Small Volume Blood Testing Validity and Acceptability for HIV-1 and Hepatitis B (TINIES for BBVs)

Study Overview
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Brief Summary
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During the Covid-19 pandemic era, patients indicated that they find a model of care incorporating remote consultations to be acceptable [1-3]. Remote accessibility to care can be enhanced by using new technology to allow small volume testing for routine blood samples. This study aims to prospectively validate the use of small volume blood sampling for routine HIV-1 and Hepatitis B Virus (HBV) viral load (VL), liver function tests (LFTs) and creatinine, and assess the acceptability of this method of blood sampling to people living with HIV (PLWH). These tests form the usual minimum required for safe monitoring on a routine basis to determine viral activity, liver and renal function in patients either on or off antiviral therapy. The UK based Doctors Laboratory TINIES small volume blood testing kits comprise microcontainers manufactured by BD Diagnostics designed for sample collection from skin puncture, along with home testing pack with lancets, instructions and Royal Mail postal packs. We will collect TINIES samples alongside routine venepuncture samples in people attending their routine clinic follow ups. We will then send kits to different participants to collect samples in their own home, along with a follow up questionnaire (written/online). Finally, we will conduct a more in-depth telephone interview for a subset of patients to qualitatively assess acceptability. Routine use of this method of testing could revolutionise care of people living with chronic blood borne viruses, for example HIV and chronic HBV. TINIES could enable remote monitoring, increasing ease of access to care, reducing clinic appointment burden in otherwise healthy individuals, and reduce labour costs in the NHS, for example, by reducing phlebotomy appointments.

Detailed Description
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Covid-19 has accelerated the move towards increased use of remote healthcare[4]. This model is well-suited to people living with chronic blood borne virus (BBV) infections, as they are often asymptomatic and need only routine monitoring to assess for disease progression, response to treatment and medication adverse effects[5, 6]. However, routine blood tests still require the patient to attend the hospital for venepuncture to collect several 6 millilitre (ml) tubes twice a year. The Covid-19 pandemic led to a decrease in routine blood monitoring for HIV and HBV, due to a combination of the patient and clinician attempting to reduce hospital exposure[2, 7]. This may have a negative impact on patient care due to missed drug toxicity or changes in viral load necessitating drug initiation or changes. Given the post covid-19 shift to remote healthcare for routine appointments is likely to continue in the NHS[1], a mechanism of remote blood monitoring would be beneficial to patients and clinicians. Screening for syphilis, hepatitis and HIV using home testing with small volume finger prick blood samples has become established in sexual health services [8, 9]. Despite this, home-test finger prick blood sampling use in routine monitoring for patients living with HIV and HBV has not been explored. Finger prick dried blood spots have been investigated as a method of collection for measuring HIV and HBV viral load, particularly in resource-limited settings[10-13]. However, the use of dried blood spots for routine monitoring in high-income setting outpatient clinics is limited by reduced sensitivity in detecting low viral loads, and reduced ability to measure other routine blood tests, including haematology and biochemistry. There are few published studies investigating HIV-1 viral load measurement on finger prick blood collected in microcontainers, and none investigating HBV viral load. Studies have found self-taken home HIV tests are acceptable to service-users and increase the uptake of HIV testing in key populations, such as MSM and trans people. In contrast, in a London black African community, TINIES for HIV screening were unpopular and it was unfeasible to scale up their use within primary care[16, 17]. Online posting of tests to be self-taken in the home environment is becoming highly acceptable to service users, while recognising this may lead to reduced uptake in certain vulnerable groups[18]. Apart from enabling ongoing monitoring in the event of a future lockdown, there are other reasons why remote testing may be beneficial in clinical care of people living with BBV. Testing at home will reduce the burden of hospital visits for otherwise healthy people, reducing time off work for appointments and travel costs. There may also be a cost reduction for both the UK Health Service (NHS), for example by reducing venepuncture appointments. Stigma of attending the hospital may reduce uptake of regular blood monitoring, and remote testing may overcome this barrier.

Official Title
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Small Volume Blood Testing Validity and Acceptability for HIV-1 and Hepatitis B

Conditions
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HIV Infections, Hepatitis B

Intervention / Treatment
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* Other: Doctors Laboratory TINIES small volume blood testing kit


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: HIV-1 positive patients attending routine clinic follow up at MMC. Patients who are expected to have a detectable viral load will be actively approached. Patients with a diagnosis of HBV attending routine outpatient follow up at MMC. >18 years of age Able to give informed consent Exclusion Criteria: Patients will need to be able to read the instructions, or follow a simple video, for home testing kits

Ages Eligible for Study
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Minimum Age: 18 Years

Sexes Eligible for Study
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All

Study Plan
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How is the study designed?
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Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| HIV: Phase 1<br>People (over 18 years) living with HIV-1 attending London Mortimer Market Centre for routine blood tests as part of their HIV care. | Other: Doctors Laboratory TINIES small volume blood testing kit<br>* Doctors Laboratory TINIES small volume blood testing kits comprise microcontainers manufactured by BD Diagnostics designed for sample collection from skin puncture, along with home testing pack with lancets, instructions and Royal Mail postal packs.<br>|
| HIV: Phase 2<br>Subset of HIV participants sent TINIES test kit to use in home environment | Other: Doctors Laboratory TINIES small volume blood testing kit<br>* Doctors Laboratory TINIES small volume blood testing kits comprise microcontainers manufactured by BD Diagnostics designed for sample collection from skin puncture, along with home testing pack with lancets, instructions and Royal Mail postal packs.<br>|
| HBV: Phase 1<br>People (over 18 years) living with HBV patients attending London Mortimer Market Centre for routine blood tests as part of their HBV care. | Other: Doctors Laboratory TINIES small volume blood testing kit<br>* Doctors Laboratory TINIES small volume blood testing kits comprise microcontainers manufactured by BD Diagnostics designed for sample collection from skin puncture, along with home testing pack with lancets, instructions and Royal Mail postal packs.<br>|
| HBV: Phase 2<br>Subset of participants sent TINIES test kit to use in home environment | Other: Doctors Laboratory TINIES small volume blood testing kit<br>* Doctors Laboratory TINIES small volume blood testing kits comprise microcontainers manufactured by BD Diagnostics designed for sample collection from skin puncture, along with home testing pack with lancets, instructions and Royal Mail postal packs.<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Detection, sensitivity and specificity of HIV RNA viral load | To determine the limit of detection, sensitivity and specificity of HIV RNA viral load quantification from finger prick whole blood collected in EDTA microcontainers tested when compared to standard venepuncture 6ml EDTA tubes. | 6 months | 
| Detection, sensitivity and specificity of HBV DNA viral load | To determine the limit of detection, sensitivity and specificity of HBV DNA viral load quantification from finger prick whole blood collected in EDTA microcontainers, compared to standard venepuncture 6ml EDTA tubes. | 6 months | 
| Feasibility and acceptability of small volume testing for home sampling | To assess the feasibility and acceptability of small volume testing for home sampling for routine blood tests for routine HIV and hepatitis B monitoring. | 12 months | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Assessing concordance between liver function test parameters from finger prick compared to standard venepuncture | Assess concordance between liver function test parameters and creatinine collected from 600µl finger prick compared to standard venepuncture 6ml EDTA tubes | 12 months | 
| Feasibility for small volume blood samples collected for other experimental markers | Investigate feasibility for small volume blood samples collected for other experimental markers e.g., host response | 12 months |