Since the beginning of the HIV epidemic three decades ago, the technology-laboratory testing to confirm infection have been updated, from ELISA followed by western blot to antigen/antibody immunoassay followed by HIV-1/HIV-2 antibody differentiation immunoassay . False-positive tests have been reported, secondary to technical issues, including improper handling and mislabeling of the sample or because of medical conditions, such as pregnancy, autoimmune disorders, or Epstein--Barr virus infection [1,2]. Even fourth generation p24 HIV antigen/antibody tests can yield false-positive results . The past year was marked by a global pandemic caused by the severe acute respiratory syndrome corona virus 2 (SARS-CoV-2), with millions of human lives lost, a devastating impact on healthcare systems and a significant financial burden worldwide. Interestingly, during the intense global effort to produce vaccines against SARS-CoV-2, the one under development by the University of Queensland, Australia, had to be abandoned as the inoculated test participants produced false-positive test results for HIV . We report the case of a patient, diagnosed with pulmonary embolism secondary to SARS-CoV-2 infection, who had a false-positive test result for HIV infection.
A 68-year-old gentleman presented with dyspnea on exertion, generalized body rash, and pain in his lower extremities bilaterally. A month prior, he was exposed to a family member who had SARS-CoV-2 infection. He was never screened by nasopharyngeal test but reported loss of smell; he denied any other upper respiratory symptoms. He has a history of chronic obstructive lung disease, coronary artery disease, hypertension, deep venous thrombosis of left leg 5 years prior, and tobacco use of 60 pack-years. On presentation, he had no fever, heart rate was 87 bpm, blood pressure 116/76 mmHg, and oxygen saturation was 97% on room air. Physical examination was notable for lymphedema of the left lower extremity, and a generalized rash with erythematous macules coalescing into patches on the trunk (anteriorly and posteriorly), arms, and upper thigh bilaterally. Laboratory data showed the following: white blood cell count 17 800 cells/μl, with neutrophilic predominance (88%); peripheral smear showed few vacuolated polymorphonuclear cells with toxic granulations. The serum creatinine was 5 mg/dl (baseline 1.1), erythrocyte sedimentation rate 71 mm/h, and D-dimer was 1651 ng/ml. A lung ventilation--perfusion scan showed multiple unchanged perfusion defects suspicious for high probability for acute pulmonary embolism. Two nasopharyngeal RT-PCR (Xpert Xpress; Cepheid, Sunnyvale, California, USA and BioFire Respiratory Panel; bioMérieux, Salt Lake City, Utah, USA) were negative for SARS-CoV-2. Due to recent exposure, history serological tests were obtained and SARS-CoV-2 IgG antibodies to nucleocapsid and spike proteins were detected (Architect Abbott, Abbott Park, Illinois, USA). The HIV antigen/antibody test, a chemiluminescent microparticle immunoassay, by the same company, Architect Abbott, was reactive. The confirmatory test, an immunochromatographic assay, was negative for HIV-1 and HIV-2 (Geenuis; Bio-Rad Laboratories, Hercules, California, USA). An HIV-1 RNA viral load was undetectable. The patient was evaluated by the dermatology team and the rash was attributed to a drug eruption caused by recent administration of terbinafine (to treat tinea pedis). The patient was treated initially with heparin infusion and later apixaban tablets with good clinical response.
To our knowledge, this is the third patient reported in the literature who had false-positive test result for HIV, following infection with SARS-CoV-2. Tan et al. previously reported two patients with SARS-CoV-2 infection, who had reactive tests, using the Abbott Architect test, which is the one we used in our patient. In fact, they tested the sera in a separate Abbott Architect machine and got the same reactive result. The immunoblot tests, however, were negative in both cases . This phenomenon might be possibly explained by cross reactivity between SARS-CoV-2 antibodies and Abbott antibody/antigen immunoassays. Interestingly, during the first SARS-COV epidemic in 2003, researchers had found that HIV and SARS-CoV viral proteins responsible for viral conformation shared sequence motifs suggesting a target for anti-SARS-COV treatment strategy .
In conclusion, immunity against SARS-CoV-2 following natural infection, or even vaccination, might possibly produce false-positive results with fourth generation HIV antigen/antibody screening tests. Physicians should be aware of this possible discordant result and proceed to further laboratory analyses before making a definite diagnosis of HIV infection.
Conflicts of interest
There are no conflicts of interest.
1. Centers for Disease Control and Prevention and Association of Public Health Laboratories. Laboratory testing for the diagnosis of HIV infection: updated recommendations. 2014. Available at: https://stacks.cdc.gov/view/cdc/23447
. [Accessed 5 March 2021]
2. Lavoie S, Caswell D, Gill MJ, Kadkhoda K, Charlton CL, Levett PN, et al. Heterophilic interference in specimens yielding false-reactive results in the Abbott 4th generation ARCHITECT HIV Ag/Ab combo assay
. J Clin Virol
3. Liu P, Jackson P, Shaw N, Heysell S. Spectrum of false positivity for the fourth generation human immunodeficiency virus diagnostic tests
. AIDS Res Ther
4. Ives M. Australia scraps Covid-19 vaccine that produced H.I.V. false positives. New York Times. 11 December 2020. Available at: https://www.nytimes.com/2020/12/11/world/australia/uq-coronavirus-vaccine-false-positive.html
. [Accessed 10 March 2021]
5. Tan SS, Chew KL, Saw S, Jureen R, Sethi R. Cross-reactivity of SARS CoV-2 with HIV chemiluminescent assay leading to false-positive results
. J Clin Pathol
2020; [Epub ahead of print].
6. Kliger Y, Levanon EY. Cloaked similarity between HIV-1 and SARS-CoV suggests an anti-SARS strategy
. BMC Microbiol