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Ambivalent experiences of people in treatment for tuberculosis-HIV coinfection: a meta-synthesis of qualitative studies

Vivências ambivalentes das pessoas em tratamento da coinfecção tuberculose-HIV: uma metassíntese de estudos qualitativos

Lucas Vinícius de Lima (https://orcid.org/0000-0002-9582-9641) – Lima, L. V. – lvl.vinicius@gmail.com – Programa de Pós-Graduação em Enfermagem, Universidade Estadual de Maringá, Maringá, Brasil. Av. Colombo, 5.790 – Bloco 02, Zona 7, 87020-900.
Gabriel Pavinati (https://orcid.org/0000-0002-0289-8219) – Pavinati, G. – gabrielpavinati00@gmail.com – Programa de Pós-Graduação em Enfermagem, Universidade Estadual de Maringá, Maringá, Brasil.
Anne Jaquelyne Roque Barrêto (https://orcid.org/0000-0002-6852-8480) – Barrêto, A. J. R. – anne.jaquelyne@academico.ufpb.br – Programa de Pós-Graduação em Enfermagem, Universidade Federal da Paraíba, João Pessoa, Brasil.
Maria Aparecida Salci (https://orcid.org/0000-0002-6386-1962) – Salci, M. A. – masalci@uem.br – Programa de Pós-Graduação em Enfermagem, Universidade Estadual de Maringá, Maringá, Brasil.
Mayckel da Silva Barreto (https://orcid.org/0000-0003-2290-8418) – Barreto, M. S. – msbarreto@uem.br – Programa de Pós-Graduação em Enfermagem, Universidade Estadual de Maringá, Maringá, Brasil.
Gabriela Tavares Magnabosco (https://orcid.org/0000-0003-3318-6748) – Magnabosco, G. T. – gtmagnabosco@uem.br – Programa de Pós-Graduação em Enfermagem, Universidade Estadual de Maringá, Maringá, Brasil.
 
Abstract
This study examined the scientific literature, by means of a systematic review with meta-synthesis (PROPSPERO No. CRD42023410141), to discover the experiences of people undergoing treatment for tuberculosis-HIV coinfection. Ten databases and reference lists were searched for original articles with qualitative data, published in Portuguese, English and/or Spanish up to 2022. The 11 studies included yielded a meta-theme comprising four themes: (i) tuberculosis-HIV coinfection diagnosis and treatment have impact on the life of the affected person; (ii) personal, social and economic vulnerabilities overlap in people with tuberculosis-HIV coinfection; (iii) medication burden and programmatic weaknesses hinder the treatment of tuberculosis-HIV coinfection; and (iv) support networks and care flows facilitate treatment of tuberculosis-HIV coinfection. Due to the diagnosis, people with tuberculosis-HIV coinfection raise biopsychosocial needs which, associated with weaknesses in health services and practitioners, adversely affect their quality of life and treatment adherence. However, social, family and health care support were revealed to be important to stimulating (self-)care and providing appropriate treatment.
Keywords: HIV; Tuberculosis; Coinfection; Systematic review; Qualitative research.

Resumo
Este estudo objetivou apreender, na literatura científica, as vivências das pessoas em tratamento da coinfecção tuberculose-HIV, a partir de uma revisão sistemática com metassíntese (PROSPERO n.º CRD42023410141). Foram buscados artigos originais com dados qualitativos, publicados em português, inglês e/ou espanhol até 2022, em dez bases de dados e nas listas de referências. Os 11 estudos incluídos geraram um meta-tema, composto por quatro temas: (i) o diagnóstico e o tratamento da coinfecção tuberculose-HIV impactam a vida da pessoa acometida; (ii) a sobreposição de vulnerabilidades pessoais, sociais e econômicas em pessoas com coinfecção tuberculose-HIV; (iii) a carga medicamentosa e as debilidades programáticas prejudicam o tratamento da coinfecção tuberculose-HIV; e (iv) as redes de apoio e os fluxos de cuidado amparam o tratamento da coinfecção tuberculose-HIV. As pessoas com coinfecção tuberculose-HIV apresentam necessidades biopsicossociais devido ao diagnóstico, as quais, associadas a fragilidades dos serviços e profissionais da saúde, influenciam negativamente na qualidade de vida e na adesão. No entanto, desvelou-se a importância do suporte social, familiar e de saúde para estimular o (auto)cuidado e proporcionar o adequado tratamento.
Palavras-chave: HIV; Tuberculose; Coinfecção; Revisão sistemática; Pesquisa qualitativa.

Introduction
Tuberculosis (TB) and human immunodeficiency virus (HIV) have persisted as challenging infections with impact on health systems, especially from the interaction between progression of the two infections1-3. Persons with HIV are around 20 times more likely to contract TB than those without the virus1,2. Also, persons with HIV commonly display unsuccessful TB treatment outcomes, including death, failure and loss to follow-up4-6.
A global collaborative movement is underway to end the TB and HIV epidemics by 2030, as stated in the third goal of the United Nations (UN) Sustainable Development Goals (SDGs)7. In that connection, substantial progress has undeniably been made in early detection by means of concomitant testing for the infections and early treatment, as antiretroviral therapy (ART) has become available for use in combination with the TB therapy regimen1,3,8.
In Brazil, between 2010 and 2021, 122,211 new cases of TB-HIV coinfection were reported in the population from 18 to 59 years of age; incidence trended downward by −4.3% per year in that period (95% confidence interval [95%CI] −5.1 to −3.7)9. Nonetheless, these infections occurring concomitantly affect Brazil disproportionately nationwide, because of the existence of high-occurrence clusters, particularly in larger urban municipalities, such as state capitals, and in areas where HIV prevalence and/or TB incidence are high10.
Note that people suffering from TB-HIV coinfection face economic, socio-cultural and behavioural barriers to effective treatment, particularly in countries with limited resources for controlling and combating these infections11,12. These obstacles result from factors relating to low levels of literacy, increasing poverty, gender inequalities, food insecurity or malnutrition, infection-related social stigmas, and poor access to and bonding with health care services11.
It must be stressed that treatment for TB-HIV coinfection entails adhering to both therapies: to HIV therapy, which is uninterrupted, and to TB therapy, which lasts at least six months in typical cases13. Although treatment for HIV and TB is complex, adherence is a prime determinant of successful TB-HIV coinfection outcomes and minimises the emergence of drug resistance, relapse and/or progression of the infections, and even death associated with these conditions14.
Person-centred care has played a prominent role in TB treatment15. It has been pointed out that, in understanding the factors in play in this follow-up—as addressed by quantitative studies4-6—it is particularly important to bear in mind that, although the biological effects are similar, the experience of treatment is individual and, accordingly, should be supported by specific strategies16,17. In that light, a compilation of the qualitative literature may be useful in enabling care to contemplate these singularities16.
As a preliminary to the study and as recommended18, a search for systematic reviews was conducted in the following databases: Joanna Briggs Institute (JBI) Evidence Synthesis, Medical Literature Analysis and Retrieval System Online, Cochrane, Database of Abstracts of Reviews of Effects and International Prospective Register of Systematic Reviews (PROSPERO), using the strategy: (“systematic review”) AND (tuberculosis OR coinfection OR “AIDS-related opportunistic infections”) AND (HIV OR “acquired immunodeficiency syndrome”).
The 2,324 publications retrieved in February 2023 were examined and, as none was a review with meta-synthesis, it was realised that to map and compile the qualitative evidence would be unprecedented. Accordingly, the aim here was to review the scientific literature to learn the experience of persons undergoing treatment for TB-HIV coinfection, given that understanding that phenomenon would assist in formulating and/or re-formulating specific, individual health care plans to foster better quality of life for this population.

Methods
Study design
This systematic review with meta-synthesis was designed to assemble qualitative discoveries and to produce recommendations to guide public policymaking. This study was conducted to JBI criteria and reported as recommended by the Preferred Reporting Items for Systematic Review and Meta-Analysis (PRISMA) checklist18,19. The protocol was registered with PROSPERO (CRD42023410141) and the dataset with supplementary material was deposited in Mendeley Data20.
Systematic reviews seek to provide a comprehensive, impartial synthesis of important studies, using rigorous, transparent search and selection methods, then to map and compile knowledge by way of the following stages18: (i) formulating the research question; (ii) specifying inclusion and exclusion criteria; (iii) locating studies; (iv) selecting studies; (v) appraising the studies’ quality; (vi) extracting data; (vii) analysing and synthesising studies; and (viii) presenting and interpreting the results.
Formulating the research question
The research question was structured by employing the mnemonic PICo: population (P), phenomenon of interest (I) and context (Co)18. In this case, P was specified as the adult population (persons aged 18 or more years old); I as experiences in the course of treatment for TB; and Co as the singularity of living with HIV. In that way, the question guiding the searches for the review was: what are the experiences of adult persons living with HIV in treatment for coinfection with TB?
Specification of inclusion and exclusion criteria
The search considered original particles with qualitative data published in Portuguese, English and/or Spanish (in which the authors are fluent) at any time prior to 2023 (as that was the year in which the review began). The search excluded repeat studies, studies not available in full and/or free of charge and those whose findings were partial and/or not relevant to the guiding question, including those centring on a health practitioners’ perspective or on TB-prevention therapy among persons with HIV.
Locating and selecting studies
First, Health Sciences Descriptors (DeCS) and Medical Subject Headings (MeSH) equivalents were identified and searches were conducted of the Virtual Health Library (VHL) and PubMed Central (PMC). Here, the terms used were: HIV, infecções oportunistas relacionadas com a aids (AIDS-related opportunistic infections), síndrome de imunodeficiência adquirida (acquired immunodeficiency syndrome), tuberculose (tuberculosis), coinfecção (coinfection) and pesquisa qualitativa (qualitative research).
Studies were located from a list of ten databases, which made it possible to construct specific search strategies and use filters to optimise the selection process (Table 1). Associations were established between the descriptors using the Boolean operators “AND” and “OR”, while the “approach type” descriptor was used only on databases where the initial search without it resulted in a vast number of publications. In addition to the timeframe of publications up to 2022, the search was refined using “original article”.
The search was conducted between April and August 2023 by two doctoral students (LVL and GP), working independently with the assistance of Rayyan, to assure a trustworthy selection. In order to assure a more inclusive article retrieval process, the databases were consulted using the Comunidade Acadêmica Federada access, provided on the Portal de Periódicos of the Coordenação de Aperfeiçoamento de Pessoal de Nível Superior/Ministry of Education (CAPES/MEC).
The studies were selected in two stages, as illustrated below in a flow diagram19. The first stage involved examining the titles and abstracts and preselecting potentially eligible studies, which were then evaluated by reading in full. The reference lists of articles selected for reading in full were also examined (reverse search), following the same stages. At that point, divergences between the reviewers on four included articles were resolved in consensus with the other researchers (Supplementary Material 1)20.
Appraising the quality of the studies
The potentially eligible studies underwent a process of evaluation guided by the JBI Critical Appraisal Checklist for Qualitative Research18. This comprises ten items to guide critical appraisal of evidence quality and credibility. Assessment on each criterion is expressed by the alternatives: “yes”, “no”, “uncertain” and “not applicable”. The articles were evaluated on the basis of 70% consistency (i.e., at least seven items assessed as “yes”) as the inclusion parameter (Supplementary Material 2)20.
Data extraction, analysis and synthesis
The data items extracted were: authors, title, year and journal of publication, theoretical and methodological frame of reference (as adopted and described by the study’s authors), participants, context, data collection and analysis techniques, main findings and final remarks. This information was presented as absolute frequency (n) and relative frequency (%). Extraction of data on the discoveries of the findings section recorded the interpretations (descriptions and syntheses) and at least one supporting illustration (a primary datum originating in the data collection)18.
These discoveries were then evaluated for congruency between interpretations and illustrations, as follows18: unquestionable discoveries were those that raised no doubts as to their consistency; questionable discoveries were those where the association between datum and illustration was dubious; and unsupported discoveries were those where the illustration did not match the interpretation. This process was performed by LVL and GP and discussed until the reviewers were in agreement (Supplementary Material 3)20.
The qualitative meta-synthesis took place in three stages18: the first involved extracting the interpretations (n=90) with their respective illustrations; in the second, the discoveries were categorised, by their similarities in theory and concept, as unquestionable (n=76) and questionable (n=10), resulting in primary findings (n=35), which were grouped into sub-themes (n=8); and, in the third stage, synthesis of the categories yielded the themes (n=4) and meta-theme (n=1), the latter containing an inclusive, explanatory description and recommendation.
Presentation and interpretation of results
The meta-synthesis took the form of a progressive concentration of data from a larger number of findings, synthesising to a decreasing number of categories and results. In addition to building a synthesis table reflecting the aggregation process, it was decided to present the review findings graphically, representing them as thematic categories arising from the studies and contemplating their interrelations, with a view to understanding and explaining the phenomenon of interest18.
Ethical considerations
For this study, the authors fulfilled the ethical responsibilities stipulated in Brazil by National Health Council Resolution No. 466, of 12 December 2012, and Resolution No. 674, of 6 May 2022. These norms categorise this study as risk-free, because it involves anonymous data in the public domain and does not involve research participants directly. Accordingly, the study was dispensed from assessment by the research ethics committee.

Results
The process of selecting from the databases and reference lists is illustrated in Figure 1. After application of the inclusion and exclusion criteria, this review comprised 11 studies21-31. By publication year, the articles numbered: 2010 (n=1; 9%), 2012 (n=1; 9%), 2015 (n=1; 9%), 2019 (n=1; 9%), 2020 (n=2; 19%), 2021 (n=2; 19%) and 2022 (n=3; 27%). The studies originated predominantly in Brazil (n=7; 64%), followed by South Africa (n=1; 9%), Angola (n=1; 9%), Ethiopia (n=1; 9%) and Ukraine (n=1; 9%) (Table 2).
The studies included were primarily exploratory (n=7; 64%), followed by descriptive (n=3; 27%) and convergent-care (n=1; 9%) studies. The data collection techniques employed were: individual interview (n=7; 64%), triangulation of methods (n=3; 27%) and focal group (n=1; 9%). The quality of the studies included was rated as: 70% (n=4; 36%), 80% (n=1; 9%), 90% (n=5; 45%) and 100% (n=1; 9%). Other information on the studies is given in Table 2.
Extraction and analysis of the discoveries yielded a meta-theme, comprising four themes: (i) diagnosis and treatment of TB-HIV coinfection have impact on the life of the person involved; (ii) personal, social and economic vulnerabilities overlap in people with TB-HIV coinfection; (iii) drug burden and programme weaknesses impair treatment of TB-HIV coinfection; and (iv) support networks and care flows favour treatment of TB-HIV coinfection (Table 3).
It was discovered that people with TB-HIV coinfection present bio-psycho-social needs resulting from the impact of the diagnosis, which adversely affect adherence. Moreover, they show a lack of knowledge of HIV and TB, engage in exposure and risk behaviour, depend on a heavy drug burden and experience inappropriate professional conduct. However, social and health care support was found to be important to fostering (self-)care and proper treatment follow-up (Figure 2).

Discussion
The findings of this systematic review revealed the complex, difficult realities of managing care for people with TB-HIV coinfection, which were associated with the burden of different therapeutic regimens, socioeconomic conditions and the social stigma attendant on both infections. On the other hand, they reaffirmed the potential of public policies and measures to support health service organisation and bonding with the professional and social network in favour of proper treatment follow-up.
Quality of life is one of the main factors in assessing the health and wellbeing of people who live with HIV32. Some discussions have suggested that this construct should be understood in the light of (at that date) the 90-90-90 goals (90% of people living with HIV knowing their serological status, 90% of people living with HIV who know their status being on ART and 90% of people living with HIV on ART achieving viral suppression)—considering a “fourth 90” to be 90% of people who achieve viral suppression enjoying good quality of life33,34.
However, a cross-sectional study that evaluated the quality of life of people living with HIV in Holland and England found that one third (35%) of the Dutch participants and nearly half (47%) the English participants reported anxiety and/or depression34. Note that several factors can contribute to these symptoms, such as the discovery of a diagnosis of HIV, its impact on relationships, stigmatisation, social isolation and the experience of living with a chronic disease34, as were also identified in this review.
Also, this complexity of factors is accentuated by the presence of TB. A study in a city in India found that, on average, people with TB-HIV scored significantly lower in the quality of life-related domains than those with HIV alone35. In that regard, studies of this public’s needs and difficulties in experiencing the health-disease process can collaborate in identifying demands and promoting quality of life36.
Coinfection with TB can also have an impact on the socioeconomic context of people with HIV. A mixed-method study of people with TB found that, even after treatment, recovery of income and employment was limited, financial difficulties persisted and interruptions to schooling continued37. This scenario underlines the need for social protection programmes for people with coinfection, given the potential for improved rates of cure and treatment adherence38.
Other factors with adverse impact on the experiences of people with TB-HIV were their scant knowledge about the infections and engaging in risk habits, such as alcohol and drug use. Meanwhile, note that health education strategies can be fundamental to follow-up, because they enable the coinfected person and collaborate towards a willingness to engage in (self-)care39,40. These measures can even motivate a change away from risk behaviour, with a view to strengthening adherence to therapy39,41.
Weak treatment adherence was intrinsically related to high drug burden. Research has shown that the occurrence of potential interactions between drugs, additive drug toxicities and problems of tolerability can undermine the treatment management process41-43. Nonetheless, the current combination of TB drugs with ART, at the right dosage and correctly timed onset, has produced appropriate clinical response and acceptable safety41.
At present, unlike the Brazilian Ministry of Health’s previous guidelines, it is recommended that persons with concomitant HIV-TB diagnoses should be treated for both infections, with a view to reducing related mortality44. Depending on the T-CD4+ lymphocyte count, ART should be started by the second week or on the eighth week of anti-TB treatment; for persons with HIV on ART prior to diagnosis of TB, treatment for TB should begin immediately44.
In addition, a lack of coordination between levels of health care and a fragile relationship with health practitioners also undermined treatment for TB-HIV coinfection. An ecological study in one Brazilian state identified greater occurrence of coinfection in municipalities with strong coverage by the Family Health Strategy45. Its authors suggested that care is fragmented and reactive, with little prospect of integrating care or of prioritising prevention and promotion measures for chronic conditions45.
In the Brazilian context, it is suggested that TB treatment should be decentralised to primary healthcare; in cases of coinfection with HIV, the patient is referred to follow-up shared, in principle, with specialised care services44. At times, however, the specialised services take over treatment completely, thus contributing to a persistent lack of care integration in the system, which can hinder access and adherence to treatment among people in more distant and peripheral areas.
It is essential to consider the historical and cultural influence of the stigma and prejudice attendant on these conditions: on the one hand, they affect patients’ choices of follow-up services and, on the other, underlie a possible lack of care on the part of health practitioners, resulting from insecurity in dealing with this population. This underscores the importance of firmly established flows between local and regional care networks, with epidemiological surveillance playing a leading role, so as to favour sharing of information on which to base care.
Establishing integrated, proactive lines of care must be a priority for TB and HIV control programmes. Some collaborative diagnostic and treatment policies applied in Latin America and the Caribbean have offered simultaneous testing for both infections and provided TB and HIV therapies in decentralised services. These have performed well in responding to the infections46. Nonetheless, there is a persistent need to reinforce coordination in health service provision.
In this review, the people undergoing treatment for TB-HIV coinfection stressed the importance of care flows and service organisation. A study in one Brazilian municipality’s outpatient service found that a regular supply of drugs, periodical testing for the infections at the facility itself and flexible appointment scheduling were factors that, jointly with the relationship and bond to the multi-profession staff, strengthened adherence to TB-HIV treatment47.
It is important to consider, from the perspective of people with coinfection, the decisive role of social and family support to follow-up care. A cross-sectional study in the capital city of Peru found that social support and quality of care significantly influenced the health education of people infected with TB48. The study’s authors also found that health education collaborated with social support and quality of care to provide opportunities for improving treatment adherence48.
The findings of this review ratify the appropriateness of multi- and inter-sector care as a priority for combating these infections, particularly TB6,9,10,49. This thinking converges with the World Health Organisation’s framework of collaborative and inter-sector measures against TB, which is designed to support countries in introducing and expanding comprehensive services centred on persons with TB and considering their comorbidities (such as HIV) and health risk factors, in order to accelerate the response by efforts to combat the disease50.
In Brazil, for example, Decree No. 11,494, of 17 April 2023, instituted the Comitê Interministerial para a Eliminação da Tuberculosis e de Outras Doenças Determinadas Socialmente (CIEDDS), with a view to proposing broad, structural policies going beyond appropriate and universal treatment, to focus on access to healthcare and sanitation measures, social inclusion, education, housing and so on. The actions of the CIEDDS should be evaluated and, if effective, can inspire countries’ efforts to eliminate TB and HIV by 2030.
In view of the foregoing, this systematic review will contribute to proposing and informing public policies, given that it has thrown in-depth theoretical light on the experiences of people undergoing treatment for TB-HIV coinfection. Accordingly, strategies designed to improve bonding and adherence to the care directed to this population should consider the individual, social and programmatic experiences revealed in this study and contemplate also the specific geographic and cultural features of the populations and countries involved.
Although there was no need for a minimum number of studies in this meta-synthesis18, one limitation of this review is the small number of publications resulting from either the lack of studies or the inclusion process. In the latter case, this situation may have resulted from the language restrictions on the search and/or on the selection process; however, no potentially eligible studies in other languages were found. Any studies indexed in databases not considered by this review would also not have been included.

Final remarks
This systematic review offered insights into the ambivalence of the experiences of people undergoing treatment for TB-HIV coinfection. The findings corroborate the need to formulate individual therapeutic projects and to propose singular strategies and interventions designed to offer opportunities for access and bonding to services and adherence to therapies. Moreover, they highlighted the need to implement and strengthen flows of information and action among health services in the care network.
It is also important that the response to combat these conditions rest on inter-sector action engaging the partners involved at all stages of care for the population, from the development of care plans to proposals for committees and laws to safeguard the right to basic health services and social wellbeing. In this way, one of the steps towards accelerating the response to eliminate these infections by 2030 is to take into consideration the specific features of the experiences of people undergoing treatment for TB and HIV.
Lastly, it is suggested that qualitative studies be undertaken to expand the understanding of the coexistence of TB and HIV beyond (non-)adherence to treatment. It would be a good idea to consider other actors involved in these experiences, such as relatives, friends and health practitioners. Moreover, such studies must seek to be more: (i) theoretically robust, by selecting frames of reference that sustain the interpretation of their data; and (ii) methodologically robust, moving beyond the descriptive-exploratory plane to become explanatory and interpretative.

Collaborators
LV Lima and G Pavinati: study conception and design, data collection, search of references, data analysis and interpretation, drafting of the article, critical review and approval of the final version. AJR Barrêto, MA Salci, MS Barreto and GT Magnabosco: data analysis and interpretation, critical review and approval of the final version.

Funding
Ministry of Science, Technology and Innovation/Conselho Nacional de Desenvolvimento Científico e Tecnológico – Brazil (MCTI/CNPq) – Process No. 445760/2023-0.

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