Here s the Point! Rapid, Point-of-Care Testing for Sexually Transmitted Infections

Transcription

1 Here s the Point! Rapid, Point-of-Care Testing for Sexually Transmitted Infections Charlotte Gaydos, MD, MPH, DrPH Professor, Division of Infectious Diseases Johns Hopkins University, Baltimore, MD Anne Rompalo, MD, ScM Professor, Division of Infectious Diseases Johns Hopkins University, Baltimore, MD Lea Widdice, MD Assistant Professor, Division of Adolescent Medicine Cincinnati Children's Hospital Medical Center Society for Adolescent Health and Medicine Annual Meeting New Orleans, LA March 8, 2017

2 Workshop Objectives Part 1 Review POC tests on the market and in the pipeline Demonstrate different venues for STI testing Part 2 Discuss barriers and benefits of POC STI testing Part 3 Apply ASSURED criteria to available POC tests

3 Here is the Point: New Point of Care Tests for STIs SAHM Workshop New Orleans March 8-11, 2017 Charlotte A. Gaydos, MS, MPH, DrPH Professor, Division of Infectious Diseases Johns Hopkins University Baltimore, Maryland

4 Objectives 1. To review the characteristics of POC STI tests currently on the U.S. and international markets and in clinical trials 2. To discuss new POC tests in the pipeline 3. To demonstrate different venues for STI testing outside the clinic, OTC or home STI testing

5 WHO Estimates of Global Prevalence of STIs in Million 143 Million HIV Total: 36.7 million Million Newly infected with HIV in 2015: 2.1 M; AIDS deaths in 2015: 1.1 M Million Chlamydia Gonorrhea Trichomonas143 Syphilis Newman et al. PLOS ONE OI: /journal.pone December 8, /

6 Background: U.S. Estimates Estimated Prevalence of Sexually Transmitted Infections in the U.S. (Total 110,197,000) Estimated New Sexually Transmitted Infections in the U.S. Each Year (Total 19,738,800) Satterwhite CL et al. Sexually Transmitted Diseases 2013;40:

7 Gaydos and Hardick POC diagnostics for sex transmit infect: Perspectives and advances. Expert Review of Anti-infective Therapy. 12: , Overview: Point-of-Care Tests for STIs Chlamydia trachomatis (CT) Neisseria gonorrhoeae (NG) Trichomonas vaginalis (TV) Syphilis Herpes Simples Virus (HSV) HIV Gaydos, C. Rapid Tests for STDs Current Infect Dis Reports 2006;8: Huppert et al. Point of Care tests for STIs: What s the Point? Point of Care Journal, 2009

8 Self-Collected Vaginal Swabs All 5 commercial NAAT assays have approval for clinician-collected and self-collected vaginal swabs for CT/NG (Aptima, M-2000, ProbeTech Qx Amplified DNA, Cobas 4800, Cepheid) Sensitivities and specificities 94.5%-100% Self-collected vaginal swabs are not FDA cleared for home collection for mailing but used in research studies Schachter STD 2005; Gaydos JCM 2010; Taylor JCM 2011; Van Der Pol STD 2012; Van Der Pol STD 2013; Gaydos JCM 2013

9 Chlamydia POC tests for STIs Gonorrhea Trichomonas Syphilis HSV HIV Gaydos and Hardick, POC diagnostics for sex transmit infect: Perspectives and advances. Expert Review of Anti-infective Therapy. 12: , 2014.

10 Chlamydia trachomatis and Neisseria gonorrhoeae Old: Culture and staining. New: PCR and other nucleic acid amplification tests (NAATs)

11 Near Patient Test for Chlamydia and Gonorrhea GeneXpert CT/NG, Cepheid (90 minutes) Sensitivity: % Specificity % FDA Cleared: CT/NG,TV; urine, cervical, vaginal swabs Gaydos et al. J Clin Microbiol. 51: , 2013

12 Ease of Use Gene Xpert by Cepheid is FDA Cleared for use for chlamydia gonorrhea & trichomonas for women and men. 1. Collect 2. Transfer 3. Insert 4. Detect Not yet CLIA Waived

13 Atlas Genetics io System Low cost instrument All reagents are on the Cartridge Ambient storage >12 month shelf-life Broad range of clinical sample types Disposable cartridge for sample Results provided as clear output CE Marked (CT); FDA clinical starting soon (CT/NG) Electrochemical label released from probe hybridized by nuclease enzyme

14 Mobi-NAAT Chlamydia Test / PCR Droplet PCR microfluidic platform / Smartphone Droplet cartridge platform C. Chiou and D. J. Shin et al., Biosens Bioelectron, 2013 AUC Fluorescence (AU) Sample identification number

15 Novel Diagnostics Hands-on time <2 minutes Hand-held Assay Automation Instrument Insert chip into device Transfer sample into chip, start On-chip DNA purification On-chip DNA amplification Detection and result display <1 < <1 Time to Result <20 minutes Sensitivity equivalent to lab qpcr test Assay was able to detect <5 EB of Chlamydia Highly specific to only Chlamydia strains Preclinical evaluation using clinical samples underway. Self-contained Microfluidic Cartridge

16 Trichomonas vaginalis Diagnostics Wet Preparation showing motile trichomonads Stained Trichomonas Electron microscope view of trichomonas on epithelial cell Wet Preparation Culture Affirm VPIII OSOM POC NAAT AmpliVue POC Solana POC AptimaT. vaginalis (ATV) Becton Dickinson (TVQ)

17 Trichomonas Test Comparisons TEST Sensitivity Specificity Wet prep 55% 65% 100% Culture 75%* 100% Affirm VPIII 46.3%** 100% OSOM POC* 83-86% >97% AmpliVue TV POC % 98.2% Solana TV POC % 98-99% TMA AptimaTV 100% 100% ProbTec TVQ 98.3% 98.3% Cepheid Xpert 98.4% 99.7% *Huppert JS. J Clin Microbiol. 2005; Nye MB. Am J Obstet Gynecol. 2009; Schwebke. JCM, 2011 Van Der Pol B. J Clin Microbiol Van Der Pol, JCM 2014;52: , Schwebke; Taylor: Posters STI & AIDS, 2013 ** Affirm compared to nucleic acid amplification test, JCM, Cartwright et al. (2013). + Gaydos et al. STD 43:369, 2016 Gaydos, et al. Expert Rev Molec Diag. 2017

18 OSOM Rapid TV Antigen Test Immunochromato-graphic TV membrane proteins Mouse antibodies Latex beads/ capillary action Huppert et al, JCM 2005; STI 2007: Sensitivity 83-90%, Specificity %

19 AmpliVue Trichomonas HDA Assay 1) simple sample preparation with 1-step dilution/heating 2) isothermal DNA amplification of target sequence specific to T. vaginalis by Helicase Dependent Amplificat. 3) lateral-flow strip based colorimetric detection in a selfcontained, disposable device. FDA cleared Sensitivity 100%; specificity 98.2% vs. culture/wet prep. Vs. NAAT PPA: % Gaydos et al. STD 43:369,2016

20 Clinical performance of the Solana POC Trichomonas Assay from cliniciancollected vaginal swabs and female urines HDA amplification Recently FDA Cleared Moderately Complex Sample Gaydos et al. CDC STD meet. Atlanta Sept 2016 Compared to NAAT reference Sensitivity Specificity Swabs 89.7% 99.0% Urine 100% 98.9% Compared to wet prep/culture Vaginal Sensitivity Specificity Asym. 100% 98.9% Sympt. 98.6% 98.5% TV prevalence swabs and/or urines 11.5%

21 Syphilis: Serologic DX requires detection of two types of antibodies Non-Treponemal RPR, VDRL Treponemal FTA-abs, TPPA, Many new automated, POC Both test types have imperfect specificity Reactive treponemal test cannot distinguish active from inactive infection VDRL: Venereal Disease Research Laboratory RPR: Rapid Plasma Reagin

22 Evolution of Syphilis Test Traditional syphilis tests - Manual RPR Nontreponemal FTA Treponemal Automated Test platforms Treponemal Rapid syphilis POC test Treponemal

23 Treponemal Syphilis Tests: EIA/CIA/POC Advantages: Automated or POC and are cost saving for large volume laboratories May detect old untreated syphilis Disadvantages: Less clinical experience with interpretation May be less sensitive than FTAab in early primary syphilis

24 Some Rapid Syphilis Tests Available in the U. S. - Immunochromatographic strip tests (ICS) Syphilis Health Check Trinity Biotech (FDA cleared, CLIA waived) Available Internationally SD Bioline Syphilis 3.0 Standard Diagnostics/ Alere Determine Syphilis TP Standard Diagnostics/ Alere Dual HIV/ Syphilis assays Multiplo TP/HIV Medmira Inc. DPP HIV/ Syphilis Chembio Diagnostics SD Bioline HIV Syphilis Duo Standard Diagnostics/ Alere (WHO Premarket qualified) INSTI HIV/Syphilis Multiplex Test - biolytical OnSite HIV/Syphilis Ab Combo Rapid Test - CTK Biotech CTK Biotech, Inc. mchip Assay

25 POC Syphilis Health CheckTM Syphilis Antibody Rapid Immunochromatographic Test Rapid qualitative screening for human TP antibodies Results in 10 minutes; 2 steps; room temperature 98% agreement to other treponemal tests Serum, plasma, whole blood or finger-stick Negative: 1 colored band in control area Positive: Colored bands in test area and control area Inconclusive: No distinct color bands in either area FDA Cleared CLIA Waived

26 Laboratory evaluations of syphilis rapid test performance PPV Meta-analysis of 33 studies from POCs Sensitivity: 75.12% to 83.78% for blood 75.98% to 92.03% for serum Specificity: 98.39% to 99.44% for blood 92.68% to 98.51% in serum Bristow et al Sex Health 12: , 2015

27 HSV POC Diagnostics

28 The IsoAmp HSV Assay (Biohelix Corp) 25 ul 25 ul Master mix 25 ul VTM 1 ml buffer min FDA-cleared for HSV in genital and oral lesions The IsoAmp HSV has a test-to-result time of <1.5 hr. Isothermal helicase-dependent amplification (HDA) technique; no nucleic acid extraction The rapid and simple characteristics of the IsoAmp HSV assay make it potentially suitable for POC testing Lemieux et al. Expert Reviews Ltd , 2012;

29 HIV CLIA-Waived Point-of-Care Rapid HIV Tests OraQuick Advance Clearview Complete Uni-Gold Recombigen INSTI Clearview Stat Pak

30 HIV-1/2 antigen/antibody combination immunoassay (+) (-) Negative for HIV-1 and HIV-2 antibodies and p24 antigen HIV-1/HIV-2 antibody differentiation immunoassay HIV-1 (+) HIV-1 (-) HIV-1 (+) HIV-1 (-) or Indeterminate HIV-2 (-) HIV-2 (+) HIV-2 (+) HIV-2 (-) HIV-1 antibodies HIV-2 antibodies HIV antibodies detected detected detected NAT (+) indicates reactive test results (-) indicates negative test results NAT: nucleic acid test NAT (+) NAT (-) Acute HIV-1 Infection Negative for HIV-1

31 Alere Determine HIV-1/2 Ag/Ab Combo Method: Lateral flow Time to Results: 20 minutes Storage Conditions: 2-30 C Shelf Life: 9 months Sample Type: Serum/plasma/whole blood Distinguishes Ag/Ab reactivity Unknown performance characteristics in the lab algorithm Data collection is underway CLIA waived for whole blood Data from plasma suggests the assay detects infection ~ 3-5 days after instrumented Ag/Ab combo assays and possibly longer delays with whole blood Masciotra et al. JCV 2013

32 Bio-Rad Geenius Supplemental assay - Confirmation and differentiation of HIV-1 and HIV-2 antibodies in initially repeatedly reactive specimens HIV confirmation and differentiation in less than 30 minutes 3 sample types : serum, plasma (5ul), whole blood (15 ul) Software that uses a validated algorithm Full traceability Limited data on performance in the lab algorithm suggests comparable to Mutlispot Delaney et al CROI 2015 abstract #621

33 Cepheid GeneXpert System Multiplex Real-Time PCR- Viral Load Plasma 1ml Qualitative Dx test from Whole blood ~ 2hour run-time AC power with potential for battery Coming?

34 Liat Analyzer Roche Multiplex Real-Time PCR- Viral Load 30 min cp/ml; 60 min-50 cp/ml Whole blood, plasma Qualitative Dx Blood or plasma AC power/battery Integrated disposable cartridge contains all reagents for prep, amp & detection

35 Alere q HIV-1/2 Detect Alere Q System Sample: 25 μl fingerstick whole blood Sealed system PCR Results in 50 minutes Data Matrix: Expiry QC, assay type, lot Information Kit shipped and stored at room temperature Alere q Analyzer Built in battery Simple procedure with built in controls Touch screen Data storage of 1000 tests Easily transportable, 17.2 lbs.

36 Considerations for HIV POC Testing Locations/populations that lab testing is difficult or not feasible Better to use POC than no test POC assays continue to improve and have good sensitivity and specificity for established infections but Be aware of assay limitations Provide informed counseling messages Oral Fluid assays will miss acute infections and some early infections 1,2 1 Stekler et al, JCV 2013, 2 Luo et al JCV 2013

37 Self-Testing Instruction Guide

38 Emergency Departments: Critical Venue HIV Tests Feasibility, Acceptability, and Accuracy

39 Correct Result? 3.3% 0.2% Trust the Result? 8.0% 0.2% Definitely Correct Very Much 96.4% Ease of Performance 0.7%0.2% Easy 91.7% Would Test Themselves if Available OTC 11.8% 3.1% Definitely 99% Somewha t Easy Not Easy 85% Probably Would Not Test 473/955 (49.5%) consented; Median age was 41 years, 59.6 % were female, 74.8% African American

40 Female Preference for Type Specimen Collection Self-collected vaginal swabs are acceptable and preferred over urine and cx to women Gaydos et al. STD

41 Use of POC Outside the Clinic Emergency Department 80% of women would definitely test themselves at home if a TV test were available OTC Pharmacy Pharmacists are ranked among the most trusted health care professionals; are accessible 24/7 Internet Iwantthekit Internet Smart Phone

42 Key Applications POC Tests Sexually Transmitted Infections Immediate treatment of positive patients Expedite appropriate therapy Reduce empirical treatment Lower risk of antibiotic resistance Improve compliance / minimize loss to follow-up Decrease forward transmission Lower risk of sequelae Improve the patient experience

43 Conclusions POCTs in primary/sti care and perhaps OCT have great potential But there are barriers to successful implementation that need to be overcome which can be costly, time consuming, and require learning new skill sets Better POC tests are coming; the future is promising

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45 POCTs for STDs What do you use? What would you use? Anne Rompalo, MD, ScM

46 Getting to know you. How often do you diagnose STDs among patients in your practice? 1.Every day 2.Once or twice per week 3.Once or twice per month 4.Once or twice per year 5.Don t see STDs in my patients

47 Getting to know you Which POCTs are currently available to you? 1. Vaginal ph 2. Urine dipstick 3. Wet mount test 4. Gram Stain 5. Affirm VP III 6. State RPR 7. Pregnancy test 8. Rapid HIV test 9. NONE!

48 Getting to know you In your opinion which is the GREATEST barrier to using POCTs in your practice 1.Too complicated Too many steps too many TIME DRIVEN steps Too much ambiguity in reading results Have to purchase an instrument 2.Increased patient wait time (interruption of work flow) 3. Reliability of the test

49 What we think we know Pros Immediate disease specific treatment Decrease disease spread Confidential notification Counseling on risk reduction Cons Barriers to use in clinical settings Diffusion of innovation Costs/reimbursem ents Follow up/return rate

50 Rapid tests for sexually transmitted infections: the way forward. Peeling RW, et al. Sex Trams Infect 2006;82:v1-v6

51 Needs Assessment of Clinicians Which organisms do Clinicians want a POC test? How sensitive; how specific? How fast does it have to be? What about cost? What about equipment? Hsieh Y-H et al. Plos One vol 6, issue 4, e19263, Hsieh Y-H et al. Point of Care 11: , 2012

52 Needs Assessment of Clinicians: Build Your Own Test For which organisms do Clinicians want a POC test? (Most say chlamydia) How sensitive?; (most important %) How specific? (99%) How fast does it have to be? (-20 min) What about cost? (second most important- $20) What about equipment? (no or little equipment) Forced Choice Questions used in a survey with multivariate analysis Hsieh Y-H et al. Plos One vol 6, issue 4, e19263, Hsieh Y-H et al. Point of Care 11: , 2012

53 Preferences in Attributes by Prioritized Test Attributes Odds Ratios * all p-values <0.05 Priority Force Choice Questions Sensitivity (%) ALL N=218 Chlamydia N= 136 Early HIV Seroconversion N=30 Syphilis N= * 18.2* 10.6* 11.8* Specificity (%) * 5.9* Cost ($) * 5.2* Time (minutes) Forced Choice Questions used in a survey with multivariate analysis Hsieh Y-H et al. Plos One vol 6, issue 4, e19263, 2011

54 What qualities do providers identify as best for POC STI tests: Do opinions differ by practice, region and country? Results: 190 subjects replied to the survey: 46% male and 54% female Europe (27%), Oceana (26%), America (22%), Africa (11%), Asia (11%) The majority (61%) were from developed countries Unreliability (19.5%) was the characteristic considered the greatest barrier for use of POCTs, followed by a technology that was laboratory-driven (12%) and complexity (12%) of performing the test. Rompalo et al ISSTDR Vienna, Austria, 2014

55 What about Patients Needs? Willingness to wait is important Willingness to self-collect specimens is important Willingness to pay is important

56 Patient Focus Group and Clinic Questionnaire about POC Tests (N =371) Specimen Type Preference Percent Cervical 15.4% Vaginal 50.9% Urine 33.7% Willingness to Pay Percent $ % $ % $ % $40 2.7% $50 8.9% Willingness to Wait Percent 20 min 59.0% 40 min 20.8% 60 min 10.8% 90 min 9.4% 16.1 Self collected vaginal 3.0 % % easy 80.9 % hard Barnes et al CDC STD Conf, Atlanta GA

57 POC tests for STIs: What do end users want? (N=58, 5 focus groups) Favorable POCTs (Rapid, Easy to read, Simple to use) Home testing acceptable better privacy Clinic-based- definitive results & immediate treatment Barriers- cost and ability to read and perform tests Hispanic patients questioned home test reliability, wanted bi-lingual instructions Rompalo et al. Sexual Health 2013;10:

58 What do OB/GYNs think? Between June and August 2016, 1000 members of the American College of OBGYN were randomly selected and invited to complete a Qualtrics survey: 600 were members of the Collaborative Ambulatory Research Network (CARN). 749 had valid s; 288 participated in and completed the survey 70% male Average year practicing = 18 30% diagnosed STDs 1-2 times/week; 45% did so 1-2 times/month Tests used: preg test (83%); dipstick (83%) wet mount (70%); vaginal ph (55%) Few used Gram stain (5%) and stat RPRs (4%). Newer POCTs were used less frequently with 25% reporting Affirm VPIII test use and only 10% using a rapid HIV test. Most common barriers were the amount of reimbursement received for performing the test (61.9%) and the payment coverage from the patient (61.3%).

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60 Assessed clinical service value of STI POCT use in a sample Outcomes: first clinical pathway Patient acceptability Whether NAAT for chlamydia and gonorrhea could be used as a POCT in practice Feasibility of non-naat POCT implementation for trichomonas and BV Impact on patient diagnosis and treatment

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63 Summary of test results Males Females Total Number of patients recruited Test results CT/NG Cepheid CT positive: N (% total) Cepheid NG positive: N (% total) 6 (17%) 1 (2.9%) 0 6 (8.6%) 1 (1.4%) Non-gonococcal urethritis (males) Based on Gram stain microscopy (urethral smear) TV (females) Based on wet mount microscopy Based on OSOM BV (females) Based on Gram stain microscopy Based on VS-SENSE 13 (37.1%) (5.7%) 3 (8.6%) 7 (20%) 24 (68.6%)

64 Patient clinical pathway timings (Males & Females)

65 Anonymous feedback questionnaire responses, by duration of patient clinic visit

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67 POC Testing and Improved Antibiotic Stewardship NG TV p-value Diagnostic Test Laboratory-Based Point-of-Care Prevalence 166/1877 (9%) 247/1492 (18%) <.001 Correctly Treated 50% 78% <.001 Undertreated 30% 20%.03 Overtreated 52% 22% <.001 TV infections detected with POC testing were more likely to be treated correctly than NG infections detected with traditional NAAT testing. Undertreatment and overtreatment were both lower when infection was detected with a POC test. Huppert, et al. STI 2013; 89

68 POC Test and Improved Antibiotic Stewardship Before POC TV Introduced After POC TV Introduced Diagnostic test TV Culture + Wet Mount OSOM TV + Wet Mount p- value Prevalence 50/249 (20%) 34/179 (34%) NS Correctly Treated 79% 88%.02 Undertreated 14% 9% NS Overtreated 23% 13%.02 Comparing TV treatment before and after the implementation OSOM rapid POC TV testing showed that, when a sensitive and specific POC test was used to detect TV, correct treatment increased and overtreatment decreased compared to before POC testing was introduced. Postenreider, Pediatrics Jun; 137(6)

69 ASSURED Criteria Criteria to guide test developers Can guide end-users in considering the suitability of a test in their clinical setting

70 Affordable Sensitive - few false negatives Specific - few false positives User friendly Rapid Robust Equipment-free Delivered

71 Affordable To patient To provider

72 Sensitivity and Specificity Consider the prevalence of disease in your population

73 User Friendly FDA determines test complexity Clinical Laboratory Improvement Amendments (CLIA) Assures quality laboratory testing Regulations include federal standards applicable to all U.S. facilities or sites that test human specimens Responsible agencies: FDA, CDC, CMS

74 User Friendly CLIA Non-waived High or moderate complexity Differ in personnel requirements Waived Easy to use Little risk of incorrect results Can be performed outside of laboratory

75 User Friendly Specimen to be collected Cleared for asymptomatic? Cleared for self-collected vaginal samples? Read-out clarity Interface with EMR

76 Readout Challenges

77 Read-out Examples

78 Rapid and Robust RAPID Turn-around time Staff time needed to conduct test ROBUST Refrigeration Clean water Climate control Calibration requirements

79 Equipment-free Storage Foot print Power Requirements Source Portable

80 Delivered FDA Clearance Test system has been reviewed by the FDA and has been determined to be substantially equivalent to a test system already legally marketed for the same use CE Mark The manufacturer has demonstrated their device complies with one of the European Union s Directives related to medical products

81 ASSURED Criteria Scoring System Score Affordable - cost/test $>$26 $11-$25 $3-$10 <$3 Sensitivity &Specificity <65% 66%-85% 83%-94% >95% User friendly Specimen used in performance studies Symptomatic only OR Endocervical only Asymptomatic OR Self-collected vaginal Asymptomatic AND Self-collected vaginal CLIA waived No Possible Yes Read-out clarity Subjective Not subjective Interface with EMR Not built in Built in RAPID Minutes to result > <11 ROBUST - Refrigeration Required None EQUIPMENT - Power Continuous AC Intermittent OR Battery available None DELIVERED - FDA cleared No In trials Yes

82 Applied ASSURED Criteria Scoring Test OIA CT Test Clearview QuickVue io Xpert CT/NG Manufacturer BioStar Alere Quidel Atlas Genetics Cepheid Affordable/cost Sensitivity User friendly Specimen (asymptomatic/vaginal) CLIA waived Read-out clarity Built-in interface EMR RAPID Minutes to result ROBUST - Refrigeration EQUIPMENT - Power DELIVERED - FDA cleared TOTAL

83 Applied ASSURED Criteria Scoring Test OIA CT Test Clearview QuickVue io Xpert CT/NG Manufacturer BioStar Alere Quidel Atlas Genetics Cepheid Affordable/cost Sensitivity 59%-74% User friendly Specimen (asymptomatic/vaginal) CLIA waived Read-out clarity Built-in interface EMR No/No No Visual No RAPID Minutes to result 20 ROBUST - Refrigeration No EQUIPMENT - Power No DELIVERED - FDA cleared 1995 TOTAL

84 Applied ASSURED Criteria Scoring Test OIA CT Test Clearview QuickVue io Xpert CT/NG Manufacturer BioStar Alere Quidel Atlas Genetics Cepheid Affordable/cost Sensitivity 59%-74% 0 User friendly Specimen (asymptomatic/vaginal) No/No 0 CLIA waived No 0 Read-out clarity Visual 0 Built-in interface EMR No 0 RAPID Minutes to result 20 2 ROBUST - Refrigeration No 0 EQUIPMENT - Power No 0 DELIVERED - FDA cleared TOTAL 5

85 Applied ASSURED Criteria Scoring Test OIA CT Test Clearview QuickVue io Xpert CT/NG Manufacturer BioStar Alere Quidel Atlas Genetics Cepheid Affordable/cost Sensitivity 59%-74% 0 50%-95% 0 25%-65% % 3 95%-100% 3 User friendly Specimen (asymptomatic/vaginal) No/No 0 No 0 Yes/No 1 Yes/Yes 3 Yes/Yes 3 CLIA waived No 0 No 0 No 0 Possible 1 Possible 1 Read-out clarity Visual 0 Visual 0 Visual 0 Pos/Neg/Ind 1 Pos/Neg/Ind 1 Built-in interface EMR No 0 No 0 No 0 Yes 3 Yes 3 RAPID Minutes to result ~12 2 ~30 min 1 ~90 min 0 ROBUST - Refrigeration No 0 Required 0 Yes 0 Required 0 None 3 EQUIPMENT - Power No 0 Intermittent 1 None 3 Continuous 0 Continuous, battery 1 DELIVERED - FDA cleared In trials TOTAL

86 Considerations for Your Clinic What test is currently used? What is the current turn-around time Problems with the current method Will POC test allow treatment at 1 st visit? Monthly test volume? Prevalence of infection in your community? Where will test be conducted: clinic, central lab, home? Regulatory system in place to support POC?

87 We are trying to POINT the WAY for POC Tests Anne Rompalo Mary Jett-Goheen Mathilda Barnes Justin Hardick Jeff Holden Laura Dize Perry Barnes Barbara Silver Lea Widdice DeAnna Owens Hillary Purcell Acknowledgments