The Centers for Disease Control and Prevention's1 5-year strategic plan for human immunodeficiency virus (HIV) prevention seeks to reduce the proportion of persons who are unaware of their HIV infection from the currently estimated level of 25% to 5%. Achieving this goal will require testing of increased numbers of persons, and the Centers for Disease Control and Prevention states that "providers in all settings . . . should ideally recommend [HIV counseling, testing, and referral (CTR)] to all clients on a routine basis to ensure that all clients who could benefit from CTR receive these services."2(p7) Even with tests as accurate (>99% sensitive and >99% specific)3 as the current third-generation HIV enzyme-linked immunosorbent assay (ELISA) coupled with Western blot or other confirmatory tests, an increasing number of false-positive results may be anticipated when large numbers of persons at low risk are tested. Cases of false-positive HIV test results have been reported.4 Public Health–Seattle & King County recently encountered 2 patients with false-positive HIV serologic test results, each of whom experienced serious psychological consequences. We describe 2 recent false-positive cases. Report of cases Case 1 A 39-year-old married man presented to the Public Health–Seattle & King County sexually transmitted disease clinic in September 2000, seeking HIV serologic testing. He gave a history of occasional orogenital sex with other men but denied insertive and receptive anal sex with men. His ELISA and Western blot results were interpreted as positive (9 Western blot bands were present: p18, p24, p32, gp41, p51, p55, p65, gp120, and gp160), and the patient was informed of the result. He notified his wife of the result, revealed to her and to other family members and friends that he had had sexual activities with other men, and sought spiritual counseling. However, further evaluation revealed an undetectable plasma HIV RNA level and a reasonably normal CD4+ lymphocyte count (740 cells/µL). Repeat HIV ELISA testing was negative in October 2000 and in January 2001. The patient expressed substantial distress and required repeated reassurance and psychological counseling. Case 2 In October 2000, a 23-year-old woman sought HIV testing from a private health care provider because of vaginal irritation, a white discharge, pelvic pain, and fear that she had acquired a sexually transmitted disease. She reported having had multiple male sex partners in her teens, that she usually used condoms, and had been in a monogamous heterosexual relationship for 3 years before testing. The positive HIV ELISA result with Western blot confirmation was followed by findings of an undetectable HIV RNA level and a reasonably normal CD4+ lymphocyte count (550 cells/µL). The physician recommended against antiretroviral treatment. An undetectable HIV RNA and a similar CD4+ lymphocyte count were obtained 4 months later, but HIV serological testing was not repeated. In October 2001, after attending the Public Health–Seattle & King County sexually transmitted disease clinic for confirmatory testing, her HIV ELISA results were negative, a result also found in March 2002. The patient described confusion, concern, and relief, as well as uncertainty about which providers and test results to trust. Comment Estimates of the frequency of false-positive HIV serologic results among low prevalence populations vary from 0.0004% to 0.0007%.3,5,6 Positive HIV test results in persons without HIV infection ("false positives") occur for several reasons,6 including the following: The presence of blood autoantibodies or other factors may turn an ELISA and Western blot test positive. This explanation seems unlikely for these 2 cases because subsequent testing (6 months later in case 1, and 12 and 17 months later in case 2) showed no antibodies to HIV. Participation in HIV vaccine studies is cited by Bartlett and Gallant6 as being the most common cause of false-positive HIV serologic results; however, neither of our 2 subjects had participated in HIV vaccine studies, and both subsequently tested HIV seronegative. Factitious HIV infection occurs when patients report HIV-seropositive results because they misunderstood the results given to them or because they want to have, or be perceived as having, HIV infection.7 It is important to confirm anonymous test results and laboratory reports using repeat serologic testing or by testing for virus. (However, 2%-9% of viral load test results may be falsely positive, usually with low viral titers.8) In our cases, further testing did not confirm infection. Another source is technical or clerical error, which seems the most likely reason that these patients were incorrectly informed that they were HIV infected. Technical and clerical errors can occur for several reasons, including when a specimen is drawn on the wrong person9; the specimen is drawn on the correct person but is mislabeled (and the client's label may get applied to another person's tube of blood); there is misaliquoting of a sample of the blood into the wrong test wells; the testing process itself, or the equipment10 or reagents, is faulty; a clerical problem results in recording of incorrect results; or the results data are archived into the wrong record. Ordinary requirements, such as repeating ELISA screening after positive test results and performing specific confirmatory tests whenever the second ELISA test results are also positive, should practically eliminate this error. We believe that the problem in these 2 cases may have resulted when some other positive specimen was mislabeled. Careful investigations at both clinics, however, did not reveal other potential sources of seropositive blood specimens. Conducting such investigations is important because someone with HIV whose specimen gets mislabeled will likely be told that he or she is uninfected and thus may transmit the infection to others. In the experience of the Public Health–Seattle & King County's HIV/AIDS [acquired immunodeficiency syndrome] Program—which has operated the main alternative HIV counseling and testing clinic in Seattle since 1986, and has provided HIV counseling and testing to more than 27 000 clients (as of early 2001)—many people who test HIV seropositive seek repeat testing spontaneously. Since mid-1992, when we began keeping careful track of clients' reports of previous HIV testing and results, among 745 persons who tested HIV seropositive, 278 (37.3%) indicated that they had had prior HIV-seropositive test results. Therefore, more than one third of persons we have found to be HIV seropositive are persons being retested. None of these persons tested HIV seronegative at retesting. Our figures may underestimate the frequency of this retesting, as it seems likely that some clients would not disclose their prior test results. Prospectively, of the 2008 persons we tested since mid-1986 whose results were initially seropositive, 186 (9.3%) returned to us for at least 1 repeat test. Two (0.10%) of these 2008 persons, as reported herein, subsequently tested HIV seronegative. Some of our clients may have sought retesting at other sites. Because HIV was not a reportable disease in Washington State until September 1, 1999—and since then the incidence of HIV has been incompletely reported—and because most HIV testing is performed in nonpublic settings,11 the true extent to which clients seek confirmatory testing after testing HIV positive is unknown and is likely to be greater than the estimates herein. We are aware that some local clinics providing clinical care to HIV-seropositive persons (including the largest such clinic in the Northwest) require repeat HIV testing for clinic entry. For the many persons who seek HIV counseling and testing anonymously, roughly 70% in our program, it can be difficult to convincingly document results to substantiate the need for care and costly laboratory testing, as well as the prescription of potentially toxic medication. Furthermore, the Centers for Disease Control and Prevention12 recommends that repeat testing on a second specimen "be considered" for persons who have positive results by HIV-1 or HIV-2 Western blot at first testing. To minimize the harm that may be done as society increasingly broadens HIV testing to include lower risk populations, we make the following recommendations: Hospitals, clinics, and other venipuncture settings should carefully review, and improve if possible, procedures designed to ensure that every tube of blood is drawn on the correct person and is labeled with the correct identity. Sites should maintain logs of blood draws and tests, so that mislabeling problems might be identified and corrected. Laboratories should also ensure optimal procedures for pairing of testing results with clients. Clients who state that their HIV test results are positive should provide identified confirmation or submit to retesting before further testing or treatment. Clinicians encountering clients (especially those at lower risk) who are testing HIV seropositive for the first time should consider recommending retesting on a second blood specimen. Clients with confirmed HIV-seropositive test results should receive early evaluation of their viral load and CD4+ lymphocyte count. Persons whose serum samples are HIV positive but who do not have detectable virus should be advised of the possibility that their earlier HIV test result was falsely positive and that they should be retested for HIV antibodies. Corresponding author: Robert W. Wood, MD, HIV/AIDS Program, Public Health–Seattle & King County, 400 Yesler Way, Third Floor, Seattle, WA 98104 (e-mail: email@example.com). Accepted for publication October 24, 2002. References 1. Centers for Disease Control and Prevention, HIV prevention strategic plan through 2005: January 2001. Available at: http://www.cdc.gov/hiv/pubs/prev-strat-plan.pdf. Accessed March 18, 2003. 2. Centers for Disease Control and Prevention, Revised guidelines for HIV counseling, testing, and referral and revised recommendations for HIV screening of pregnant women. MMWR Morb Mortal Wkly Rep. 2001;50(RR-19)7Available at: http://www.cdc.gov/mmwr/pdf/rr/rr5019.pdf. Accessed March 18, 2003.Google Scholar 3. Kleinman SBusch MPHall L et al. False-positive HIV-1 test results in a low-risk screening setting of voluntary blood donation. JAMA. 1998;2801080- 1085PubMedGoogle ScholarCrossref 4. Mylonakis EPaliou MGreenbough TC et al. Report of a false-positive HIV test result and the potential use of additional tests in establishing HIV serostatus. Arch Intern Med. 2000;1602386- 2388PubMedGoogle ScholarCrossref 5. Burke DSBrundage JFRedfield RR et al. Measurement of the false positive rate in a screening program for human immunodeficiency virus infections. N Engl J Med. 1988;319961- 964PubMedGoogle ScholarCrossref 6. Bartlett JGGallant JE 2001-2002 Medical Management of HIV Infection. Baltimore, Md Division of Infectious Diseases, Johns Hopkins University2001;Available at: http://www.hopkins-aids.edu/publications/book/book_toc.html. Accessed March 20, 2003. 7. Craven DESteger KALa Chapelle RAllen DM Factitious HIV infection: the importance of documenting infection. Ann Intern Med. 1994;121763- 766PubMedGoogle ScholarCrossref 8. Rich JDMerriman NAMylonakis E et al. Misdiagnosis of HIV infection by HIV-1 plasma viral load testing: a case series. Ann Intern Med. 1999;13037- 39PubMedGoogle ScholarCrossref 9. Ascher DPRoberts C Determination of the etiology of seroreversals in HIV testing by antibody fingerprinting. J Acquir Immune Defic Syndr. 1993;6241- 244PubMedGoogle Scholar 10. Parry JVMortimer PPFriderich PConnell JA Faulty washers and soiled micropipettors may generate false positive serological results. Clin Diagn Virol. 1997;7173- 181PubMedGoogle ScholarCrossref 11. Centers for Disease Control and Prevention, HIV counseling and testing in publicly funded sites annual report 1997 and 1998. Available at: http://www.cdc.gov/hiv/pubs/cts98.pdf. Accessed March 20, 2003. 12. O'Brien TRGeorge JREpstein JSHolmberg SDSchochetman G Testing for antibodies to human immunodeficiency virus type 2 in the United States. MMWR Recomm Rep. 1992;41(RR-12)1- 9Google Scholar
Archives of Internal Medicine – American Medical Association
Published: Aug 11, 2003
Keywords: hiv infections
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