Journal Article > ReviewFull Text
Clin Infect Dis. 2024 March 20; Volume 78 (Issue 3); 730-741.; DOI:10.1093/cid/ciad653
Hasan T, Medcalf E, Nyang'wa BT, Egizi E, Berry C, et al.
Clin Infect Dis. 2024 March 20; Volume 78 (Issue 3); 730-741.; DOI:10.1093/cid/ciad653
BACKGROUND
Effectiveness, safety, tolerability, and adherence are critical considerations in shifting to shorter tuberculosis (TB) regimens. Novel 6-month oral regimens that include bedaquiline (B), pretomanid (Pa), and linezolid (L), with or without a fourth drug, have been shown to be as or more effective than the established longer regimens for the treatment of multidrug-resistant/rifampicin-resistant TB (MDR/RR-TB). We aimed to evaluate the safety and tolerability of linezolid in BPaL-containing regimens for the treatment of MDR/RR-TB among recently completed clinical trials.
METHODS
A review and meta-analysis was undertaken including published and unpublished data from clinical trials, conducted between 2010 and 2021, that evaluated regimens containing BPaL for the treatment of MDR/RR-TB. Individual patient data were obtained. For each BPaL-containing regimen, we evaluated the frequency and severity of treatment-related adverse events. The risk difference of adverse events for each regimen was calculated, in comparison to patients assigned to receiving the lowest cumulative exposure of linezolid.
RESULTS
Data from 3 clinical trials investigating 8 unique BPaL-containing regimens were included, comprising a total of 591 participants. Adverse events were more frequent in groups randomized to a higher cumulative linezolid dose. Among patients who were randomized to a daily dose of 1200 mg linezolid, 68 of 195 (35%) experienced a grade 3–4 adverse event versus 89 of 396 (22%) patients receiving BPaL-containing regimens containing 600 mg linezolid.
CONCLUSIONS
Regimens containing BPaL were relatively well tolerated when they included a daily linezolid dose of 600 mg. These novel regimens promise to improve the tolerability of treatment for MDR/RR-TB.
Effectiveness, safety, tolerability, and adherence are critical considerations in shifting to shorter tuberculosis (TB) regimens. Novel 6-month oral regimens that include bedaquiline (B), pretomanid (Pa), and linezolid (L), with or without a fourth drug, have been shown to be as or more effective than the established longer regimens for the treatment of multidrug-resistant/rifampicin-resistant TB (MDR/RR-TB). We aimed to evaluate the safety and tolerability of linezolid in BPaL-containing regimens for the treatment of MDR/RR-TB among recently completed clinical trials.
METHODS
A review and meta-analysis was undertaken including published and unpublished data from clinical trials, conducted between 2010 and 2021, that evaluated regimens containing BPaL for the treatment of MDR/RR-TB. Individual patient data were obtained. For each BPaL-containing regimen, we evaluated the frequency and severity of treatment-related adverse events. The risk difference of adverse events for each regimen was calculated, in comparison to patients assigned to receiving the lowest cumulative exposure of linezolid.
RESULTS
Data from 3 clinical trials investigating 8 unique BPaL-containing regimens were included, comprising a total of 591 participants. Adverse events were more frequent in groups randomized to a higher cumulative linezolid dose. Among patients who were randomized to a daily dose of 1200 mg linezolid, 68 of 195 (35%) experienced a grade 3–4 adverse event versus 89 of 396 (22%) patients receiving BPaL-containing regimens containing 600 mg linezolid.
CONCLUSIONS
Regimens containing BPaL were relatively well tolerated when they included a daily linezolid dose of 600 mg. These novel regimens promise to improve the tolerability of treatment for MDR/RR-TB.
Journal Article > ResearchFull Text
J Infect Dev Ctries. 2021 September 29; Volume 15 (Issue 09.1); 17S-24S.; DOI:10.3855/jidc.14601
Doltu S, Ciobanu A, Sereda Y, Persian R, Ravenscroft L, et al.
J Infect Dev Ctries. 2021 September 29; Volume 15 (Issue 09.1); 17S-24S.; DOI:10.3855/jidc.14601
INTRODUCTION
The Republic of Moldova is among the 18 high priority countries for tuberculosis (TB) in Europe. This study compared adherence and short and long-term TB treatment outcomes for TB patients who experienced asynchronous Video Observed Treatment (aVOT) during three months of outpatient treatment versus Directly Observed Treatment (DOT) in operational conditions in 2016-2017 in Chisinau.
METHODOLOGY
We used secondary data from the 2016-2017 Randomized Clinical Trial (RCT) that piloted the aVOT Strategy in Chisinau and data from the national TB register. Relative risk was selected as a measure of association in analysis of treatment strategies (aVOT and DOT under operational conditions) and short and long-term treatment outcomes.
RESULTS
From 647 TB patients included in the study, 169 followed the treatment strategy in the RCT (83 in aVOT and 86 in DOT) and 478 were on DOT in operational conditions. Those in aVOT were more likely to have favourable short-term outcome than patients with DOT in operational conditions (RR 0.07; p < 0.001). TB recurrence as an indicator for the long-term outcome, was observed in group with DOT in operational conditions (40 cases, p = 0.006).
CONCLUSIONS
This study demonstrated that the aVOT treatment strategy was associated with better adherence and both short and long-term TB treatment favourable outcomes. aVOT as a new patient-centred approach supporting TB patients on improving treatment adherence and outcomes might be recommended as an alternative to DOT strategy in the Republic of Moldova.
The Republic of Moldova is among the 18 high priority countries for tuberculosis (TB) in Europe. This study compared adherence and short and long-term TB treatment outcomes for TB patients who experienced asynchronous Video Observed Treatment (aVOT) during three months of outpatient treatment versus Directly Observed Treatment (DOT) in operational conditions in 2016-2017 in Chisinau.
METHODOLOGY
We used secondary data from the 2016-2017 Randomized Clinical Trial (RCT) that piloted the aVOT Strategy in Chisinau and data from the national TB register. Relative risk was selected as a measure of association in analysis of treatment strategies (aVOT and DOT under operational conditions) and short and long-term treatment outcomes.
RESULTS
From 647 TB patients included in the study, 169 followed the treatment strategy in the RCT (83 in aVOT and 86 in DOT) and 478 were on DOT in operational conditions. Those in aVOT were more likely to have favourable short-term outcome than patients with DOT in operational conditions (RR 0.07; p < 0.001). TB recurrence as an indicator for the long-term outcome, was observed in group with DOT in operational conditions (40 cases, p = 0.006).
CONCLUSIONS
This study demonstrated that the aVOT treatment strategy was associated with better adherence and both short and long-term TB treatment favourable outcomes. aVOT as a new patient-centred approach supporting TB patients on improving treatment adherence and outcomes might be recommended as an alternative to DOT strategy in the Republic of Moldova.
Journal Article > ResearchFull Text
Public Health Action. 2014 October 21; Volume 4 (Issue 2); S64-6.; DOI:10.5588/pha.14.0043
Dolgusev O, Obevzenco N, Padalco O, Pankrushev S, Ramsay AR, et al.
Public Health Action. 2014 October 21; Volume 4 (Issue 2); S64-6.; DOI:10.5588/pha.14.0043
This cohort study assessed drug susceptibility testing (DST) patterns and associated treatment outcomes from Transnistria, Moldova, from 2009 to 2012. Of 1089 newly registered tuberculosis (TB) patients with available DST results, 556 (51%) had some form of drug resistance, while 369 (34%) had multidrug-resistant TB (MDR-TB). There were four cases of extensively drug-resistant TB. MDR-TB patients had poor treatment success (45%); human immunodeficiency virus positivity and a history of incarceration were associated with an unfavourable treatment outcome. This first study from Trans-nistria shows a high level of drug-resistant TB, which constitutes a major public health problem requiring urgent attention.
Journal Article > ResearchFull Text
PLOS One. 2013 July 23; Volume 8 (Issue 7); DOI:10.1371/journal.pone.0068445
Marshall C, Curtis A, Spelman T, O'Brien DP, Greig J, et al.
PLOS One. 2013 July 23; Volume 8 (Issue 7); DOI:10.1371/journal.pone.0068445
To identify associations between specific WHO stage 3 and 4 conditions diagnosed after ART initiation and all cause mortality for patients in resource-limited settings (RLS). DESIGN, SETTING: Analysis of routine program data collected prospectively from 25 programs in eight countries between 2002 and 2010.
Journal Article > ResearchFull Text
Public Health Action. 2014 October 21; Volume 4 (Issue 2); S59-63.; DOI:10.5588/pha.14.0047
Ciobanu A, Domente L, Soltan V, Bivol S, Severin L, et al.
Public Health Action. 2014 October 21; Volume 4 (Issue 2); S59-63.; DOI:10.5588/pha.14.0047
SETTING
Tuberculosis (TB) health facilities in the Republic of Moldova, where various incentives were provided to TB patients to improve treatment outcomes.
OBJECTIVE
To compare treatment outcomes among new drug-susceptible TB patients registered for treatment before (2008) and after (2011) introduction of incentives.
DESIGN
Retrospective cohort study using data from the national electronic patient database and incentive registers.
RESULTS
Of 2378 patients registered in 2011, 1895 (80%) received incentives (cash, food vouchers, travel reimbursement). Compared to 2008 (no incentives, n = 2492), the patients registered with incentives in 2011 had higher treatment success (88% vs. 79%, P < 0.001) and lower proportions of unsuccessful outcomes: loss to follow-up (5% vs. 10%, P < 0.001), death (5% vs. 6%, P = 0.03) and failure (2% vs. 5%, P < 0.001). In multivariate analysis (log-binomial regression) using the intention-to-treat approach, provision of incentives was independently associated with an overall reduction in unsuccessful outcomes of 50% (RR 0.5, 95%CI 0.45-0.62, P < 0.001), after adjusting for other confounders such as sex, age, education, occupation, residence, homelessness, type of TB and human immunodeficiency virus status.
CONCLUSION
Provision of incentives to TB patients significantly improved treatment success rates and needs to continue. Treatment retention increased, thus potentially preventing drug resistance, a serious problem in the Republic of Moldova.
Tuberculosis (TB) health facilities in the Republic of Moldova, where various incentives were provided to TB patients to improve treatment outcomes.
OBJECTIVE
To compare treatment outcomes among new drug-susceptible TB patients registered for treatment before (2008) and after (2011) introduction of incentives.
DESIGN
Retrospective cohort study using data from the national electronic patient database and incentive registers.
RESULTS
Of 2378 patients registered in 2011, 1895 (80%) received incentives (cash, food vouchers, travel reimbursement). Compared to 2008 (no incentives, n = 2492), the patients registered with incentives in 2011 had higher treatment success (88% vs. 79%, P < 0.001) and lower proportions of unsuccessful outcomes: loss to follow-up (5% vs. 10%, P < 0.001), death (5% vs. 6%, P = 0.03) and failure (2% vs. 5%, P < 0.001). In multivariate analysis (log-binomial regression) using the intention-to-treat approach, provision of incentives was independently associated with an overall reduction in unsuccessful outcomes of 50% (RR 0.5, 95%CI 0.45-0.62, P < 0.001), after adjusting for other confounders such as sex, age, education, occupation, residence, homelessness, type of TB and human immunodeficiency virus status.
CONCLUSION
Provision of incentives to TB patients significantly improved treatment success rates and needs to continue. Treatment retention increased, thus potentially preventing drug resistance, a serious problem in the Republic of Moldova.