Risks of requiring a dedicated molecular specimen for HIV diagnosis and a potential strategy for mitigation

Abstract

Background HIV screening (i.e. antigen/antibody) tests are followed by a supplemental (i.e. antibodyonly) if the screen is positive. Discrepant results can result from two scenarios: a false-positive screening test or acute HIV infection. These scenarios can be distinguished by a molecular HIV test, but due to contamination concerns, our laboratory recently implemented a policy requiring a second specimen dedicated for molecular HIV testing. Our objective was to (1) characterize the effect of this policy on the time-to-diagnosis for patients with discrepant screening and supplemental test results, and (2) explore "strength of positivity" as an interim predictor of screening test accuracy while awaiting confirmatory test results. Methods Data from our laboratory information system, electronic health record, and instrument logs were used to collate data for all HIV testing performed at Barnes-Jewish Hospital (BJH) between January 1, 2014 and October 18, 2017. Results Requiring a dedicated specimen for molecular testing significantly increased the time-to-diagnosis for patients with discrepant screening and supplemental HIV tests (p = 0.0084). This policy also contributed to loss-to-followup, with 0/35 discrepant cases lost-to-followup prior to policy implementation compared to 2/10 after implementation. However, by optimizing the signal-tocutoff (S/CO) ratio of the screening test, we were able to more accurately distinguish false-positives from acute-HIV prior to molecular testing (sensitivity of 100%, specificity of 89%). Conclusions We propose utilizing quantitative fourth-generation assay results (S/CO) ratios as a predictor of infection true positivity in situations where the screening assay is reactive but the supplemental test is negative and confirmatory molecular results are not immediately available.

Missed Opportunities for HIV Confirmatory Testing Using an Institutional Testing Algorithm Without Reflex to HIV Nucleic Acid Testing

“…12 A study evaluating the effects of requiring a dedicated sample for HIV NAT found a significant increase in the time between the screening test and HIV NAT. 13 Our results are in line with these previously published results.…”

“…A study evaluating the real-world performance of the current HIV testing algorithm in the United States found that 22% of testing encounters with a positive screening test and negative confirmatory test were incomplete because of lack of a sample for the HIV NAT 12 . A study evaluating the effects of requiring a dedicated sample for HIV NAT found a significant increase in the time between the screening test and HIV NAT 13 . Our results are in line with these previously published results.…”

Reflex Human Immunodeficiency Virus (HIV) Type 1 RNA Testing Enables Timely Differentiation of False-Positive Results From Acute HIV Infection

“…Given the large volume of HIV screening tests performed, streamlined detection of true-positive HIV tests permitted growth of routine, opt-out HIV screening while allowing staff to prioritize contacting patients with true-positive results rather than tracking individuals with discordant results. It can be difficult to reach patients who require additional testing for HIV confirmation, and others may outright refuse to undergo further testing [ 14 , 15 ]. In fact, the limited number of unconfirmed discordant cases following implementation of reflex HIV-1 RNA testing resulted from insufficient sample (6–10 mL blood sample required) to perform the HIV-1 RNA assay and subsequent inability to make patient contact.…”

“…In fact, the limited number of unconfirmed discordant cases following implementation of reflex HIV-1 RNA testing resulted from insufficient sample (6–10 mL blood sample required) to perform the HIV-1 RNA assay and subsequent inability to make patient contact. In the absence of HIV RNA assay results, use of the signal-to-cutoff ratio of the screening assay may also mitigate this problem, which can help distinguish between false-positive and acute (true-positive) results before confirmatory testing is available [ 15 , 16 ].…”