Acute Dengue Fever Causes False-Positive Reactivity in OraQuick Rapid HIV-1/2 Antibody Test

Abstract

To the Editors: The OraQuick ADVANCE Rapid HIV-1/2 Antibody Test, from OraSure Technologies Inc., detects antibodies to HIV-1 and HIV-2 in 20 minutes. This immunoassay can be performed on oral fluid, fingerstick whole blood, venipuncture whole blood, and plasma specimens. The manufacturer reports a sensitivity of 99.3% (95% confidence interval: = 98.4% to 99.7%) and specificity of 99.8% (95% confidence interval: = 99.6% to 99.9%) for use of the test with oral fluid specimens.1 However, false-positive results have been detected, including in test kits close to the expiration date. One study found a false-positive rate of 1.17% in test kits used with ≤1 month remaining until expiration.2 It is noted that these results came from an older version of the OraQuick ADVANCE test kit. Accuracy of both oral and blood HIV screening tests may also be affected by concomitant tropical infections. In sub-Saharan Africa, false-positive HIV enzyme-linked immunosorbent assay (ELISA) results were associated with a diagnosis of human African trypanosomiasis,3 urinary schistosomiasis,4 uncomplicated malaria,5 and visceral leishmaniasis.6 These false-positive results in HIV antibody detection testing have been attributed to polyclonal B-cell activation and/or high concentration of rheumatoid factor-like anti-immunoglobulin antibodies seen in these infections.3-6 In Colombia, 1 study postulated that parasitic proteins similar to the reverse transcriptase could be a possible cause of false positive HIV ELISA tests in patients infected by Trypanosoma cruzi.7 Since December 2008, we have been using the OraQuick test kit on oral fluid as part of a study in the Duke University Hospital Emergency Department to determine whether rapid HIV testing can be effectively offered and accepted as a routine screening test. Recently, a false-positive result occurred in a patient presenting with acute Dengue fever. The patient had just returned to the United States after traveling abroad to the island of Guadeloupe, French West Indies, for 3 weeks where she recalled receiving multiple mosquito bites. She was admitted to Duke University Hospital after presenting to the Emergency Department with acute HIV-like symptoms of recurrent fevers, night sweats, nausea, vomiting, headache, joint aches, and rash. Her initial temperature was 37.3°C, but she reported fevers up to 39.4°C at home. The patient had an erythematous, raised, nonpruritic maculopapular rash on her lower extremities. Upon presentation, her white blood cells was low at 1600 cells × 109/L with an absolute lymphocyte count of 500. Her platelets were low at 88 × 109/L and ultimately dropped to 47 during her hospitalization. Her aspartate aminotransferase was slightly elevated at 77 U/L. In Guadeloupe, she had serologies drawn, which were positive for Dengue. Acute and convalescent serologies drawn at Duke were sent to the North Carolina State Laboratory and also confirmed to be positive. As there are no reports of malaria in Guadeloupe,8 a blood smear was not performed. Her initial and repeat OraQuick oral swabs were positive. The patient denied any recent high-risk behaviors that would place her at risk for acute HIV infection and had tested negative for HIV 2 years ago. As part of our protocol for confirmation of a preliminary reactive test, a Western Blot was performed which was indeterminate with a faint band at p24. Further workup demonstrated a negative serum HIV ELISA and an undetectable HIV viral load. Although both OraQuick tests used had expiration dates ≤1 month from time of use, it is not clear if this was a contributing factor as we were using the newer version of the kit. More likely, the diagnosis of acute Dengue contributed to the false-positive result. There is only one other report documenting HIV-1 false-positive rapid ELISA tests in patients with Dengue fever.9 In this study, false-positive HIV screening tests on sera occurred in 4 of the 9 patients with Dengue, though there was no information on the mechanism by which Dengue infection triggered the false-positive reactivity. Our findings indicate that false positives may occur with rapid HIV assays, particularly in the case of concomitant infections. This may be a greater concern in resource-poor regions where diseases such as Dengue are most prevalent and as rapid HIV tests become more widely used. Alice Mao Chidera Obi-Gwacham Tamsey Hill, DMin Catherine Ryan, MSHSA Arthur Hendricks, MDiv Mehri McKellar, MD Division of Infectious Diseases and Department of Medicine, Duke University Durham, NC