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HIV/AIDS
Protocol
Impact of armed conflicts on HIV treatment outcomes in sub-Saharan Africa: protocol for a systematic review and meta-analysis
  1. Hafte Kahsay Kebede1,2,
  2. Hailay Gesesew3,4,
  3. Paul Ward2
  1. 1 Pharmacy school, Mekelle University, Mekelle, Ethiopia
  2. 2 Research center for Public Health, Equity, and Human Flourshing, Torrens University Australia, Adelaide, South Australia, Australia
  3. 3 Epidemiology, Mekelle University, Mekelle, Ethiopia
  4. 4 Public Health, Flinders University, Adelaide, South Australia, Australia
  1. Correspondence to Hafte Kahsay Kebede; maymegeltana{at}gmail.com

Abstract

Introduction Armed conflicts have significant negative impacts on the entire healthcare system in general and HIV care system in particular. Sub-Saharan Africa is suffering from a disproportionate double burden of armed conflict and HIV infection. Nevertheless, the impact of the armed conflict on the HIV treatment outcomes in conflict settings in sub-Saharan Africa has not been thoroughly and systematically synthesised. This protocol outlines a review that aims to summarise the available evidence on the impact of armed conflict on HIV treatment outcomes in sub-Saharan Africa.

Methods and analysis A systematic review of all quantitative studies that assess the impact of armed conflicts on HIV treatment outcomes will be conducted. The systematic search will start with a preliminary search of Google Scholar, followed by implementation of the full search strategy across five databases (MEDLINE, PubMed, CINAHL, SCOPUS and Web of Science) and the screening of titles and abstracts then relevant full texts. Bibliographies will be reviewed to identify additional relevant studies. We will include studies conducted in sub-Saharan Africa that were published in English between 1 January 2002 and 31 December 2022. Methodological validity of the included studies will be assessed using standardised critical appraisal instruments from the Joanna Briggs Institute (JBI) Meta-Analysis of Statistics Assessment and Review Instrument. Data will be extracted using standardised JBI instruments and analysed through narrative synthesis, and meta-analyses and regression. Heterogeneity will be assessed using I2 and Χ2 tests.

Ethics and dissemination Since this study will not involve gathering primary data, formal ethical approval is not required. Journal publications, conference presentations and a media release will be used to share the study findings.

PROSPERO registration number CRD42022361924.

  • HIV & AIDS
  • Health policy
  • Health & safety
http://creativecommons.org/licenses/by-nc/4.0/

This is an open access article distributed in accordance with the Creative Commons Attribution Non Commercial (CC BY-NC 4.0) license, which permits others to distribute, remix, adapt, build upon this work non-commercially, and license their derivative works on different terms, provided the original work is properly cited, appropriate credit is given, any changes made indicated, and the use is non-commercial. See: http://creativecommons.org/licenses/by-nc/4.0/.

https://doi.org/10.1136/bmjopen-2022-069308

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    STRENGTHS AND LIMITATIONS OF THIS STUDY

    • This review will synthesise evidence of HIV treatment outcomes in conflict areas in sub-Saharan Africa, a disproportionately affected region with respect to both HIV and armed conflict.

    • The systematic review will not include studies or reports in languages other than English, which is a source of information bias.

    • The systematic review will only include quantitative studies, even though qualitative and mixed methodologies are recognised as important in understanding factors influencing treatment outcomes among patients with HIV on antiretroviral therapy.

    • Comparability may be difficult because of the broad time window and changes in HIV services and therapy during the period covered by the search; furthermore, treatment outcomes such as loss to follow-up, immunological gain (CD4 gain) and virological suppression have no gold-standard measurements, making meta-analysis challenging.

    • If key terms and concepts are not mentioned in the title or abstract, some relevant articles may be missed.

    Introduction

    HIV/AIDS has been a significant public health issue since its emergence four decades ago.1–3 In particular, sub-Saharan Africa (SSA), where two-thirds (25.6 million) of all HIV infections and 65% of all AIDS-related deaths occur, is the hardest-hit continent.4 Since the introduction of voluntary counselling and testing in 1990s5 and antiretroviral therapy (ART) in 2000s,6 significant progress has been made in lowering the incidence, prevalence and death rates of HIV/AIDS-related diseases.1–4 There are ongoing initiatives worldwide to guarantee that HIV treatment is supported by the most recent scientific research.7 Due to the advancements made in HIV testing and treatment over the past 20 years, as well as the vastly increased global access to antiretrovirals and the transformation of HIV treatment into a chronic treatable disease, the global community has been inspired to make a commitment to ending the epidemic. Global treatment experts at the United Nations Program on HIV and AIDS (UNAIDS) and partners set an ambitious goal of ending the epidemic by 2030.8 In order to meet these goals, additional measures have been taken, including the adoption and implementation of the ‘treat all’ recommendation and the rapid ART initiation, which is adopted by 96% countries.9 10

    Despite unprecedented efforts to increase the number of people tested for HIV and started on ART, some parts of the world, including SSA, continue to lag.3 7 11–19 Thus, HIV infection rates are increasing,4 HIV treatment rates are declining and AIDS-related deaths are increasing.4 Furthermore, some countries, particularly in West and Central Africa, as well as in Southern Africa, frequently experience stockouts of HIV-related supplies, including medications.7 Armed conflicts, cultural, social and economic factors, among other things, have hampered global efforts to combat the epidemic and its detrimental effects.7 20–27

    Armed conflicts are thought to have a significant negative impact on the health of the populations they affect,7 26–31 because it has an impact on people’s access to healthcare and their quality of life through political instability, the breakdown of social and healthcare systems, underfunding, insecurity, poverty, a large influx of refugees and/or internally displaced people (IDP),32–51 and the deterioration of already weak health systems.40 52 Patients with HIV are especially vulnerable and have poorer health outcomes because the disease requires strict adherence to treatment because providing people with regular HIV care and ensuring a continuous supply of drugs in conflict zones can be difficult.7 The provision of HIV testing, treatment and adherence services was further complicated by stigmatisation,7 governments’ lack of political will to expand these services as well as a lack of donor commitment to close the funding gap. This in turn leads to increased HIV incidence, prevalence, and related morbidity and mortality.53 54 However, HIV care in conflict settings falls to the bottom of the priority list despite unique features of armed conflict, including its length, scope and difficulty in pinpointing the exact conflict site or data.55 56 As a result, less than 20% of people in conflict situations receive ART.57 Additionally, HIV services are scarce or non-existent in conflict-affected countries, such as the Central African Republic, South Sudan and parts of Yemen, making treatment challenging to access.57

    According to the WHO, 1.8 billion people live in conflict-affected areas around the world,58 and 89.3 million people will have been displaced from their homes as a result of war and violence by the end of 2021.59 Because of the large number of people living with HIV worldwide (38.4 million),4 the geographical overlap of high HIV prevalence with conflict,4 60 the social and economic consequences of HIV on societies, less attention to HIV over other emergency healthcare needs, and the scope and severity of damage to healthcare, societal and physical infrastructures caused by armed conflict, researchers must investigate how war affects HIV treatment.

    However, there have not been many systematic reviews investigating the intertwined connection between HIV and conflict. There were few systematic reviews54 61–65 that have paid close attention to HIV’s prevalence and incidence. None of the systematic reviews assessed the impact of armed conflict on HIV treatment outcomes. Given the nature of HIV, the importance of HIV treatment in reducing HIV incidence and prevalence, the double burden of HIV and conflict in SSA, the already fragile healthcare system in SSA, poverty and displacement, we argue that a conflict will have a significant negative impact on HIV treatment outcomes in SSA, and that this is an area of research that requires systematic synthesis and detailed exploration. Hence, this review will synthesise the impact of armed conflict on HIV treatment outcomes among patients with HIV affected by armed conflicts in SSA. HIV treatment outcomes include retention, attrition, lost to follow-up (LTFU), clinical failure, immunological failure, treatment failure, viral suppression/virological failure and mortality.

    Methods and analysis

    Study registration

    This systematic review was registered in the International Prospective Register for Systematic Reviews, with the registration number CRD42022361924.

    Population and context

    The review will synthesise peer-reviewed primary studies and grey literature reporting on the impact of armed conflict on HIV treatment outcomes among patients with HIV on ART in SSA. We will limit the context to SSA due to the fact that SSA is disproportionately affected by both HIV66 and armed conflict,64 67–70 weaponisation of the already fragile healthcare system,71 72 and lack of finance and clear directives to address HIV care in conflict-affected settings.

    The study group will consist of patients with HIV who have received ART within the last 20 years, who reside in conflict-affected areas, or who were displaced, either internal or external displacement, as a result of conflict.

    The review will include studies conducted in English language between 2002 and 2022. We selected 2002 as the start date as most SSA countries introduced HIV care and treatment programmes in 2002.73

    Search strategy

    A systematic literature search will be conducted in order to identify studies and reports on the impact of armed conflict on the HIV treatment outcomes. First, a preliminary search of Google Scholar was conducted to create title search phrases for three previously established themes connected to the study issue: concept 1 (conflict): (abuse or assault or attack) or “armed conflict” or violence or war); concept 2 (“HIV Care”) or (HIV or AIDS or ART or highly active antiretroviral therapy (HAART) or “HIV testing” or “linkage to HIV care” or “viral suppression” or “HIV incidence”); and concept 3 (SSA) (list of all African countries).

    Then, a comprehensive search strategy (online supplemental material 1), using all determined keywords and index terms, will be applied in the following five databases: MEDLINE, PubMed, CINAHL, SCOPUS and Web of Science. To execute the whole search strategy in the five databases, the three concepts—concepts 1, 2 and 3—will be linked together by the operator “AND”. We will then run the systematic search strategy in each database; titles and abstracts from each database will be screened in order to choose pertinent titles and abstracts for a full-text screening, to be exported to EndNote and remove duplicates, exported to Covidence, and then screen the titles and abstracts in the Covidence system. In order to reduce publication bias and incorporate field knowledge, additional searches of unpublished studies and various sources of grey literature from the Médecins Sans Frontières, UNAIDS, WHO and Save the Children will also be carried out with the search term [[[war] OR [conflict]] AND [[hiv] OR [hiv/aids]] AND [[outcome] OR [consequence]. Bibliographies of all articles will be reviewed to identify additional relevant studies.

    Supplemental material

    Eligibility criteria

    Studies will be considered eligible if their full texts are available in English and they meet the following criteria: (1) studies reported on patients with HIV who have been on ART regardless of age, gender or sex; (2) studies from areas of ongoing conflict, IDP centres or refugee camps; (3) studies carried out between 1 January 2002 and 31 December 2022; (4) studies from SSA; (5) quantitative studies such as systematic reviews, clinical trials, prospective and retrospective cohort studies, case–control studies, cross-sectional studies and case series, and reports of international organisations; (6) studies on HIV treatment outcomes such as retention, attrition, LTFU, clinical failure, immunological failure, treatment failure, viral suppression/virological failure or mortality; (7) studies that reported HIV care outcomes among conflict-affected populations in addition to other diseases or populations only if the HIV care data were separately analysed or reported; (8) studies that include both conflict and non-conflict-affected populations, if disaggregated data for conflict-affected populations are provided.

    We will exclude: (1) studies published in languages other than English; (2) opinion pieces or viewpoints published in media outlets; (3) studies that took place on broad humanitarian perspectives without mentioning conflict or not reporting disaggregated data for conflict-affected populations; (4) studies that include current or former military populations; (5) studies from countries other than SSA; (6) studies reported from African refugees settled outside SSA; (7) studies reported before 2002; (8) studies reporting on patients with HIV who were not on ART.

    Study selection and quality assessment

    Only quantitative studies conducted in SSA will be considered for inclusion. These included: systematic reviews, clinical trials, prospective and retrospective cohort studies, case–control studies, cross-sectional studies and case series.

    We will do a multistep process to filter the search results. First, two reviewers will independently review the complete texts of all potentially eligible studies to determine whether they fit the eligibility requirements after screening the search results using titles and abstracts. After that, methodological validity of the included reviews will be evaluated using standardised Joanna Briggs Institute (JBI) appraisal instruments (38). The questionnaire includes 9 questions for cohort studies, 10 for experimental investigations and 11 for studies including systematic reviews. For each article, we will calculate the ratio of methodological quality scores using the number of ‘Y’s (yes) as a numerator, and the sum of ‘U’s (unclear), ‘N’s (no) and ‘Y’s as a denominator. We will exclude ‘NA’ (not applicable) from the ratio calculation. Disagreements among reviewers about whether to include these papers will be resolved through discussion and consensus. To ensure quality, the risk of bias will be assessed using the Agency for Healthcare Research and Quality criteria (high, moderate, low and unclear risk).74 The tool evaluates biases in selection, performance, detection, attrition and reporting.75 High risk of bias is implied if there is significant bias, that is, error in study design, data analysis and reporting that invalidates the findings. Moderate risk of bias is demonstrated when there is no enough evidence to invalidate the study but susceptibility of a bias. Low risk of bias is indicated if the bias is low and results are valid. Unclear risk of bias is assumed if it is difficult to judge the studies as a result of poor report. Authors of primary studies will be contacted via email if there are missing or unclear data.

    Data extraction

    For papers selected to be included in the review, data will be extracted using the standardised data extraction tool from JBI Meta-Analysis of Statistics Assessment and Review Instrument.76 The data extracted will include specific details about the authors, publication year, country of study, populations, sample size and summary of HIV treatment outcomes.

    Types of interventions and comparators

    The review will consider impact of armed conflict on HIV treatment outcomes.

    Types of outcome measures

    This systematic review will consider studies that included the impact of armed conflict on HIV treatment outcomes among patients with HIV affected by armed conflicts in SSA. HIV treatment outcomes include retention, attrition, LTFU, clinical failure, immunological failure, treatment failure, viral suppression/virological failure and mortality. Therefore, depending on the availability of data rate of adherence, LTFU, immunological gain, virological non-suppression, treatment failure and mortality will be analysed. Moreover, predictors for each outcome variable will be analysed. HIV incidence, HIV prevalence, HIV test and linkage to care will not be part of the review, only HIV treatment outcomes.

    Operational definitions

    There is no universally accepted definition of armed conflict, as it is an umbrella word for a wide range of ideas and activities, such as conflict, war, violence, terrorism, or catastrophic loss of civilian life, a civil unrest, massive displacement, and violations of human rights and international humanitarian law. While we put the definition of conflict as follows, we would like to remain open to additional definitions by authors.

    Armed conflict: is a situation in which states or other organised parties fight against each other by way of military force. Armed conflicts shall be of international and non-international armed conflicts. It also includes any military confrontation of the United Nations’ Peace Force.

    Attacks on healthcare: included events stemming from armed conflicts and wars that threaten the health and safety of patients with HIV as reported by the authors. Violence, threatened/actual intimidation and interference, misuse or misrepresentation of the protected status of healthcare fall under this category. Facilities, transports, patients, personnel and related issues fall under the category of healthcare.

    Conflict-affected areas: are areas experiencing an armed conflict, fragile post-conflict regions, areas with poor or non-existent administration and security, such as failed states, and areas with pervasive and systematic violations of international law, including human rights abuses. The area may be a region, a country, an area within a country, or an area that crosses one or more country boundaries. The impact of conflict may extend beyond the region of conflict to include surrounding areas and those hosting displaced persons. As a result, our definition remains open to the definition of authors.

    Conflict-affected populations: include individuals, groups, and communities affected by and remaining in conflict-affected areas, as well as those forcibly displaced such as refugees and IDP. Conflict may have an impact on those who host IDP and refugees. As a result, our definition remains open to author definition.

    Humanitarian crisis: includes events stemming from armed conflicts and wars that threaten the health and safety of the community.

    IDP: those who have been forced or compelled to leave their homes, often due to armed conflict or other forms of violence, and who stay within their country’s borders.

    Post-conflict: the time periods of armed conflicts included acute, chronic and recovery time periods. In its literal meaning, the adjective ‘post-conflict’ refers to the period of time immediately following a conflict, when open combat is over. Nevertheless, despite its linguistic simplicity, the phrase is more challenging to define practically in terms of time, response, transformation and sustainability. Therefore, our definition remains open to author definition.

    Refugees: people who are outside their country of birth due to conflict, war, widespread violence, or feared persecution and who as a result need international protection.

    Data management, analysis and synthesis

    A summary of results and the topically organised outcomes of chosen studies will be presented in the final review. First, we will take the following data from each included study/report and describe them: authors, publication year, country of study, populations, sample size and summary of HIV treatment outcomes. Results will be reported in accordance with the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) statement.77

    Meta-regression and meta-analyses will be used if data are available to assess the relationship between armed conflict and HIV treatment outcomes. Once clinical and statistical heterogeneity has been determined, data from two or more studies will be pooled for meta-regression and meta-analyses.78 79 The Cochran Q test (Χ2 test for heterogeneity or Χ2 test for homogeneity)79 will be used to determine whether the outcomes of individual studies are further away from the common effect, that is, beyond chance—statistical heterogeneity is declared if the alpha level of the Cochran Q test is less than 10% (p=0.1). Higgins I2 will be used to quantify the degree of heterogeneity, that is, the total variation across studies caused by heterogeneity. I2 values of 0%, 25–50% and 50–75% are considered to have no, low or medium heterogeneity, respectively.79

    When moderate statistical heterogeneity is detected, the random-effects model is used; however, when low or no statistical heterogeneity is detected, the fixed-effects model is used.80 81 However, if the number of studies reporting HIV treatment outcomes is small, we will only consider a fixed-effects model regardless of the level of heterogeneity (n<5).80 81 Effect sizes will be expressed as relative risk, HR and mean difference (for continuous data) (and their 95% CIs) for the experimental and cohort studies.82 If I2 is above 75%, the study will be excluded from the meta-analytical calculation. Using RevMan V.5 software, the meta-analysis will be carried out separately for each target and intervention of interest.83 A sensitivity test will also be performed by excluding and including small studies, as well as deviant results from the remaining studies (outliers). To assess publication bias, a funnel plot will be used.

    GRADE (Grading of recommendations assessment, development and evaluation) will be used to assess the strength of the body of evidence, as described in detail elsewhere.84 The review will be reported using the PRISMA statement once the analysis is completed.85

    Patient and public involvement

    None.

    Ethics and dissemination

    Since this study will not involve gathering primary data, formal ethical approval is not required. Journal publications, conference presentations and a media release will be used to share the study findings.

    Ethics statements

    Patient consent for publication

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    Footnotes

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    • Contributors Conceptualisation—HKK, HG and PW. Methodology—HKK, HG and PW. Writing (original draft preparation)—HKK. Writing (review and editing)—HKK and PW. All authors have read and agreed to the published version of the manuscript.

    • Funding The authors have not declared a specific grant for this research from any funding agency in the public, commercial or not-for-profit sectors.

    • Competing interests None declared.

    • Patient and public involvement Patients and/or the public were not involved in the design, or conduct, or reporting, or dissemination plans of this research.

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