Influenza Vaccination and False Positive HIV Results
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《新英格兰医药杂志》
To the Editor: Six weeks after an occupational needle-stick injury, a 35-year-old man presented to a clinic in the Los Angeles area for testing to rule out acute infection with the human immunodeficiency virus (HIV). The patient had no other risk factors for HIV infection and reported having had no symptoms suggestive of an acute retroviral syndrome. His recent medical history was notable only for his having received an influenza vaccination 11 days before presentation.
His test for hepatitis C antibody was negative, but an enzyme immunoassay for HIV type 1 (HIV-1) was repeatedly reactive, and the result on a Western blot assay that was performed as part of the clinical protocol to confirm a reactive enzyme immunoassay was indeterminate, with a single band that was positive for glycoprotein 160 (GP160). An HIV nucleic acid amplification test was ordered to rule out cross-reactivity caused by the influenza vaccination; the patient's viral load was undetectable by this method. In accordance with accepted screening algorithms,1 we thus considered the patient to be HIV-negative with a high level of confidence. At one month, his viral load remained undetectable (<50 copies per milliliter), and the results on Western blotting had reverted to nonreactive.
A case–control study2 of 101 blood donors who had been vaccinated against influenza and 191 matched controls showed that recent inoculation with any brand of influenza vaccine was significantly associated with a false positive screening assay for HIV antibodies. Guidelines of both Johns Hopkins and the New York State Department of Health list influenza vaccination as a known cause of indeterminate results on Western blotting for HIV antibodies.3 Furthermore, digital reconstructions of both molecules demonstrate a striking homology between the transmembrane domains of HIV-1 envelope proteins and the influenza envelope protein hemagglutinin, although whether this homology accounts for the false positive assay reactions is unclear.4
The HIV GP160 protein exists only in the intracellular domain, where it is cleaved into GP41 and GP120 oligomers. Since GP160 itself is not present in mature HIV virions,5 GP160 proteins and antibodies against these proteins should be absent not only from the Western blot assays but also in most cases from the serum of HIV-infected patients.
Given the escalating international awareness of various influenza strains, it is very important to remind patients and clinicians that influenza vaccination may cause cross-reactivity with HIV antibody assays. The time course for such cross-reactivity remains uncertain. Moreover, if the screening algorithm for acute HIV infection had called for the use of a nucleic acid amplification test instead of the Western blot assay to confirm the enzyme immunoassay, the index patient would not have received an indeterminate result.
Christian P. Erickson, M.D.
USHealthworks
Los Angeles, CA 90245
christianerickson@alumni.duke.edu
Todd McNiff, M.D., M.S.P.H.
Mount Sinai Medical Center
Miami Beach, FL 33140
Jeffrey D. Klausner, M.D., M.P.H.
San Francisco Department of Public Health
San Francisco, CA 94103
References
Pilcher CD, Fiscus SA, Nguyen TQ, et al. Detection of acute infections during HIV testing in North Carolina. N Engl J Med 2005;352:1873-1883.
Simonsen L, Buffington J, Shapiro CN, et al. Multiple false reactions in viral antibody screening assays after influenza vaccination. Am J Epidemiol 1995;141:1089-1096.
Reasons for false-positive, false-negative, and indeterminate results in assays for the detection of antibodies against HIV. (Table.) (Accessed March 10, 2006, at http://www.hivguidelines.org/public_html/a-tests/a-tests-tbl1.htm.)
Chan DC, Fass D, Berger JM, Kim PS. Core Structure of gp41 from the HIV envelope glycoprotein. Cell 1997;89:263-273.
Pinter A, Honnen WJ, Tilley SA, et al. Oligomeric structure of gp41, the transmembrane protein of human immunodeficiency virus type 1. J Virol 1989;63:2674-2679.
His test for hepatitis C antibody was negative, but an enzyme immunoassay for HIV type 1 (HIV-1) was repeatedly reactive, and the result on a Western blot assay that was performed as part of the clinical protocol to confirm a reactive enzyme immunoassay was indeterminate, with a single band that was positive for glycoprotein 160 (GP160). An HIV nucleic acid amplification test was ordered to rule out cross-reactivity caused by the influenza vaccination; the patient's viral load was undetectable by this method. In accordance with accepted screening algorithms,1 we thus considered the patient to be HIV-negative with a high level of confidence. At one month, his viral load remained undetectable (<50 copies per milliliter), and the results on Western blotting had reverted to nonreactive.
A case–control study2 of 101 blood donors who had been vaccinated against influenza and 191 matched controls showed that recent inoculation with any brand of influenza vaccine was significantly associated with a false positive screening assay for HIV antibodies. Guidelines of both Johns Hopkins and the New York State Department of Health list influenza vaccination as a known cause of indeterminate results on Western blotting for HIV antibodies.3 Furthermore, digital reconstructions of both molecules demonstrate a striking homology between the transmembrane domains of HIV-1 envelope proteins and the influenza envelope protein hemagglutinin, although whether this homology accounts for the false positive assay reactions is unclear.4
The HIV GP160 protein exists only in the intracellular domain, where it is cleaved into GP41 and GP120 oligomers. Since GP160 itself is not present in mature HIV virions,5 GP160 proteins and antibodies against these proteins should be absent not only from the Western blot assays but also in most cases from the serum of HIV-infected patients.
Given the escalating international awareness of various influenza strains, it is very important to remind patients and clinicians that influenza vaccination may cause cross-reactivity with HIV antibody assays. The time course for such cross-reactivity remains uncertain. Moreover, if the screening algorithm for acute HIV infection had called for the use of a nucleic acid amplification test instead of the Western blot assay to confirm the enzyme immunoassay, the index patient would not have received an indeterminate result.
Christian P. Erickson, M.D.
USHealthworks
Los Angeles, CA 90245
christianerickson@alumni.duke.edu
Todd McNiff, M.D., M.S.P.H.
Mount Sinai Medical Center
Miami Beach, FL 33140
Jeffrey D. Klausner, M.D., M.P.H.
San Francisco Department of Public Health
San Francisco, CA 94103
References
Pilcher CD, Fiscus SA, Nguyen TQ, et al. Detection of acute infections during HIV testing in North Carolina. N Engl J Med 2005;352:1873-1883.
Simonsen L, Buffington J, Shapiro CN, et al. Multiple false reactions in viral antibody screening assays after influenza vaccination. Am J Epidemiol 1995;141:1089-1096.
Reasons for false-positive, false-negative, and indeterminate results in assays for the detection of antibodies against HIV. (Table.) (Accessed March 10, 2006, at http://www.hivguidelines.org/public_html/a-tests/a-tests-tbl1.htm.)
Chan DC, Fass D, Berger JM, Kim PS. Core Structure of gp41 from the HIV envelope glycoprotein. Cell 1997;89:263-273.
Pinter A, Honnen WJ, Tilley SA, et al. Oligomeric structure of gp41, the transmembrane protein of human immunodeficiency virus type 1. J Virol 1989;63:2674-2679.