (age ≤ 14 years) enrolled for treatment at seven units of programmatic management of drug-resistant TB (PMDT) in Pakistan. The baseline and follow-up information of enrolled participants from treatment initiation until the end of treatment were retrieved from electronic nominal recording and reporting system. World Health Organization (WHO) defined criterion was used for deciding treatment outcomes. The outcomes of “cured” and “treatment completed” were collectively grouped as successful, whereas “death”, “treatment failure” and “lost to follow-up” were grouped together as unsuccessful outcomes. Multivariable binary logistic regression analysis was used to find factors associated with unsuccessful outcomes. A p-value < 0.05 reflected statistically significant findings. Results A total of 213 children RR/MDR-TB (84 RR and 129 MDR-TB) were included in the study. Majority of them were females (74%), belonged to the age group 10–14 years (82.2%) and suffered from pulmonary TB (85.9%). A notable proportion (37.1%) of patients had no history of previous TB treatment. Patients were resistant to a median of two drugs (interquartile range: 1–4) and 23% were resistant to any second line anti-TB drug. A total of 174 (81.7%) patients achieved successful treatment outcomes with 144 (67.6%) patients being cured and 30 (14.1%) declared treatment completed. Among the 39 (18.3%) patients with unsuccessful outcomes, 35 (16.4%) died and 4 (1.9%) experienced treatment failure. In multivariable analysis, the use of ethambutol had statistically significant negative association with unsuccessful outcomes (odds ratio = 0.36, p-value = 0.02). Conclusions In this study, the WHO target of successful treatment outcomes (≥ 75%) among childhood RR/MDR-TB patients was achieved. The notable proportion of patients with no history of previous TB treatment (37.1%) and the disproportionately high number of female patients (74%) respectively stress for infection control measures and provision of early and high quality care for female drug susceptible TB patients.

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Predictive model of unfavorable outcomes for multidrug-resistant tuberculosis

Revista de Saúde Pública ◽

10.11606/s1518-8787.2019053001151 ◽

2019 ◽

Vol 53 ◽

pp. 77 ◽

Cited By ~ 1

Author(s):

Luiz Henrique Arroyo ◽

Antônio Carlos Vieira Ramos ◽

Mellina Yamamura ◽

Thais Zamboni Berra ◽

Luana Seles Alves ◽

...

Keyword(s):

Risk Factors ◽

Treatment Outcomes ◽

Predictive Model ◽

Illicit Drugs ◽

Temporal Trend ◽

Multidrug Resistant ◽

The State ◽

Resistant Tuberculosis ◽

Multidrug Resistant Tuberculosis ◽

Mdr Tb

OBJECTIVE: to analyze the temporal trend, identify the factors related and elaborate a predictive model for unfavorable treatment outcomes for multidrug-resistant tuberculosis (MDR-TB). METHODS: Retrospective cohort study with all cases diagnosed with MDR-TB between the years 2006 and 2015 in the state of São Paulo. The data were collected from the state system of TB cases notifications (TB-WEB). The temporal trend analyzes of treatment outcomes was performed through the Prais-Winsten analysis. In order to verify the factors related to the unfavorable outcomes, abandonment, death with basic cause TB and treatment failure, the binary logistic regression was used. Pictorial representations of the factors related to treatment outcome and their prognostic capacity through the nomogram were elaborated. RESULTS: Both abandonment and death have a constant temporal tendency, whereas the failure showed it as decreasing. Regarding the risk factors for such outcomes, using illicit drugs doubled the odds for abandonment and death. Besides that, being diagnosed in emergency units or during hospitalizations was a risk factor for death. On the contrary, having previous multidrug-resistant treatments reduced the odds for the analyzed outcomes by 33%. The nomogram presented a predictive model with 65% accuracy for dropouts, 70% for deaths and 80% for failure. CONCLUSIONS: The modification of the current model of care is an essential factor for the prevention of unfavorable outcomes. Through predictive models, as presented in this study, it is possible to develop patient-centered actions, considering their risk factors and increasing the chances for cure.

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Treatment outcomes and antiretroviral uptake in Multidrug-Resistant Tuberculosis and HIV coinfected Patients in Sub Saharan Africa. A Systematic Review and Meta-Analysis

10.21203/rs.2.10131/v2 ◽

2019 ◽

Author(s):

Elvis Dzelamonyuy Chem ◽

Marie Claire Van Hout ◽

Vivian Hope

Keyword(s):

Treatment Outcomes ◽

Meta Analysis ◽

Multidrug Resistant ◽

Pooled Analysis ◽

Sub Saharan Africa ◽

Resistant Tuberculosis ◽

Multidrug Resistant Tuberculosis ◽

Mdr Tb ◽

Sub Saharan ◽

Hiv Negative

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Effectiveness and cardiovascular safety of delamanid-containing regimens in adults with multidrug-resistant or extensively drug-resistant tuberculosis: A nationwide cohort study from Belarus, 2016-18

Monaldi Archives for Chest Disease ◽

10.4081/monaldi.2021.1647 ◽

2021 ◽

Vol 91 (1) ◽

Author(s):

Vera Auchynka ◽

Ajay M.V. Kumar ◽

Hennadz Hurevich ◽

Yuliia Sereda ◽

Varvara Solodovnikova ◽

...

Keyword(s):

Treatment Outcomes ◽

Multivariable Analysis ◽

Multidrug Resistant ◽

New Drugs ◽

Resistant Tuberculosis ◽

Unsuccessful Treatment ◽

Mdr Tb ◽

Ecg Abnormalities ◽

Culture Conversion

To address the sub-optimal treatment outcomes among patients with multidrug-resistant (MDR-TB) and extensively drug-resistant tuberculosis (XDR-TB), the National TB Programme in Belarus started using new drugs such as bedaquiline and delamanid in 2015-16. In this study, we assessed cardiovascular safety and effectiveness (culture conversion, treatment outcomes and post-treatment recurrence) of delamanid-containing regimens among adults (>18 years) with MDR-TB or XDR-TB from June 2016 to February 2018. This was a nationwide cohort study involving analysis of routinely collected programme data from the national and six regional TB hospitals. Cardiovascular adverse events (AEs) were classified as serious or not, based on international guidelines. We conducted Cox proportional hazards regression and calculated adjusted hazards ratio(aHR) and 95% confidence intervals(CI) to evaluate factors associated with AEs and unsuccessful treatment outcomes (death, failure and lost-to-follow-up). Of 125 patients enrolled (35, 28% females; mean age 43 years), 85(68%) had XDR-TB. All the patients received delamanid and 20 patients received both delamanid and bedaquiline. Cardiovascular AEs (177 episodes in total), were observed in the majority (73%) of patients but were mild and managed easily. The most common cardiovascular AEs were QTcF prolongation (64/177, 36%) and other electrocardiography (ECG) abnormalities (40/177, 23%). There were two instances of serious AEs leading to death, both of which were not related to delamanid. In multivariable analysis, male sex (aHR 0.72; 95% CI 0.51-0.99), and baseline ECG abnormalities (aHR 1.68; 95% CI 1.19-2.36) were associated with cardiovascular AEs. Median time to culture conversion was 1.1 months (interquartile range: 1.0-2.1). Culture conversion was observed in 115 (92%) patients at six months of treatment and 110 (88%) completed the treatment successfully. Loss to follow-up, failure and death were observed in 6%, 4% and 2% patients respectively. Among those assessed at 12 months post-treatment (n=33), recurrence was seen in one patient. The only factor associated with unsuccessful treatment outcomes in multivariable analysis was baseline Hepatitis C co-infection (aHR 3.61; 95% CI 1.09-11.95). In conclusion, treatment using delamanid-containing regimens was effective and had a favourable safety profile. We hope our findings inform the development of national clinical guidelines and scale-up of new drugs in other countries.

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