1. Bernard M. Branson, M.D. Associate Director for Laboratory Diagnostics Divisions of HIV/AIDS Prevention National Center for HIV, STD, and TB Prevention Centers for Disease Control and Prevention Changes in HIV Testing Practices and Counseling Recommendations FDA Blood Products Advisory Committee Meeting November 3, 2005

2. Outline Role of rapid HIV tests in the HHS “Advancing HIV Prevention” Initiative Postmarketing surveillance: rapid HIV tests and home sample collection HIV tests CDC’s planned revisions of counseling recommendations Anticipated value of an OTC vs CLIA-waived test Validating HIV tests for home use

3. Four priority strategies: 1. Make voluntary HIV testing a routine part of medical care 2. Implement new models for diagnosing HIV infections outside medical settings 3. Prevent new infections by working with persons diagnosed with HIV and their partners 4. Further decrease perinatal HIV transmission Advancing HIV Prevention MMWR April 18, 2003

4. Number HIV infected 1,039,000 – 1,185,000 Number unaware of their HIV infection 252,000 - 312,000 Estimated number of 40,000 new infections annually Awareness of HIV status among Persons with HIV, United States Glynn et al 2005 HIV Prevention Conference

5. Role for Rapid HIV Tests Increase receipt of test results: In 2000, 31% did not return for results of HIV- positive conventional tests at publicly funded sites Increase feasibility of testing in acute-care settings with same-day results Increase number of venues where testing can be offered to high-risk persons Increase identification of HIV-infected pregnant women so they can receive effective prophylaxis

6. Rapid HIV Screening in Acute Care Settings Cook County ED, Chicago2.3% Grady ED, Atlanta2.7% Johns Hopkins ED, Baltimore3.2% King-Drew Med Center, Los Angeles1.3% CDC HIV testing sites: 1.1% New HIV+Study site

7. Rapid HIV Screening in Medical Settings Demonstration ProjectNo. tested % HIV+ New York City Bronx- Lebanon: 2 clinics, 1 ED 2,3552% Los Angeles 2 clinics, 1 ED 4,8161% Alameda County (Oakland) 1 ED 3,7461.2% Massachusetts 1 outpatient, 1 inpatient, 1 clinic 5,6810.7% Wisconsin 3 clinics 1,5550.4% CDC, preliminary data - Sept 2005

8. Rapid HIV Testing in Non-Clinical Settings Community-based organizationNo. Tested% HIV+ AIDS Healthcare Foundation, L.A.2,3181.6% Bienestar, L.A.1,9022.9% CHAG, Detroit2,0111.5% Continuum, San Francisco1,7721.8% HSP of Dorchester, Boston4,6181.1% Kansas City Free Clinic1,8261.1% The Night Ministry, Chicago1,8671.2% Whitman Walker, Washington DC4,2450.7% 20,6591.4% CDC, preliminary data - Sept 2005

9. HIV Screening with OraQuick in MIRIAD Mother Infant Rapid Intervention At Delivery Testing of pregnant women in labor for whom no HIV test results are available; 12 hospitals in 5 cities: Atlanta, Chicago, Miami, New Orleans, New York 7680 women screened 54 (0.7%) new HIV infections identified 6 false positive OraQuick tests, no false negatives 15 false-positive EIAs: 7 p24 only, 8 WB negative Specificity: OraQuick 99.92%; EIA 99.80% Positive predictive value: OraQuick 90%; EIA 76% Bulterys et al, JAMA July 2004

10. Performance of OraQuick Rapid HIV Test 4 studies comparing OraQuick with whole blood and oral fluid to EIA/Western blot: Known HIV+ persons – Los Angeles Prospective testing, HIV testing clinic and STD clinics – Los Angeles, Phoenix Pregnant women – 5 MIRIAD cities Outreach settings – Minneapolis

11. Performance of OraQuick: Known HIV+ NWhole bloodOral fluid Known HIV+ 57699.5% (98.5-99.9)98.4% (97.1-99.3) - On HAART 39099.2% (97.8-99.8)97.7% (95.6-98.9) - Not on HAART 186100% (98.4-100) Sensitivity

12. Performance of OraQuick: Prospective Testing SensitivitySpecificity OraQuick - Whole blood - Oral fluid 99.7% (98.3-100) 99.1% (97.3-99.8) 99.9% (99.8-100) 99.6% (99.4-99.7) Serum EIA-99.7% (99.6-99.8) Combined study population: 327 HIV-positive by reference tests 12,010 HIV-negative by reference tests

13. Postmarketing Surveillance: 2003 20,585 rapid whole blood HIV tests 392 (1.9%) confirmed HIV-positive 21 (5.4%) reactive OraQuick had negative or indeterminate confirmatory test results 10 resolved as true positive on follow-up 4 resolved as false-positive on follow-up 7 with unsuccessful follow-up

14. Postmarketing Surveillance: 2004-2005 No. of Tests HIV Seropositivity Median % (range) Estimated Specificity Median % (range) PPV Median % (range) RT whole blood83,6440.9 (0.1-2.8)99.9 (99.7-100)97.3 (76.5-100) RT oral fluid17,2201.2 (0.3-2.4)99.8 (99.4-100)94.5 (66.7-100) Conventional31,8111.5 (0.5-5.1)--- Project-specific median (range) for confirmed HIV seropositivity, specificity and positive predictive value of OraQuick (347 testing sites, 14 project areas) CDC, preliminary data - Oct 2005

15. Postmarketing Surveillance: 2004-2005 Received Negative Results Median % (range) Received Preliminary Positive Results Median % (range) Received Confirmed Positive Results Median % (range) Rapid99.7 (90.6-100)100 (87.5-100)90.6 (43.7-100) Conventional79.9 (29.1-98.9)---83.3 (44.4-100) Project-specific median (range) of clients who received test results (347 testing sites in 14 project areas) CDC, preliminary data - Oct 2005

16. Postmarketing Surveillance: 2004-2005 Quality assurance outcomes, 154 sites, 7 project areas January 1, 2005 to June 30, 2005 35,188 persons tested –4 (0.01%) invalid test results 1,086 controls run –median 2.7% (range 0.5% - 9.7%) of all tests –2 controls reported as “invalid” 2 sites each reported testing clients on one day when temperature was out of range 1 site reported one day when tests kits were stored outside recommended temperature range CDC, preliminary data - Oct 2005

17. Postmarketing Surveillance: Home Sample Collection HIV Testing User characteristics, May 1996 – September 1997 All UsersHIV+ UsersHIV Prevalence Female38%15%0.4% Male62%85%1.4% African American5%16%2.7% White85%69%0.7% Hispanic5%12%2.6% Heterosexual77%23%0.3% Bisexual male8%27%3.1% MSM10%38%3.5% IDU1%6%4.1% Data available for 76,373 (59%) of 165,194 users -JAMA 1998

18. Postmarketing Surveillance: Home Sample Collection HIV Testing 58% of all users and 49% of users who tested HIV positive had never been tested before. HIV prevalence: 0.8% among those with no previous test 0.7% among those with previous negative test -JAMA 1998

19. Postmarketing Surveillance: Home Sample Collection HIV Testing HIV-positive users: –23% had a source of follow-up care –65% accepted referrals for care –12% were already receiving antiretroviral therapy Psychological distress: –7% expressed shock at unexpected positive result –5% hung up immediately, without counseling HIV-negative users: –82% received recorded message only –29% called more than once –12% elected to speak with a counselor Analysis of counselors “call log” and telephone results -JAMA 1998

20. HIV Testing, Persons Age 18-64, 2002 (Excluding Blood Donation) NHISBRFSS Ever tested for HIV37.8%43.5% Tested in past year10.0%12.2% - One or more risk factors21.5%26.8% - Pregnant women48.4%54.0% Estimated no. persons tested during preceding 12 months 16-18 million 21-22 million NHIS: National Health Interview Survey BRFSS: Behavioral Risk Factor Surveillance System - MMWR December 3, 2004

21. HIV Testing, Persons Age 18-64, 2002 Source of Most Recent Test Private doctor/HMO43.5% Hospital, ED, outpatient clinic22.4% Public source23.5% At home5.1% Other location4.8% National Health Interview Survey - MMWR December 3, 2004

22. Changes in Testing and Counseling Recommendations Routine HIV screening in health care settings in high prevalence communities or facilities Opt-out consent for pregnant women, with written or verbal notification that testing will be done Written or verbal information about HIV Prevention counseling in conjunction with HIV testing not required in health care settings Retesting at least annually for persons at high risk Ensure linkage to care for persons who test positive

23. Rationale for Proposed Changes High levels of knowledge about HIV, availability of effective treatment, experience with HIV testing Many HIV-infected persons access health care but are not tested for HIV until symptomatic Inconclusive evidence about prevention benefits from typical counseling for persons who test negative Substantial reductions in high-risk sexual behavior among persons aware of HIV infection 68% reduction in unprotected intercourse with partners not known to be HIV-positive Prevention counseling encouraged for high risk persons but does not have to occur in context of HIV testing

24. Potential Value of OTC vs CLIA-Waived Test Persons unwilling to be tested in other settings Persons who retest frequently Knowledge of partner’s status as a prevention intervention Local requirements for laboratories beyond CLIA requirements that impede HIV testing

25. Potential Validation Studies Observed self-testing at high risk venues Counselor provides client with “OTC” device –Observes specimen collection and testing –Documents client reaction to test result –Verifies client interpretation of test result Select 2 to 3 settings serving clients with different characteristics Minimum 500 clients in setting with HIV prevalence of 3% to 5%