Pre-exposure prophylaxis (PrEP) is a proven biomedical strategy for preventing HIV infection in high-risk populations; however, the existing body of literature highlights inconsistency in outcome measurement as a major concern. Developing a Core Outcome Set (COS) for PrEP studies could reduce inconsistency, improve evidence synthesis, and ensure that outcomes relevant to all stakeholders are captured. Therefore, this review aims to systematically identify and map all outcomes reported in studies on PrEP for HIV prevention to inform COS development. This scoping review will follow the methodology of the Joanna Briggs Institute and will be reported in accordance with the Preferred Reporting Items for Systematic Reviews and Meta-Analyses guidelines. We will include studies involving any population using or eligible for PrEP, reporting outcomes related to PrEP, and conducted in any setting. Eligible study designs will include randomized controlled trials, cohort studies, case-control studies, and cross-sectional studies. There will be no restriction on year of publication; however, only studies published in English will be included. Electronic databases including MEDLINE, EMBASE, Cochrane Library, CINAHL, Web of Science, and Global Market Insights (GMI) will be searched. Search terms will include variations of “PrEP,” “outcome,” “endpoint,” and “measure.” Study selection and data extraction will be conducted independently by two reviewers using Covidence and DistillerSR (Version 2), with disagreements resolved through consensus or consultation with a third reviewer. Outcomes will be categorized using the Core Outcome Measures in Effectiveness Trials (COMET) initiative taxonomy. Frequencies of outcome reporting will be calculated and summarized. Quantitative and qualitative analyses will be conducted using STATA version 18.0 and QDA Miner Lite. Stakeholders involved in PrEP research and implementation will be engaged to refine outcome domains and support COS development. Findings will be disseminated through peer-reviewed publications, conference presentations, plain-language summaries, and preprint repositories, and will inform a subsequent Delphi survey or other consensus process. Ethical approval is not required for this review. The protocol will be registered with the COMET initiative and the International Platform of Registered Systematic Review and Meta-analysis Protocols (INPLASY)
Lawrence Mbuagbaw1, Roseline Dzekem Dine1, Nataly Ayoub1, Haranie Sivakumar1, Guillaume Fontaine2, Shirin Golchi2, Moodie Zoe3, Lara Maleyeff2, Marc Parsons2
Affiliations
1. McMaster University, Department of Health Research Methods, Evidence and Impact, Hamilton, ON, Canada
2. McGill University, Implementation Science Laboratory, Montreal, QC, Canada
3. University of Winnipeg, Winnipeg, Manitoba, Canada
Emails
1. mbuagblc@mcmaster.ca
2. diner@mcmaster.ca
3. ayoubn1@mcmaster.ca
4. sivakh3@mcmaster.ca
5. guil.fontaine@mcgill.ca
6. shirin.golchi@mcgill.ca
7. zoe@fredhutch.org
8. lara.maleyeff@mcgill.ca
9. marc.parsons@mail.mcgill.ca
Contributions
1. Conceptualization, acquisition of funding, and drafting of the study protocol
2. Drafting of the study protocol and data screening
3. Data screening
4. Data screening
5. Conceptualization and acquisition of funding
6. Conceptualization and acquisition of funding
7. Conceptualization and acquisition of funding
8. Conceptualization and acquisition of funding
9. Conceptualization and acquisition of funding
Disease Category: Infectious disease
Disease Name: HIV/AIDS
Age Range: 0 - 120
Sex: Either
Nature of Intervention: Prevention
- Researchers
- Systematic review of outcomes measured in trials
- Systematic review
11. Methods
11.1 Framework
This review will follow the Joanna Briggs Institute (JBI) methodology for scoping reviews and be reported in line with the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines. (10)
11.2 Eligibility Criteria
• Inclusion Criteria:
• Population: Any population using or eligible for PrEP
• Concept: Outcomes related to PrEP for HIV prevention
• Context: Any setting
• Study Types: RCTs, cohort studies, case-control, cross-sectional,
• Timeframe: No date restrictions
• Language: English
• Exclusion Criteria:
• Studies not related to PrEP
• Outcomes unrelated to PrEP (e.g., PEP, ART outcomes)
• Editorials, opinion pieces, protocols
• Non-English publications
• Reviews, qualitative studies, and modelling studies
• Article for which the full text cannot be retrieved
11.3 Interventions
We included PrEP studies that studied any PrEP regimen. The regimen, whether allocated individually or within a cluster, delivered online or in-person by any provider, will be included.
• Any PrEP regimen versus no other intervention
• Any PrEP regimen versus other types of intervention
• Any PrEP regimen versus another PrEP regimen
11.4 Information Sources and Search Strategy
A systematic search will be conducted on electronic databases such as MEDLINE, EMBASE, COCHRANE, CINAHL, GLOBAL MARKET INSIGHTS (GMI), and WEB of SCIENCE. Search terms included variations of 'PrEP', 'outcome', 'endpoint', 'measure', and will be refined with a librarian.
11.5 Study Selection
All article titles and abstracts will be screened independently by two reviewers using Covidence. Full-text screening of the included articles will then be conducted using DistillerSR Version 2. Any discrepancies will be resolved through discussion or by consultation with a third reviewer.
11.6 Data Extraction
A standardized data extraction form will be used to collect data. The form will be designed in DistillerSR Version 2 to capture study characteristics (authors, publication type, country, WHO region, sample size, setting, study design, income level, and PrEP regimen), participant characteristics (population, inclusion criteria, mean or median age, and gender), and reported outcomes (including implementation, service, and client outcomes), with additional details extracted for each outcome captured.
The form will be piloted on 10 studies and revised as necessary to ensure rigor and completeness in the data extraction process. Disagreements during data extraction will be resolved by consensus, and if two extractors are unable to reach a consensus, a third reviewer will be consulted.
11.7 Study outcomes
We aim to capture the following outcomes: PrEP uptake/initiation, HIV incidence (effectiveness), adherence to PrEP, persistence on PrEP, drug resistance, breakthrough infections, safety, adverse events, behavioral changes (e.g., condom use, number of partners), social support, internalized stigma, psychological distress, self-efficacy, treatment satisfaction, and quality of life. We will also capture any additional outcomes related to how PrEP results are measured, to inform reporting in future studies.
11.8 Data Synthesis
Outcomes will be grouped thematically using the Core Outcome Measures in Effectiveness Trials (COMET) initiative taxonomy. (11) Frequencies of outcome occurrence will be calculated and grouped according to types, for instance, clinical, behavioural, patient-reported outcomes (PROs), implementation, and laboratory, based on the approach suggested by Levac et al.(12)
11.9 Data Management
Collected data will be stored on a password-protected system and backed up in the cloud. Missing data will be identified and handled appropriately. Stored quantitative data will be converted in STATA version 18.0, and qualitative data in QDA Miner Lite, where further cleaning and analysis will be conducted. Any discrepancies will be resolved through consensus. Extracted data will be verified to ensure accuracy and relevance to PrEP.
12. Stakeholder Involvement
We will invite stakeholders (clinicians, researchers, public health, community members, people with lived experience) in the PrEP scope around the world to refine outcome categories and COS development.
13. Dissemination Plan
Results will be shared via peer-reviewed publication, conference presentations, plain-language summaries, preprint repositories, and integrated into a Delphi survey or other consensus process.
14. Ethics and Registration
As a scoping review of existing literature, this study will not require ethical approval, as data will be extracted from previously published sources. Any conflicts of interest regarding the inclusion or exclusion of articles in this scoping review will be disclosed. However, our protocol will be registered with COMET initiative and the International Platform of Registered Systematic Review and Meta-analysis Protocols (INPLASY)