Uptake and challenges with daily oral pre-exposure prophylaxis among men who have sex with men and transgender women, suburban Yangon, Myanmar.

BACKGROUND: Pre-exposure prophylaxis (PrEP) is effective for human immunodeficiency virus (HIV) prevention in risk groups. We assessed PrEP uptake and 12-month retention among men who have sex with men (MSM) and transgender women (TGW) in Myanmar during the coronavirus disease 2019 pandemic and a political crisis. METHODS: Using prospectively collected data, we assessed the proportion of persons eligible, initiated and retained 12 months on PrEP. We calculated HIV and syphilis incidence among those initiated on PrEP. Predictors of compliance to scheduled visits were assessed with fractional logistic regression. RESULTS: Among 652 persons screened between July and December 2020, 85.3% were eligible and 38.8% initiated PrEP. The daily pill burden was the main reason (86.5%) for refusing PrEP. A history of HIV post-exposure prophylaxis (PEP) and having an HIV-positive partner not on anti-retroviral therapy (ART) was associated with PrEP uptake (p<0.05). The 12-month retention among those initiating PrEP was 43.0%. Age ≥25 y, a history of PEP and having an HIV-positive partner not on ART predicted better compliance with scheduled visits (p<0.05). HIV incidence among PrEP initiators was 3.1 per 100 person-years (95% confidence interval [CI] 1.3 to 7.4) and syphilis incidence was 17.6 per 100 person-years (95% CI 12.3 to 25.1). CONCLUSIONS: A PrEP program for MSM and TGW in Myanmar was implemented successfully under difficult circumstances. Alternative strategies are needed addressing PrEP uptake and retention.

Correction: Translating drug resistant tuberculosis treatment guidelines to reality in war-torn Kandahar, Afghanistan: A retrospective cohort study.

[This corrects the article DOI: 10.1371/journal.pone.0237787.].

Correction: Viraemic-time predicts mortality among people living with HIV on second-line antiretroviral treatment in Myanmar: A retrospective cohort study.

[This corrects the article DOI: 10.1371/journal.pone.0271910.].

Computer-aided detection thresholds for digital chest radiography interpretation in tuberculosis diagnostic algorithms.

Objectives: Use of computer-aided detection (CAD) software is recommended to improve tuberculosis screening and triage, but threshold determination is challenging if reference testing has not been performed in all individuals. We aimed to determine such thresholds through secondary analysis of the 2019 Lesotho national tuberculosis prevalence survey. Methods: Symptom screening and chest radiographs were performed in participants aged ≥15 years; those symptomatic or with abnormal chest radiographs provided samples for Xpert MTB/RIF and culture testing. Chest radiographs were processed using CAD4TB version 7. We used six methodological approaches to deal with participants who did not have bacteriological test results to estimate pulmonary tuberculosis prevalence and assess diagnostic accuracy. Results: Among 17 070 participants, 5214 (31%) had their tuberculosis status determined; 142 had tuberculosis. Prevalence estimates varied between methodological approaches (0.83-2.72%). Using multiple imputation to estimate tuberculosis status for those eligible but not tested, and assuming those not eligible for testing were negative, a CAD4TBv7 threshold of 13 had a sensitivity of 89.7% (95% CI 84.6-94.8) and a specificity of 74.2% (73.6-74.9), close to World Health Organization (WHO) target product profile criteria. Assuming all those not tested were negative produced similar results. Conclusions: This is the first study to evaluate CAD4TB in a community screening context employing a range of approaches to account for unknown tuberculosis status. The assumption that those not tested are negative - regardless of testing eligibility status - was robust. As threshold determination must be context specific, our analytically straightforward approach should be adopted to leverage prevalence surveys for CAD threshold determination in other settings with a comparable proportion of eligible but not tested participants.

Development of antepartum risk prediction model for postpartum hemorrhage in Lagos, Nigeria: A prospective cohort study (Predict-PPH study).

OBJECTIVES: There is currently a limited ability to accurately identify women at risk of postpartum hemorrhage (PPH). We conducted the "Predict-PPH" study to develop and evaluate an antepartum prediction model and its derived risk-scoring system. METHODS: This was a prospective cohort study of healthy pregnant women who registered and gave birth in five hospitals in Lagos, Nigeria, from January to June 2023. Maternal antepartum characteristics were compared between women with and without PPH. A predictive multivariable model was estimated using binary logistic regression with a backward stepwise approach eliminating variables when P was greater than 0.10. Statistically significant associations in the final model were reported when P was less than 0.05. RESULTS: The prevalence of PPH in the enrolled cohort was 37.1%. Independent predictors of PPH such as maternal obesity (adjusted odds ratio [aOR] 3.25, 95% confidence interval [CI] 2.47-4.26), maternal anemia (aOR 1.32, 95% CI 1.02-1.72), previous history of cesarean delivery (aOR 4.24, 95% CI 3.13-5.73), and previous PPH (aOR 2.65, 95% CI 1.07-6.56) were incorporated to develop a risk-scoring system. The area under the receiver operating characteristic curve (AUROC) for the prediction model and risk scoring system was 0.72 (95% CI 0.69-0.75). CONCLUSION: We recorded a relatively high prevalence of PPH. Our model performance was satisfactory in identifying women at risk of PPH. Therefore, the derived risk-scoring system could be a useful tool to screen and identify pregnant women at risk of PPH during their routine antenatal assessment for birth preparedness and complication readiness.

Challenges and knowledge gaps in the management of non-tuberculous mycobacterial pulmonary disease in sub-Saharan African countries with a high tuberculosis burden: a scoping review.

INTRODUCTION: In sub-Saharan African (SSA) countries endemic for tuberculosis (TB), previous TB is a significant risk factor for non-tuberculous mycobacterial pulmonary disease (NTM-PD). The deployment of GeneXpert MTB/RIF in pulmonary TB diagnostic work-up regularly identifies symptomatic patients with a positive smear microscopy but negative GeneXpert, indicative of NTM presence. This scoping review outlines recent evidence for NTM-PD diagnosis and management in SSA. OBJECTIVE: The review's objective was to outline the risk factors, available diagnostics, management options and outcomes of NTM-PD in high-burden TB settings in SSA using the population-concept-context framework. DESIGN AND DATA SOURCES: We searched existing literature from PubMed, Web of Science, African Journals Online, Google Scholar and grey literature. Studies published between January 2005 and December 2022 were retained. Data were extracted into Rayyan software and Mendeley and summarised using Excel. RESULTS: We identified 785 potential articles, of which 105 were included in the full-text review, with 7 papers retained. Included articles used international criteria for diagnosing NTM-PD. Multiple papers were excluded due to non-application of the criteria, suggesting challenging application in the SSA setting. Identified risk factors include previous TB, smoking and mining. Most commonly, chest radiography and not CT was used for the radiological diagnosis of PD, which may miss early changes related to NTM-PD. Molecular methods for NTM species identification were employed in research settings, usually at referral centres, but were unavailable for routine care. Most studies did not report a standardised approach to treatment and they were not offered treatment for the specific disease, marking a lack of guidance in treatment decision-making. When treatment was provided, the outcome was often not reported due to the lack of implementation of standardised outcome definitions. CONCLUSIONS: These outlined challenges present a unique opportunity for researchers to undertake further studies in NTM-PD and proffer solutions more applicable to SSA.

A four-drug standardized short regimen for highly resistant TB in South-West Nigeria.

BACKGROUND: Patients with TB resistant to rifampicin (Rr-TB), and those with additional resistance to fluoroquinolones (pre-XDR-TB), should be treated with bedaquiline-pretomanid-linezolid-moxifloxacin and bedaquiline-pretomanid-linezolid, respectively. However, pretomanid is not yet widely available. METHODS: This is a pragmatic prospective single-arm study investigating the efficacy and safety of 9 mo of bedaquiline-delamanid-linezolid-clofazimine in patients with pre-XDR-TB or Rr-TB unresponsive to Rr-TB treatment in Nigeria. RESULTS: From January 2020 to June 2022, 14 of 20 patients (70%) successfully completed treatment, five died and one was lost-to-follow-up. No one experienced a treatment-emergent grade three/four event. Treatment success was higher compared with global pre-XDR-TB treatment outcomes. CONCLUSIONS: While pretomanid is unavailable, highly resistant TB can be treated with bedaquiline-delamanid-linezolid-clofazimine.

Implementation of the advanced HIV disease care package with point-of-care CD4 testing during tuberculosis case finding: A mixed-methods evaluation.

During TB-case finding, we assessed the feasibility of implementing the advanced HIV disease (AHD) care package, including VISITECT CD4 Advanced Disease (VISITECT), a semiquantitative test to identify a CD4≤200cells/µl. Adult participants with tuberculosis symptoms, recruited near-facility in Lesotho and South-Africa between 2021-2022, were offered HIV testing (capillary blood), Xpert MTB/RIF and Ultra, and MGIT culture (sputum). People living with HIV (PLHIV) were offered VISITECT (venous blood) and Alere tuberculosis-lipoarabinomannan (AlereLAM, urine) testing. AHD was defined as a CD4≤200cells/µl on VISITECT or a positive tuberculosis test. A CD4≤200cells/µl on VISITECT triggered Immy cryptococcal antigen (Immy CrAg, plasma) testing. Participants were referred with test results. To evaluate feasibility, we assessed i) acceptability and ii) intervention delivery of point-of-care diagnostics among study staff using questionnaires and group discussions, iii) process compliance, and iv) early effectiveness (12-week survival and treatment status) in PLHIV. Predictors for 12-week survival were assessed with logistic regression. Thematic content analysis and triangulation were performed. Among PLHIV (N = 676, 48.6% of 1392 participants), 7.8% were newly diagnosed, 81.8% on ART, and 10.4% knew their HIV status but were not on ART. Among 676 PLHIV, 41.7% had AHD, 29.9% a CD4≤200cells/µl and 20.6% a tuberculosis diagnosis. Among 200 PLHIV tested with Immy CrAg, 4.0% were positive. The procedures were acceptable for study staff, despite intervention delivery challenges related to supply and the long procedural duration (median: 73 minutes). At 12 weeks, among 276 PLHIV with AHD and 328 without, 3.3% and 0.9% had died, 84.8% and 92.1% were alive and 12.0% and 7.0% had an unknown status, respectively. Neither AHD nor tuberculosis status were associated with survival. Implementing AHD care package diagnostics was feasible during tuberculosis-case finding. AHD was prevalent, and not associated with survival, which is likely explained by the low specificity of VISITECT. Challenges with CD4 testing and preventive treatment uptake require addressing.

Systematic review on cumulative HIV viraemia among people living with HIV receiving antiretroviral treatment and its association with mortality and morbidity.

BACKGROUND: We performed a systematic review to generate evidence on the association between cumulative human immunodeficiency virus (HIV) viraemia and health outcomes. METHODS: Quantitative studies reporting on HIV cumulative viraemia (CV) and its association with health outcomes among people living with HIV (PLHIV) on antiretroviral treatment (ART) were included. We searched MEDLINE via PubMed, Embase, Scopus and Web of Science and conference abstracts from 1 January 2008 to 1 August 2022. RESULTS: The systematic review included 26 studies. The association between CV and mortality depended on the study population, methods used to calculate CV and its level. Higher CV was not consistently associated with greater risk of acquire immunodeficiency syndrome-defining clinical conditions. However, four studies present a strong relationship between CV and cardiovascular disease. The risk was not confirmed in relation of increased hazards of stroke. Studies that assessed the effect of CV on the risk of cancer reported a positive association between CV and malignancy, although the effect may differ for different types of cancer. CONCLUSIONS: CV is associated with adverse health outcomes in PLHIV on ART, especially at higher levels. However, its role in clinical and programmatic monitoring and management of PLHIV on ART is yet to be established.

Incidental radiological findings during clinical tuberculosis screening in Lesotho and South Africa: a case series.

BACKGROUND: Chest X-ray offers high sensitivity and acceptable specificity as a tuberculosis screening tool, but in areas with a high burden of tuberculosis, there is often a lack of radiological expertise to interpret chest X-ray. Computer-aided detection systems based on artificial intelligence are therefore increasingly used to screen for tuberculosis-related abnormalities on digital chest radiographies. The CAD4TB software has previously been shown to demonstrate high sensitivity for chest X-ray tuberculosis-related abnormalities, but it is not yet calibrated for the detection of non-tuberculosis abnormalities. When screening for tuberculosis, users of computer-aided detection need to be aware that other chest pathologies are likely to be as prevalent as, or more prevalent than, active tuberculosis. However, non--tuberculosis chest X-ray abnormalities detected during chest X-ray screening for tuberculosis remain poorly characterized in the sub-Saharan African setting, with only minimal literature. CASE PRESENTATION: In this case series, we report on four cases with non-tuberculosis abnormalities detected on CXR in TB TRIAGE + ACCURACY (ClinicalTrials.gov Identifier: NCT04666311), a study in adult presumptive tuberculosis cases at health facilities in Lesotho and South Africa to determine the diagnostic accuracy of two potential tuberculosis triage tests: computer-aided detection (CAD4TB v7, Delft, the Netherlands) and C-reactive protein (Alere Afinion, USA). The four Black African participants presented with the following chest X-ray abnormalities: a 59-year-old woman with pulmonary arteriovenous malformation, a 28-year-old man with pneumothorax, a 20-year-old man with massive bronchiectasis, and a 47-year-old woman with aspergilloma. CONCLUSIONS: Solely using chest X-ray computer-aided detection systems based on artificial intelligence as a tuberculosis screening strategy in sub-Saharan Africa comes with benefits, but also risks. Due to the limitation of CAD4TB for non-tuberculosis-abnormality identification, the computer-aided detection software may miss significant chest X-ray abnormalities that require treatment, as exemplified in our four cases. Increased data collection, characterization of non-tuberculosis anomalies and research on the implications of these diseases for individuals and health systems in sub-Saharan Africa is needed to help improve existing artificial intelligence software programs and their use in countries with high tuberculosis burden.

Piloting a new method to estimate action thresholds in medicine through intuitive weighing.

OBJECTIVES: In clinical decision-making, physicians take actions such as prescribing treatment only when the probability of disease is sufficiently high. The lowest probability at which the action will be considered, is the action threshold. Such thresholds play an important role whenever decisions have to be taken under uncertainty. However, while several methods to estimate action thresholds exist, few methods give satisfactory results or have been adopted in clinical practice. We piloted the adapted nominal group technique (aNGT), a new prescriptive method based on a formal consensus technique adapted for use in clinical decision-making. DESIGN, SETTING AND PARTICIPANTS: We applied this method in groups of postgraduate students using three scenarios: treat for rifampicin-resistant tuberculosis (RR-TB), switch to second-line HIV treatment and isolate for SARS-CoV-2 infection. INTERVENTIONS: The participants first summarise all harms of wrongly taking action when none is required and wrongly not taking action when it would have been useful. Then they rate the statements on these harms, discuss their importance in the decision-making process, and finally weigh the statements against each other. MAIN OUTCOME MEASURES: The resulting consensus threshold is estimated as the relative weights of the harms of the false positives divided by the total harm, and averaged out over participants. In some applications, the thresholds are compared with an existing method based on clinical vignettes. RESULTS: The resulting action thresholds were just over 50% for RR-TB treatment, between 20% and 50% for switching HIV treatment and 43% for COVID-19 isolation. These results were considered acceptable to all participants. Between sessions variation was low for RR-TB and moderate for HIV. Threshold estimates were moderately lower with the method based on clinical vignettes. CONCLUSIONS: The aNGT gives sensible results in our pilot and has the potential to estimate action thresholds, in an efficient manner, while involving all relevant stakeholders. Further research is needed to study the value of the method in clinical decision-making and its ability to generate acceptable thresholds that stakeholders can agree on.

Attrition one year after starting antiretroviral therapy before and after the programmatic implementation of HIV "Treat All" in Sub-Saharan Africa: a systematic review and meta-analysis.

INTRODUCTION: Evidence on the real-world effects of "Treat All" on attrition has not been systematically reviewed. We aimed to review existing literature to compare attrition 12 months after antiretroviral therapy (ART) initiation, before and after "Treat All" was implemented in Sub-Saharan Africa and describe predictors of attrition. METHODS: We searched Embase, Google Scholar, PubMed, and Web of Science in July 2020 and created alerts up to the end of June 2023. We also searched for preprints and conference abstracts. Two co-authors screened and selected the articles. Risk of bias was assessed using the modified Newcastle-Ottawa Scale. We extracted and tabulated data on study characteristics, attrition 12 months after ART initiation, and predictors of attrition. We calculated a pooled risk ratio for attrition using random-effects meta-analysis. RESULTS: Eight articles and one conference abstract (nine studies) out of 8179 screened records were included in the meta-analysis. The random-effects adjusted pooled risk ratio (RR) comparing attrition before and after "Treat All" 12 months after ART initiation was not significant [RR = 1.07 (95% Confidence interval (CI): 0.91-1.24)], with 92% heterogeneity (I2). Being a pregnant or breastfeeding woman, starting ART with advanced HIV, and starting ART within the same week were reported as risk factors for attrition both before and after "Treat All". CONCLUSIONS: We found no significant difference in attrition before and after "Treat All" one year after ART initiation. While "Treat All" is being implemented widely, differentiated approaches to enhance retention should be prioritised for those subgroups at risk of attrition. PROSPERO NUMBER: CRD42020191582 .

Relationship Between LTA4H Promotor Polymorphism and Tuberculosis-Associated Immune Reconstitution Inflammatory Syndrome and Its Prevention With Prednisone.

The development of paradoxical tuberculosis-associated immune reconstitution inflammatory syndrome (TB-IRIS) and its prevention using prednisone may potentially be mediated by the LTA4H genotype. We assessed this hypothesis in a clinical trial evaluating prednisone to prevent TB-IRIS. We did not find an association between LTA4H genotype and TB-IRIS incidence or prednisone efficacy.

High rate of adverse drug reactions with a novel tuberculosis re-treatment regimen combining triple doses of both isoniazid and rifampicin.

OBJECTIVES: High-dose rifampicin (R) and isoniazid (H) are known to be safe but were not yet combined in a single regimen. The primary objective of the TRIple-DOse RE-treatment (TRIDORE) study is to determine whether a 6-month firstline regimen with triple dose of both R and H (intervention arm; 6R3H3ZE) is non-inferior in terms of safety compared to a normal-dose regimen (6RHZE) in previously treated patients with R-susceptible (Rs) recurrent tuberculosis (TB). DESIGN/METHODS: TRIDORE is an ongoing pragmatic open-label multi-stage randomized clinical trial. RESULTS: Between March 2021 and February 2022, 127 consenting patients were randomly assigned to either the intervention or control arm: 62 and 65 were treated with 6R3H3ZE and 6RHZE, respectively. Of 127, 111 (87.4%) were male and the median age (interquartile range) was 37 (30-48) years. The median body mass index at enrollment was 18.1 (16.3-19.7) kg/m2. Drugrelated severe adverse events (AEs) (grade III-V) were significantly more frequent when 6R3H3ZE was used (5/62 vs 0/65, P = 0.03, difference weighted for site 8% [95% confidence interval: 1.0,14.3]). The Data and Safety Monitoring Board recommended publishing our interim safety data analysis. CONCLUSION: We show that the combination of triple-dose R with triple-dose H in a re-treatment regimen for patients with Rs-TB causes excess drug-related AEs.

Initial programme theory for community-based ART delivery for key populations in Benue State, Nigeria: a realist evaluation study.

BACKGROUND: The community-based antiretroviral therapy delivery (CBART) model was implemented in Benue State in Nigeria to increase access of key populations living with HIV (KPLHIV) to antiretroviral treatment. Key populations (KP) are female sex workers, men who have sex with men, persons who inject drugs, and transgender people. Evidence shows that the CBART model for KP (KP-CBART) can improve HIV outcomes along the cascade of HIV care and treatment in sub-Saharan Africa. However, how KP-CBART works, for whom, why, and under what circumstances it generates specific outcomes are not yet clear. Therefore, the aim of this study is to identify the initial programme theory (IPT) of the KP-CBART in Benue State using a realist approach. METHOD: The study design is exploratory and qualitative, exploring the implementation of KP-CBART. We reviewed the intervention logic framework & guidelines for the KP-CBART in Nigeria, conducted a desk review of KP-CBART in Sub-Saharan Africa (SSA) and interviewed programme managers in the Benue HIV programme between November 2021 and April 2022. Findings were synthesized using the Context-Mechanism-Outcome (CMO) heuristic tool to explain the relationship between the different types of CBART models, contextual factors, actors, mechanisms and outcomes. Using a generative causality logic (retroduction and abduction), we developed, following a realist approach, CMO configurations (CMOc), summarized as an empirically testable IPT. RESULT: We developed 7 CMOc and an IPT of the KP-CBART. Where KPLHIV receive ART in a safe place while living in a setting of punitive laws, harassment, stigma and discrimination, KP will adhere to treatment and be retained in care because they feel safe and trust the healthcare providers. Where KPLHIV are involved in the design, planning and implementation of HIV services; medication adherence and retention in care will improve because KP clients perceive HIV services to be KP-friendly and participate in KP-CBART. CONCLUSION: Implementation of CBART model where KPLHIV feel safe, trust healthcare providers, and participate in HIV service delivery can improve medication adherence and retention in care. This programme hypothesis will be tested and refined in the next phase of the realist evaluation of KP-CBART.

Near point-of-care HIV viral load testing: Cascade after high viral load in suburban Yangon, Myanmar.

INTRODUCTION: HIV viral load (VL) testing in resource-limited settings is often centralised, limiting access. In Myanmar, we assessed outcomes according to VL access and the VL cascade (case management after a first high VL result) before and after near point-of-care (POC) VL was introduced. METHODS: Routine programme data from people living with HIV (PLHIV) on antiretroviral therapy (ART) were used. We assessed the odds of getting a VL test done by year. Attrition and mortality two years after ART initiation were compared between three groups of PLHIV with different access to VL testing using Kaplan-Meier analysis. We compared VL cascades in those with a first VL result before and after near POC VL testing became available. With logistic regression, predictors of confirmed virological failure after a first high VL in the POC era were explored. RESULTS: Among 4291 PLHIV who started ART between July 2009 and June 2018, 794 (18.5%) became eligible for VL testing when it was not available, 2388 (55.7%) when centralised laboratory-based VL testing was available, and 1109 (25.8%) when near POC VL testing was available. Between 2010 and 2019, the odds of getting a VL test among those eligible increased with each year (OR: 5.21 [95% CI: 4.95-5.48]). Attrition and mortality were not different in the three groups. When comparing PLHIV with a first VL result before and after implementation of the near POC VL testing, in the latter, more had a first VL test (92% versus 15%, p<0.001), less had a first high VL result (5% versus 14%, p<0.001), and more had confirmed virological failure (67% versus 47%, p = 0.013). Having a first VL ≥5000 copies/mL after near POC implementation was associated with confirmed virological failure (adjusted OR: 2.61 [95% CI: 1.02-6.65]). CONCLUSION: Near POC VL testing enabled rapid increase of VL coverage and a well-managed VL cascade in Myanmar.

Evaluation of tuberculosis diagnostic test accuracy using Bayesian latent class analysis in the presence of conditional dependence between the diagnostic tests used in a community-based tuberculosis screening study.

Diagnostic accuracy studies in pulmonary tuberculosis (PTB) are complicated by the lack of a perfect reference standard. This limitation can be handled using latent class analysis (LCA), assuming independence between diagnostic test results conditional on the true unobserved PTB status. Test results could remain dependent, however, e.g. with diagnostic tests based on a similar biological basis. If ignored, this gives misleading inferences. Our secondary analysis of data collected during the first year (May 2018 -May 2019) of a community-based multi-morbidity screening program conducted in the rural uMkhanyakude district of KwaZulu Natal, South Africa, used Bayesian LCA. Residents of the catchment area, aged ≥15 years and eligible for microbiological testing, were analyzed. Probit regression methods for dependent binary data sequentially regressed each binary test outcome on other observed test results, measured covariates and the true unobserved PTB status. Unknown model parameters were assigned Gaussian priors to evaluate overall PTB prevalence and diagnostic accuracy of 6 tests used to screen for PTB: any TB symptom, radiologist conclusion, Computer Aided Detection for TB version 5 (CAD4TBv5≥53), CAD4TBv6≥53, Xpert Ultra (excluding trace) and culture. Before the application of our proposed model, we evaluated its performance using a previously published childhood pulmonary TB (CPTB) dataset. Standard LCA assuming conditional independence yielded an unrealistic prevalence estimate of 18.6% which was not resolved by accounting for conditional dependence among the true PTB cases only. Allowing, also, for conditional dependence among the true non-PTB cases produced a 1.1% plausible prevalence. After incorporating age, sex, and HIV status in the analysis, we obtained 0.9% (95% CrI: 0.6, 1.3) overall prevalence. Males had higher PTB prevalence compared to females (1.2% vs. 0.8%). Similarly, HIV+ had a higher PTB prevalence compared to HIV- (1.3% vs. 0.8%). The overall sensitivity for Xpert Ultra (excluding trace) and culture were 62.2% (95% CrI: 48.7, 74.4) and 75.9% (95% CrI: 61.9, 89.2), respectively. Any chest X-ray abnormality, CAD4TBv5≥53 and CAD4TBv6≥53 had similar overall sensitivity. Up to 73.3% (95% CrI: 61.4, 83.4) of all true PTB cases did not report TB symptoms. Our flexible modelling approach yields plausible, easy-to-interpret estimates of sensitivity, specificity and PTB prevalence under more realistic assumptions. Failure to fully account for diagnostic test dependence can yield misleading inferences.

The therapeutic threshold in clinical decision-making for TB.

Because TB control is still hampered by the limitations of diagnostic tools, diagnostic uncertainty is common. The decision to offer treatment is based on clinical decision-making. The therapeutic threshold, test threshold and test-treatment threshold can guide in making these decisions. This review summarizes the literature on methods to estimate the therapeutic threshold that have been applied for TB. Only five studies estimated the threshold for the diagnosis of TB. The therapeutic threshold can be estimated by prescriptive methods, based on calculations, and by descriptive methods, deriving the threshold from observing clinical practice. Test and test-treatment thresholds can be calculated using the therapeutic threshold and the characteristics of an available diagnostic test. Estimates of the therapeutic threshold for pulmonary TB from intuitive descriptive approaches (20%-50%) are higher than theoretical prescriptive calculations (2%-3%). In conclusion, estimates of the therapeutic threshold for pulmonary TB depend on the method used. Other methods exist within the field of decision-making that have yet to be implemented or adapted as tools to estimate the TB therapeutic threshold. Because clinical decision-making is a core element of TB management, it is necessary to find a new, clinician-friendly way to unbiasedly estimate context-specific, agreed upon therapeutic thresholds.

Advanced HIV disease and associated attrition after re-engagement in HIV care in Myanmar from 2003 to 2019: a retrospective cohort study.

BACKGROUND: The burden of advanced HIV disease (AHD) and predictors of outcomes among people living with HIV (PLHIV) re-engaging in care are not well known. METHODS: We conducted a retrospective cohort study of PLHIV who re-engaged in care after being lost to follow-up (LFU), from 2003 to 2019, in Myanmar. We calculated the incidence rates of attrition after re-engagement and performed Cox regression to identify risk factors for attrition. RESULTS: Of 44 131 PLHIV who started antiretroviral treatment, 12 338 (28.0%) were LFU at least once: 7608 (61.6%) re-engaged in care, 4672 (61.4%) with AHD at re-engagement. The death and LFU rates were 2.21-fold (95% CI 1.82 to 2.67) and 1.46-fold (95% CI 1.33 to 1.61) higher among patients who re-engaged with AHD (p>0.001). Death in patients who re-engaged with AHD was associated with male sex (adjusted HR [aHR] 2.63; 95% CI 1.31 to 5.26; p=0.006), TB coinfection (aHR 2.26; 95% CI 1.23 to 4.14; p=0.008) and sex work (aHR 7.49, 95% CI 2.29 to 22.52; p<0.001). History of intravenous drug use was identified as a predictor of being LFU. CONCLUSIONS: Re-engagement in HIV care in Myanmar is frequent and those who re-engage carry a high burden of AHD. As AHD at re-engagement is associated with higher attrition rates, implementation of differentiated interventions that enable earlier linkage to care and prompt identification and management of AHD in this population is necessary.

Definitive outcomes in patients with rifampicin-resistant tuberculosis treated in Niger from 2012 to 2019: A retrospective cohort study.

BACKGROUND: Outcomes of retreatment for rifampicin-resistant tuberculosis (RR-TB) are rarely reported. We report 'definitive outcomes' after a cascade approach to RR-TB treatment. After a bacteriologically adverse outcome for the 9-months fluoroquinolone-based Short Treatment Regimen (STR), patients were retreated with a bedaquiline-based regimen (BDQ-regimen). METHODS: A Retrospective cohort study of RR-TB patients treated with the STR during 2012-2019 and retreated with a BDQ-regimen in case of failure or relapse was conducted. Definitive relapse-free cure took into account BDQ-regimen outcomes. RESULTS: Of 367 patients treated with the STR, 20 (5.4%) experienced failure or relapse. Out of these 20 patients, 14 started a BDQ-regimen, of whom none experienced failure or relapse. Definitive end of treatment outcomes of STR after revising with third-line BDQ-regimen outcomes, 84.7% (311/367) were cured relapse-free, 10.6% (39/367) died during treatment and 3.0% (11/367) were lost to follow-up during treatment with either the STR or BDQ-regimen. Six patients (1.6%; 6/367) with STR failure/relapse died before starting a BDQ-regimen. No patient had definitive treatment failure or relapse and remained without treatment. CONCLUSIONS: If fluoroquinolone resistance is excluded or rare, it is beneficial to use fluoroquinolone as the core drug for a first RR-TB treatment regimen and to safeguard bedaquiline for those in need of retreatment.