Analysis of False-Negative Human Immunodeficiency Virus Rapid Tests Performed on Oral Fluid in 3 International Clinical Research Studies

Clin Infect Dis. 2017 Jun 15;64(12):1663-1669. doi: 10.1093/cid/cix228.

Abstract

Background.: The OraQuick Advance Rapid HIV-1/2 Test is a point-of-care test capable of detecting human immunodeficiency virus (HIV)-specific antibodies in blood and oral fluid. To understand test performance and factors contributing to false-negative results in longitudinal studies, we examined results of participants enrolled in the Botswana TDF/FTC Oral HIV Prophylaxis Trial, the Bangkok Tenofovir Study, and the Bangkok MSM Cohort Study, 3 separate clinical studies of high-risk, HIV-negative persons conducted in Botswana and Thailand.

Methods.: In a retrospective observational analysis, we compared oral fluid OraQuick (OFOQ) results among participants becoming HIV infected to results obtained retrospectively using enzyme immunoassay and nucleic acid amplification tests on stored specimens. We categorized negative OFOQ results as true-negative or false-negative relative to nucleic acid amplification test and/or enzyme immunoassay, and determined the delay in OFOQ conversion relative to the estimated time of infection. We used log-binomial regression and generalized estimating equations to examine the association between false-negative results and participant, clinical, and testing-site factors.

Results.: Two-hundred thirty-three false-negative OFOQ results occurred in 80 of 287 seroconverting individuals. Estimated OFOQ conversion delay ranged from 14.5 to 547.5 (median, 98.5) days. Delayed OFOQ conversion was associated with clinical site and test operator (P < .05), preexposure prophylaxis (P = .01), low plasma viral load (P < .02), and time to kit expiration (P < .01). Participant age, sex, and HIV subtype were not associated with false-negative results. Long OFOQ conversion delay time was associated with antiretroviral exposure and low plasma viral load.

Conclusions.: Failure of OFOQ to detect HIV-1 infection was frequent and multifactorial in origin. In longitudinal trials, negative oral fluid results should be confirmed via testing of blood samples.

Keywords: HIV; immunosorbent techniques; oral fluid; point-of-care testing.; serodiagnosis.

Publication types

  • Observational Study

MeSH terms

  • AIDS Serodiagnosis*
  • Adult
  • Botswana / epidemiology
  • Clinical Studies as Topic
  • False Negative Reactions
  • Female
  • HIV Antibodies / analysis*
  • HIV Antibodies / blood
  • HIV Infections / diagnosis*
  • HIV Infections / epidemiology
  • HIV Infections / virology
  • HIV-1 / genetics
  • HIV-1 / immunology
  • HIV-1 / isolation & purification*
  • HIV-2 / genetics
  • HIV-2 / immunology
  • HIV-2 / isolation & purification
  • Humans
  • Immunoenzyme Techniques
  • Male
  • Point-of-Care Systems*
  • Polymerase Chain Reaction
  • Pre-Exposure Prophylaxis
  • Reagent Kits, Diagnostic
  • Regression Analysis
  • Retrospective Studies
  • Saliva / immunology*
  • Sensitivity and Specificity
  • Thailand / epidemiology
  • Viral Load

Substances

  • HIV Antibodies
  • Reagent Kits, Diagnostic