https://orcid.org/0000-0003-2275-3540
Figures
Abstract
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.
Citation: Salomon A, Law S, Johnson C, Baddeley A, Rangaraj A, Singh S, et al. (2022) Interventions to improve linkage along the HIV-tuberculosis care cascades in low- and middle-income countries: A systematic review and meta-analysis. PLoS ONE 17(5): e0267511. https://doi.org/10.1371/journal.pone.0267511
Editor: Gabriel O. Dida, The Technical University of Kenya, KENYA
Received: December 22, 2021; Accepted: April 9, 2022; Published: May 12, 2022
Copyright: © 2022 Salomon et al. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.
Data Availability: All relevant data are within the manuscript and its Supporting Information files.
Funding: This study was funded by United States Agency for International Development through the World Health Organization. The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.
Competing interests: We have read the journal’s policy and the authors of this manuscript have the following competing interests: AD is a member of the Editorial Board of PLOS ONE. This does not alter our adherence to PLOS ONE policies on sharing data and materials. The remaining authors have declared that no competing interests exist. The opinions expressed in the manuscript are those of the authors alone. They do not purport to reflect the opinions or views of the World Health Organization, or The Global Fund to Fight AIDS, Tuberculosis and Malaria, or its members.
Introduction
HIV and tuberculosis (TB) are inextricably linked [1]. TB is the leading opportunistic infection among people living with HIV (PLHIV), responsible for approximately 30% of all AIDS-related deaths. HIV, through weakening of the immune system, is the leading risk factor for development of TB disease in people with TB infection, and contributes to 15% of TB-related deaths [2]. The World Health Organization (WHO) recommends offering routine HIV testing to all patients with presumptive and diagnosed TB, routine TB screening for TB symptoms of all PLHIV, and starting all patients with TB and HIV on both anti-retroviral therapy and anti-TB treatment (ATT) [3,4]. These strategies have helped to reduce morbidity and mortality from HIV-associated TB, saving an estimated 7.3 million lives since 2005.2, 3 Nevertheless, significant gaps remain in the TB-HIV care cascade particularly the detection of co-morbidity, and subsequent linkage to treatment. In 2019, 31% of people with TB remained unaware of their HIV status; fewer than half of those estimated to have HIV coinfection received ART. Among PLHIV, an estimated 44% of TB remained undetected and, therefore, untreated [2,5]. Resource-limited settings that face dual burdens of disease continue to report the worst outcomes in TB-HIV [2,5].
Gaps in linkage between the HIV and TB care cascades may be partly explained by the inadequate adoption and implementation of global recommendations within country programs, slow scale-up of new technologies, particularly rapid TB diagnostics, and disparate funding, monitoring and evaluation systems for HIV and TB [5]. Programmatic guidance for the integration of TB and HIV services such as successful models and implementation considerations is also limited. Published reviews have focused on the effect of specific interventions such as patient food support, workplace programs, and private-public partnerships, and focused on prevention of TB disease in PLHIV, and adherence to ART and/or ATT in those receiving dual treatment [6–11]. This systematic review uniquely assesses the full spectrum of non-clinical interventions targeted to patients, providers and programs in low- and middle-income countries (LMICs), and focusses on two critical underexplored outcomes in the TB-HIV care cascade–testing and diagnosis of TB or HIV co-morbidity in people with one known infection, and subsequent linkage to its treatment. Our overarching goal was to inform the WHO 2020 HIV Service Delivery Guidelines update.
Methods
This multi-method systematic review and meta-analysis adhered to PRISMA (Preferred Reporting Items for Systematic Reviews and Meta-Analyses) [12] and SWiM (Synthesis Without Meta-Analysis) [13] reporting guidelines (S1 File: PRISMA Checklist). The review protocol is registered with the International Prospective Register of Systematic Reviews (PROSPERO; Reg# CRD42018109629 –S2 File: Systematic review protocol). This review did not require ethics review.
Research questions
The systematic review focused on two questions:
- In patients with TB disease in LMICs, what interventions improve HIV testing and linkage to ART (PICO 1).
- In people living with HIV in LMICs, what interventions improve TB case-detection and linkage to ATT (PICO 2).
Search strategy and selection criteria
With the assistance of medical librarians, we searched three electronic databases (Medline (OVID), Embase, Embase Classic) for peer-reviewed articles and conference abstracts published between 1 Jan 2003 and 9 July 2021, three conference abstract databases (International AIDS Society, Conference on Retroviruses and Opportunistic Infections, and Union World Conference on Lung Health) in 2017 and 2018, and reference lists from included studies. The search strategy used the following key terms and their appropriate synonyms: 1) tuberculosis, AND 2) human immunodeficiency virus (HIV), AND 3) diagnosis or detection or screening or testing, or referral or linkage or coordination or integration, or treatment initiation, AND 4) low and middle-income countries. The full search strategy can be found in S3 File: Search Strategy.
We included primary observational, quasi-experimental and experimental (randomized controlled) studies that: 1) examined the effect of a patient-, provider-, or health system-level intervention; 2) implemented the intervention in people known to have HIV, TB disease, or both; 3) reported on one or more of our primary outcomes (Table 1); 4) had at least two study arms (e.g. a control and intervention arm); and 5) was conducted in an LMIC (GNI per capita <12,695 USD per year, as defined by the World Bank) [14]. Secondary outcomes included mortality rate, time to ART initiation, and time to ATT initiation. We excluded studies examining surgical, biomedical, or diagnostic tools/algorithms; secondary analyses/reviews, commentaries, editorials, case reports (<10 participants) and qualitative studies; non-English studies; and studies with interventions implemented at a “population-level” (i.e., not explicitly among PLHIV or active TB), such as mass/community HIV testing or TB screening and testing campaigns. We did not apply age or other demographic restrictions.
Data extraction and analysis
Two reviewers (AS, SL) screened all titles and abstracts, followed by full reports of potentially relevant studies; discrepancies were resolved with a third reviewer (AD or VS). Two reviewers (AS, SL) extracted the following data into MS Excel (Microsoft Corporation, Redmond, Washington): primary and secondary outcomes, setting, participant characteristics, standard of care, study interventions, funding sources, and indicators of quality. Authors were systematically contacted for further information when necessary. For included studies, three reviewers (AS, SL, AD) determined primary and secondary outcomes that were potentially affected by the study intervention (i.e., occurred downstream of, and plausibly linked to, the intervention), and estimated unadjusted risk ratios (RRs) and 95% confidence intervals accordingly. Where reported, we used adjusted risk ratios (aRRs) or adjusted hazard ratios (aHRs). We used forest plots to display all effect estimates, including pooled estimates where appropriate, according to the four primary outcomes, and estimated statistical heterogeneity (I2). All statistical analyses were performed using STATA 15.1 (StataCorp, College Station, Texas).
We performed random-effects meta-analyses (DerSimonian and Laird method) for studies implementing interventions that could be pooled (co-location interventions only). For remaining studies which had a high-level of heterogeneity (based on intervention/s, study setting, and populations), we performed a narrative synthesis of the intervention impact. Here, a “narrative synthesis” refers to “an approach to the systematic review and synthesis of findings from multiple studies that relies primarily on the use of words and text to summarise and explain the findings of the synthesis” [15]. Interventions that involved co-location and a second intervention (such as patient education or dedicated personnel) were classified as co-location interventions only. Interventions that involved more than one non-co-location intervention (such as patient education and dedicated personnel) were classified as both. Interventions involving current WHO standard of care strategies, including task-shifting services from specialized to less specialized workers, systematic HIV testing using provider-initiated, opt-out approaches, systematic TB screening and/or testing using standardized tools, health care worker training in TB-HIV care, as well as facility-specific operational improvements [4,16–18] were excluded from analysis, though we note their inclusion in intervention and/or comparator arms. We also performed a narrative synthesis of implementation facilitators and barriers based on the primary outcome(s) affected by interventions, and cost and resource considerations [13].
Quality assessment
Two reviewers (AS, SL) assessed quality of all included studies using the Risk of Bias in Non-randomized Studies of Interventions (ROBINS-I) [19] tool for non-randomized and non-comparative studies, and the Cochrane Risk-of-Bias tool for randomized trials (cluster or individual) [20] (S4 File: Quality Assessments); we did not exclude studies based on quality. We also developed GRADE evidence profiles for all interventions, pooled and non-pooled [21] (S5 File: Grade Evidence Profiles).
Results
Overview
The search strategy identified 21,516 unique studies; 23 studies were eligible, contributing 53 study arms (23 standard of care and 30 intervention) and 84,884 participants (Fig 1). Studies were implemented in LMICs in four WHO regions: Africa (n = 17), South-East Asia (n = 2), Europe (n = 2), and the Americas (n = 2). One study from Peru [22] was implemented in a community setting; remaining studies were in primary health facilities (i.e., hospitals, clinics). Eight studies were limited to adolescents and adults (≥ 12 years), one excluded infants ≤18 months, and three excluded prisoners; others had no demographic-based exclusions. No studies disaggregated results by age or other demographics. Primary outcomes were reported with the following frequencies (Table 2): 1) HIV testing = 7 studies; 2) ART initiation = 16 studies; 3) TB case-detection = 5 studies; and 4) ATT initiation = 2 studies. Six studies reported on more than one outcome. Six studies reported on secondary outcomes (S6 File: Secondary Outcomes). Two studies were randomized controlled trials (RCTs) [23,24]; others were observational.
PRISMA = Preferred Reporting Items for Systematic Reviews and Meta-Analyses.
We analyzed five categories of interventions (Table 3) across 23 studies, including: 1) Co-location (n = 13) of screening, testing and/or treatment services for TB and HIV, at the same facility and/or by the same provider; 2) Patient education and counselling (n = 6) on TB-HIV coinfection; 3) Dedicated personnel (n = 4) to support TB-HIV service delivery; 4) Patient peer support (n = 2) to support TB-HIV service delivery; and 5) Patient financial support (n = 1) (S7 File: Interventions identified in control and intervention arms).
Three studies implemented a single intervention [26,30,38]. Three studies had two distinct interventions [22,36,42]. Eighteen studies implemented a standard of care (SOC) strategy alongside an analyzable intervention [23–25,27–29,31–37,39–41,43,44] (Table 4); effect of the SOC strategy was not analyzed but its concurrent implementation was considered in GRADE certainty assessments.
Co-location
For PICO 1, we identified eight combinations of co-location, ranging from only co-locating HIV testing with TB services at the same facility, to co-located testing and treatment of HIV and TB at the same facility and by the same provider (Fig 2). In all eight studies reporting on HIV testing, test rates improved when co-located with TB services, regardless of whether it was at the same facility or by the same provider, and there was no apparent difference between the two models of increasing co-location. Likewise, ART initiation improved with almost all combinations of co-location, except for two studies where testing was co-located at the same facility and treatment delivered by the same provider [33,40], and one study where testing alone was delivered by the same provider [28]. In two of these three studies, negative or null effects on ART initiation rates were attributed to clinics’ inability to absorb increased numbers of PLHIV identified through the co-located model [28,33]. There was no strong evidence to suggest that a single model of co-location out-performed others in improving outcomes in PICO 1.
For PICO 2, we identified one combination of co-location in a single study where TB screening and testing was co-located with HIV services [25] (Fig 3). This model improved TB case-detection, identifying an approximate additional 59 cases per 1,000 (RR 1.56, 95% 1.08–2.25). ATT initiation did not improve; the baseline rate was already 100%.
ATT = Anti-tuberculosis Treatment.
Five studies described needs and considerations pertinent to the success of co-location interventions [28,33,35,37,40]. They include dedicated counselling spaces, infection control measures (e.g., ventilation, UV lighting, outdoor clinics and sputum booths, personal protective equipment, and infection control officers), improved filing, records and communication, synchronized appointments including pharmacy services, and personnel for allied patient support such as nutrition, outreach, tracing and social/adherence support.
Patient education and counselling
Patient education and counselling interventions covered a range of topics. For PICO 1, one study reported on HIV testing and two other studies on ART initiation; all demonstrated significant improvements (Fig 4). Psychosocial counselling about depression and substance use, among other topics, to households affected by HIV (and TB) improved HIV test rates in a community-based study in Peru (RR 3.17, 95% CI 2.24–4.49) [22]. Educating and counselling about TB-HIV and ART improved ART initiation among TB patients at a hospital in Russia (RR 3.22, 95%CI 1.92–5.41) [39] and at clinics in South Africa (RR 1.10, 95% CI 1.07–1.14) [36]. Three studies implemented co-interventions (i.e., financial support and peer supporters or other dedicated personnel to deliver the educational component) [22,36,42]. Remaining studies implemented facility-specific operational improvements as well (e.g., supplemental data collection forms, expedited ART initiation for TB patients diagnosed with HIV) [39,43,44].
*All studies implemented concurrent interventions and/or SOC strategies. Only the first author of each study is listed. ATT = Anti-tuberculosis treatment.
Patient education interventions were more heterogenous in studies examining PICO 2, ranging from group presentations to one-on-one education sessions delivered by diverse personnel including peer supporters, counsellors and nurses (Fig 4). All studies implemented co-interventions. TB case-detection improved in only one study in Cambodia where newly diagnosed PLHIV were educated about the increased risk of TB by HIV counsellors using a scripted message (RR = 1.53, 95% 1.18–1.98); health care worker training and facility-specific operational improvements were part of the intervention package [43]. In two other studies implemented at HIV clinics, one in Uganda where group presentations about TB were delivered by peer supporters [42], and one in Botswana where nurses educated patients on sputum induction techniques [44], TB case-detection did not improve. ATT initiation also did not improve in the one study reporting on this outcome; the baseline rate was high (94%) [42].
Dedicated personnel
Dedicated personnel were introduced to support a variety of TB-HIV services. For PICO 1, having a dedicated HIV testing services counsellor systematically test all TB patients significantly improved the HIV test rate in a study in Nigeria (RR 2.73, 95% CI 2.33–3.22); importantly, systematic HIV testing for TB patients was absent at baseline [27]. Dedicated personnel did not however appear to have a strong effect on ART initiation in this and two other studies from South Africa, one utilizing professional nurses to support facility-level operations [24] and one utilizing adherence counsellors and lay workers to deliver patient education and counselling [36] (Fig 5). One possible reason for the lack of demonstrable effect on ART initiation with dedicated personnel may be a result of their involvement on earlier parts of the care cascade (i.e., conducting screening or testing, and not involved in linkage to treatment). These studies also implemented co-interventions, including co-location of TB and HIV services [24,27] and patient education and counselling [36].
*All studies implemented concurrent interventions and/or SOC strategies. Only the first author of each study is listed.
For PICO 2, addition of dedicated nurses to support TB screening and testing improved TB case-detection in two arms of the same intervention at an HIV clinic in Botswana; however, this intervention also newly introduced systematic TB screening which was not present at baseline. [23] (Fig 5). No studies examined the effect of dedicated personnel on ATT initiation.
Two studies described considerations pertinent to the success of such interventions [28,36]. One study reported that provision of a transport allowance enabled personnel to attend the clinic [28], and another study recommended adopting a task-sharing approach to decongest clinics and facilitate an overall decreased consumption of clinic resources [36].
Patient peer support
Patient peers were introduced to support services related to TB-HIV care. For PICO 1, only one study, from Tanzania, examined the effect of patient peer support on ART initiation and did not have an apparent effect. The rate of ART initiation was high at baseline (94.4%) [31] (Fig 6).
*All studies implemented concurrent interventions and/or SOC strategies. Only the first author of each study is listed. ATT = Anti-tuberculosis treatment.
Likewise, for PICO 2, only one study from Uganda examined the effect of patient peer support on both TB case-detection and ATT initiation, with no apparent effect on either outcome [42] (Fig 6). Here, peer supporters gave group presentations about TB in HIV clinic waiting areas, encouraging patients to self-report TB symptoms. Authors believed this was ineffective due to stigma attached to self-identifying TB symptoms, language barriers, and potentially sub-optimal screening by peer supporters. The intervention was not designed to focus on ATT initiation, as peer support was delivered during an early part of the care cascade, during TB testing but before diagnosis. The baseline ATT initiation rate was also high (94.7%) [42].
Studies implementing peer support deemed the skills, fluency in local languages, and enthusiasm of peers to be key considerations [23,42,43].
Patient financial support
For PICO 1, only one study examined the effect of patient financial support and demonstrated improved rates of HIV testing (RR = 3.17, 95% 2.24–4.49) [22] (Fig 7). Here, TB-affected households in Peru received food/cash transfers, vocational training, and microfinance strategies, in addition to psychosocial counselling. No studies examined the effect of patient financial support on PICO 2.
*All studies implemented concurrent interventions and/or SOC strategies. Only the first author of each study is listed. ATT = Anti-tuberculosis treatment.
General considerations for implementing TB-HIV interventions
Several studies described implementation considerations for specific types of interventions. Fourteen studies described general considerations for interventions seeking to link patients to TB and HIV services, which centered on facilities’ and programs’ capacity to absorb increases in new TB and/or HIV diagnoses (laboratory capacity and supply chain management for tests and treatment [25,26,30,32,37,42,44]), data management (creation of single patient files and data sharing between TB and HIV programs [25,26,31,43]), human resources (health care worker burden, turnover and shortage [23,24,32,37,40,42]), health care worker competencies and perceptions (TB and/or HIV risk misperceptions, reluctance to manage TB and HIV, difficulties diagnosing TB in PLHIV or managing complications such as IRIS, and negative attitudes towards patients [25,32,37,40,43]); and patient perceptions (risk misperceptions, TB and/or HIV stigma, concerns about treatment side effects and clinic commutes to access treatment [25,42,43]). For a summary of all implementation barriers and facilitators by outcome, including cost analyses, see S8 File: Implementation Considerations.
Discussion
This systematic review is the first instance of presenting the full spectrum of interventions seeking to improve identification of HIV or TB disease among people with one known infection, and initiation of co-treatment in people with both. We identified a several interventions supporting these points of linkage to the TB-HIV care cascades, which build upon the findings of other reviews that have focused on other points of linkage such as TB prevention in PLHIV or retention in HIV or TB care [6–11]. The results were presented to the WHO Service Delivery guidelines meeting in October 2020 to inform the 2021 Updated Recommendations on Service Delivery for Treatment and Care of People Living with HIV [45].
The most noteworthy findings of the review centered on the consistent effectiveness of co-located HIV and TB services in improving rates of HIV testing and ART initiation among people with TB, and likewise improving TB case-detection among PLHIV. This validates prior recommendations to link patients to integrated TB-HIV care by providing services at the same time and location [4]. Several studies reported on the time saved and coordination gained from attending to both infections within a single facility as compared to referring patients to another site [29,34,38]. Nonetheless, in 2019, of the 30 high burden TB-HIV countries only 11 had reported having countrywide co-location of HIV and TB testing, and only five countries reported delivering ART and ATT within the same facility [5]. The studies described herein offer blueprints to guide the future operationalization of co-location interventions and help fill these gaps.
Also of note, several studies suggested that providing HIV and TB services at not only the same facility but also by the same provider could help to reduce patient “juggling” and losses to follow-up seen when services were delivered by different providers or clinics within a single facility [40]; typically, due to perceived patient stigmas [25,32,42] or the poor integration of medical information systems [37]. However, heightening the degree of integration to the level of the same provider (or same set of providers) did not have a consistently greater effect on HIV testing or ART initiation when compared to facility-level integration.
Overall, most interventions reviewed were multi-component and included facility-specific operational improvements as well as strategies that are today considered to be standard of care. Nonetheless, when implemented as part of a broader intervention package, the introduction of dedicated personnel to support delivery of TB-HIV services improved HIV testing in people with TB and TB case-detection rates in PLHIV. Similarly, patient education and counselling about TB-HIV coinfection and financial support improved HIV testing and ART initiation in people with TB [22,32,36]. The effect on TB case-detection in PLHIV was mixed but rates of TB testing universally improved in studies implementing patient education and counselling as well as peer support interventions, pointing to critical achievements in the provision and uptake of TB test services [42–44].
Technical or resource barriers reported within reviewed studies, may have contributed to the observed lack of effect or consistent effect of interventions that held promise. Many of these barriers have been previously described [5,46–50], and point to a need for wider health systems strengthening to build human resource competencies, and programmatic foresight to allocate resources to accommodate potential increases in patient volume. Concurrent efforts are also needed to correct prevailing misperceptions and gaps in knowledge around TB-HIV risk, dual diagnosis, and co-treatment. Such investments will likely support continuity of care for patients with complex multiple conditions in the face of disruptions to HIV and TB programs such as those experienced during the COVID-19 pandemic [51,52].
This review also highlighted gaps in innovation with respect to the published literature. For example, we found relatively few studies (5/23) seeking to improve TB testing and treatment among PLHIV, and no studies implemented in settings with low baseline rates of TB treatment initiation. Community-based interventions, where the most vulnerable populations may be more easily reached, and that have been shown to improve TB screening and testing [53] as well as HIV testing [54] in the general population, were scarce. Other novel intervention designs that have improved outcomes in HIV or TB, such as differentiated service delivery and m-Health or virtual interventions [55–58], were also not identified. Programs may consider adapting successful models to better link people with HIV and TB disease to integrated care. Not surprisingly, given the difficulties of designing RCTs around various models of integrated TB-HIV care, most evidence was sourced from observational studies.
The review has several limitations. First, only interventions implemented among participants with known HIV or TB disease were included. Studies were thus largely facility based. Studies assessing linkages between HIV and TB services from community to facility among people not yet diagnosed with either infection, or studies which sought to integrate TB screening and HIV testing for the broader population were also excluded, though they have reported improved identification of PLHIV and TB disease [59–61]. Second, interventions and standards of care were highly heterogenous with much overlap, particularly co-location and provider-initiated HIV testing. To mitigate this limitation, we only pooled results for co-location interventions (by level of co-location), which we deemed methodologically homogenous; for the remaining interventions of interest, we narratively described and compared interventions and their effects. Studies also spanned wide timelines, before and after important policy changes were instituted, such as opt-out HIV testing in 2007 [17] and ART initiation for all people with TB regardless of CD4 count in 2016 [18] amidst diverse country and population contexts. Third, few studies reported on intervention cost or feasibility, and thus successes may be limited to relatively better resourced environments within LMICs. Finally, we included studies indexed in only two databases (Medline and EMBASE), and only in English, therefore potentially limiting the thoroughness of our results.
Conclusion
In supporting the latest WHO recommendations on HIV service delivery, this review emphasizes the effectiveness of co-locating HIV and TB testing and treatment services to improve outcomes in HIV testing, ART initiation and TB case-detection in people with HIV and TB disease. Various models of HIV and TB test and treatment service co-location are exemplified in the studies reviewed that offer critical insights into implementation facilitators and barriers. The evidence further suggests that provision of joint services at the same facility, even if delivered by distinct sets of providers, may be sufficient to achieve improvements in early TB-HIV outcomes. Other patient-centered interventions such as financial or peer support and allocating dedicated personnel for TB-HIV service delivery show promise. Future implementation research would benefit from evaluating the distinct effectiveness of these patient-centered interventions, and of adapting community-based approaches, virtual approaches, and differentiated service delivery models to address patient and health system needs in the context of TB-HIV co-morbidity.
Supporting information
S2 File. Systematic Review Protocol (PROSPERO).
https://doi.org/10.1371/journal.pone.0267511.s002
(PDF)
S7 File. Interventions identified in control and intervention arms.
https://doi.org/10.1371/journal.pone.0267511.s007
(DOCX)
Acknowledgments
We thank McGill University librarians Genevieve Gore and Martin Morris for assisting with our search strategy, and authors of primary papers contacted in the process of our review.
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