Does undernutrition increase the risk of lost to follow-upwards in adults living with HIV in sub-Saharan Africa? Protocol for a systematic review and meta-analysis

Loading

  1. http://orcid.org/0000-0003-2822-2062Animut Alebeli,2,
  2. Daniel Demant2,three,
  3. Pammla Petrucka4,5,
  4. David Sibbritttwo
  1. 1 College of Health Science, Debre Markos University, Debre Markos, Ethiopia
  2. ii School of Public Helath, Faculty of Health, University of Applied science Sydney, Ultimo, New Southward Wales, Australia
  3. 3 School of Public Wellness and Social Work, Faculty of Wellness, Queensland Academy of Engineering, Kelvin Grove, QLD, Australia
  4. 4 University of Saskatchewan, Saskatoon, Saskatchewan, Canada
  5. 5 Nelson Mandela African Institute of Science and Engineering science, Arusha, Tanzania
  1. Correspondence to Animut Alebel; animut.a23{at}gmail.com

Abstract

Introduction Undernutrition is considered a marker for poor prognosis among people living with HIV (PLHIV), particularly in sub-Saharan Africa (SSA), where undernutrition and HIV are both highly prevalent. Show suggests that undernutrition (body mass index <18.5 kg/mii) is i of the main factors that significantly increases the risk of lost to follow-up (LTFU) in PLHIV. All the same, primary studies in SSA accept reported inconsistent findings on the relationship between undernutrition and LTFU among adults living with HIV. To the best of our knowledge, no systematic review which aimed to summarise the bachelor evidence. Hence, this review aims to decide the pooled consequence of undernutrition on LTFU amongst adults living with HIV in SSA.

Methods and assay PubMed, EMBASE, Spider web of Science, Scopus, and, for grey literature, Google Scholar will exist systematically searched to include relevant articles published since 2005. Studies reporting the effect of undernutrition on LTFU in adults living with HIV in SSA will be included. The Newcastle-Ottawa Calibration will be used for quality cess. Data from eligible studies will be extracted using a standardised data extraction tool. Heterogeneity between included studies will exist assessed using Cochrane Q-test and I2 statistics. The Egger's and Begg's tests at a five% significance level will be used to evaluate publication bias. As heterogeneity is predictable, the pooled effect size will be estimated using a random-furnishings model. The concluding effect size will be reported using the adjusted Hr with a 95% CI.

Ethics and dissemination Ethical approval is not required for a protocol for a systematic review. The results of this systematic review will exist published in a peer-reviewed journal and will be publicly available.

PROSPERO registration number CRD42021277741.

  • epidemiology
  • HIV & AIDS
  • diet & dietetics
  • diet

http://creativecommons.org/licenses/by-nc/four.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, whatsoever changes made indicated, and the use is not-commercial. See: http://creativecommons.org/licenses/past-nc/4.0/.

Statistics from Altmetric.com

  • epidemiology
  • HIV & AIDS
  • nutrition & dietetics
  • nutrition

Strengths and limitations of this study

  • To the best of our cognition, this is the commencement systematic review and meta-assay protocol designed to examine the effect of undernutrition on lost to follow-upwardly amidst adults living with HIV in sub-Saharan Africa.

  • The protocol included a comprehensive (detailed) searching strategy plans to include all eligible studies as much every bit possible.

  • This protocol planned to quantify the concluding pooled effect size using adjusted HR to control for potential confounding factors.

  • The protocol is reported according to the Preferred Reporting Items for Systematic Reviews and Meta-Analysis Protocol checklist to ensure quality.

  • Every bit different study designs and clinically heterogeneous participants are eligible for this protocol, these may be the possible sources of heterogeneity.

Introduction

HIV remains a global public wellness challenge. Of the 38 million worldwide HIV cases at the terminate of 2019, more than two-thirds (25.vii million) were living in sub-Saharan Africa (SSA).1 Though there is no cure for HIV, antiretroviral (ARV) drugs tin can suppress viral replication and reduce or eliminate HIV transmission adventure.2 ARV also assists people living with HIV (PLHIV) to live comparably healthy.3 The rapid calibration-upward of antiretroviral therapy (Fine art), especially in resources-limited settings, is one of the most remarkable achievements in the global efforts against HIV.4 Globally, admission to Art has increased dramatically from vii% in 2005 to 67% in 2019.i 5

ART is a daily medication,6 7 requiring a lifelong commitment to be effective.8 Lost to follow-upwardly (LTFU) from ART profoundly affects success rates. LTFU is defined as when patients exercise not return to the Fine art dispensary within 90 days (sixty days after the adjacent appointment) from the final clinic visit.nine Information technology has become an emerging problem in many low- and middle-income countries (LMICs), including SSA.x 11 A meta-assay from 42 LMICs plant that nearly 35% of all patients initiated on ART either died or were LTFU at 36 months of follow-up.10 An additional meta-analysis from SSA has shown that up to 40% of patients were LTFU or died.12 PLHIV lost to ART are at college take a chance of treatment failure, viral rebound, mortality and opportunistic infections (OIs).13 14 The common contributing factors for LTFU are low CD4, advanced WHO clinical staging (III and IV), poor Art adherence, low baseline torso weight, weight loss >ten% and undernutrition (low body mass index (BMI)).15–23

Undernutrition is considered a marker for poor prognosis among PLHIV, peculiarly in SSA, where both undernutrition and HIV are highly prevalent.24 While both atmospheric condition are global problems, they are nearly prevalent in the world'southward poorest areas, such as SSA. SSA accounted for 23% of all people suffering from undernutrition and 68% of all PLHIV worldwide.25 26 Undernutrition is characterised by a deficit in macronutrients and/or micronutrients, leading to trunk composition changes and macerated function.27 28 HIV and undernutrition are interrelated. HIV reduces food intake, reduces nutrient assimilation and increases free energy requirements.29–31 At the aforementioned time, undernutrition hastens disease progression and increases the occurrence and recurrence of OIs.30 32 Undernutrition significantly increases the risk of bloodshed, treatment failure, and LTFU among PLHIV.33–41

Studies have shown that undernutrition (ie, BMI <18.5 kg/m2) is one of the main factors that significantly increases the risk of LTFU amid adults living with HIV.42–47 This finding may reflect that undernourished patients are more likely to develop OIs and later died simply were under-reported to the HIV clinics due to a passive reporting system.48 For example, a meta-analysis in SSA conducted by our team constitute that the risk of developing TB in undernourished adults living with HIV is twice that of well-nourished counterparts.49 In addition, undernourished patients may non be able to report to the health facility for ART refills and complete their appointments in the same mode also-nourished patients.l Additional study from Uganda has reported that overweight (BMI >thirty kg/gtwo) patients living with HIV are at lower hazard of LTFU compared with well-nourished patients living with HIV.48

At that place have been extensive chief studies on the human relationship betwixt undernutrition and LTFU among adults living with HIV in SSA.42 45–48 50–57 Nonetheless, these individual studies have reported inconsistent findings. Some studies showed that undernutrition significantly increases the adventure of LTUF amid adults living with HIV.42–47 Conversely, a few studies found that undernutrition and LTFU amidst adults living with HIV have no significant clan.47 Estimating the pooled effect of undernutrition on LTFU amid adults living with HIV is of import to provide evidence for healthcare workers and policymakers in designing specific interventions to minimise undernutrition-related LTFU among adults living with HIV. However, to the best of our knowledge, there is no systematic review and meta-analysis, which summarised available bear witness to show the pooled effect of undernutrition on LTFU among adults living with HIV in SSA. Thus, this review protocol has been designed to address this gap. This systematic review protocol is designed to estimate the pooled effect of undernutrition on LTFU amid adults living with HIV in SSA. The authors will follow this protocol during the literature search, data analysis, and reporting of results.

Review question

Does undernutrition increase the risk of LTFU among adults living with HIV in SSA?

The PICO framework

  • Participants/population: adults (aged ≥15 years) living with HIV.

  • Intervention(south)/exposure(s) group: undernourished adults living with HIV.

  • Comparator(s)/control grouping: well-nourished adults living with HIV.

  • Outcome(southward) of involvement: LTFU from ART.

Methods and assay

Information sources and search strategy

This systematic review protocol is prepared post-obit the Preferred Reporting Items for Systematic Reviews and Meta-Assay Protocol (PRISMA) checklist (online supplemental additional file 1).58 The following databases volition be searched: PubMed, EMBASE (Elsevier), Spider web of Science, Scopus, and, for grey literature, Google Scholar (encounter online supplemental boosted file ii for draft search strategy for PubMed). Additional studies volition be identified through a review of reference lists of included studies. An updated search will be undertaken prior to the final manuscript submission in order to retain currency. Search limitation will include English language publications, human being subjects and a publication engagement since 2005 aligning with the first year in which payment-free Fine art was available in most African countries. A line-by-line search will exist conducted from each database, and a split searching strategy will be developed for each database, depending on the functions and search interface of databases. The search findings will exist exported and managed through Covidence software.

Supplemental cloth

Supplemental material

Study pick and eligibility criteria

The systematic review volition consider all studies reporting the association betwixt undernutrition and LTFU among adults (aged ≥15 years) living with HIV in SSA. Studies reported the association between undernutrition and LTFU in relative risk (RR) or Hr will be considered for meta-analysis. Studies providing incomplete data, descriptive statistics only, review articles, case reports, editorial comments, non-aligned outcomes of involvement, conference papers and qualitative studies will exist excluded. Additionally, studies conducted amidst HIV-infected significant women will be excluded equally the chance of undernutrition, and nutritional assessment tools used for pregnant women are singled-out from non-pregnant individuals.59 Articles including only malnourished adults living with HIV will too not be considered for this review due to a lack of controls (ie, well-nourished adults living with HIV).

The chief author (AA) will assess the titles and abstracts of potentially relevant studies. Then, two reviewers, (AA and DD), will determine the inclusion and exclusion of full-texts based on the predetermined criteria. A third reviewer volition exist invited in cases of disagreement. The flow chart for this systematic review is described in figure ane.

Figure 1

  • Download figure
  • Open up in new tab
  • Download powerpoint

Figure ane

Flow chart of written report selection for a systematic review and meta-analysis of the event of undernutrition on LTFU in adults living with HIV in SSA. LTFU, lost to follow-upwards; SSA, sub-Saharan Africa.

Data extraction and direction

A standardised data extraction tool volition be adapted from the Joanna Briggs Institute (JBI).60 The following variables will be extracted: main author proper name, publication twelvemonth, written report design, state/countries where the report was conducted, written report/follow-upwardly menses, sample size, sex/gender of the participants, LTFU charge per unit/proportion, adjusted confounders for LTFU (ie, sexual activity, residence, historic period, altitude from wellness facility, Art regimen, functional status, CD4 cell count, WHO clinical staging, Art adherence, OIs, cotrimoxazole preventive therapy, and isoniazid preventive therapy) and adapted Hour (AHR) for time-to-issue analysis/adjusted OR/adjusted hazard ratio (ARR) with 95% CIs. Any queries on primary article information collection or critical appraisement will lead to contact with respective authors. Failure to brand the necessary connectedness volition upshot in the commodity beingness excluded from our review. The primary author (AA) will excerpt data from included studies. To assure information quality, extracted data will exist double-checked by another author (DD).

Outcomes

The outcome of this review is LTFU among adults living with HIV. LTFU volition be identified equally events in which patients not returning to the ART clinic within 90 days (60 days afterwards the next engagement) from the last dispensary visit.nine Undernourished adults living with HIV will be considered as exposed the group to approximate the issue size of undernutrition on LTFU. Undernutrition (underweight) reflects an individual with a BMI of less than eighteen.v kg/chiliad2. The severity of undernutrition is further classified as severe (BMI <16 kg/m2), moderate (BMI 16–16.99 kg/m2) or mild (BMI 17–18.48 kg/mtwo).61

Risk of bias in individual studies

The Newcastle-Ottawa Scale (NOS) quality cess tool will exist used to assess the risk of bias in individual studies.62 The NOS is a validated tool with grading from zero to nine for case–command and cohort studies.63 The tool has iii components: selection, comparability, and issue/exposure. The selection office is scored from zero to 4 stars, and the comparability is scored from naught to two stars. The outcome/exposure is mainly related to the statistical analysis and cofounding treatment mechanisms, which is scored from zip to 3 stars. Furthermore, to minimise the subjective interpretation of bias from scoring the NOS, iii reviewers (AA, DD, and DS) will assess the quality of individual studies with consensus existence achieved on all instances. Inter-rater reliability volition exist assessed using Cohen'south kappa statistics. Finally, the quality score of each study volition be calculated as the sum of scores.

Information synthesis

All statistical analyses will be done using Stata (5.xvi) statistical software. The effect of undernutrition on LTFU will be estimated using the AHR by because undernutrition equally exposure variable. RRs, rate ratios and incidence density ratios volition be directly used as run a risk ratios. Adult HIV patients with BMI ≥18.five kg/gii will exist considered not-exposed (control group). In order to adjust for primary studies reporting AHRs considering undernourished adults living with HIV as a reference category, new AHRs with their 95% CIs will be estimated by considering the reciprocal of the reported AHRs to ensure consistency and uniformity.64 If a written report does not report RR/Hour simply reports the regression coefficient (β), we volition undertake conversion into RR/60 minutes by exponentiation of the coefficient (ie, RR=exp(β)).65 The outcome size (pooled AHR) volition exist estimated based on two nutritional condition categories (undernutrition vs well nourished). If reported AHR is based on the severity level of undernutrition (mild, moderate and severe), categories will be considered in the subgroup analyses. Finally, those studies reporting nutritional condition (BMI) equally a continuous variable and cantankerous-exclusive studies reported ORs which are not eligible for meta-analysis volition be addressed using a narrative synthesis arroyo.

Heterogeneity between included studies volition exist assessed using Cochrane Q-exam and I2 statistics. The I2 value volition be interpreted as: 0% to xl% (might not be important); xxx% to threescore% (may represent moderate heterogeneity; fifty%–90% (may correspond substantial heterogeneity); and 75%–100% (considerable heterogeneity).66 As heterogeneity is predictable, the pooled effect size and 95% CI will be estimated using a random-furnishings model with logit transformation and back transformation. Finally, all relevant findings will be presented using text, tables, and woods plots.

Subgroup and sensitivity analyses

When considerable heterogeneity (I2 ≥75%) is detected, potential sources of heterogeneity will be investigated using subgroup and meta-regression analyses. If appropriate, sub-grouping analyses will be conducted using different variables based on country, pattern, degree of undernutrition, sample size, and publication year. Furthermore, sensitivity analysis will be washed by sequential removal of individual studies from the analysis.

Meta-bias

If more eight private studies are included in a meta-analysis, funnel plots will be used to assess publication bias graphically.67 The Egger's and Begg'south tests at a 5% significance level will exist used to confirm publication bias.68 In the presence of significant publication bias, trim and fill analyses volition exist done, and adjusted effect sizes volition be reported.

Patient and public involvement statement

No involvement of patients or the public occurred during design, deport, reporting or dissemination plans in this inquiry.

Discussion

LTFU from ART became a significant public health problem equally Art was rapidly scaled up.4 10 11 Bear witness shows that undernutrition significantly increases the gamble of LTUF among adults living with HIV.42–47 Therefore, understanding the impact of undernutrition on LTFU is essential in designing advisable interventions. However, there is no systematic review and meta-analysis summarising available evidence about the pooled effect of undernutrition on LTFU among adults living with HIV in SSA. Thus, nosotros propose this systematic review and meta-analysis protocol which is feasible, accessible, and timely. This review is the offset systematic review examining the result of undernutrition on LTFU among adults living with HIV in SSA to the all-time of our knowledge.

This review will synthesise all the available studies reporting the effect of undernutrition on LTFU among adults living with HIV in SSA. Findings will be presented at conferences in poster or oral presentations. In addition, the terminal manuscript will be published in a peer-reviewed journal for broader dissemination. Furthermore, the final manuscript will report any reason for meaning changes to the protocol following publication.

This review has a number of strengths and limitations. The final manuscript of this review volition be reported in line with the PRISMA guidelines.69 This review volition pursue a comprehensive search strategy to include all eligible studies. Predefined eligibility criteria concerning population, exposure, control and outcomes will be applied. The final pooled effect size will be reported using AHR to control potential confounders. Despite these strengths, information technology is essential to acknowledge the possible anticipated limitations. By limiting our search to studies published in the English language, we are potentially missing a few important not-English studies. Varying definitions of LTFU and follow-up elapsing of the included studies may limit the comparability of data. All studies included in our systematic review might not exist included in our meta-assay as studies might report BMI in different categories.

Ideals and dissemination

Ethical approving is not required for a protocol for a systematic review. The results of this systematic review will be published in a peer-reviewed journal and will exist publicly available.

Ethics statements

Patient consent for publication

Supplementary materials

  • Supplementary Information

    This web simply file has been produced by the BMJ Publishing Group from an electronic file supplied past the author(s) and has non been edited for content.

    • Information supplement 1
    • Data supplement 2

Request Permissions

If you wish to reuse any or all of this article please employ the link below which will take you to the Copyright Clearance Center's RightsLink service. You will exist able to become a quick toll and instant permission to reuse the content in many different ways.

Copyright information:

© Author(southward) (or their employer(due south)) 2021. Re-employ permitted under CC BY-NC. No commercial re-use. See rights and permissions. Published by BMJ. http://creativecommons.org/licenses/by-nc/iv.0/ This is an open admission commodity distributed in accord with the Artistic Commons Attribution Non Commercial (CC Past-NC iv.0) license, which permits others to distribute, remix, arrange, build upon this piece of work not-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 utilize is non-commercial. Encounter: http://creativecommons.org/licenses/past-nc/4.0/.