The epidemiology, transmission, diagnosis, and management of drug-resistant tuberculosis-lessons from the South African experience.

Drug-resistant tuberculosis (DR-TB) threatens to derail tuberculosis control efforts, particularly in Africa where the disease remains out of control. The dogma that DR-TB epidemics are fueled by unchecked rates of acquired resistance in inadequately treated or non-adherent individuals is no longer valid in most high DR-TB burden settings, where community transmission is now widespread. A large burden of DR-TB in Africa remains undiagnosed due to inadequate access to diagnostic tools that simultaneously detect tuberculosis and screen for resistance. Furthermore, acquisition of drug resistance to new and repurposed drugs, for which diagnostic solutions are not yet available, presents a major challenge for the implementation of novel, all-oral, shortened (6-9 months) treatment. Structural challenges including poverty, stigma, and social distress disrupt engagement in care, promote poor treatment outcomes, and reduce the quality of life for people with DR-TB. We reflect on the lessons learnt from the South African experience in implementing state-of-the-art advances in diagnostic solutions, deploying recent innovations in pharmacotherapeutic approaches for rapid cure, understanding local transmission dynamics and implementing interventions to curtail DR-TB transmission, and in mitigating the catastrophic socioeconomic costs of DR-TB. We also highlight globally relevant and locally responsive research priorities for achieving DR-TB control in South Africa.

Differentiated service delivery framework for people with multidrug-resistant tuberculosis and HIV co-infection.

INTRODUCTION: For people living with HIV/AIDS, care is commonly delivered through Differentiated Service Delivery (DSD). Although people with multidrug-resistant tuberculosis (MDR-TB) and HIV/AIDS experience severe treatment associated challenges, there is no DSD model to support their treatment. In this study, we defined patterns of medication adherence and characterized longitudinal barriers to inform development of an MDR-TB/HIV DSD framework. METHODS: Adults with MDR-TB and HIV initiating bedaquiline (BDQ) and receiving antiretroviral therapy (ART) in KwaZulu-Natal, South Africa, were enrolled and followed through the end of MDR-TB treatment. Electronic dose monitoring devices (EDM) measured BDQ and ART adherence. Longitudinal focus groups were conducted and transcripts analyzed thematically to describe discrete treatment stage-specific and cross-cutting treatment challenges. RESULTS: 283 participants were enrolled and followed through treatment completion (median 17.8 months [IQR 16.5-20.2]). Thirteen focus groups were conducted. Most participants (82.7%, 234/283) maintained high adherence (mean BDQ adherence 95.3%; mean ART adherence 85.5%), but an adherence-challenged subpopulation with <85% cumulative adherence (17.3%, 49/283) had significant declines in mean weekly BDQ adherence from 94.9% to 39.9% (p<0.0001) and mean weekly ART adherence from 83.9% to 26.6% (p<0.0001) over 6 months. Psychosocial, behavioral, and structural obstacles identified in qualitative data were associated with adherence deficits in discrete treatment stages, and identified potential stage specific interventions. CONCLUSION: A DSD framework for MDR-TB/HIV should intensify support for adherence-challenged subpopulations, provide multi-modal support for adherence across the treatment course and account for psychosocial, behavioral, and structural challenges linked to discrete treatment stages.

Patient perceptions of video directly observed therapy for tuberculosis: a systematic review.

Virtual modes of tuberculosis (TB) treatment monitoring have become increasingly relevant in the last decade with the advancements and increasing accessibility of technology. We conducted a systematic review comparing people with TB's perceptions of standard directly observed therapy (DOT) versus video directly observed therapy (vDOT). Studies were obtained from MEDLINE and EMBASE between January 1, 1974 and February 4, 2021. Of the 22 articles reviewed, a qualitative thematic analysis was performed, drawing on common themes from people with TB's perception of their care. 21 studies showed relative preference for and acceptance of vDOT over DOT. Factors that increased acceptability toward vDOT included cost and time saving, personal sense of empowerment, convenience, and privacy. Studies also showed greater adherence to treatment and subsequent improved health outcomes. vDOT has the potential to be an empowering, person-centered treatment modality for TB therapy. The role of social determinants such as place of residence, access to technology, and patient-provider communication requires further exploration.

Adaptive evaluation of mHealth and conventional adherence support interventions to optimize outcomes with new treatment regimens for drug-resistant tuberculosis and HIV in South Africa (ADAP-TIV): study protocol for an adaptive randomized controlled trial.

BACKGROUND: Highly effective, short-course, bedaquiline-containing treatment regimens for multidrug-resistant tuberculosis (MDR-TB) and integrase strand transfer inhibitor (INSTI)-containing fixed dose combination antiretroviral therapy (ART) have radically transformed treatment for MDR-TB and HIV. However, without advances in adherence support, we may not realize the full potential of these therapeutics. The primary objective of this study is to compare the effect of adherence support interventions on clinical and biological endpoints using an adaptive randomized platform. METHODS: This is a prospective, adaptive, randomized controlled trial comparing the effectiveness of four adherence support strategies on a composite clinical outcome in adults with MDR-TB and HIV initiating bedaquiline-containing MDR-TB treatment regimens and receiving ART in KwaZulu-Natal, South Africa. Trial arms include (1) enhanced standard of care, (2) psychosocial support, (3) mHealth using cellular-enabled electronic dose monitoring, and (4) combined mHealth and psychosocial support. The level of support will be titrated using a differentiated service delivery (DSD)-informed assessment of treatment support needs. The composite primary outcome will include survival, negative TB culture, retention in care, and undetectable HIV viral load at month 12. Secondary outcomes will include individual components of the primary outcome and quantitative evaluation of adherence on TB and HIV treatment outcomes. DISCUSSION: This trial will evaluate the contribution of different modes of adherence support on MDR-TB and HIV outcomes with WHO-recommended all-oral MDR-TB regimens and ART in a high-burden operational setting. We will also assess the utility of a DSD framework to pragmatically adjust levels of MDR-TB and HIV treatment support. TRIAL REGISTRATION: ClinicalTrials.gov NCT05633056. Registered on 1 December 2022.

Adaptive evaluation of mHealth and conventional adherence support interventions to optimize outcomes with new treatment regimens for drug-resistant tuberculosis and HIV in South Africa (ADAP-TIV): Study protocol for an adaptive randomized controlled trial.

Background: Highly effective, short course, bedaquiline-containing treatment regimens for multidrug-resistant tuberculosis (MDR-TB) and integrase strand transfer inhibitor (INSTI)-containing fixed dose combination antiretroviral therapy (ART) have radically transformed treatment for MDR-TB and HIV. However, without advances in adherence support, we may not realize the full potential of these therapeutics. The primary objective of this study is to compare the effect of adherence support interventions on clinical and biological endpoints using an adaptive randomized platform. Methods: This is a prospective, adaptive, randomized controlled trial comparing the effectiveness of four adherence support strategies on a composite clinical outcome in adults with MDR-TB and HIV initiating bedaquiline-containing MDR-TB treatment regimens and receiving ART in KwaZulu-Natal, South Africa. Trial arms include 1) enhanced standard of care; 2) psychosocial support; 3) mHealth using cellular- enabled electronic dose monitoring; 4) combined mHealth and psychosocial support. The level of support will be titrated using a differentiated service delivery (DSD)-informed assessment of treatment support needs. The composite primary outcome will be include survival, negative TB culture, retention in care and undetectable HIV viral load at month 12. Secondary outcomes will include individual components of the primary outcome and quantitative evaluation of adherence on TB and HIV treatment outcomes. Discussion: This trial will evaluate the contribution of different modes of adherence support on MDR-TB and HIV outcomes with WHO recommended all-oral MDR-TB regimens and ART in a high-burden operational setting. We will also assess the utility of a DSD framework to pragmatically adjust levels of MDR-TB and HIV treatment support.

Do private providers initiate anti-tuberculosis therapy on the basis of chest radiographs? A standardised patient study in urban India.

Background: The initiation of anti-tuberculosis treatment (ATT) based on results of WHO-approved microbiological diagnostics is an important marker of quality tuberculosis (TB) care. Evidence suggests that other diagnostic processes leading to treatment initiation may be preferred in high TB incidence settings. This study examines whether private providers start anti-TB therapy on the basis of chest radiography (CXR) and clinical examinations. Methods: This study uses the standardized patient (SP) methodology to generate accurate and unbiased estimates of private sector, primary care provider practice when a patient presents a standardized TB case scenario with an abnormal CXR. Using multivariate log-binomial and linear regressions with standard errors clustered at the provider level, we analyzed 795 SP visits conducted over three data collection waves from 2014 to 2020 in two Indian cities. Data were inverse-probability-weighted based on the study sampling strategy, resulting in city-wave-representative results. Findings: Amongst SPs who presented to a provider with an abnormal CXR, 25% (95% CI: 21-28%) visits resulted in ideal management, defined as the provider prescribing a microbiological test and not offering a concurrent prescription for a corticosteroid or antibiotic (including anti-TB medications). In contrast, 23% (95% CI: 19-26%) of 795 visits were prescribed anti-TB medications. Of 795 visits, 13% (95% CI: 10-16%) resulted in anti-TB treatment prescriptions/dispensation and an order for confirmatory microbiological testing. Interpretation: One in five SPs presenting with abnormal CXR were prescribed ATT by private providers. This study contributes novel insights to empiric treatment prevalence based on CXR abnormality. Further work is needed to understand how providers make trade-offs between existing diagnostic practices, new technologies, profits, clinical outcomes, and the market dynamics with laboratories. Funding: This study was funded by the Bill & Melinda Gates Foundation (grant OPP1091843), and the Knowledge for Change Program at The World Bank.

Use of standardised patients to assess tuberculosis case management by private pharmacies in Patna, India: A repeat cross-sectional study.

As the first point of care for many healthcare seekers, private pharmacies play an important role in tuberculosis (TB) care. However, previous studies in India have showed that private pharmacies commonly dispense symptomatic treatments and broad-spectrum antibiotics over-the-counter (OTC), rather than referring patients for TB testing. Such inappropriate management by pharmacies can delaye TB diagnosis. We assessed medical advice and OTC drug dispensing practices of pharmacists for standardized patients presenting with classic symptoms of pulmonary TB (case 1) and for those with sputum smear positive pulmonary TB (case 2), and examined how practices have changed over time in an urban Indian site. We examined how and whether private pharmacies improved practices for TB in 2019 compared to a baseline study conducted in 2015 in the city of Patna, using the same survey sampling techniques and study staff. The proportion of patient-pharmacist interactions that resulted in correct or ideal management, as well as the proportion of interactions resulting in antibiotic, quinolone, and corticosteroid are presented, with standard errors clustered at the provider level. To assess the difference in case management and the use of drugs across the two cases by round, a difference in difference (DiD) model was employed. A total of 936 SP interactions were completed over both rounds of survey. Our results indicate that across both rounds of data collection, 331 of 936 (35%; 95% CI: 32-38%) of interactions were correctly managed. At baseline, 215 of 500 (43%; 95% CI: 39-47%) of interactions were correctly managed whereas 116 of 436 (27%; 95% CI: 23-31%) were correctly managed in the second round of data collection. Ideal management, where in addition to a referral, patients were not prescribed any potentially harmful medications, was seen in 275 of 936 (29%; 95% CI: 27-32%) of interactions overall, with 194 of 500 (39%; 95% CI: 35-43%) of interactions at baseline and 81 of 436 (19%; 95% CI: 15-22%) in round 2. No private pharmacy dispensed anti-TB medications without a prescription. On average, the difference in correct case management between case 1 vs. case 2 dropped by 20 percent points from baseline to the second round of data collection. Similarly, ideal case management decreased by 26 percentage points between rounds. This is in contrast with the dispensation of medicines, which had the opposite effect between rounds; the difference in dispensation of quinolones between case 1 and case 2 increased by 14 percentage points, as did corticosteroids by 9 percentage points, antibiotics by 25 percentage points and medicines generally by 30 percentage points. Our standardised patient study provides valuable insights into how private pharmacies in an Indian city changed their management of patients with TB symptoms or with confirmed TB over a 5-year period. We saw that overall, private pharmacy performance has weakened over time. However, no OTC dispensation of anti-TB medications occurred in either survey round. As the first point of contact for many care seekers, continued and sustained efforts to engage with Indian private pharmacies should be prioritized.

Artificial intelligence-based computer aided detection (AI-CAD) in the fight against tuberculosis: Effects of moving health technologies in global health.

Computer Aided Detection software based on Artificial Intelligence (AI-CAD), combined with chest X-rays have recently been promoted as an easy fix for a complex problem: ending TB by 2030. WHO has recommended the use of such imaging devices in 2021 and many partnerships have helped propose benchmark analysis and technology comparisons to facilitate their "market access". Our aim is to examine the socio-political and health issues that stem from using AI-CAD technology in a global health context conceptualized as a set of practice and ideas organizing global intervention "in the life of others". We also question how this technology, which is not yet fully implemented in routine use, may limit or amplify some inequalities in the care of tuberculosis. We describe AI-CAD through Actor-Network-Theory framework to understand the global assemblage and composite activities associated with detection through AI-CAD, and interrogate how the technology itself may consolidate a specific configuration of "global health". We explore the various dimensions of AI-CAD "health effects model": technology design, development, regulation, institutional competition, social interaction and health cultures. On a broader level, AI-CAD represents a new version of global health's accelerationist model centered on "moving and autonomous-presumed technologies". We finally present key aspects in our research which help discuss the theories mobilized: AI-CAD ambivalent insertion in global health, the social lives of its data: from efficacy to markets and AI-CAD human care and maintenance it requires. We reflect on the conditions that will affect AI-CAD use and its promises. In the end, the risk of new detection technologies such as AI-CAD is indeed that the fight against TB could be reduced to one that is purely technical and technological, with neglect to its social determinants and effects.

"Live a normal life": Constructions of resilience among people in mixed HIV status relationships in Canada.

Positive Plus One is a mixed-methods study of long-term mixed HIV-serostatus relationships in Canada (2016-19). Qualitative interviews with 51 participants (10 women, 41 men, including 27 HIV-positive and 24 HIV-negative partners) were analyzed using inductive thematic analysis to examine notions of relationship resilience in the context of emerging HIV social campaigns. Relationship resilience meant finding ways to build and enact life as a normal couple, that is, a couple not noticeably affected by HIV, linked to the partner with HIV maintaining viral suppression and achieving "undetectable = untransmittable" (U = U). Regardless of serostatus, participants with material resources, social networks, and specialized care were better able to construct resilience for HIV-related challenges within their relationships. Compared to heterosexual couples and those facing socioeconomic adversity, gay and bisexual couples were easier able to disclose, and access capital, networks and resources supporting resilience. We conclude that important pathways of constructing, shaping, and maintaining resilience were influenced by the timing of HIV diagnosis in the relationship, access to HIV-related information and services, disclosure, stigma and social acceptance.

Disclosure of HIV-serodiscordant relationships and association with viral suppression: results from the Positive Plus One study.

BACKGROUND: Little is known about the effects of disclosure of HIV-serodiscordant relationships on clinical outcomes. We aimed to evaluate the effect of relationship disclosure on HIV viral suppression, and hypothesized that disclosure by HIV-positive and HIV-negative partners would be associated with viral suppression in the HIV-positive partner. METHODS: We conducted a Canadian national online and telephone-administered survey of HIV-positive and HIV-negative partners in serodiscordant relationships. The primary outcome was self-reported viral suppression. Multivariable analyses were undertaken using Firth logistic regression. RESULTS: We recruited 540 participants in current serodiscordant relationships (n = 228 HIV-negative; n = 312 HIV-positive). Similar proportions of HIV-positive and HIV-negative partners disclosed their relationship to healthcare professionals (82% v. 76%, p = 0.13). Among HIV-positive partners, disclosure of the relationship to healthcare professionals increased the odds of viral suppression (aOR = 4.7; CI: 2.13, 10.51) after adjusting for age, education, and relationship turmoil due to HIV. Increasing age (aOR = 1.28; 95% CI = 1.07, 1.55) and education (aOR = 2.43; 95% CI = 1.15, 5.26) were also associated with viral suppression. Among HIV-negative partners, relationship disclosure was not associated with viral suppression and HIV-negative heterosexual men were less likely to report that their HIV-positive partners were virally suppressed (aOR = 0.24; CI: 0.09, 0.61). CONCLUSIONS: Disclosure of HIV-serodiscordant status by HIV-positive participants to healthcare professionals was associated with increased odds of viral suppression. Similar effects were not evident among HIV-negative participants. Future work should explore factors that empower relationship disclosure and incorporate them into supportive services for HIV-serodiscordant relationships.

Interventions to improve linkage along the HIV-tuberculosis care cascades in low- and middle-income countries: A systematic review and meta-analysis.

INTRODUCTION: In support of global targets to end HIV/AIDS and tuberculosis (TB) by 2030, we reviewed interventions aiming to improve TB case-detection and anti-TB treatment among people living with HIV (PLHIV) and HIV testing and antiretroviral treatment initiation among people with TB disease in low- and middle-income countries (LMICs). METHODS: We conducted a systematic review of comparative (quasi-)experimental interventional studies published in Medline or EMBASE between January 2003-July 2021. We performed random-effects effect meta-analyses (DerSimonian and Laird method) for interventions that were homogenous (based on intervention descriptions); for others we narratively synthesized the intervention effect. Studies were assessed using ROBINS-I, Cochrane Risk-of-Bias, and GRADE. (PROSPERO #CRD42018109629). RESULTS: Of 21,516 retrieved studies, 23 were included, contributing 53 arms and 84,884 participants from 4 continents. Five interventions were analyzed: co-location of test and/or treatment services; patient education and counselling; dedicated personnel; peer support; and financial support. A majority were implemented in primary health facilities (n = 22) and reported on HIV outcomes in people with TB (n = 18). Service co-location had the most consistent positive effect on HIV testing and treatment initiation among people with TB, and TB case-detection among PLHIV. Other interventions were heterogenous, implemented concurrent with standard-of-care strategies and/or diverse facility-level improvements, and produced mixed effects. Operational system, human resource, and/or laboratory strengthening were common within successful interventions. Most studies had a moderate to serious risk of bias. CONCLUSIONS: This review provides operational clarity on intervention models that can support early linkages between the TB and HIV care cascades. The findings have supported the World Health Organization 2020 HIV Service Delivery Guidelines update. Further research is needed to evaluate the distinct effect of education and counselling, financial support, and dedicated personnel interventions, and to explore the role of community-based, virtual, and differentiated service delivery models in addressing TB-HIV co-morbidity.

A national recruitment strategy for HIV-serodiscordant partners living in Canada for the Positive Plus One study: a mixed-methods study.

BACKGROUND: With the recent shift in focus to addressing HIV risk within relationships and couple-based interventions to prevent HIV transmission, successful recruitment of individuals involved in HIV-serodiscordant relationships is crucial. This paper evaluates methods used by the Positive Plus One (PP1) study to recruit and collect data on a diverse national sample of dyads and individuals involved in current or past HIV-serodiscordant relationships, discusses the strengths and limitations of the recruitment approach, and makes recommendations to inform the interpretation of study results and the design of future studies. METHODS: PP1 used a multi-pronged approach to recruit adults involved in a current or past HIV-serodiscordant relationship in Canada from 2016 to 2018 to complete a survey and an interview. Upon survey completion, index (first recruited) partners were invited to recruit their primary current HIV-serodiscordant partner. We investigated participant enrollment by recruitment source, participant-, relationship-, and dyad-level sociodemographic characteristics, missing data, and correlates of participation for individuals recruited by their partners. RESULTS: We recruited 613 participants (355 HIV-positive; 258 HIV-negative) across 10 Canadian provinces, including 153 complete dyads and 307 individuals who participated alone, and representing 460 HIV-serodiscordant relationships. Among those in current relationships, HIV-positive participants were more likely than HIV-negative participants to learn of the study through an ASO staff member (36% v. 20%, p < 0.001), ASO listserv/newsletter (12% v. 5%, p = 0.007), or physician/staff at a clinic (20% v. 11%, p = 0.006). HIV-negative participants involved in current relationships were more likely than HIV-positive participants to learn of the study through their partner (46% v. 8%, p < 0.001). Seventy-eight percent of index participants invited their primary HIV-serodiscordant partner to participate, and 40% were successful. Successful recruitment of primary partners was associated with longer relationship duration, higher relationship satisfaction, and a virally suppressed HIV-positive partner. CONCLUSIONS: Our findings provide important new information on and support the use of a multi-pronged approach to recruit HIV-positive and HIV-negative individuals involved in HIV-serodiscordant relationships in Canada. More creative strategies are needed to help index partners recruit their partner in relationships with lower satisfaction and shorter duration and further minimize the risk of "happy couple" bias.

Dual pharmaceutical citizenship: Exploring biomedicalization in the daily lives of mixed HIV-serostatus couples in Canada.

Positive Plus One is the first large-scale mixed methods study of mixed HIV serostatus couples in Canada. We aimed to understand how biomedicalization i.e., a social process of commodification and expansion of the jurisdiction of medicine over health, influenced the everyday relationships of these couples. We completed 51 semi-structured interviews among a purposive sample of HIV-positive (n = 27) and HIV-negative (n = 24) partners in current or past mixed-serostatus relationships. Participants were recruited after completing an online survey where they consented to be re-contacted for qualitative interviews. Participants represented a diversity of sexual orientations, gender identities, and other sociodemographic characteristics. Drawing on inductive thematic analysis to identify patterns within couples, across serostatus and sexual orientations, we argue that everyday lives of mixed-serostatus couples were shaped by biomedical knowledge and enacted through routine adherence to obtain and maintain viral load undetectability. Our findings illustrated the importance of learning biomedical knowledge for mixed-serostatus couples in this study, the empowering influence of undetectable = untransmittable (UU) discourse, and its role in rendering HIV mundane through routine ART adherence. We introduce the concept of 'dual pharmaceutical citizenship' to underscore a process by which particular biopolitical and biomedical expectations are fulfilled in mixed-serostatus relationships. These findings have implications for people who do not readily accept or have access to biomedical knowledge, particularly when treatment-as-prevention frames a "right" and "wrong" approach to HIV management. Future studies should focus on couples where at least one partner does not readily accept or have access to biomedical knowledge.

Social capital and HIV-serodiscordance: Disparities in access to personal and professional resources for HIV-positive and HIV-negative partners.

As people living with HIV are living longer lives, they have a correspondingly greater opportunity to enjoy long-term romantic and sexual partnerships, including with persons who do not live with HIV ("serodiscordant" relationships). In these dyads, asymmetries may emerge in access to social resources between partners. In this paper we examined how serodiscordant couples access informal (interpersonal, such as family and friends) and formal (practitioner, such as doctor or social worker) social resources for health. We recruited 540 participants in current serodiscordant relationships, working with 150 AIDS service organizations and HIV clinics across Canada from 2016 to 2018. Our findings demonstrate that partners with HIV have greater access to formal resources than their partners (through health care professionals, therapists/counselors/support workers), while both persons have similar access to resources through informal social relationships (family and friends). Furthermore, the findings indicated that HIV positive partners accessed more varied forms of support through formal ties, compared to HIV negative persons. We offer recommendations for changes to how HIV-negative partners in a serodiscordant relationship are served and cared for, and particularly, the importance of moving toward dyad-focused policies and practices.

Bedaquiline Adherence Measured by Electronic Dose Monitoring Predicts Clinical Outcomes in the Treatment of Patients With Multidrug-Resistant Tuberculosis and HIV/AIDS.

BACKGROUND: Novel regimens have revolutionized multidrug-resistant tuberculosis (MDR-TB) treatment; however, medication adherence remains challenging and poorly characterized. We hypothesized that bedaquiline adherence, measured using electronic dose monitoring, would predict MDR-TB treatment outcomes. SETTING: This is a prospective cohort study conducted in KwaZulu-Natal, South Africa. METHODS: Adults with MDR-TB and HIV initiating bedaquiline and on antiretroviral therapy (ART) were eligible. Separate electronic dose monitoring devices measured bedaquiline and ART adherence through 6 months, calculated as observed versus expected doses. Whole-genome sequencing was performed to identify bedaquiline resistance-associated variants. RESULTS: From November 2016 through February 2018, 199 participants with MDR-TB and HIV were enrolled and followed up through treatment completion (median 17.2 months interquartile range 12.2-19.6). The median bedaquiline adherence was higher than ART adherence (97 vs. 89%, P < 0.001) but correlated (r2 = 0.68, P < 0.001). High bedaquiline adherence (≥90%) compared with lower adherence was associated with improved end of treatment successful outcome (83.4% vs. 46.3%, P < 0.001), decreased mortality (11.0% vs. 29.6% P = 0.004), and improved retention in care through end of treatment (94.5% vs. 79.6% P = 0.002). Modeling identified a highly significant but linear association between bedaquiline adherence and outcome. On multivariable analysis, bedaquiline adherence was independently associated with mortality and outcome. Bedaquiline resistance-associated variants were seen in 12% (7/57) of sequenced isolates (7% baseline, 5% emergent) with only 28.6% experiencing successful treatment outcome. CONCLUSIONS: Bedaquiline adherence through 6 months independently predicted end of MDR-TB treatment outcome, but a specific bedaquiline adherence threshold was not identified. Interventions to optimize bedaquiline adherence are urgently needed to improve MDR-TB HIV treatment outcomes.

Prescribing practices for presumptive TB among private general practitioners in South Africa: a cross-sectional, standardised patient study.

INTRODUCTION: Medicine prescribing practices are integral to quality of care for leading infectious diseases such as tuberculosis (TB). We describe prescribing practices in South Africa's private health sector, where an estimated third of people with TB symptoms first seek care. METHODS: Sixteen standardised patients (SPs) presented one of three cases during unannounced visits to private general practitioners (GPs) in Durban and Cape Town: TB symptoms, HIV-positive; TB symptoms, a positive molecular test for TB, HIV-negative; and TB symptoms, history of incomplete TB treatment, HIV-positive. Prescribing practices were recorded in standardised exit interviews and analysed based on their potential to contribute to negative outcomes, including increased healthcare expenditures, antibiotic overuse or misuse, and TB diagnostic delay. Factors associated with antibiotic use were assessed using Poisson regression with a robust variance estimator. RESULTS: Between August 2018 and July 2019, 511 SP visits were completed with 212 GPs. In 88.5% (95% CI 85.2% to 91.1%) of visits, at least one medicine (median 3) was dispensed or prescribed and most (93%) were directly dispensed. Antibiotics, which can contribute to TB diagnostic delay, were the most common medicine (76.5%, 95% CI 71.7% to 80.7% of all visits). A majority (86.1%, 95% CI 82.9% to 88.5%) belonged to the WHO Access group; fluoroquinolones made up 8.8% (95% CI 6.3% to 12.3%). Factors associated with antibiotic use included if the SP was asked to follow-up if symptoms persisted (RR 1.14, 95% CI 1.04 to 1.25) and if the SP presented as HIV-positive (RR 1.11, 95% CI 1.01 to 1.23). An injection was offered in 31.9% (95% CI 27.0% to 37.2%) of visits; 92% were unexplained. Most (61.8%, 95% CI 60.2% to 63.3%) medicines were not listed on the South African Primary Healthcare Essential Medicines List. CONCLUSION: Prescribing practices among private GPs for persons presenting with TB-like symptoms in South Africa raise concern about inappropriate antimicrobial use, private healthcare costs and TB diagnostic delay.

Acceptability, feasibility, and impact of a pilot tuberculosis literacy and treatment counselling intervention: a mixed methods study.

BACKGROUND: There is a need for innovative strategies to improve TB testing uptake and patient retention along the continuum of TB care early-on in treatment without burdening under-resourced health systems. We used a mixed methods approach to develop and pilot test a tuberculosis literacy and counselling intervention at an urban clinic in KwaZulu Natal, South Africa, to improve TB testing uptake and retention in tuberculosis care. METHODS: We engaged in discussions with clinic staff to plan and develop the intervention, which was delivered by senior social work students who received one-week training. The intervention included: 1) group health talks with all patients attending the primary clinic; and 2) individual counselling sessions, using motivational interviewing techniques, with newly diagnosed tuberculosis patients. We compared social work students' tuberculosis knowledge, attitudes, and practices before and after their training. We assessed the change in number of tuberculosis diagnostic tests performed after implementation via an interrupted time series analysis with a quasi-Poisson regression model. We compared pre- and post-intervention probabilities of treatment initiation and completion using regression analyses, adjusting for potential baseline confounders. We conducted focus groups with the students, as well as brief surveys and one-on-one interviews with patients, to assess acceptability, feasibility, and implementation. RESULTS: During the study period, 1226 individuals received tuberculosis diagnostic testing and 163 patients started tuberculosis treatment, of whom 84 (51.5%) received individual counselling. The number of diagnostic tuberculosis tests performed increased by 1.36 (95%CI 1.23-1.58) times post-intervention, adjusting for background calendar trend. Probabilities of TB treatment initiation and treatment completion increased by 10.1% (95%CI 1.5-21.3%) and 4.4% (95%CI -7.3-16.0%), respectively. Patients found the counselling sessions alleviated anxiety and increased treatment self-efficacy. Social work students felt the clinic staff were collaborative and highly supportive of the intervention, and that it improved patient engagement and adherence. CONCLUSIONS: Engaging clinic staff in the development of an intervention ensures buy-in and collaboration. Education and counselling before and early-on in tuberculosis treatment can increase tuberculosis testing and treatment uptake. Training junior social workers can enable task-shifting in under-resourced settings, while addressing important service gaps in tuberculosis care.

Quality of care for tuberculosis and HIV in the private health sector: a cross-sectional, standardised patient study in South Africa.

BACKGROUND: South Africa has high burdens of tuberculosis (TB) and TB-HIV, yet the quality of patient care in the private sector is unknown. We describe quality of TB and TB-HIV care among private general practitioners (GPs) in two South African cities using standardised patients (SPs). METHODS: Sixteen SPs presented one of three cases during unannounced visits to private GPs in selected high-TB burden communities in Durban and Cape Town: case 1, typical TB symptoms, HIV-positive; case 2, TB-specified laboratory report, HIV-negative and case 3, history of incomplete TB treatment, HIV-positive. Clinical practices were recorded in standardised exit interviews. Ideal management was defined as relevant testing or public sector referral for any reason. The difference between knowledge and practice (know-do gap) was assessed through case 1 vignettes among 25% of GPs. Factors associated with ideal management were assessed using bivariate logistic regression. RESULTS: 511 SP visits were completed with 212 GPs. Respectively, TB and HIV were ideally managed in 43% (95% CI 36% to 50%) and 41% (95% CI 34% to 48%) of case 1, 85% (95% CI 78% to 90%) and 61% (95% CI 73% to 86%) of case 2 and 69% (95% CI 61% to 76%) and 80% (95% CI 52% to 68%) of case 3 presentations. HIV status was queried in 35% (95% CI 31% to 39%) of visits, least with case 1 (24%, 95% CI 18% to 30%). The difference between knowledge and practice was 80% versus 43% for TB and 55% versus 37% for HIV, resulting in know-do gaps of 37% (95% CI 19% to 55%) and 18% (95% CI -1% to 38%), respectively. Ideal TB management was associated with longer visit time (OR=1.1, 95% CI 1.1 to 1.2), female GPs (3.2, 95% CI 2.0 to 5.1), basic symptom inquiry (2.0, 95% CI 1.7 to 2.3), HIV-status inquiry (OR=11.2, 95% CI 6.4 to 19.6), fewer medications dispensed (OR=0.6, 95% CI 0.5 to 0.7) and Cape Town (OR=2.2, 95% CI 1.5 to 3.1). Similar associations were observed for HIV. CONCLUSIONS: Private providers ideally managed TB more often when a diagnosis or history of TB was implied or provided. Management of HIV in the context of TB was less than optimal.