66 Reasons to Think Twice About HIV Tests

Most people are surprised to learn that you don’t need to have HIV in order to test HIV positive. More than 60 factors—all documented in the medical literature or acknowledged by test manufacturers—are known to elicit the production of antibodies that can cause false positive results on HIV antibody tests, even in people with no possible exposure to HIV and no potential risks for AIDS.

Before consulting the list, it’s important to note that having or having had a condition included here does not necessarily mean that you will register positive on HIV tests. Testing positive depends on what antibodies you have accumulated over the course of your life and the particular characteristics of individual HIV tests.

As a general rule, the more exposure you’ve had to foreign antigens, proteins and infectious agents, the more various antibodies you will have in your system. Although greater amounts of antibodies increase your potential for cross-reacting antibodies that can cause an HIV test to go positive, having or having had several of the conditions known to produce cross-reacting antibodies does not guarantee you will experience false positive results on HIV tests. Also, certain conditions among those listed are more likely than others to produce antibodies that can cause you to register HIV positive.

Even conditions well known to produce cross-reactions on HIV tests may not cause all people having experienced those conditions to falsely test positive. For example, some but not all people who have had blood transfusions, multiple pregnancies or an organ transplant will make HLA antibodies, and some but not all HIV test kits will be contaminated with HLA antigens to which these persons’ HLA antibodies can react. When the two circumstances of HLA antibodies in the person and HLA antigens in the tests coincide, positive HIV tests may result due to HLA cross-reactivity.

Some cross-reacting factors listed have been documented to occur only with ELISA HIV antibody tests while others have been documented for both the ELISA and the HIV Western Blot. However, before we can conclude that factors documented to cross react only on ELISA tests will not affect the outcome of the Western Blot tests, we must consider that both the ELISA and the Western Blot use the same proteins as markers for HIV. In other words, even though the Western Blot is popularly regarded as more accurate than the ELISA (and thus widely used to confirm positive ELISA results), in fact, Western Blot tests use the same proteins as the ELISA making false positive results likely to carry over from the ELISA to the Western Blot and raising serious questions about using one test to confirm the other.

Despite claims that Western Blot is a more accurate test than the ELISA, the Western Blot does little more than separate out the same alleged HIV proteins used on the ELISA into individual categories or bands rather than grouping them all together like on the ELISA. Unlike the ELISA which gives a “yes” (positive) or “no” (negative) answer, the Western Blot test is regarded as HIV positive when enough of the individual bands or proteins add up to the particular total required by whatever institution is interpreting the test result. For example, the US Food and Drug Administration, the US Centers for Disease Control, the World Health Organization, the Red Cross, and the US Department of Defense all have different standards for what proteins indicate a positive HIV Western Blot This means that the same test result may be regarded as positive or negative depending on which institution is interpreting the results. Also, which proteins add up to a positive Western Blot depend on what country you test in. For example, a combination regarded as a positive result in France may be considered negative in Germany or Australia. To make matters more complicated, in the United Kingdom the Western Blot is considered unreliable for use in clinical settings (for use on patients) and a positive HIV diagnosis there is given based on two positive ELISA tests.

In any case, since false positive reactions to every so-called HIV protein have been documented in the medical literature, it is not possible to state that Western Blot bands represent the various proteins to HIV. Instead, a growing number of scientists assert that positive Western Blot bands represent reactions to several different non-HIV antibodies and that all positive HIV test results may be false positive.

Finally, this list cannot be considered complete as conditions may exist that can cause false-positive reactions on HIV antibody tests that have yet to be published in the medical literature

66 Factors Known to Cause False Positive Reactions on HIV Antibody Tests
List and references compiled by Christine Johnson

1. Anti-carbohydrate antibodies (52,19,13)
2. Naturally-occurring antibodies (5,19)
3. Passive immunization: receipt of gamma globulin or immune globulin (as prophylaxis against infection which contains antibodies) (18, 26, 60, 4, 22, 42, 43, 13)
4. Leprosy (2, 25)
5. Tuberculosis (25)
6. Mycobacterium avium (25)
7. Systemic lupus erythematosus (15, 23)
8. Renal (kidney) failure (48, 23, 13)
9. Hemodialysis/renal failure (56, 16, 41, 10, 49)
10. Alpha interferon therapy in hemodialysis patients (54)
11. Flu (36)
12. Flu vaccination (30, 11, 3, 20, 13, 43)
13. Herpes simplex I (27)
14. Herpes simplex II (11)
15. Upper respiratory tract infection (cold or flu) (11)
16. Recent viral infection or exposure to viral vaccines (11)
17. Prior pregnancy (58, 53, 13, 43, 36, 65)
18. Malaria (6, 12)
19. High levels of circulating immune complexes (6, 33)
20. Hypergammaglobulinemia (high levels of antibodies) (40, 33)
21. False positives on other tests, including RPR (rapid plasma reagent) test for syphilis (17, 48, 33, 10, 49)
22. Rheumatoid arthritis (36)
23. Hepatitis B vaccination (28, 21, 40, 43)
24. Tetanus vaccination (40)
25. Organ transplantation (1, 36)
26. Renal transplantation (35, 9, 48, 13, 56)
27. Anti-lymphocyte antibodies (56, 31)
28. Anti-collagen antibodies (found in gay men, haemophiliacs, Africans of both sexes and people with leprosy) (31)
29. Serum-positive for rheumatoid factor, antinuclear antibody (both found in rheumatoid arthritis and other autoantibodies) (14, 62, 53)
30. Autoimmune diseases (44, 29, 1O, 40, 49, 43)
31. Systemic lupus erythematosus, scleroderma, connective tissue disease, dermatomyositis Acute viral infections, DNA viral infections (59, 48, 43, 53, 40, 13)
32. Malignant neoplasms (cancers) (40)
33. Alcoholic hepatitis/alcoholic liver disease (32, 48, 40, 10, 13, 49, 43, 53)
34. Primary sclerosing cholangitis (48, 53)
35. Hepatitis (54)
36. "Sticky" blood (a condition common in people of African origin) (38, 34, 40)
37. Antibodies with a high affinity for polystyrene (used in the test kits) (62, 40, 3)
38. Blood transfusions, multiple blood transfusions (65, 63, 36, 13, 49, 43, 41)
39. Multiple myeloma (10, 43, 53)
40. HLA antibodies (to Class I and II leukocyte antigens) (7, 46, 63, 48, 10, 13, 49, 43, 53)
41. Anti-smooth muscle antibody (48)
42. Anti-parietal cell antibody (48)
43. Anti-hepatitis A IgM (antibody) (48)
44. Anti-Hbc IgM (48)
45. Administration of human immunoglobulin preparations pooled before 1985 (10)
46. Hemophilia (10, 49)
47. Hematologic malignant disorders/lymphoma (43, 53, 9, 48, 13)
48. Primary biliary cirrhosis (43, 53, 13, 48)
49. Stevens-Johnson syndrome (9, 48, 13)
50. Q-fever with associated hepatitis (61)
51. Heat-treated specimens (51, 57, 24, 49, 48)
52. Lipemic serum (blood with high levels of fat or lipids) (49)
53. Hemolyzed serum (blood where haemoglobin is separated from the red cells) (49)
54. Hyperbilirubinemia (10, 13)
55. Globulins produced during polyclonal gammopathies (which are seen in AIDS risk groups) (10, 13, 48)
56. Healthy individuals as a result of poorly-understood cross-reactions (10)
57. Normal human ribonucleoproteins (48, 13)
58. Other retroviruses (8, 55, 14, 48, 13)
59. Anti-mitochondrial antibodies (48, 13)
60. Anti-nuclear antibodies (48, 13, 53)
61. Anti-microsomal antibodies (34)
62. T-cell leukocyte antigen antibodies (48, 13)
63. Proteins on the filter paper used in test kits (13)
64. Epstein-Barr virus (37)
65. Visceral leishmaniasis (45)
66. Receptive anal intercourse (39, 64)

REFERENCES
1.Agbalika F, Ferchal F, Garnier J-P, et al. 1992. False-positive antigens related to emergence of a 25-30 kD protein detected in organ recipients. AIDS. 6:959-962.
2.Andrade V, Avelleira JC, Marques A, et al. 1991. Leprosy as a cause of false-positive results in serological assays for the detection of antibodies to HIV-1. Intl. J. Leprosy. 59:125.
3.Arnold NL, Slade RA, Jones MM, et al. 1994. Donor follow up of influenza vaccine-related multiple viral enzyme immunoassay reactivity. Vox Sanguinis. 67:191.
4.Ascher D, Roberts C. 1993. Determination of the etiology of seroreversals in HIV testing by antibody fingerprinting. AIDS. 6:241.
5.Barbacid M, Bolgnesi D, Aaronson S. 1980. Humans have antibodies capable of recognizing oncoviral glycoproteins: Demonstration that these antibodies are formed in response to cellular modification of glycoproteins rather than as consequence of exposure to virus. Proc. Natl. Acad. Sci. 77:1617-1621.
6.Biggar R, Melbye M, Sarin P, et al. 1985. ELISA HTLV retrovirus antibody reactivity associated with malaria and immune complexes in healthy Africans. Lancet. ii:520-543.
7.Blanton M, Balakrishnan K, Dumaswala U, et al. 1987. HLA antibodies in blood donors with reactive screening tests for antibody to the immunodeficiency virus. Transfusion. 27(1):118.
8.Blomberg J, Vincic E, Jonsson C, et al. 1990. Identification of regions of HIV-1 p24 reactive with sera which give "indeterminate" results in electrophoretic immunoblots with the help of long synthetic peptides. AIDS Res. Hum. Retro. 6:1363.
9.Burkhardt U, Mertens T, Eggers H. 1987. Comparison of two commercially available anti-HIV ELISA's: Abbott HTLV-III ELA and DuPont HTLV-III ELISA. J. Med. Vir. 23:217.
10.Bylund D, Ziegner U, Hooper D. 1992 Review of testing for human immunodeficiency virus. Clin. Lab. Med. 12:305-333.
11.Challakere K, Rapaport M. 1993. False-positive human immunodeficiency virus type 1 ELISA results in low-risk subjects. West. J. Med. 159(2):214-215.
12.Charmot G, Simon F. 1990. HIV infection and malaria. Revue du practicien. 40:2141.
13.Cordes R, Ryan M. 1995. Pitfalls in HIV testing. Postgraduate Medicine. 98:177.
14.Dock N, Lamberson H, O'Brien T, et al. 1988. Evaluation of atypical human immunodeficiency virus immunoblot reactivity in blood donors. Transfusion. 28:142.
15.Esteva M, Blasini A, Ogly D, et al. 1992. False positive results for antibody to HIV in two men with systemic lupus erythematosus. Ann. Rheum. Dis. 51:1071-1073.
16.Fassbinder W, Kuhni P, Neumayer H. et al. 1986. Prevalence of antibodies against LAV/HTLV-III [HIV] in patients with terminal renal insufficiency treated with hemodialysis and following renal transplantation. Deutsche Medizinische Wochenschrift. 111:1087.
17.Fleming D, Cochi S, Steece R. et al. 1987. Acquired immunodeficiency syndrome in low-incidence areas. JAMA. 258(6):785.
18.Gill MJ, Rachlis A, Anand C. 1991. Five cases of erroneously diagnosed HIV infection. Can. Med. Asso. J. 145(12):1593.
19.Healey D, Bolton W. 1993. Apparent HIV-1 glycoprotein reactivity on Western blot in uninfected blood donors. AIDS. 7:655-658.
20.Hisa J. 1993. False-positive ELISA for human immunodeficiency virus after influenza vaccination. JID. 167:989.
21.Isaacman S. 1989. Positive HIV antibody test results after treatment with hepatitis B immune globulin. JAMA. 262:209.
22.Jackson G, Rubenis M, Knigge M, et al. 1988. Passive immunoneutralisation of human immunodeficiency virus in patients with advanced AIDS. Lancet, Sept. 17:647.
23.Jindal R, Solomon M, Burrows L. 1993. False positive tests for HIV in a woman with lupus and renal failure. NEJM. 328:1281-1282.
24.Jungkind D, DiRenzo S, Young S. 1986. Effect of using heat-inactivated serum with the Abbott human T-cell lymphotropic virus type III [HIV] antibody test. J. Clin. Micro.23:381.
25.Kashala O, Marlink R, Ilunga M. et al. 1994. Infection with human immunodeficiency virus type 1 (HIV-1) and human T-cell lymphotropic viruses among leprosy patients and contacts: correlation between HIV-1 cross-reactivity and antibodies to lipoarabionomanna. J. Infect. Dis. 169:296-304.
26.Lai-Goldman M, McBride J, Howanitz P, et al. 1987. Presence of HTLV-III [HIV] antibodies in immune serum globulin preparations. Am. J. Clin. Path. 87:635.
27.Langedijk J, Vos W, Doornum G, et al. 1992. Identification of cross-reactive epitopes recognized by HIV-1 false-positive sera. AIDS. 6:1547-1548.
28.Lee D, Eby W, Molinaro G. 1992. HIV false positivity after hepatitis B vaccination. Lancet. 339:1060.
29.Leo-Amador G, Ramirez-Rodriguez J, Galvan-Villegas F, et al. 1990. Antibodies against human immunodeficiency virus in generalized lupus erythematosus. Salud Publica de Mexico. 32:15.
30.Mackenzie W, Davis J, Peterson D. et al. 1992. Multiple false-positive serologic tests for HIV, HTLV-1 and hepatitis C following influenza vaccination, 1991. JAMA. 268:1015-1017.
31.Mathe G. 1992. Is the AIDS virus responsible for the disease? Biomed & Pharmacother. 46:1-2.
32.Mendenhall C, Roselle G, Grossman C, et al. 1986. False-positive tests for HTLV-III [HIV] antibodies in alcoholic patients with hepatitis. NEJM. 314:921.
33.Moore J, Cone E, Alexander S. 1986. HTLV-III [HIV] seropositivity in 1971-1972 parenteral drug abusers - a case of false-positives or evidence of viral exposure? NEJM. 314:1387-1388.
34.Mortimer P, Mortimer J, Parry J. 1985. Which anti-HTLV-III/LAV [HIV] assays for screening and comfirmatory testing? Lancet. Oct. 19, p873.
35.Neale T, Dagger J, Fong R, et al. 1985. False-positive anti-HTLV-III [HIV] serology. New Zealand Med. J. October 23.
36.Ng V. 1991. Serological diagnosis with recombinant peptides/proteins. Clin. Chem. 37:1667-1668.
37.Ozanne G, Fauvel M. 1988. Perfomance and reliability of five commercial enzyme-linked immunosorbent assay kits in screening for anti-human immunodeficiency virus antibody in high-risk subjects. J. Clin. Micro. 26:1496.
38.Papadopulos-Eleopulos E. 1988. Reappraisal of AIDS - Is the oxidation induced by the risk factors the primary cause? Med. Hypo. 25:151.
39.Papadopulos-Eleopulos E, Turner V, and Papadimitriou J. 1993. Is a positive Western blot proof of HIV infection? Bio/Technology. June 11:696-707.
40.Pearlman ES, Ballas SK. 1994. False-positive human immunodeficiency virus screening test related to rabies vaccination. Arch. Pathol. Lab. Med. 118-805.
41.Peternan T, Lang G, Mikos N, et al. Hemodialysis/renal failure. 1986. JAMA. 255:2324.
42.Piszkewicz D. 1987. HTLV-III [HIV] antibodies after immune globulin. JAMA. 257:316.
43.Profitt MR, Yen-Lieberman B. 1993. Laboratory diagnosis of human immunodeficiency virus infection. Inf. Dis. Clin. North Am. 7:203.
44.Ranki A, Kurki P, Reipponen S, et al. 1992. Antibodies to retroviral proteins in autoimmune connective tissue disease. Arthritis and Rheumatism. 35:1483.
45.Ribeiro T, Brites C, Moreira E, et al. 1993. Serologic validation of HIV infection in a tropical area. JAIDS. 6:319.
46.Sayers M, Beatty P, Hansen J. 1986. HLA antibodies as a cause of false-positive reactions in screening enzyme immunoassays for antibodies to human T-lymphotropic virus type III [HIV]. Transfusion. 26(1):114.
47.Sayre KR, Dodd RY, Tegtmeier G, et al. 1996. False-positive human immunodeficiency virus type 1 Western blot tests in non-infected blood donors. Transfusion. 36:45.
48.Schleupner CJ. Detection of HIV-1 infection. In: (Mandell GI, Douglas RG, Bennett JE, eds.) Principles and Practice of Infectious Diseases, 3rd ed. New York: Churchill Livingstone, 1990:1092.
49.Schochetman G, George J. 1992. Serologic tests for the detection of human immunodeficiency virus infection. In AIDS Testing Methodology and Management Issues, Springer-Verlag, New York.
50.Simonsen L, Buffington J, Shapiro C, et al. 1995. Multiple false reactions in viral antibody screening assays after influenza vaccination. Am. J. Epidem. 141-1089.
51.Smith D, Dewhurst S, Shepherd S, et al. 1987. False-positive enzyme-linked immunosorbent assay reactions for antibody to human immunodeficiency virus in a population of midwestern patients with congenital bleeding disorders. Transfusion. 127:112.
52.Snyder H, Fleissner E. 1980. Specificity of human antibodies to oncovirus glycoproteins; Recognition of antigen by natural antibodies directed against carbohydrate structures. Proc. Natl. Acad. Sci. 77:1622-1626.
53.Steckelberg JM, Cockerill F. 1988. Serologic testing for human immunodeficiency virus antibodies. Mayo Clin. Proc. 63:373.
54.Sungar C, Akpolat T, Ozkuyumcu C, et al. Alpha interferon therapy in hemodialysis patients. Nephron. 67:251.
55.Tribe D, Reed D, Lindell P, et al. 1988. Antibodies reactive with human immunodeficiency virus gag-coated antigens (gag reactive only) are a major cause of enzyme-linked immunosorbent assay reactivity in a bood donor population. J. Clin. Micro. April:641.
56.Ujhelyi E, Fust G, Illei G, et al. 1989. Different types of false positive anti-HIV reactions in patients on hemodialysis. Immun. Let. 22:35-40.
57.Van Beers D, Duys M, Maes M, et al. Heat inactivation of serum may interfere with tests for antibodies to LAV/HTLV-III [HIV]. J. Vir. Meth. 12:329.
58.Voevodin A. 1992. HIV screening in Russia. Lancet. 339:1548.
59.Weber B, Moshtaghi-Borojeni M, Brunner M, et al. 1995. Evaluation of the reliability of six current anti-HIV-1/HIV-2 enzyme immunoassays. J. Vir. Meth. 55:97.
60.Wood C, Williams A, McNamara J, et al. 1986. Antibody against the human immunodeficiency virus in commercial intravenous gammaglobulin preparations. Ann. Int. Med. 105:536.
61.Yale S, Degroen P, Tooson J, et al. 1994. Unusual aspects of acute Q fever-associated hepatitis. Mayo Clin. Proc. 69:769.
62.Yoshida T, Matsui T, Kobayashi M, et al. 1987. Evaluation of passive particle agglutination test for antibody to human immunodeficiency virus. J. Clin. Micro. Aug:1433.
63.Yu S, Fong C, Landry M, et al. 1989. A false positive HIV antibody reaction due to transfusion-induced HLA-DR4 sensitization. NEJM.320:1495. 64. National Institue of Justice, AIDS Bulletin. Oct. 1988.
64.National Institute of Justice AIDS Bulletin October 1988
65.Abbot Laboratories, literature accompanying HIV-1 EIA [ELISA] Antibody Test

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