HIV point of care testing

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HIV point of care testing

• Noah Hoffman, June 2006

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(No Transcript)
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Time course of typical HIV infection
www.med.sc.edu85/lecture/hiv_time_course.jpg
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HIV detection how soon after infection?

• Window period the time between infection and
  seroconversion
• Symptoms usually appear 2 weeks after infection
• p24 reduces window period by about 6 days
• Nucleic Acid detection reduces window period to
  about 11 days after infection
• Serology
• IgM detected an average of 5 days after onset of
  symptoms
• IgG detected an average of 11 days after onset of
  symptoms
• Almost all patients are seropositive by 3 mos
  after infection
• Period of highest risk for infection is primary
  infection high viral load without symptoms or
  detectable antibodies

UpToDate Laboratory testing of donated blood,
Primary HIV-1 infection Diagnosis and treatment
AIDS Volume 14(15) 20 October 2000 pp 2333-2339
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algorithm for laboratory testing of HIV infection
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Motivation for point of care testing

• Rapid TAT
• Permits immediate decision support
• Ensure follow-up for positive results
• Provide immediate counseling
• Available in resource-poor areas

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Useful settings for rapid HIV testing

• Labor and delivery
• Occupational exposure
• Emergency Department
• Outreach for high-risk patients

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Performance of rapid POC HIV tests
http//www.cdc.gov/hiv/rapid_testing/materials/Lab
orDeliveryRapidTesting.pdf
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PPV of rapid POC HIV tests
http//www.cdc.gov/hiv/rapid_testing/materials/Lab
orDeliveryRapidTesting.pdf
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Trinity Biotech Uni-Gold Recombigen test principle

• Recombinant HIV proteins immobilized on a
  nitrocellulose strip and on colloidal gold
  beneath the test region of the strip
• anti-HIV antibodies binds to antigens on the
  nitrocellulose and colloidal gold particles
• the antibody-gold complex appears on the strip as
  a pink/red band

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Uni-Gold Recombigen

• CLIA-waived for finger stick, whole blood
  moderate complexity with serum, plasma
• Store at room temperature
• Screens for HIV-1
• Results in 10 minutes

http//www.cdc.gov/hiv/rapid_testing/materials/USC
A_Branson.ppt
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Add 1 drop specimen to well
http//www.cdc.gov/hiv/rapid_testing/materials/USC
A_Branson.ppt
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Add 4 drops of wash solution
http//www.cdc.gov/hiv/rapid_testing/materials/USC
A_Branson.ppt
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Positive
Negative
Read results in 10 -12 minutes
http//www.cdc.gov/hiv/rapid_testing/materials/USC
A_Branson.ppt
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Regulation of POC HIV testing

• CLIA waived
• whole blood
• venipuncture whole blood
• CLIA moderate
• serum
• Requirements for testing under CLIA waiver
• Sale is restricted to clinical laboratories (Any
  agency that has a CLIA Certificate of Waiver and
  performs the OraQuick test is considered a
  clinical laboratory.)
• A quality assurance plan is in place
• Staff have been trained to perform the test using
  manufacturer's instructions
• Clients receive a Subject Information pamphlet
  before the test is given and receive appropriate
  information when results are provided

http//www.cdc.gov/hiv/rapid_testing/materials/rol
tCLIA.htm
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Delaney, et al. Ability of Untrained Users to
Perform Rapid HIV Antibody Screening Tests.
Abstract, American Public Health Association
Annual Meeting, October 2002.

• Study of OraQuick test
• Health care workers with no lab experience
• Incorrectly performed tests gave result of
  invald (so no incorrect result given to
  patient)

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Outcomes of Counseling and One-Time Screening for
HIV Infection after 3 Years in 3 Hypothetical
Cohorts of 10 000 Asymptomatic Adolescents and
Adults
Chou, R. et. al. Ann Intern Med 200514355-73
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Confirmation of positive rapid tests (OraQuick)
CDC guidelines

• All preliminary 's must be followed up with
  either a Western blot or immunofluorescent assay
  (IFA) for confirmation.
• Confirmatory testing can be done on blood
  (plasma, serum or dried blood spots) or oral
  fluid specimens. Urine testing should not be
  performed due to its lower sensitivity
• With blood specimens, enzyme immunoassay (EIA)
  screening tests prior to the Western blot or IFA
  confirmatory test are optional. If an EIA is
  performed, even if it is non-reactive, the
  specimen must proceed to Western blot or IFA
  testing. For oral fluid testing, both EIA and
  Western blot testing should be performed to
  confirm results.

http//www.cdc.gov/hiv/rapid_testing/materials/qa-
guide.htm
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Follow up testing for negative confirmatory result

• Recommended to rule out specimen mixup or
  false-negative confirmatory test
• For blood specimens, a confirmatory test should
  be repeated with a new specimen
• For oral fluid specimens, a repeat confirmatory
  test with a blood specimen should be done, since
  the oral fluid test is less sensitive than the
  blood test.

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Rapid HIV-1 Antibody Testing during Labor and
Delivery for Women of Unknown HIV Status

• The CDC provides recommendations for rapid
  testing of mothers in labor with unknown HIV
  status
• 40 of the mothers of the 280370 HIV-infected
  infants born in 2000 were not known to have HIV
  infection before delivery
• When ARV prophylaxis is administered during
  labor or within the first 12 hours after birth,
  the risk of perinatal HIV transmission is reduced
  from 25 to 913
• Diagnosis offers opportunity for close follow up
  and referral after delivery

http//www.cdc.gov/hiv/rapid_testing/rt-labordeli
very.htm
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Key elements of CDC recommendations for rapid
perinatal HIV testing

• Consider establishing standing orders (e.g.,
  provide routine rapid HIV testing if there is no
  documentation of prenatal HIV test results unless
  the woman declines
• CDC recommends an opt-out approach, in which
  women are informed that HIV testing will be
  routinely done if her HIV status is unknown
  during labor and delivery but that she may
  decline testing
• Ensure confidentiality
• A positive (or reactive) result from a rapid HIV
  test is considered a preliminary positive and
  must be followed up with a confirmatory test

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Approach to a positive rapid HIV test in labor
and delivery setting

• Confirm result
• Begin antiretroviral prophylaxis for mother and
  neonate
• all ARV prophylaxis will be stopped if the
  confirmatory test result is negative
• Management of labor
• artificial rupture of membranes and invasive
  monitoring should be avoided
• Episiotomy should be avoided if clinically
  appropriate.
• There is no evidence that C-section reduces risk
  of MTCT in an uncomplicated pregnancy once
  membranes have ruptured C-section may be
  indicated before membrane rupture
• postpone breastfeeding until the confirmatory
  results are available
• Ensure follow up for mother and baby!

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Experience with LD rapid HIV testing MIRIAD
study

• Multicenter study of acceptance of HIV testing
  sensitivity, specificity, PPV TAT.
• Ora-Quick test was evaluated
• 7381 of 91707 women eligible
• 84 consent rate
• 34 positives (7/1000)
• sens 100, spec 99.9, PPV 90 (76 for EIA)
• TAT for blood collection to result 66 minutes
  (28 hours for EIA)

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Occupational HIV exposure 1995-2004 (CDC data)

• 28,010 occupational exposures to blood and body
  fluids
• 1,350 (5.3) to HIV-positive sources
• 15,301 (60.0) to HIV-negative sources
• 8,859 (34.7) to sources of unknown HIV status
• 58.4 of people exposed to known HIV source took
  PEP
• Median time to initiation of therapy was 2 hours

MMWR 2005 54(RR09)1-17
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Risk of HIV transmission by exposure type
Antiretroviral postexposure prophylaxis after
sexual, injection-drug use, or other
nonoccupational exposure to HIV in the United
States. MMWR. 2005, 541-20. PMID 15660015
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Risk factors following occupational exposure to
HIV

• Route of exposure
• Percutaneous exposure to HIV-infected blood
  0.3 average risk
• Mucous membrane exposure 0.09
• Nonintact skin ? (probably lt MM)
• Type/mechanism/circumstance of injury
• Higher risk deep injury, visible blood on/in
  needle, hollow needle, intravenous/intraarterial
  procedure
• Source of material
• Patients with terminal disease (higher viral
  load, presence of more virulent stains?)

MMWR. 2005. Vol 54, No RR91
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Treatment following occupational exposure to HIV

• Less severe, eg solid needle or superficial
  injury.
• More severe, eg large-bore hollow needle, deep
  puncture, visible blood on device, or needle used
  in patients artery or vein.

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Rationale for POCT HIV test of source in
occupational exposure

• Can avoid empirical PEP
• Avoid side effects
• Expense of therapy
• Reassure employee
• Reduces duration of uncertainty

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References

• Rapid HIV-1 Antibody Testing during Labor and
  Delivery for Women of Unknown HIV Status A
  Practical Guide and Model Protocol (CDC)
  http//www.cdc.gov/hiv/rapid_testing/rt-labordeli
  very.htm
• Bulterys M, et al. Rapid HIV-1 testing during
  labor a multicenter study. JAMA. 2004,
  292219-23. PMID 15249571
• Updated U.S. Public Health Service Guidelines for
  the Management of Occupational Exposures to HIV
  and Recommendations for Postexposure Prophylaxis
  MMWR. 2005. Vol 54, No RR91