#AWARE.HIV Europe: Supporting Healthcare Professionals to Find Undiagnosed HIV in European Hospitals: An Effectiveness-implementation Trial.

Overview

The #aware.hiv Europe study is a real-world, multicenter, stepped-wedge cluster randomized, effectiveness-implementation trial designed to evaluate whether the introduction of dedicated HIV teams in hospitals can improve HIV testing rates among patients presenting with HIV indicator conditions across ten European countries. Study Design: The study employs a stepped-wedge design, whereby clusters of hospitals transition sequentially from a control phase (routine care) to an intervention phase. All patient data are collected retrospectively from routine care, while prospective data are gathered at the healthcare professional level. The project spans four years and involves hospitals from the Netherlands, Belgium, United Kingdom, Germany, Spain, France, Italy, Romania, Poland, and Ukraine. This design allows for comparison of HIV testing rates and related outcomes before and after the implementation across different settings and time points. Intervention: The core intervention involves the establishment of hospital-based HIV teams. Each team is led by an HIV specialist and supported by nurses and data collectors. Their responsibilities include: Identification and Surveillance: Screening routine electronic health records for HIV indicator conditions using predefined ICD-10 codes and verifying cases that warrant HIV testing. Audit \& Feedback: Providing targeted recommendations to treating physicians when an HIV test is indicated but has not been performed, thereby prompting action. Education \& Training: Delivering training sessions to healthcare professionals to improve their knowledge and attitudes towards HIV testing, prevention, and care. Enabling Environment: Implementing digital solutions and other support mechanisms to streamline testing processes, reduce stigma, and enhance overall guideline adherence. Linkage to prevention: Improving linkage to the locally available preventive services. The intervention is intended to integrate seamlessly into routine hospital care, thereby reinforcing existing guidelines while addressing the current diagnostic testing gap. Endpoints and Outcome Measures: Primary Endpoint: The change in HIV testing rate among patients diagnosed with HIV indicator conditions before and after the implementation of HIV teams. Key Secondary Endpoints: The change in the incidence of new HIV diagnoses among patients with HIV indicator conditions. Variations in HIV testing rates across different countries, medical specialties, and types of indicator conditions, as well as over time. Assessment of the cascade of HIV diagnosis, including the proportion of patients identified with an indicator condition, the offer and acceptance of HIV testing, and documented reasons for non-testing. Evaluation of the cascade of HIV care and prevention, including linkage to HIV care, achievement of viral suppression, and referral and uptake of preventive services. Changes in healthcare professionals' knowledge, attitudes, and levels of stigma towards HIV. Implementation outcomes such as fidelity of HIV team activities, resource utilization, cost-effectiveness, and sustainability of the intervention. Analysis of contextual factors, barriers, and facilitators impacting the implementation process, using established frameworks like CFIR and RE-AIM. Impact: By introducing HIV teams and systematically monitoring their effect on HIV testing practices, the study aims to enhance early HIV diagnosis and improve patient outcomes. The findings will contribute to evidence-based guidelines and may promote the adoption of similar interventions across European healthcare settings, ultimately reducing HIV-associated morbidity, mortality, and transmission rates. This project not only addresses a critical diagnostic gap in HIV care but also provides valuable insights into the effective implementation of complex interventions in routine clinical practice.

Interventions

• Behavioral HIV team implementation
  A local hiv team will be implemented in a certain hospital. This will result in different activities, with a focus on: * audit and feedback (reminding health care professionals to test for hiv) * stigma reduction (raising awareness on existing hiv stigma towards hiv) * education (increasing knowledge on hiv among health care professionals) * linkage to prevention and care (improving pathways for hiv care and prevention)

Primary outcome measures

• HIV testing rate in patients with HIV indicator conditions [Time frame: Comparison between 1 year of implementation and a control phase lasting between 6 to 18 months, depending on the site's randomization in the stepped-wedge trial design.]

Secondary outcome measures (12)

• HIV incidence in patients with HIV indicator conditions [Time frame: Comparison between 1 year of implementation and a control phase lasting between 6 to 18 months, depending on the site's randomization in the stepped-wedge trial design.]
• Subgroup analysis 1: HIV testing rate by country and region [Time frame: Comparison between 1 year of implementation and a control phase lasting between 6 to 18 months, depending on the site's randomization in the stepped-wedge trial design.]
• Subgroup analysis 2: HIV testing rate by HIV indicator condition [Time frame: Comparison between 1 year of implementation and a control phase lasting between 6 to 18 months, depending on the site's randomization in the stepped-wedge trial design.]
• Subgroup analysis 3: HIV testing rate by medical specialty [Time frame: Comparison between 1 year of implementation and a control phase lasting between 6 to 18 months, depending on the site's randomization in the stepped-wedge trial design.]
• Subgroup analysis 4: HIV testing rate over time [Time frame: Comparison between 1 year of implementation and a control phase lasting between 6 to 18 months, depending on the site's randomization in the stepped-wedge trial design.]
• Cascade 1: The cascade of HIV diagnosis [Time frame: Comparison between 1 year of implementation and a control phase lasting between 6 to 18 months, depending on the site's randomization in the stepped-wedge trial design.]
• Cascade 1b: The cascade of HIV diagnosis - reasons for not testing for HIV [Time frame: Comparison between 1 year of implementation and a control phase lasting between 6 to 18 months, depending on the site's randomization in the stepped-wedge trial design.]
• Cascade 1c: The cascade of HIV diagnosis - descriptions of existing consent procedures in different hospital sites [Time frame: Description of consent procedures as documented during the 1-year implementation phase across different hospital sites.]
• Cascade 2: The cascade of HIV care [Time frame: Comparison between 1 year of implementation and a control phase lasting between 6 to 18 months, depending on the site's randomization in the stepped-wedge trial design.]
• Cascade 3: The cascade of HIV prevention [Time frame: Comparison between 1 year of implementation and a control phase lasting between 6 to 18 months, depending on the site's randomization in the stepped-wedge trial design.]
• HIV stigma indicators among health care professionals [Time frame: Assessed at baseline (before implementation) and at 12 months (after 1 year of implementation).]
• Implementation science 1: Assessment of key barriers and facilitators over time (CFIR) [Time frame: Every 3 months during the implementation phase (first year). Every 6 months during the continuation phase (up to 3 years post-implementation).]

Eligibility criteria

Since this study involves screening individuals presenting to a specific hospital through a hospital-wide intervention, the inclusion and exclusion criteria are established at the hospital level.

Inclusion criteria

• Standard of care: HIV testing for HIV indicator conditions should be part of routine care in the country, and any prevailing guidelines on HIV testing and prevention policies can be integrated.
• Management approval: Hospital management must be willing to allocate resources and provide authorization for the proposed activities, including Surveillance, Audit \& Feedback, Education \& Training, Linkage to Prevention, and fostering an Enabling Environment, including stigma reduction.
• Resources: Assembling an HIV team led by a local HIV expert should be viable considering the available human resources.
• Data collection: There should be an IT specialist and IT infrastructure capable of flagging a pre-defined set of HIV indicator conditions and monitoring the project's implementation effects with feedback loops to healthcare professionals.
• Quality assurance: Continuous linkage for care and access to antiretroviral therapy must be assured.
• Ethics and Regulatory Compliance: Provision for ethical and regulatory compliance is necessary.

Exclusion criteria

Any hospital that does not meet the inclusion criteria will be excluded from participation. We will not use data of patients who have objected against the use of their data for research.

Criteria are shown verbatim from the registry (in English). Final eligibility is always assessed by the study center.

Healthy volunteers: Yes

Study design

Allocation

N/A

Model

Sequential

Masking

Open label

Primary purpose

Diagnostic

Study locations

Netherlands · 5 centers

• Rijnstate ziekenhuis — Arnhem
• Stichting Catharina Ziekenhuis — Eindhoven
• University Medical Center Groningen — Groningen
• Stichting Maasstad Ziekenhuis — Rotterdam
• Haga Ziekenhuis — The Hague

Romania · 5 centers

• Central Military Emergency University Hospital "Dr. Carol Davila" — Bucharest
• Clinical Emergency Hospital "Prof. Dr. Agrippa Ionescu" — Bucharest
• National Institute for Infectious Diseases "Prof. Dr. Matei Bals" — Bucharest
• Fundeni Clinical institute — Bucharest
• Spitalul Universitar de Urgență București — Bucharest

Germany · 4 centers

• St. Joseph Krankenhaus Berlin Tempelhof — Berlin
• Charité Universitätsmedizin Berlin — Berlin
• Cologne University Hospital — Cologne
• Klinikum der Technischen Universität München (TUM) — München

Poland · 3 centers

• SPZZOZ Janów Lubelski — Janów Lubelski
• Wojewodzki Szpital Zespolony — Kielce
• Państwowy Instytut Medyczny MSWiA w Warszawie — Warsaw

Spain · 3 centers

• Hospital Universitario La Paz-Carlos III — Madrid
• Infanta Leonor — Madrid
• La Princesa — Madrid

Italy · 2 centers

• Ospedale San Raffaele S.r.l — Milan
• L'Istituto Nazionale per le Malattie Infettive "L. Spallanzani" IRCCS — Roma

Ukraine · 2 centers

• Central city clinical hospital of Ivano-Frankivsk city council — Ivano-Frankivsk
• Lviv National Medical University — Lviv

United Kingdom · 2 centers

• Buckinghamshire Healthcare NHS Trust — Aylesbury
• Royal Free London — London

Belgium · 1 center

• University Hospital Ghent — Ghent

France · 1 center

• European hospital of Marseille — Marseille

Publications

• Jordans CCE, Vliegenthart-Jongbloed K, Osbak KK, Hanssen JLJ, van Beek J, Vriesde M, van Holten N, Dorama W, van der Sluis D, de Steenwinkel J, van Kampen J, Verbon A, Roukens AHE, Rokx C. Implementing HIV teams sustainably improves HIV indicator condition testing rates in hospitals in the Netherlands: the #aware.hiv clinical trial. AIDS. 2025 Jul 1;39(8):995-1004. doi: 10.1097/QAD.000000000000416 PMID 40053486
• Jordans CCE, Vliegenthart-Jongbloed KJ, van Bruggen AW, van Holten N, van Beek JEA, Vriesde M, van der Sluis D, Verbon A, Roukens AHE, Stutterheim SE, Rokx C. Unmasking Individual and Institutional HIV Stigma in Hospitals: Perspectives of Dutch Healthcare Providers. AIDS Behav. 2024 Sep;28(9):3184-3195. doi: 10.1007/s10461-024-04404-0. Epub 2024 Jun 13. PMID 38869755
• Vliegenthart-Jongbloed KJ, Vasylyev M, Jordans CCE, Bernardino JI, Nozza S, Psomas CK, Voit F, Barber TJ, Skrzat-Klapaczynska A, Sandulescu O, Rokx C; #aware.hiv Europe Project. Systematic Review: Strategies for Improving HIV Testing and Detection Rates in European Hospitals. Microorganisms. 2024 Jan 25;12(2):254. doi: 10.3390/microorganisms12020254. PMID 38399659

Identifiers

NCT: NCT06900829 · MEC-2024-0236

Primary sources (government registries)

• ClinicalTrials.gov (US NIH)

View this study on ClinicalTrials.gov ↗