Point-of-care HIV testing Joanne Stekler, MD MPH Associate Professor University of Washington December 5, 2016 Disclaimer: The findings and conclusions in this presentation are those of the author(s) and do not necessarily represent the views of the Division of HIV/AIDS Prevention at the Centers for Disease Control and Prevention.
Objectives 1. Learn about advantages and disadvantages of point-of-care HIV tests. 2. Learn about issues re: point-of-care HIV testing in context of pre-exposure prophylaxis (PrEP).
Fiebig et al. AIDS, 2003 Sep 5; 17(13): 1871-9
HIV test Method Window 1 st gen EIA (Ab) viral lysate ~ 4-6 wks 2 nd gen EIA (Ab) purified HIV-1/2 Ag or recombinant 3 rd gen EIA (Ab) synthetic peptide, 4 th gen assay (Ab plus p24 Ag) Pooled HIV RNA (HIV NAAT) antigen sandwich detects IgM detects either antibody or p24 Ag ~ 3-4 wks ~ 2-3 wks ~ 2 wks <1-2 wks Adapted from Stekler CID 2007
Oraquick Advance DPP HIV 1/2 Chembio Sure Check INSTI HIV 1/2 Chembio Stat Pak Uni-Gold Recombigen Slide courtesy of Bernie Branson
Determine HIV-1/2 Ag/Ab Combo (Alere)
Advantages Patient Preference? Potential Avoidance of Blood Draw/ Biohazard More Persons Receive Results Disadvantages Potential for Preliminary False-Positive Results Longer window period
# HIV-positive Cumulative HIVpositive Cumulative Sensitivity OraQuick 314 (2.0%) 314 77% EIA 40 (0.3%) 354 87% NAAT 52 (0.3%) 406 100%
APTIMA (-26) Architect Combo (-20) Bio-Rad Combo (-19) Determine Combo (-15) GS 1/2+O (-12) INSTI (-9) Multi-Spot (-7) Reveal G3 (-6) COMPLETE HIV-1/2 (-5) HIV-1/2 STAT-PAK (-5) OraQuick (-1) Unigold (-2) WB positive Vironostka (+) 2 25 20 15 10 Modified from Masciotra et al, J Clin Virol 2011 and Owen et al, J Clin Micro 2008 Slide courtesy of Bernie Branson 5 0 Days before WB positive
POC tests (each test on separate fingerstick) OraQuick (oral fluids and fingerstick) Uni-Gold or INSTI Determine HIV-1/2 Ag/Ab EIA PHSKC: 3 rd gen Genetic Systems HIV-1/HIV-2 Plus O EIA PIC: 4 th gen Abbott ARCHITECT HIV Ag/Ab Combo assay NAAT PHSKC: 27-specimen master pools (3x3x3 matrix) Abbott RealTime HIV-1 RNA assay McNemar s exact tests compared numbers of cases detected
STD Clinic & Gay City PIC Total n=3404 n=34 n=3438 Concordant Positive POC Tests 82 (77%) 18 100 Discordant POC Antibody Tests 10 (9%) 13 23 All POC Negative/EIA Positive 6 (6%) 0 6 Acute (EIA Neg / NAAT Pos) 9 (8%) 2 11 Total HIV Positive 107 (3.1%) 33 140 Stekler, J Clin Virol 2016; Stekler, J Clin Virol 2013; O Neal, JAIDS 2012
# tested # AHI detected Taegtmeyer PLoSOne 2011 UK 953 none Rosenberg JID 2012 Malawi 838 0/8 Kilembe PLoSOne 2012 Rwanda, Zambia 1/52 Conway PLoSOne 2014 Australia 3190 0/9 Duong J Clin Microbiol 2014 Swaziland 18,172 0/13 Stekler J Clin Virol 2016 US 3438 1/11 >26,591 2/93
N tested Specificity (95% CI) OraQuick (oral fluid) 2109/2112 = 99.86% (99.59-99.97) OraQuick (fingerstick) 2107/2107 = 100% (99.82-100) Uni-Gold 1561/1561 = 100% (99.76-100) INSTI 543/544 = 99.82% (98.98-100) Determine Combo 1468/1483 = 98.99% (98.34-99.43) GS HIV-1/HIV-2 Plus O antibody (EIA) 2091/2095 = 99.81% (99.51-99.95) Stekler, J Clin Virol, 2016 Meta-analysis Overall pooled specificity (plasma, serum, WB) 99.1% (97.3-99.8) Smallwood et al. PLoS One 2016 11(2)
Point-of-care HIV tests are not all the same. Oral fluid is significantly inferior and should be the specimen type of last resort. Determine Combo, although a 4 th generation POC test, is not equivalent to lab-based testing when looking for AHI. But it still may pick up a case or two. Other factors may impact device choice Cost Time (1 minute v 20-30 minutes) Blood volume (5 v 50µL)
When starting PrEP, use the test with shortest window period available. Do not use oral fluid tests. (starting PrEP during AHI resistance) Do not ask people to remain abstinent/use condoms while waiting out the window period. Screen for symptoms of AHI If symptoms and recent exposure delay PrEP start *Almost all* symptomatic AHI will test pos on lab 4 th gen But. There is a 2 nd window period. PrEP may lead to delayed seroconversion and falsenegative tests, particularly with oral fluid tests.
HIV testing in PrEP Analysis of False Negative HIV Tests Based on Oral Fluid in 3 Clinical Trials (Curlin, CROI 2016, #635) - 208 false negative OQOF results among 28% of 290 seroconverters. - Median OQOF reactivity delay time was 98 (range 14-547) days. The Effect of Oral Pre-exposure Prophylaxis on the Progression of HIV-1 Seroconversion (Donnell, HIVR4P 2016, #OA03.01) - 138 seroconversions - Slight delay in Fiebig progression and delayed detection in some using fingerstick HIV tests