Correspondence

Withdrawal of Conclusion: False Positive Tests for HIV in a Woman with Lupus

N Engl J Med 1994; 331:881-882September 29, 1994

Article

To the Editor:

A letter published in the April 29, 1993, issue of the Journal reported apparently false positive serologic tests for human immunodeficiency virus type 1 (HIV-1) in a Haitian woman with systemic lupus erythematosus and end-stage renal disease1. Three serum specimens obtained at six-week intervals were strongly reactive for HIV-1 antibodies by enzyme-linked immunosorbent assay (ELISA), and Western blotting revealed the full array of HIV-1-specific bands. However, tests for serum p24 antigen, culture of peripheral-blood mononuclear cells (PBMCs) for HIV-1, and a polymerase-chain-reaction (PCR) test for HIV-1 DNA were all negative. The authors therefore reasoned that the serologic results were due to autoantibodies, often present in patients with systemic lupus erythematosus.

Though Western blotting of serum from persons with lupus (without HIV-1 infection) may detect antibodies against HIV-1 gag proteins,2 these indeterminate patterns may also be present in persons without lupus3. We (J.P. and B.P.) were intrigued by the results described in the letter1 and contacted the authors for permission to restudy this patient. One year had passed since the original virologic studies, and there had been no change in the patient's clinical status. Her absolute CD4+ count was 275 per cubic millimeter (13 percent of total T lymphocytes). We confirmed the previously reported serologic results, including negative results from serum p24 antigen (before and after acid dissociation of immune complexes). PBMCs were obtained on two occasions over a three-week period for culture and PCR. HIV-1 culture was performed according to standard methods,4 and PCR as previously described5.

HIV-1 was isolated from PBMC cultures on both occasions, and the PCR was positive for HIV-1 DNA sequences. HIV-1 was identified after only 8 days of culture on the first occasion; 49 days were required on the second attempt. Furthermore, two rounds of PCR were required on both occasions in order to identify HIV-1-specific sequences. The patient was informed of these results, counseled, and advised about appropriate therapy for HIV-1 infection.

These results underscore the dynamic nature of the HIV-1 load in the peripheral blood. Protocols for PBMC culture specify that cultures be maintained anywhere from 14 to 35 days. Thus, it is possible that HIV-1 might have been isolated had the original culture been kept longer. Likewise, the PCR in the original report was run with only one round of amplification, as opposed to the two rounds used here.

It should be emphasized that the presence of the full complement of HIV-1-specific reactions on Western blotting remains a reliable method for diagnosing HIV-1 infection. Cultures for HIV-1 may require longer than standard periods of observation, and multiple rounds of PCR may be required in order to identify the virus.

Jacob Povolotsky, M.D., Ph.D.
Bruce Polsky, M.D.
Memorial Sloan-Kettering Cancer Center

Jeffrey Laurence, M.D.
New York Hospital-Cornell Medical Center, New York, NY 10021

R. Jindal, M.D.
Maritza Rozon-Solomon, R.N.
Lewis Burrows, M.D.
Mount Sinai Medical Center, New York, NY 10029

5 References

1. 1

   Jindal R, Solomon M, Burrows L. False positive tests for HIV in a woman with lupus and renal failure. N Engl J Med 1993;328:1281-1282
   Full Text | Web of Science | Medline

2. 2

   Ranki A, Kurki P, Riepponen S, Stephansson E. Antibodies to retroviral proteins in autoimmune connective tissue disease: relation to clinical manifestations and ribonucleoprotein autoantibodies. Arthritis Rheum 1992;35:1483-1491
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   Povolotsky J, Gold JW, Chein N, Baron P, Armstrong D. Differences in human immunodeficiency virus type 1 (HIV-1) anti-p24 reactivities in serum of HIV-1-infected and uninfected subjects: analysis of indeterminate Western blot reactions. J Infect Dis 1991;163:247-251
   CrossRef | Web of Science | Medline

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   Dimitrov DH, Melnick JL, Hollinger FB. Microculture assay for isolation of human immunodeficiency virus type 1 and for titration of infected peripheral blood mononuclear cells. J Clin Microbiol 1990;28:734-737
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   Laurence J, Grimison B, Rodriguez-Alfageme C, Astrin SM. A model system for regulation of chronic HIV-1 infection in peripheral B lymphocytes. Virology 1993;196:433-441
   CrossRef | Web of Science | Medline