HIV prevention and missed opportunities among people with recently acquired HIV infection: Α protocol for a systematic review
1Institute for Global Health, University College London, UK
2Department of Hygiene, Epidemiology and Medical Statistics, Medical School, National and Kapodistrian University of Athens, Athens, Greece
3Mortimer Market Centre, Central and North West London NHS Foundation Trust, undefined
4National Centre of Epidemiology, Carlos III Health Institute, Madrid, Spain
5Centro de Investigación Biomédica en Red Enfermedades Infecciosas, Madrid, Spain
6Department of Infectious Diseases, Amsterdam Infection & Immunity Institute, Amsterdam University Medical Centres, Amsterdam, The Netherlands
7HIV Monitoring Foundation, Amsterdam, The Netherlands
8Department of Surgical, Medical, Dental and Morphological Sciences with Interest Transplant, University of Modena and Reggio Emilia, Modena, Italy
9INSERM CESP U1018, APHP Hôpital de Bicêtre, Le Kremlin-Bicêtre, Paris-Saclay University, Gifsur-Yvette, France
10Paris, Paris, Île-de-France, France
11Department of Infectious Diseases, Karolinska University Hospital, Stockholm, Sweden
12INSERM, Institut Pierre Louis d’Epidémiologie et de Santé Publique, Sorbonne Université, AP- HP, Hôpital St Antoine, Paris, France
13INSERM, BPH, U1219, CIC-EC 1401, Universite Bordeaux, Bordeaux, France
14INRIA SISTM Team, Talence, France
15Inserm, IRD, SESSTIM, ISSPAM, Aix-Marseille Université, Marseille, France
16Southern Alberta HIV Clinic, Calgary, Alberta, Canada
*Corresponding author: Argyro Karakosta, a.karakosta@ucl.ac.uk; akarakosta@med.uoa.grAbstract
Background
Individuals who have recently acquired HIV represent a unique population because the time frame since HIV acquisition is relatively short and identification of missed HIV prevention opportunities is, therefore, closer to real time and less subject to recall bias. Identifying prevention measures used and missed opportunities for using them, can help stop further HIV transmission.
Objectives
This systematic review aims to synthesise current global evidence on uptake of HIV prevention methods among people with recently acquired HIV from 2007, the year that the concept of ART as a prevention method was first introduced.
Methods and analysis
MEDLINE/PubMed, EMBASE, PsycINFO, Cochrane and Web of Science databases, will be searched for articles published January 2007 - July 2023. Eligible studies will be those that reported on HIV prevention methods among people with recently acquired HIV. Quality assessment of the studies selected will be undertaken, and reporting of the systematic review will be informed by Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines.
Results
The results of the systematic review will be available by the end of January 2024.
Conclusions
The findings will be of key relevance to researchers, healthcare providers including third sector organisations/ community groups and policymakers, as they will offer insight into better understanding of missed or failed HIV prevention efforts and will help ensure future efforts meet the needs of those in need of them.
Article notes
Competing Interest Statement
Conflicts of interest The funders did not participate in the study design and will not intervene in its process, analysis or publication of the findings. ST has received speaker honoraria and consultancy fees from Gilead Sciences. CC has received speaker/moderator honoraria and advisory board fees from Gilead Sciences, GSK/ViiV and MSD as well as an unrestricted Gilead Sciences Nordic Fellowship Research Grant. CS has received funding from Gilead Sciences, ViiV Healthcare and Janssen-Cilag for participation in Advisory Boards, speaker panels and for preparation of educational materials. MVdV has received consultancies fees for participation in advisory boards and research grants from Gilead, MSD and ViiV all paid to his institution. FB has received funding from Gilead Sciences Ltd for preparation and delivery of educational materials. IJ has received teaching fees from ViiV Healthcare and advisory fees from Gilead Sciences. GT has received research grants and advisory board fees from Gilead, all paid to her institution, and MJG has received honoraria for ad hoc participation in national Advisory boards of Gilead Merck and ViiV.
Funding Statement
Yes
Introduction
HIV prevention has changed dramatically over the past three decades and effective combination prevention, that includes Pre-Exposure Prophylaxis (PrEP) and treatment as prevention (TasP) [1,2] as components, means elimination of HIV transmission is now feasible. As a consequence, prevention is a key component of the ambitious agenda set in 2021 by the global HIV community, “End Inequalities. End AIDS”. As part of the United Nations Declaration on Ending AIDS [3], Member States also committed to 95% of people at risk of HIV infection having access to appropriate, person-centred and effective combination prevention options by 2025. However, despite antiretroviral therapy (ART) being freely available to people living with HIV for many years [1] and widening access to PrEP [4,5], HIV transmission remains high, with around 1.5 million people estimated to have acquired HIV in 2021 [6]. Multiple HIV prevention strategies exist to reduce the risk of HIV acquisition and transmission; however, they remain underutilised [7].
Acute HIV infection (AHI, defined here as the first four weeks following HIV acquisition), and primary HIV infection (PHI, defined here as the six-month period following acquisition) [8], are a period of high infectiousness and may contribute disproportionately to ongoing HIV transmission [9]. People with recently acquired HIV are most likely to accurately recall the circumstances around acquisition, allowing identification and understanding of missed opportunities for HIV prevention. Studies of individuals with recently acquired HIV can provide useful insights for HIV prevention efforts and lead to a decline of transmission.
We propose undertaking a systematic review to synthesise current global evidence on prior access to and uptake of HIV prevention interventions among people with recently acquired HIV. To prevent duplication of reviews, a preliminary search of similar protocols and reviews was conducted in July 2023 using the Cochrane Library, MEDLINE, Embase, PubMed, Web of Science, PsycINFO and The International Prospective Register of Systematic Reviews (PROSPERO) databases. No review protocol or systematic review on this topic was identified. Rather, systematic reviews on recently acquired HIV, identified through searches of these databases, examined the diagnostic, clinical and public health implications of identifying and treating people with recently acquired HIV [10-18]. A consistent theme among these studies was the important contribution of people with recently acquired HIV to HIV epidemics, as several groups have reported disproportionate rates of onward HIV transmission from individuals with acute infection, although this issue remains controversial [11]. According to these studies, transmission clusters tend to be driven by recently acquired undiagnosed infection, and although estimates are highly variable, recently acquired HIV has been identified as the source for between 10% and 50% of all transmissions [18]. During the earliest stages of HIV infection plasma viral load levels increase exponentially, and this comprises a dominant factor predicting transmission to sexual partners [19]. In addition, discrepancies in the reported contribution of recently acquired HIV infection to ongoing epidemics could be explained by differences in epidemic stage, definitions of “early HIV”, and variation in sexual behaviours (i.e., anal vs. vaginal intercourse, partner change rates, etc.) [13,18,19]. Even in a well-established HIV epidemic where the role of recently acquired HIV generally appears to be lower, detection of persons with recently acquired HIV provides an opportunity to intervene at the earliest possible stage of infection [12] to reduce the risk of missed opportunities for prevention of onward HIV transmission.
A better understanding of missed or failed HIV prevention opportunities will help ensure prevention efforts better meet those in need of them. This systematic review aims to synthesise current global evidence on uptake of HIV prevention methods among people with recently acquired HIV. Specifically, this systematic review seeks to answer the following questions: 1) What HIV prevention methods have people with recently acquired HIV used, if any? 2) What are the structural and behavioural barriers to the uptake, use of, and adherence to HIV prevention methods?
Materials and Methods
This will be a systematic review designed to summarise evidence of prior access to and uptake of HIV prevention methods among people who had recently acquired HIV infection. The review will commence in September 2023. This protocol has been developed in accordance with the Preferred Reporting Items for Systematic Review and Meta-Analysis Protocols (PRISMA-P) guidelines [20] [Appendix 1] and reporting of the synthesised findings will also be informed by PRISMA guidelines [21]. Additionally, this protocol is registered in PROSPERO (CRD42023454414). Important amendments to this protocol will be published along with the results of the systematic review.
For this review, recently acquired HIV will mean HIV acquisition within the 12 months preceding HIV diagnosis. For each included study we will document the criteria used to establish recency, with the gold standard being the availability of an HIV-negative antibody test within 12 months of the first positive one, or other laboratory evidence of acute HIV infection.
Searches
We will search peer reviewed articles on the access and use of HIV prevention interventions among people with recent HIV infection, published in English, from 1 January 2007 to 17 July 2023 (2007 being the year that the concept of ART as a prevention method was introduced [22]). From our search, we will identify studies that assessed at least one of: HIV prevention, condom use, uptake of HIV testing, PrEP, post exposure prophylaxis (PEP), harm reduction (i.e., needle exchange, opioid substitution therapy (OSP), etc.), counselling. The search will be performed in the following databases:
- CINAHL Plus
- MEDLINE
- PubMed
- PsycINFO
- Web of Science
- EMBASE
The following search strategy will be adapted for all databases.
Searches will combine key terms relating to HIV/AIDS (HIV, AIDS, human immunodeficiency virus, etc.) with terms related to recently acquired HIV (seroconverter, acute infection, recent infection, recently acquired, etc.) and terms related to preventions methods (condoms, preexposure prophylaxis, HIV testing, counselling, treatment, combination prevention, etc.). See Appendix 2 for full search strategy.
Types of study to be included
All types of epidemiological studies including randomised controlled trials (RCTs), case-control studies, and cohort studies, both with and without a control group, will be included. RCTs where the intervention is some type of prevention will not be considered, except if baseline information about prevention is mentioned. Qualitative studies will be excluded as our group has recently published a systematic review of qualitative literature on recently acquired HIV [8]. Studies that are not peer-reviewed will also be excluded. Studies employing mixed methods approaches will be included where the quantitative component is presented in sufficient detail. We will not include grey literature or review articles.
Participants/population
This review will include studies from any country on adults aged 16 years and over who have recently acquired HIV and where use of at least one HIV prevention method is measured.
The review will exclude studies which focus on people who have recently been diagnosed with HIV, but where the time of HIV acquisition is not known, or if no HIV prevention method is mentioned. We will exclude studies in those aged under 16.
Intervention(s), exposure(s)
The focus of this review is on prevention methods among people with recently acquired HIV. Preliminary engagement with the literature suggests that this will include: mapping of current HIV prevention methods among people with recently acquired HIV and factors affecting the use of prevention measures (address barriers to uptake, use of, and adherence to strategies to prevent HIV transmission).
Main outcome(s)
The expected outcomes are identifying the prevention methods used, and not used, by people with recently acquired HIV and identifying the barriers to uptake of, use of, and adherence to strategies to prevent HIV acquisition.
Eligibility criteria
This review will include studies which report on adults aged 16 years and over who have recently acquired HIV and where use of at least one HIV prevention method is measured, published between 1/1/2007 and 31/7/2023, and written in English.
Exclusion criteria
No known time of HIV acquisition/ seroconversion, younger than 16 years of age, published earlier than 2007 or recruitment of population earlier than 2007. Studies combining adults and paediatric/adolescent patients will be included only if able to disaggregate results by age to identify those aged ≥16.
Study selection
Potential articles will be collected in the systematic review software Covidence [23]. Duplicates will be removed by AK using Covidence software. Based on the pre-specified eligibility criteria, studies will be selected using a two-staged approach; titles and abstracts will be examined first and then the full-text of all potential eligible studies will be retrieved and screened. AK and ER-B will independently screen a sample of 100 citations to pre-test and refine coding guidance based on the inclusion criteria and until at least 90% agreement is achieved. Disagreements about eligibility will be resolved through discussion. AK will then screen the remaining citations for inclusion in the review using the pre-tested coding guidance. Full-text of all potentially eligible studies will be retrieved and AK and ER-B will assess all full text articles to determine final study selection. Differences will be resolved through consensus, with input on eligibility from a third reviewer (FB) when necessary. Citations that do not meet the inclusion criteria will be excluded and the reason for exclusion will be recorded at the full-text screening.
Assessment of risk of bias and quality of evidence
The quality of each included study will be assessed by using the Newcastle Ottawa Scale (NOS) for cohort studies and modified NOS for cross-sectional and case-control studies [24]. We assume that there will be no or very few RCTs on this topic and we will, therefore, use the National Institute for Health and Care Excellence (UK) Quality Appraisal of Intervention Studies tool (derived from Jackson et al., 2006 [25]) as a risk of bias assessment tool. Each paper included in the review will be quality assessed by AK and ER-B. All disagreements will be resolved through consensus. FB will be consulted to discuss any discrepancies in study quality assessment.
Data extraction
Data will be extracted from the final articles using a standardised form in Covidence. This will include: 1) characteristics of the study: author, year of publication, study objective, country and context, 2) methodological characteristics: study design, research questions and/or hypotheses, study population, definition of recently acquired HIV used, sample characteristics, type of prevention’/s’ measure/s mentioned, 3) main findings and conclusions.
Data synthesis
A narrative (descriptive) synthesis of the data will be conducted, after a final list of papers has been compiled. This discussion will be tailored around the type of prevention strategy, target population characteristics, barriers to uptake, use of and adherence to prevention strategies.
Provided the studies are sufficiently homogeneous and comparable regarding study design, percentages will be pooled through meta-analysis or even meta-regression to explain part of the variability.
Reporting of the systematic review will be informed by Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines [21], as mentioned before.
PROSPERO registration number
CRD42023454414
Patient and Public Involvement (PPI)
Community members have been involved in the conception and design of this protocol and will contribute to interpretation and dissemination of findings.
Ethics and dissemination
Ethics approval is not required for a systematic review. Findings of the systematic review will be disseminated through open access publication in a peer-reviewed journal. The findings will be of interest to researchers, healthcare practitioners, policymakers, and HIV community partners.
Results
This review will be undertaken as part of the CASCADE Collaboration, a mixed methods international study investigating the medical and lived experiences of people with recently acquired HIV (https://www.cascadestudy.net/) [26]. We expect that the review will be completed by the end of January 2024. We will report the results based on the identified outcomes as specified above.
Discussion
Despite new and effective interventions and declines in HIV incidence across Western Europe, a significant number of people continue to acquire HIV. In this systematic review, we are committed to producing evidence that addresses barriers in access to HIV prevention. People who have recently acquired HIV are a unique, and ideal group, in whom to study these clinically and public health relevant questions, and to assess prevention methods used. We believe that our data are extremely relevant to ongoing HIV prevention efforts.
The review will provide evidence to inform the provision of HIV treatment and prevention services. The expected outcomes are identifying the prevention methods used, whether they are used appropriately and effectively by people with recently acquired HIV, and examining the structural and behavioural barriers to uptake, use of, and adherence to HIV prevention measures.
Data Availability
No datasets were generated or analysed during the current study.
Collaborators
CASCADE Collaboration: CASCADE Executive Committee: Santiago Moreno (Chair), Fiona Burns, Rafael Eduardo Campo, Harmony Garges, Cristina Mussini, Nikos Pantazis, Barbara Pinto, Kholoud Porter, Caroline Sabin, Shema Tariq, Giota Touloumi, Vani Vannappagari, Alain Volny Anne, Lital Young. CASCADE Scientific Steering Committee: John Gill (co-chair), Kholoud Porter (co-chair), Christina Carlander, Rafael Eduardo Campo, Harmony Garges, Sophie Grabar, Inma Jarrín, Laurence Meyer, Barbara Pinto, Giota Touloumi, Marc van der Valk, Vani Vannappagari, Alain Volny Anne, Linda Wittkop, Lital Young. CASCADE Social Science subcommittee: Shema Tariq (Chair), Agnes Aisam, Diana Barger, Udi Davidovich, Marie Dos Santos, Lars Eriksson, Eli Fitzgerald, John Gill, Sophie Grabar, Inma Jarrín, Argyro Karakosta, Hartmut Krentz, Cristina Mussini, Emily Jay Nicholls, Nicoletta Policek, Elisa Ruiz-Burga, Chris Sandford, Bruno Spire, Inés Suárez-García, Giota Touloumi, Alain Volny Anne.
Supporting Information
S1 Appendix 1. PRISMA-P (preferred reporting items for systematic review and meta-analysis protocols) 2015 checklist: recommended items to address in a systematic review protocol.
S2 Appendix 2. Full systematic review database search string
Abbreviations
- HIV
- Human Immunodeficiency Virus
- ART
- Antiretroviral Therapy
- PrEP
- Pre-Exposure Prophylaxis
- TasP
- Treatment as Prevention
- AHI
- Acute HIV Infection
- PHI
- Primary HIV Infection
- PRISMA-P
- Preferred Reporting Items for Systematic Review and Meta-Analysis Protocols
- PRISMA
- Preferred Reporting Items for Systematic Review and Meta-Analysis
- PEP
- Post Exposure Prophylaxis
- OSP
- Opioid Substitution Therapy
- RCTs
- Randomized controlled trials
- NOS
- Newcastle Ottawa Scale
Supporting Information
S1 Appendix 1
PRISMA-P (preferred reporting items for systematic review and meta-analysis protocols) 2015 checklist: recommended items to address in a systematic review protocol.
From: Shamseer L, Moher D, Clarke M, Ghersi D, Liberati A, Petticrew M, Shekelle P, Stewart LA, the PRISMA-P Group. Preferred reporting items for systematic review and meta-analysis protocols (PRISMA-P) 2015: elaboration and explanation. BMJ. 2015;349:g7647.