Abstract

BackgroundThe Centers for Disease Control and Prevention (CDC) recommends universal HIV screening with a fourth-generation HIV-1/2 antigen–antibody immunoassay followed by an HIV-1/-2 antibody differentiation immunoassay. Discordant results require nucleic acid testing (NAT) to distinguish acute HIV from false positives. In practice, NAT can be delayed, leaving clinicians and patients in limbo. Better understanding of factors associated with acute HIV vs. false positivity among discordant HIV tests is needed.MethodsFrom 2014 to 2018, positive fourth-generation HIV-1/-2 enzyme-linked immunosorbent assay (ELISA) tests were retrospectively analyzed across centers in the Harris Health system in Houston, Texas. Discordant results were defined as a positive fourthgeneration HIV-1/2 ELISA with a negative HIV-1/-2 antibody confirmation test and were resolved via NAT (if possible). Duplicate results and patients with a previously positive HIV-1 viral load were excluded. Results were analyzed (Fisher’s exact test or Chi square) by year, setting (clinic/hospital), sex, age, race, and comorbid conditions (pregnancy, rheumatoid arthritis, lupus, hepatitis B and syphilis [rapid plasma reagin, or RPR>1:4] for associations with acute HIV vs. false positivity).ResultsOf 7,077 positive fourth-generation HIV-1/2 ELISA tests, 488 (13%) discordant cases were identified. Eighty-six (18%) represented acute HIV while 322 (66%) were false positives; 80 remained unresolved (no NAT performed). Median time to resolution via NAT was 21 days. Clinic setting, female sex, older age, non-Black race, and negative RPR status were associated with significantly higher rates of false positivity vs. acute HIV (P < 0.02 for all associations).ConclusionIn this large HIV testing program in a multicenter metropolitan health system, 66% of discordant fourth-generation HIV tests represented false positives. Several clinical factors correlated with a higher rate of false positivity, likely reflecting the impact of disease prevalence on the positive predictive value of any diagnostic test. Clinicians may consider these factors when counseling their patients during the limbo period. Efforts to expedite NAT to resolve discordant cases is paramount to reducing diagnostic uncertainty.Disclosures All authors: No reported disclosures.

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