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

Number of newly diagnosed HIV infections among patients with an HIV indicator condition, compared between the control and implementation phases.

Difference in HIV testing rate within and between countries, as well as between geographic regions (West: Netherlands, Belgium, UK, Germany; South: France, Italy, Spain; East: Poland, Romania, Ukraine), comparing the control and implementation phases.

Difference in HIV testing rate across different HIV indicator conditions, comparing the control and implementation phases.

Difference in HIV testing rate across medical specialties, comparing the control and implementation phases.

Change in HIV testing rate over time, comparing the control and implementation phases.

Proportion of patients with a confirmed HIV indicator condition (focus population) who were offered an HIV test (reach) and who accepted testing (uptake), compared between the control and implementation phases.

Qualitative analysis of documented reasons why patients with an HIV indicator condition did not receive an HIV test. Reasons will be classified according to predefined categories used in the study database:

No reason registered (1) Patient was not seen again (2) Advice to the general practitioner or public health to test (3) No perceived indication or risk factors (4) Alternative diagnosis/explanation (5) No recommendation in local protocol (6) Patient refused (7) Shared decision-making not to test (8) Lack of time or opportunity (9) Planned but not performed (10) Already tested (confirmed) (11) Already tested (not confirmed or inadequate according to the SOP) (12) Palliative care or patient deceased during follow-up (13) Other (14)

Qualitative description of the consent procedures in place for HIV testing across different hospital sites. This includes:

The types of consent procedures in use, such as verbal or written consent. National or institutional guidelines or local standard procedures that shape consent practices.

Data will be collected per site to document existing practices without assessing implementation or adherence.

Proportion of patients with a confirmed HIV indicator condition who were newly diagnosed with HIV (focus population) and subsequently linked or re-linked to routine HIV care (reach), with viral suppression as an indicator of successful engagement in care (uptake), compared between the control and implementation phases.

Proportion of patients with a confirmed HIV indicator condition who met the eligibility criteria for HIV prevention (focus population), were appropriately referred to prevention services (reach), and engaged in prevention interventions (uptake), compared between the control and implementation phases.

Descriptive assessment of self-reported HIV stigma among licensed healthcare professionals, including physicians, nurse practitioners, and physician assistants, before and after implementation. Stigma will be measured using a validated questionnaire developed by the Health Policy Project and USAID, and adapted from the ECDC survey published in Annex 1 of the report: "HIV stigma in the healthcare setting. Monitoring implementation of the Dublin Declaration on partnership to fight HIV/AIDS in Europe and Central Asia 2024."

The survey includes self-reported responses on multiple dimensions of HIV stigma, expressed as percentages of participants reporting:

1. Fear of HIV infection
2. Institutional facilitators and barriers
3. Negative attitudes towards people with HIV
4. Observed stigma in clinical settings.

This is a descriptive outcome measure, reporting the proportion of participants endorsing each stigma-related item before and after the intervention.

Description:

Descriptive assessment of perceived barriers and facilitators to implementing and sustaining the HIV team intervention in hospital settings. Barriers and facilitators will be assessed based on a structured survey, capturing key constructs from the Consolidated Framework for Implementation Research (CFIR): Intervention characteristics, Outer setting, Inner setting, Characteristics of individuals and the Implementation process.

Survey items will be derived from a systematic review of barriers and facilitators to HIV indicator condition-based testing. The review will be published separately.

Data will be collected via an online survey in Castor, administered to the HIV team lead at each participating site

Proportion of patients with HIV indicator conditions who received an HIV test with direct (= feedback) or indirect (= other implementation strategies) involvement of the HIV team, stratified by:

• Country, hospital, and specialty to assess variation in reach
• Equity analysis: evaluating differences in testing uptake by age and sex

Proportion of individuals who test HIV-positive among:

All individuals tested for HIV (primary analysis). All individuals identified with an HIV indicator condition (secondary analysis).

Assessment of the impact of the HIV indicator condition-based testing approach on CD4 count at HIV diagnosis, measured as a continuous variable to assess shifts in stage at presentation.

Primary analysis:

Mean CD4 count at HIV diagnosis in the intervention phase vs. control phase (continuous variable).

Secondary analysis:

Distribution of CD4 counts at diagnosis (percentiles and quartiles) to evaluate changes in the proportion of late-stage diagnoses.

Proportion of patients diagnosed with advanced HIV (CD4 <200 cells/µL) in both phases.

Proportion of patients diagnosed with late-stage HIV (CD4 <350 cells/µL) in both phases.

Proportion of patients diagnosed at higher CD4 thresholds (e.g., >500 cells/µL) to assess shifts towards earlier diagnosis.

Hospital adoption rate (%): Proportion of participating hospitals that have adopted all core components of HIV indicator condition-based testing.

as well as: Degree of adoption across the hospital (%): Proportion of hospital departments (inpatients, outpatients, SEH, IC) that are included in the surveillance of HIV indicator condition-based testing.

This outcome assesses the degree to which the #aware.hiv Europe implementation strategies were delivered as intended across participating hospitals.

Percentage of flagged potential HIV indicator conditions that were assessed by the HIV team (surveillance) Percentage of untested indicator conditions for which HIV testing advice was provided to physicians (feedback) Number of teaching sessions delivered compared to the intended frequency, with a minimum of one session every three months in the implementation phase (teaching).

Number of stigma-reducing events organized, with a minimum requirement of one event in the implementation phase (stigma).

This outcome assesses the extent to which the #aware.hiv Europe implementation strategies were adapted to fit the local context while maintaining core components across participating hospitals.

The number and type of modifications made to the implementation strategy at the hospital level will be assessed using qualitative data collected via a structured questionnaire. Responses will be categorized according to the key components of the implementation strategy:

• Audit and Feedback
• Teaching and Education
• Enabling Environment (including stigma reduction)
• Linkage to Prevention

This outcome assesses how acceptable and appropriate the #aware.hiv Europe implementation strategies are perceived by healthcare professionals authorised to request HIV tests, using questions embedded in the hospital-wide stigma questionnaire.

Cost-effectiveness will be estimated by calculating the budget impact and Quality-Adjusted Life Years (QALYs) saved to define an Incremental Cost-Effectiveness Ratio (ICER).

The epidemiological impact will be estimated by quantifying the number of earlier HIV diagnoses achieved through the intervention, and modelling the resulting reduction in the number of person-years spent living with undiagnosed HIV. In addition, the number of secondary HIV infections potentially averted due to earlier diagnosis and treatment initiation will be estimated.

Estimate the reduction in average time from infection to diagnosis based on clinical data and literature.

Calculate the total number of person-years with undiagnosed HIV prevented through earlier detection.

Use published transmission rates for undiagnosed individuals to model the number of secondary infections averted.

If available, incorporate local or national modelling tools (e.g., ECDC HIV Modelling Tool) to support these estimates.