Common Variable Immunodeficiency and Testing for HIV-1
http://www.100md.com
《新英格兰医药杂志》
To the Editor: With expanded testing for human immunodeficiency virus type 1 (HIV-1) with the use of an enzyme-linked immunosorbent assay (ELISA) in the general population supported by the findings of two recent studies,1,2 the causes of false positive and false negative results by ELISA in specific subgroups increase in importance. The known causes of false negative test results include testing within the window period, non–clade B virus, infection with HIV type 2, end-stage AIDS, and agammaglobulinemia. To date, there have been no documented instances of patients with common variable immunodeficiency or hypogammaglobulinemia in whom HIV-1 infection developed but whose test results were negative by ELISA — though given an inherent inability to produce specific antibodies, the possibility is not far-fetched.
We care for a 34-year-old man with common variable immunodeficiency who receives intravenous gamma globulin infusions every four weeks. He was HIV-1–negative both by ELISA and according to the viral RNA load (Amplicor HIV-1 Monitor test kit, Roche Diagnostics) in October 2003. In early May 2004, the patient was found to have an HIV-1 RNA load of 1300 copies per milliliter. A subsequent ELISA for HIV-1, performed in early June 2004, was negative, with an HIV-1 RNA load in early June of 100,000 copies per milliliter and in late June of 300,000 copies per milliliter. The results of a repeated ELISA remained negative two weeks after the assay in late June and also as of early February 2005. The virus was found to be HIV-1 clade–B according to genetic analysis. The patient reported having had two sexual relationships in the six months before receiving the diagnosis of HIV-1 infection, and the second partner had tested positive for HIV-1 by ELISA. Our patient's HIV-negative result by ELISA in early February 2005 occurred at least 10 months after infection — well beyond the window period for HIV-1 seroconversion.
Reliance solely on HIV-1 antibody testing for expanded population testing, either by ELISA or by rapid testing, would risk missing cases of HIV-1 in patients with humoral immunodeficiency in whom the vulnerability to certain pathogens is increased. In light of our patient's status and the plausibility of the mechanism, common variable immunodeficiency should be considered a possible cause of a false negative result by ELISA for HIV-1 in a patient with HIV-1. Alternative methods of diagnosis of HIV-1 infection, such as nucleic acid amplification testing, should be considered for patients with common variable immunodeficiency in whom HIV-1 infection is suspected in the face of a negative result by ELISA for HIV-1. Conversely, patients who are not known to have common variable immunodeficiency but remain seronegative for HIV-1 for whom known causes of false negative results by ELISA for HIV-1 have been ruled out may need a workup for an underlying immunodeficiency.
This case, albeit rare, lends support to two recently published studies on the use of nucleic acid amplification testing of "minipools" as the preferred method of screening blood and organ donations to prevent the transmission of HIV-1 from seronegative donors.3,4
Yoram C. Padeh, M.D.
Montefiore Medical Center
Bronx, NY 10467
Arye Rubinstein, M.D.
Albert Einstein College of Medicine
Bronx, NY 10461
Jenny Shliozberg, M.D.
Montefiore Medical Center
Bronx, NY 10467
jshliozb@montefiore.org
References
Sanders GD, Bayoumi AM, Sundaram V, et al. Cost-effectiveness of screening for HIV in the era of highly active antiretroviral therapy. N Engl J Med 2005;352:570-585.
Paltiel AD, Weinstein MC, Kimmel AD, et al. Expanded screening for HIV in the United States -- an analysis of cost-effectiveness. N Engl J Med 2005;352:586-595.
Stramer SL, Glynn SA, Kleinman SH, et al. Detection of HIV-1 and HCV infections among antibody-negative blood donors by nucleic acid-amplification testing. N Engl J Med 2004;351:760-768.
Zou S, Dodd RY, Stramer SL, Strong DM. Probability of viremia with HBV, HCV, HIV, and HTLV among tissue donors in the United States. N Engl J Med 2004;351:751-759.
We care for a 34-year-old man with common variable immunodeficiency who receives intravenous gamma globulin infusions every four weeks. He was HIV-1–negative both by ELISA and according to the viral RNA load (Amplicor HIV-1 Monitor test kit, Roche Diagnostics) in October 2003. In early May 2004, the patient was found to have an HIV-1 RNA load of 1300 copies per milliliter. A subsequent ELISA for HIV-1, performed in early June 2004, was negative, with an HIV-1 RNA load in early June of 100,000 copies per milliliter and in late June of 300,000 copies per milliliter. The results of a repeated ELISA remained negative two weeks after the assay in late June and also as of early February 2005. The virus was found to be HIV-1 clade–B according to genetic analysis. The patient reported having had two sexual relationships in the six months before receiving the diagnosis of HIV-1 infection, and the second partner had tested positive for HIV-1 by ELISA. Our patient's HIV-negative result by ELISA in early February 2005 occurred at least 10 months after infection — well beyond the window period for HIV-1 seroconversion.
Reliance solely on HIV-1 antibody testing for expanded population testing, either by ELISA or by rapid testing, would risk missing cases of HIV-1 in patients with humoral immunodeficiency in whom the vulnerability to certain pathogens is increased. In light of our patient's status and the plausibility of the mechanism, common variable immunodeficiency should be considered a possible cause of a false negative result by ELISA for HIV-1 in a patient with HIV-1. Alternative methods of diagnosis of HIV-1 infection, such as nucleic acid amplification testing, should be considered for patients with common variable immunodeficiency in whom HIV-1 infection is suspected in the face of a negative result by ELISA for HIV-1. Conversely, patients who are not known to have common variable immunodeficiency but remain seronegative for HIV-1 for whom known causes of false negative results by ELISA for HIV-1 have been ruled out may need a workup for an underlying immunodeficiency.
This case, albeit rare, lends support to two recently published studies on the use of nucleic acid amplification testing of "minipools" as the preferred method of screening blood and organ donations to prevent the transmission of HIV-1 from seronegative donors.3,4
Yoram C. Padeh, M.D.
Montefiore Medical Center
Bronx, NY 10467
Arye Rubinstein, M.D.
Albert Einstein College of Medicine
Bronx, NY 10461
Jenny Shliozberg, M.D.
Montefiore Medical Center
Bronx, NY 10467
jshliozb@montefiore.org
References
Sanders GD, Bayoumi AM, Sundaram V, et al. Cost-effectiveness of screening for HIV in the era of highly active antiretroviral therapy. N Engl J Med 2005;352:570-585.
Paltiel AD, Weinstein MC, Kimmel AD, et al. Expanded screening for HIV in the United States -- an analysis of cost-effectiveness. N Engl J Med 2005;352:586-595.
Stramer SL, Glynn SA, Kleinman SH, et al. Detection of HIV-1 and HCV infections among antibody-negative blood donors by nucleic acid-amplification testing. N Engl J Med 2004;351:760-768.
Zou S, Dodd RY, Stramer SL, Strong DM. Probability of viremia with HBV, HCV, HIV, and HTLV among tissue donors in the United States. N Engl J Med 2004;351:751-759.