1985: First HIV-1 ELISA Approved by FDA 10,264 reported cases of AIDS in the United States

Traditional Diagnostic HIV Testing Since inception, testing technology driven by blood screening needs: High volume Maximal sensitivity but… Complex equipment Technically demanding Centralized, time-consuming Expensive

1987: What is the Role of Diagnostic Testing in the Prevention and Control of HIV? 35,068 reported cases of AIDS in the United States

1989: Western Blot 161,073 reported cases of AIDS in the United States

The Roll-out of Rapid HIV Testing The United States Bernard M. Branson, M.D. Associate Director for Laboratory Diagnostics Division of HIV/AIDS Prevention – CDC 12th CROI - February 23, 2005

The Roll-out of Rapid HIV Testing CLIA-waived The Roll-out of Rapid HIV Testing in The United States Bernard M. Branson, M.D. Associate Director for Laboratory Diagnostics Division of HIV/AIDS Prevention – CDC 12th CROI - February 23, 2005

HIV Screening with OraQuick in the MIRIAD Study 4/30/2019 HIV Screening with OraQuick in the MIRIAD Study To date 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 4 infants infected; 3 of these in utero Specificity: OraQuick 99.92%; EIA 99.80% Positive Predictive value: OraQuick 90%; EIA 76% These are the results of PMTCT with rapid testing in labor and delivery in the U.S. In this study, conventional EIA testing was performed on all persons, in addition to the rapid test. The OraQuick rapid test showed no false-negative test results, and fewer false-positive tests than the EIA. Bulterys et al, JAMA July 2004 Poster 788 Rapid Tests for HIV

4/30/2019 Perinatally Acquired AIDS Cases by Year of Diagnosis, 1981–2002, United States Number of cases Year of diagnosis 85 86 87 88 89 90 91 92 93 94 95 96 97 98 99 00 01 02 81 82 83 84 Rapid Tests for HIV

Multispot HIV-1/HIV-2 Uni-Gold Recombigen Reveal G2 OraQuick Advance

2003-05 AHP Rapid Testing Demonstration Projects 4/30/2019 2003-05 AHP Rapid Testing Demonstration Projects Routine Testing in Medical Settings Rapid Testing in Short-Stay Corrections Settings Rapid Testing in Non-Medical Settings PCRS with Rapid Testing Social Networks Total Orgs Funded 4 HDs 7 CBOs 6 HDs 9 CBOs Total Number Tested 6,506 12,300 8,060 179 1,048 Total HIV-positive (percent) 58 (0.9%) 196 (1.7%) 134 (1.6%) 15 (8%) 74 (7%) Through December 2004 Rapid Tests for HIV

Laboratory Diagnostics 4/30/2019 Symptoms p24 Antigen HIV RNA HIV ELISA* HIV infection can be detected weeks before antibody tests turn positive The presence of HIV can be detected using tests that detect HIV directly in the blood, as early as 1-2 weeks after infection. Antibody tests take one to nine weeks longer. The big question is: do people show up for HIV tests during the first few weeks after infection? If not, the question of when different tests detect HIV would be moot. BUT IF THEY DO, we could be missing a lot of HIV infections with our HIV testing practices, which rely on HIV antibody detection alone. 0 1 2 3 4 5 6 7 8 9 10 Weeks Since Infection *3rd generation, IgM-sensitive EIA *2nd generation EIA After Fiebig et al, AIDS 2003; 17(13):1871-9 *viral lysate EIA Rapid Tests for HIV

EIAs Used by Public Health Labs FDA approval date % used by PHL labs, 2004 Vironostika HIV-1 Microelisa 1987 63% Abbott HIVAB HIV-1/2 1992 20% Genetic Systems rLAV 1998 Gen Sys HIV-1/HIV-2 2000 18% Gen Sys HIV-1/2 Plus O 2003 10% Vironostika HIV-1 Plus O 2% viral lysate EIA

EIAs Used by Public Health Labs FDA approval date % used by PHL labs, 2004 Vironostika HIV-1 Microelisa 1987 63% Abbott HIVAB HIV-1/2 1992 20% Genetic Systems rLAV 1998 Gen Sys HIV-1/HIV-2 2000 18% Gen Sys HIV-1/2 Plus O 2003 10% Vironostika HIV-1 Plus O 2% viral lysate EIA 2nd generation EIA

EIAs Used by Public Health Labs FDA approval date % used by PHL labs, 2004 Vironostika HIV-1 Microelisa 1987 63% Abbott HIVAB HIV-1/2 1992 20% Genetic Systems rLAV 1998 Gen Sys HIV-1/HIV-2 2000 18% Gen Sys HIV-1/2 Plus O 2003 10% Vironostika HIV-1 Plus O 2% viral lysate EIA 2nd generation EIA 3rd generation, IgM-sensitive EIA

Monitor Performance of EIAs FDA approval date % used by PHL labs, 2004 Vironostika HIV-1 Microelisa 1987 63% Abbott HIVAB HIV-1/2 1992 20% Genetic Systems rLAV 1998 Gen Sys HIV-1/HIV-2 2000 18% Gen Sys HIV-1/2 Plus O 2003 10% Vironostika HIV-1 Plus O 2% viral lysate EIA 2nd generation EIA 3rd generation, IgM-sensitive EIA

As New EIAs Are Used by Public Health Labs FDA approval date % used by PHL labs, 2004 Vironostika HIV-1 Microelisa 1987 63% Abbott HIVAB HIV-1/2 1992 20% Genetic Systems rLAV 1998 Gen Sys HIV-1/HIV-2 2000 18% Gen Sys HIV-1/2 Plus O 2003 10% Vironostika HIV-1 Plus O 2% viral lysate EIA 2nd generation EIA 3rd generation, IgM-sensitive EIA

Pooled RNA Screening for Early HIV Infection

Awareness of Serostatus among Persons with HIV, United States 4/30/2019 Awareness of Serostatus among Persons with HIV, United States Number HIV infected 850,000 - 950,000 Number unaware of their HIV infection 180,000 - 280,000 Rapid Tests for HIV

~25% Unaware of Infection 4/30/2019 Awareness of Serostatus Among People with HIV and Estimates of Transmission ~25% Unaware of Infection Accounting for: ~55% of New Infections Currently, in the United States, there are an estimated 850,000-950,000 people who are infected with HIV. Of those, the majority of people, an estimated 670,000-770,000 – or 75% – are aware of their status. But that leaves 25% – or 180,000 to 280,000 people – unaware they are infected with HIV. It has been estimated that infections transmitted from this group account for 27,000, or 2/3, of the 40,000 new infections per year. The importance of getting these individuals tested and into treatment that includes prevention interventions is critical. ~75% Aware of Infection ~45% of New Infections People Living with HIV/AIDS: 850,000-950,000 New Sexual Infections Each Year: ~36,000 Rapid Tests for HIV

What is the Role of Diagnostic Testing in the Prevention and Control of HIV? 21-24 million diagnostic HIV tests each year 16-18 million persons tested

Challenges Cost Regulatory constraints The role for antibody diagnostics More new developments