Rapid HIV Testing: Policy & Regulatory Issues

Rapid HIV Testing

Trinity Uni-Gold Performance Evaluation

Policy & Regulatory Issues

AFAO National ForumOctober 2014

Phillip [email protected]

Background

• HIV diagnoses among gay and bisexual men (GBM) have increased in the past decade

• HIV testing and treatment is a key prevention focus

• ~10% of GBM have never tested (ARTB, CSRH)

• Only 20% of high risk GBM have re-tested after 6 months (Guy, 2010)

• Barriers to HIV testing include time constraints, not wanting to return for results

• Rapid testing aims to increase the acceptability and convenience of HIV testing

Immunochromatography (ICT)(lateral flow)

Sample

IgG Ab

α-HIV Ab

HIV-Ag

α –hu-IgG

label

HIV Ab Hu-IgG

Rapid HIV testing in NSWPhase 1 Phase 22011-2012 2013-2014Sydney Rapid HIV Testing study NSW Rapid Test Evaluation FrameworkNHMRC Program Grant NSW MoH, NHMRC Program Grant FeasibilityAcceptabilityTest performance

Acceptability & SustainabilityTest performanceCostImpact

4 sexual health clinics 13 sexual health clinics/hospitals6 community-based sites (4 peer-led partnerships with SHCs)1 general practice

Determine Ag/Ab HIV 1/2 Combo Conventional serology in parallel

Trinity Uni-GoldConventional serology in parallel

GBM, aged 18+ years GBM, aged 18+ years

Acceptability of rapid testing (after result)Duration of clinic visit today vs last time (%)

Shorter 27.2About the same 35.9Longer 36.8

Stress & anxiety of testing today vs last time (%)

More stress & anxiety 7.1Similar to last time 33.5Less stress & anxiety 59.4

Comfort of f/prick vs venipuncture today (%)

Less comfortable 13.7About the same 24.6More comfortable 58.2

Acceptability of rapid testing (after result)

%

Satisfied with rapid test result delivery 98.6

Satisfied with rapid testing overall 98.6

Would recommend rapid testing to others 88.5

Would prefer a rapid test next time 78.7

Damian Conway, ASHM 2012. Sydney Rapid HIV Testing Study


AcceptabilityTest performanceCostImpact




MSM, aged 18+ years MSM, aged 18+ years

Performance of the Trinity Biotech Uni-Gold HIV 1/2 rapid test as a first-line screening

assay for gay and bisexual men

Keen P, Conway DP, Cunningham P, McNulty A, Couldwell DL, Davies SC, Smith DE, Gray J, Holt M, O’Connor CC, Finlayson R, McAllister J, Hughes B, Carmody C, Varma R, Smith D, Read P,

Callander D, Guy, R.

Kirby Institute, UNSW

Australasian Sexual Health Conference, Sydney, October 2014

Adapted from McMichael AJ etal Nature Rev Immuno 2010


4th Gen


4th GenRapid Tests

4th Gen Test Reactive

4th Gen Test Reactive

ACUTE ESTABLISHED

Positive Western blot

Negative or Indeterminate Western blot

+Positive

p24antigen OR HIV-1 RNA

Negative HIV test <3 months

or

Performance overallReference test results

TotalPositive Negative

Trinity Unigoldresult

Positive 50 5 55

Negative 11 7179 7190

Total 61 7184 7245

False positiveTrue positive

False negative True negative




Positive 50 5 55

Negative 11 7179 7190

Total 61 7184 7245






Positive 50 5 55

Negative 11 7179 7190

Total 61 7184 7245






Positive 50 5 55

Negative 11 7179 7190

Total 61 7184 7245






Positive 50 5 55

Negative 11 7179 7190

Total 61 7184 7245






Positive 50 5 55

Negative 11 7179 7190

Total 61 7184 7245



Reference test

Acute Established Overall

Uni-Gold Pos 12 38 50

Neg 11 0 11

Total 23 38 61

Sensitivity in acute and established cases

Sensitivity in acute and established cases

% 95% CI

Acute 52.2 26.8-69.4

Established 100 90.1-100*

Overall 82.0 70.0-90.6

* one-sided 97.5% confidence interval

% 95% CI

Sensitivity 82.0 70.0-90.6

Specificity 99.9 99.8-100

Positive predictive value 90.9 80.0-97.0

Negative predictive value

99.9 99.7-99.9

Performance overall

Conclusions/discussion

• In this population Trinity failed to detect 48% of acute infections

• 38% of men diagnosed with HIV were acute infections

Can people at risk of recent infection be effectively identified if only rapid tests are used?

Should all who have rapid tests have parallel lab tests?

What will happen when the current NSW trial ends?

• NSW HIV PoCT Framework

• Regulatory obstacles

NSW MoH HIV PoCT Framework – in Development

• Will provide guidance to NSW Health supported non-laboratory services for offering HIV PoCT post-trials

• Will establish a quality framework for procurement, batch release testing, other quality management processes

• Guidance and supporting materials for:– Worker training and competency assessment– Eligibility – Client information– Data collection – Standard operating procedures

Regulatory Issues – Some Barriers Remain

• Current TGA licensing conditions preclude eg. Peer educators from administering rapid HIV tests – To date, peer educators have been able to participate in

community-based rapid HIV testing services through research trials with TGA waivers

• Performance benchmarks for licensing of rapid HIV tests – Australian Committee on Medical Devices: advice to TGA that

rapid tests should be 100% sensitive in western blot positive specimens

Acknowledgments

Funding• NSW Ministry of Health• NHMRC Program Grant• In-kind support from study sites

Steering Committee/Investigators• A/Prof Rebecca Guy, Kirby Institute, UNSW• Dr Damian Conway, Kirby Institute, UNSW• A/Prof Martin Holt, Centre for Social

Research in Health, UNSW• A/Prof Anna McNulty, Sydney Sexual Health

Centre• Dr Deborah Couldwell, Western Sydney

Sexual Health Centre• Prof Don Smith, Albion Street Centre• Dr Stephen Davies, North Shore Sexual

Health Service• Philip Cunningham, St Vincent’s Hospital

Darlinghurst• James Gray, ACON• Phillip Keen, Kirby Institute, UNSW

Study Investigators • A/Prof Catherine O’Connor, RPA Sexual Health

Centre• Dr Robert Finlayson, Taylor Square Private Clinic• John McAllister, Immunology & Infectious

Diseases Unit, St. Vincent’s Hospital• Dr Brian Hughes, Hunter New England Health

Services• Dr Chris Carmody, Liverpool Sexual Health Clinic• Dr Rick Varma, Nepean and Blue Mountains

Sexual Health Clinics • Dr David Smith, Lismore Sexual Health Service• Dr Phillip Read, Kirketon Road Centre• Dr Rob Pickles, Newcastle Sexual HealthService • A/Prof Lewis Marshall, Fremantle Hospital• A/Prof Jenny McCloskey, Ainslie House, Royal

Perth Hospital• Dr David Baker, East Sydney Doctors• Dr Denton Callander, The Kirby Institute, UNSW

AcknowledgmentsTraining Support• Philip Cunningham, Paula Runnals, Timmy

Lockwood, Craig Leeman, Vickie Knight, Levinia Crooks, Kim Wilson, Karen Seager, Damian Conway, Brent Clifton, Terry Walkinshaw, James Gray, Karl Johnson, Jane Costello, Linda Deriu, Walter Shepherd

Data Analysis Support• Muhammad Jamil, Denton Callander, Rebecca

Guy

Rapid Testing Site Coordinators• Timmy Lockwood• Vickie Knight• Chanelle Stowers• Nicky Sharp• Elizabeth Griggs• Terry Walkinshaw• James Gray• Amanda Townsend• Karen Biggs• Pradeep Kumar

Rapid Testing Site Coordinators (cont’.)• Sangeetha Eswarappa• Sandhya Goundar• Sharon Doughty• Rachel Poga• Simon Wright• Maggie Smith• Anthony Price• Mary Florance• Andrew Koh• Michael O’Reilly• Katherine Allardice• Leah Akierman• Ian McLoughlin• Kate Salisbury• Sarah Holliday• Brett Dubois

Lab support• Craig Leeman, Mee Ling Munier, Syddpath,

SEALS South, SEALS North, Pathology North, Hunter, Northern Rivers Pathology, Pathology West, ICPMR Westmead Hospital, Royal Prince Alfred Hospital

False negative acute cases

Previous HIV test RNA p24 Antigen HIV Antibody Western

Blot

1 <3M N/A + - -

2 >3m + + - -

3 Never + + - -

4 >3M N/A + - +/-

5 Never + + + -

6 >3M + + + +/-

7 <3M N/A + + +/-

8 >3M + + + +/-

9 >3M + + + +/-

10 >3M + invalid + +/-

11 <3M + + + +

+ = Positive - = Negative-/+ = Indeterminate

© ASHM 2013

Relative sensitivity (Acute HIV)

Biorad H

IV-1 p24 antigen

Abbott A

rchitect HIV-1/2 A

g/Ab (4

th gen)G

enscreen HIV-1/2 A

b (3rd gen)

Alere H

IV-1/2 Ag/A

b combo

Alere H

IV-1/2 Ab

Trinity Unigold H

IV-1/2 Ab

Biorad H

IV-1/2 Multispot A

b

Insti HIV-1/2 A

b

Orasure O

raQuick H

IV-1/2 Ab

Sensitivity (%)

100 90 80 70 60 50 40H

IV-1 Western B

lot

Cunningham etal ASHM 2013

SAN FRANCISCO AIDS FOUNDATION / MAGNET

33

Magnet Express Model

Magnet, SF: Additional Diagnoses Detected by RNA Testing

Rapid Tests RNA Test Additional infections detected

%

2010-2011 88 10 11.4

2011-2012 103 19 18.4

2012-2013 71 15 21.2

A Key Challenge in Introducing Rapid HIV PoCT

• Rapid HIV tests are not suitable for testing in people who have had a very recent risk exposure

• Recent risk exposure is a key reason why some men present for HIV testing

• Testing services need to explain the longer window period required by rapid HIV tests

• 4th Generation laboratory tests preferred for recent exposure


RNA

Opportunities

• The strength of rapid tests is in screening HIV negative people

• 98-99% of gay men will get a true negative result, with no need to return for results

• Opportunity to increase the convenience of testing for most gay men and reinvigorate HIV testing

• Opportunity to create new types of testing services through introducing peer testing staff

Limitations

• Longer window periods• Should all who have rapid tests have parallel lab tests?• Can people at risk of recent infection be screened?

• Some results will be false-reactive (‘false-positive’)

• Requires more work at the point of care

• Rapid HIV tests are screening tests• Lab testing is required on reactive rapid HIV tests to confirm

an HIV diagnosis

Conclusions/discussion

• Uni-Gold had sensitivity similar to Determine Ag/Ab HIV 1/2 Combo – Uni-Gold overall sensitivity: 82.0% (95%CI: 70.0-90.6)– Determine Combo overall sensitivity: 87.2% (95%CI: 72.6-95.7)

• 100% sensitivity in established infections

• Excellent specificity

• High PPV


AcceptabilityTest performanceCostImpact – uptake and frequency




MSM, aged 18+ years MSM, aged 18+ years

% 95% CI





99.9 99.7-99.9

Performance overall

% 95% CI





99.9 99.7-99.9

Performance overall

Trinity Uni-Gold HIV 1/2 rapid test

Non-reactive

(negative)

Reactive Invalid

Finger-stick blood 10-minute incubation time

Rapid tests as screening tests• Rapid tests are used as first-line screening tests in many

countries

• If reactive, confirmation by:• Lower income countries: 2 or 3 different rapid tests

(second/third tests more specific)• Higher income countries: Conventional HIV serology

• First line test should be highly sensitive

• Few evaluations of the performance of Trinity Uni-Gold as first line screening assay

Why Introduce Rapid HIV Testing in Australia?

• Highly sensitive and specific tests are important features of a high quality testing system.

• The testing process only starts when someone presents for, or is offered an HIV test.

• Many structural and psychological barriers to HIV testing among gay men and MSM may be reduced by rapid HIV testing

Rapid HIV Tests at PoCT: Advantages

• Robust and easy to use– Most require:

• 10-20 mins to perform• Minimal equipment• Minimal technical skill

• Increased access to HIV testing

• Results available quickly; can speed diagnosis, counselling and linkage to care

Do homosexual men have HIV tests more frequently

if offered rapid point-of-care HIV testing in a sexual

health centre? Read T1,2, Morrow A2 , Hocking J3, Bradshaw C1,2,4, Grulich A5, Fairley CK1,2* and Chen M1,2*1.Melbourne School of Population Health, University of Melbourne

2.Melbourne Sexual Health Centre, Alfred Health, Melbourne

3.Centre for Women’s Health, Gender and Society, School of Population Health, University of Melbourne

4.School of Social and Preventive Medicine, Monash University, Melbourne

5.Kirby Institute, University of New South Wales, Sydney

*joint last authors

47

Time to first test (years)

0.00

0.25

0.50

0.75

1.00

Pro

por

tion

test

ed o

nce

0 .5 1 1.5Time

arm = control arm = rapid

Proportion having first HIV test over time

A Key Challenge in Introducing Rapid HIV PoCT

• Rapid HIV tests are not suitable for testing in people who have had a very recent risk exposure

• Recent risk exposure is a key reason why some men present for HIV testing

• Testing services need to explain the longer window period required by rapid HIV tests

• 4th Generation laboratory tests preferred for recent exposure

Background• HIV diagnoses among gay and bisexual men (GBM) have

increased in the past decade

• HIV testing and treatment is a key prevention focus

• ~10% of GBM have never tested (ARTB, CSRH)

• Only 20% of high risk GBM have re-tested after 6 months (Guy, 2010)

• Barriers to HIV testing include time constraints, not wanting to return for results

• Rapid testing aims to increase the acceptability and convenience of HIV testing

Test performance evaluation• June 2013 – 30 June 2014 • 20 study sites across NSW• HIV Reference Testing

– 4th generation Ab/Ag combo assay• p24Antigen (separately)• HIV Antibody (separately)• Western Blot

• Analysis• Trinity Uni-Gold v’s reference tests

– Sensitivity: overall, acute and established– Specificity: overall

Performance of the Trinity Biotech Uni-Gold HIV 1/2 rapid test as a first-line screening

assay for gay and bisexual men

Keen P, Conway DP, Cunningham P, McNulty A, Couldwell DL, Davies SC, Smith DE, Gray J, Holt M, O’Connor CC, Finlayson R, McAllister J, Hughes B, Carmody C, Varma R, Smith D, Read P,

Callander D, Guy, R.

Kirby Institute, UNSW

Australasian Sexual Health Conference, Sydney, October 2014

In the era of effective antiretroviral treatment, HIV testing serves as the gateway to improved health and survival among persons with HIV infection and decreased transmission within communities.

(Branson, B. et. al. JAAIDS 2013)

Health & Medicine

Rapid HIV Testing: Policy & Regulatory Issues