AIDS in the United States 1997 Consensus Conference Recommendations: Change PHS regulations, allow rapid test results SUDS test unacceptable Mandate to CDC: Make more rapid tests available Develop diagnostic algorithms using rapid tests 587,429 reported cases of AIDS in the United States

CDC Efforts and the Availability of Rapid Tests Based on identified public health need: Encourage manufacturers to commercialize rapid tests in the United States. Conduct clinical trials to establish test performance in settings of intended use. Provide data for PMA applications to speed FDA approval. Evaluate use of specific combinations of rapid tests to increase predictive value.

4/13/2019 Rapid Tests for HIV 4

Walter Reed Army Institute of Research HIV Diagnostic Laboratory 5

Results: Retrospective Study Walter Reed Army Institute of Research HIV Diagnostic Laboratory APHL Mar’ 2000

Seroconversion Panels 9th CROI, 2002

June 2001 BPAC: CLIA Waiver Should HIV rapid tests be eligible under standard CLIA criteria for waiver? In favor: CDC, NASTAD, CA Office of AIDS Prevention Programs Opposed: CLIAC, ASCP, ASM, AACC, ASCLS Concerns: Accuracy with untrained users; positive predictive value; confirmatory testing; quality control; counseling http://www.fda.gov/ohrms/dockets/ac/01/transcripts/3760t1_01.pdf

Methods 1: Untrained Users 4/13/2019 Methods 1: Untrained Users 130 participants from staff at HIV testing sites: 93 from Los Angeles testing site, 37 from Arizona STD clinic 129 hospital personnel: from Atlanta, Chicago, Miami, New Orleans, and New York The study was conducted in several parts. 130 participants were recruited from staff at HIV testing sites – 93 from the West Hollywood STD clinic and from the HIV testing clinic at the Los Angeles Gay and Lesbian Center. The participants each tested 3 serum specimens that had been obtained from patients. 37 participants were recruited from staff at the the Maricopa County STD clinic in Phoenix, Arizona. This group tested a panel of 4 plasma specimens that had been specially constructed to include negative, weak positive, and strong positive specimens. Rapid Tests for HIV

Invalid results were recorded for 37 (8.6% ) tests 4/13/2019 Results: Outcomes of 427 Tests Performed by 130 Untrained Users at HIV Testing Sites Invalid results were recorded for 37 (8.6% ) tests False Negative Correct At the HIV testing sites, participants performed a total of 427 tests. 37 of these (8.6%) were performed incorrectly, and a result of “invalid” was recorded. Participants obtained the correct result with 379 (97.2%) of the remaining 390 tests. Participants obtained incorrect (false-negative) results for 7 (1.8%) of the known positive specimens. All of these were with the weak-positive specimen, which showed a faint band on the test. Participants obtained false-positive results for 4 (1%) of the known negative specimens. 7 (1.8%) 379 (97.2%) False Positive 4 (1.0%) Rapid Tests for HIV

Invalid results were recorded for 50 (9.6% ) tests 4/13/2019 Results: Outcomes of 516 Tests Performed by 129 Untrained Health Care Workers Invalid results were recorded for 50 (9.6% ) tests Correct False Negative Results from the 129 untrained health care workers were similar. 50 (9.6%) of the 516 tests were performed incorrectly and gave an invalid result. Of the remaining 466 specimens, the rapid test result was correct for 448 (96.1%). There were 9 incorrect false-negative results, all with the weak-positive specimen, and 9 incorrect false-positive results. 9 (1.9%) 448 (96.1%) False Positive 9 (1.9%)* Rapid Tests for HIV

4/13/2019 Results: after Training: 5325 Tests Performed by 213 Health Care Workers Invalid 3 (0.06%) Correct False Negative Performance of the test improved considerably after a brief description and demonstration of the procedure. All participants correctly performed the test procedure. The supervising laboratory technician documented that the test was performed correctly in the 3 instances for which valid results were obtained. Thus, the invalid results were most likely due to a faulty device. Overall, the 213 participants obtained correct results for 99.7% of the 5300 tests they performed. 14 false-negative and 3 false-positive results were observed. 5305 (99.7%) 14 (0.26%) False Positive 3 (0.06%) Rapid Tests for HIV

Positive Predictive Value: Remember the tradeoffs… Good News: More HIV-positive people receive their test results. Bad News: Some people will receive a false-positive result before confirmatory testing.

Positive Predictive Value: Newborn Screening Specificity PPV PKU 99.7 2.65% Galactosemia 0.57% Hypothyroidism 98.3 1.77% Adrenal Hyperplasia 99.0 0.53% Newborn Screening results , 1993 Arch Pediatr Adolesc Med, July 2000

Overall, no statistically significant difference in STD incidence in HIV-negative persons after rapid HIV counseling vs standard 2-session counseling Behavior was similar in both groups Incidence of new STD 17-19% within 1 year

Role of the AD for Lab Diagnostics

The argument that less-than-perfect waived testing is better than none in some cases carries special weight when battling HIV. “If you have a population where 30 percent of people don’t come back to get their results, as the CDC says is true for people testing for HIV in certain settings, then you can never have a senxitivity [for any test] tat’s greater than 70 percent.” - Sheldon Campbell, MD, PhD CAP Point-of-Care Testing Committee

Collect oral fluid specimens by swabbing gums with test device. Reduce hazards, facilitate testing in field settings

Read results in 10 minutes Positive Negative Read results in 10 minutes

HIV-1 & HIV-2 Positive Negative Reactive Control Recombinant HIV-1 Peptide HIV-2 Peptide HIV-1 HIV-1 & HIV-2 Positive Negative