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.

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.

Electronic Dose Monitoring Identifies a High-Risk Subpopulation in the Treatment of Drug-resistant Tuberculosis and Human Immunodeficiency Virus.

BACKGROUND: In generalized drug-resistant tuberculosis (DR-TB) human immunodeficiency virus (HIV) epidemics, identifying subpopulations at high risk for treatment failure and loss to care is critically important to improve treatment outcomes and prevent amplification of drug resistance. We hypothesized that an electronic dose-monitoring (EDM) device could empirically identify adherence-challenged patients and that a mixed-methods approach would characterize treatment challenges. METHODS: A prospective study of patients with DR-TB HIV on antiretroviral therapy (ART) initiating bedaquiline-containing regimens in KwaZulu-Natal, South Africa. Separate EDM devices measured adherence for bedaquiline and ART. Patients with low adherence (<85%) to both bedaquiline and ART were identified as high risk for poor outcomes. Baseline survey, study visit notes, and focus group discussions characterized treatment challenges. RESULTS: From December 2016-February 2018, 32 of 198 (16%) enrolled patients with DR-TB HIV were identified as dual-adherence challenged. In a multivariate model including baseline characteristics, only receiving a disability grant was significantly associated with dual nonadherence at 6 months. Mixed-methods identified treatment barriers including alcohol abuse, family conflicts, and mental health issues. Compared with adherent patients, dual-adherence-challenged patients struggled to prioritize treatment and lacked support, and dual-adherence-challenged patients experienced higher rates of detectable HIV viral load and mortality than more adherent patients. CONCLUSIONS: EDM empirically identified a subpopulation of patients with DR-TB HIV with dual-adherence challenges early in treatment. Mixed-methods revealed intense psychosocial, behavioral, and structural barriers to care in this subpopulation. Our data support developing differential, patient-centered, adherence support interventions focused on psychosocial and structural challenges for subpopulations of at-risk DR-TB HIV patients.

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.

Antibiotic prescription practices in primary care in low- and middle-income countries: A systematic review and meta-analysis.

BACKGROUND: The widespread use of antibiotics plays a major role in the development and spread of antimicrobial resistance. However, important knowledge gaps still exist regarding the extent of their use in low- and middle-income countries (LMICs), particularly at the primary care level. We performed a systematic review and meta-analysis of studies conducted in primary care in LMICs to estimate the prevalence of antibiotic prescriptions as well as the proportion of such prescriptions that are inappropriate. METHODS AND FINDINGS: We searched PubMed, Embase, Global Health, and CENTRAL for articles published between 1 January 2010 and 4 April 2019 without language restrictions. We subsequently updated our search on PubMed only to capture publications up to 11 March 2020. Studies conducted in LMICs (defined as per the World Bank criteria) reporting data on medicine use in primary care were included. Three reviewers independently screened citations by title and abstract, whereas the full-text evaluation of all selected records was performed by 2 reviewers, who also conducted data extraction and quality assessment. A modified version of a tool developed by Hoy and colleagues was utilized to evaluate the risk of bias of each included study. Meta-analyses using random-effects models were performed to identify the proportion of patients receiving antibiotics. The WHO Access, Watch, and Reserve (AWaRe) framework was used to classify prescribed antibiotics. We identified 48 studies from 27 LMICs, mostly conducted in the public sector and in urban areas, and predominantly based on medical records abstraction and/or drug prescription audits. The pooled prevalence proportion of antibiotic prescribing was 52% (95% CI: 51%-53%), with a prediction interval of 44%-60%. Individual studies' estimates were consistent across settings. Only 9 studies assessed rationality, and the proportion of inappropriate prescription among patients with various conditions ranged from 8% to 100%. Among 16 studies in 15 countries that reported details on prescribed antibiotics, Access-group antibiotics accounted for more than 60% of the total in 12 countries. The interpretation of pooled estimates is limited by the considerable between-study heterogeneity. Also, most of the available studies suffer from methodological issues and report insufficient details to assess appropriateness of prescription. CONCLUSIONS: Antibiotics are highly prescribed in primary care across LMICs. Although a subset of studies reported a high proportion of inappropriate use, the true extent could not be assessed due to methodological limitations. Yet, our findings highlight the need for urgent action to improve prescription practices, starting from the integration of WHO treatment recommendations and the AWaRe classification into national guidelines. TRIAL REGISTRATION: PROSPERO registration number: CRD42019123269.

Interventions to improve retention-in-care and treatment adherence among patients with drug-resistant tuberculosis: a systematic review.

The global loss to follow-up (LTFU) rate among drug-resistant tuberculosis (DR-TB) patients remains high at 15%. We conducted a systematic review to explore interventions to reduce LTFU during DR-TB treatment.We searched for studies published between January 2000 and December 2017 that provided any form of psychosocial or material support for patients with DR-TB. We estimated point estimates and 95% confidence intervals of the proportion LTFU. We performed subgroup analyses and pooled estimates using an exact binomial likelihood approach.We included 35 DR-TB cohorts from 25 studies, with a pooled proportion LTFU of 17 (12-23)%. Cohorts that received any form of psychosocial or material support had lower LTFU rates than those that received standard care. Psychosocial support throughout treatment, via counselling sessions or home visits, was associated with lower LTFU rates compared to when support was provided through a limited number of visits or not at all.Our review suggests that psychosocial support should be provided throughout DR-TB treatment in order to reduce treatment LTFU. Future studies should explore the potential of providing self-administered therapy complemented with psychosocial support during the continuation phase.

A Qualitative Evaluation of the Acceptability of an Interactive Voice Response System to Enhance Adherence to Isoniazid Preventive Therapy Among People Living with HIV in Ethiopia.

Interactive voice response (IVR) is increasingly used to monitor and promote medication adherence. In 2014, we evaluated patient acceptability toward IVR as part of the ENRICH Study, aimed to enhance adherence to isoniazid preventive therapy for tuberculosis prevention among HIV-positive adults in Ethiopia. Qualitative interviews were completed with 30 participants exposed to 2867 IVR calls, of which 24 % were completely answered. Individualized IVR options, treatment education, and time and cost savings facilitated IVR utilization, whereas poor IVR instruction, network and power malfunctions, one-way communication with providers, and delayed clinic follow-up inhibited utilization. IVR acceptability was complicated by HIV confidentiality, mobile phone access and literacy, and patient-provider trust. Incomplete calls likely reminded patients to take medication but were less likely to capture adherence or side effect data. Simple, automated systems that deliver health messages and triage clinic visits appear to be acceptable in this resource-limited setting.

A scoping review and thematic analysis of social and behavioural research among HIV-serodiscordant couples in high-income settings.

BACKGROUND: While HIV incidence has stabilized in many settings, increases in health and wellbeing among many people living with HIV/AIDS suggest that the number of HIV-serodiscordant relationships is growing. Given the deficit of reviews addressing social and behavioural characteristics of HIV-serodiscordant couples within high-income settings, our objective was to understand the scope of the published literature, identify evidence gaps, and suggest future research needs. METHODS: Ten electronic databases were searched. Studies were included if they were reported in English, used primary data, were from the combination antiretroviral (cART) era (>1996), reported on social or behavioural aspects, included any fraction of primary (i.e., stable) relationships, and were conducted in high-income settings. Studies that identified their unit of analysis as either the dyad or individual member of the couple were included. Studies were coded according to a thematic framework. RESULTS: Included studies (n = 154) clustered into eight themes: risk behaviours (29%), risk management (26%), reproductive issues (12%), relationship quality (9%), serostatus disclosure (7%), adherence to antiretroviral therapy (7%), vulnerability (5%), and social support (3%). The proportion of studies conducted among heterosexual couples, same-sex male couples, and mixed cohorts were 42%, 34%, and 24%, respectively. Most studies (70%) were conducted in the United States, 70% of all studies were quantitative (including interventions), but only one-third were focused on couples (dyads) where both partners are recruited to a study. Over 25% of studies focused on sexual risk among same-sex male couples. CONCLUSIONS: Future research efforts should focus on the interrelationship of risk management strategies and relationship quality, social determinants of health and wellbeing, HIV testing, vulnerable populations, reproductive issues among same-sex couples, disclosure of serodiscordant status to social networks, dyadic studies, population-based studies, and interventions to support risk management within couples. Additional population-based studies and studies among marginalized groups would be helpful for targeting research and interventions to couples that are most in need. As HIV-positive partners are typically the link to services and research, innovative ways are needed for reaching out to HIV-negative partners. Our review suggests that significantly more research is needed to understand the social and behavioural contexts of HIV-serodiscordant relationships.

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.

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.

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.

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.

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.

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.

Social constraints to TB/HIV healthcare: accounts from coinfected patients in South Africa.

There is a growing imperative to improve the coordination and collaboration of tuberculosis (TB) and HIV healthcare services in response to escalating rates of TB/HIV coinfection. Patient-specific challenges associated with the delivery of TB/HIV care have been minimally explored in this regard. As part of a larger study conducted in South Africa, this article highlights coinfected patients' experiences with TB and HIV healthcare in light of their broader social environments. Qualitative, in-depth interviews were conducted with 40 adult, coinfected patients (24 women and 16 men) and eight key-informant healthcare workers at three urban/peri-urban, ambulatory, public health clinics in the high-burden province of KwaZulu-Natal. Transcribed interviews were analyzed under a modified grounded theory approach to capture subjective meanings of healthcare experience subsequent to patients' codiagnosis with TB and HIV. Emerging analytic themes highlighted critical sociomedical constraints to TB/HIV care in relation to patients' income and employment, eligibility for social assistance and antiretroviral treatment, fears around illness disclosure, social and material support, and treatment adherence. Patients' healthcare experiences were bound by their poor access to essential resources, multiple life responsibilities, disparate gender roles, limits within the healthcare system, and the stigmatizing social symbolism of their illness. Overlapping social inequalities perpetuated coinfected patients' experiences with stigma and collectively mediated their health decisions around disclosure, adherence, and retention in medical care. The study urges a contextualized understanding of the social challenges associated with TB/HIV healthcare and helps inform more patient-sensitive and socially responsive interventions against the co-epidemic.