Download Human immunodeficiency virus testing pitfalls and clinical suspicion

American Journal of Emergency Medicine xxx (2014) xxx–xxx
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American Journal of Emergency Medicine
journal homepage: www.elsevier.com/locate/ajem
Case Report
Human immunodeficiency virus testing pitfalls and
clinical suspicion☆,☆☆,★
Abstract
Universal human immunodeficiency virus (HIV) screening was
recommended in 2012, and major improvements in HIV testing
have occurred in the past decade, but identification of HIV infected
individuals remains inadequate in the United States. We report the
case of a seronegative HIV-infected man who despite clinical and
laboratory findings of acquired immunodeficiency syndrome,
repeatedly tested nonreactive to third-generation HIV enzyme
immunoassays (EIAs) and Western blot testing. Serologic diagnosis
in this case required fourth-generation EIA testing due to the
seronegativity of standard testing. The fourth-generation HIV EIA
was positive presumably because it detects p24 HIV antigen as well
as antibodies, unlike rapid HIV tests and third-generation HIV EIAs.
This case highlights not only the importance of frontline providers
to understand the different testing methodologies for HIV screening
and their limitations but the importance of clinical suspicion
as well.
A 43-year-old previously healthy man presented to the emergency
department with a 2-month history of fatigue, dyspnea, cough, and
weight loss. He immigrated to the United States from India in the late
1990s. His only sexual encounters were all with males, and within 3
years, with inconsistent barrier precautions. He denied history of
previous HIV testing, history of transfusion, use of recreational drugs,
and was unaware of any recent sick contacts. On presentation, he was
afebrile and normotensive but tachypneic and tachycardic with an
oxygen saturation of 91% with 4-L nasal cannula oxygen supplementation. He was cachectic with body mass index of 15 kg/m 2. Lung
examination revealed bibasilar crackles. His physical examination was
otherwise normal. His laboratory results revealed white blood cell
count of 1.8/mm 3 with 43% neutrophils and 18% lymphocytes and
normal serum chemistry measurements. Rapid HIV testing (Clearview
HIV1/2 STAT-PAK; Alere, Waltham, MA) obtained in our emergency
department was nonreactive. Ground-glass opacities were seen in
chest computed tomographic imaging. Bronchoscopy with bronchoalveolar lavage revealed Pneumocystis jiroveci pneumonia (PJP),
although testing for other pathogens was negative.
Despite clinical and laboratory evidence of acquired immunodeficiency syndrome, third-generation HIV enzyme immunoassay (EIA)
(ADVIA Centaur XP, Washington D.C.) and Western blot (Cambridge
☆
☆☆
★
this
Funding: None.
Conflict of interest: None.
Authorship: All authors had access to the data and played a role in writing
manuscript.
Biotech, Rockville, MD) were negative. His presentation CD4 count
was quantitated at 2/mm 3, and HIV viral load was 3 million copy/mL.
His fourth-generation HIV EIA (ARCHITECT HIV Ag/Ab Combo; Abbott,
Abbott Park, IL), performed at the Wisconsin State Laboratory of
Hygiene, was 12-fold above the cut-off positive result. Systemic
glucocorticoids and high-dose trimethoprim/sulfamethoxazole for
PJP were initiated in addition to highly active antiretroviral therapy
(HAART) with emtricitabine, tenofovir, darunavir, and ritonavir. His
clinical course gradually improved, and he was discharged to a longterm acute care facility after 6 weeks of hospitalization. Upon discharge,
his HIV RNA decreased to 575000 copy/mL, and CD4 count increased to
28/mm3, in spite of persistent negative third-generation HIV EIA and
Western blot. Phenotypic analysis of his HIV strain revealed subtype B
virus common in North America with multiple resistance mutations. Of
note, serum immunoglobulin (Ig) IgG, IgM, IgE, and IgA were obtained
with levels all within the reference ranges.
Identification of HIV-infected individuals in the United States
remains inadequate, despite policy recommendations for universal
HIV screening [1]. There is ongoing effort to increase HIV testing in
emergency departments without slowing visits [2-4]. Although
every opportunity to test should be capitalized on, no test is perfect
including rapid HIV antibody test [5,6]. There remains a falsenegative rate due to several factors including the inability of the
assay to recognize all antibody responses especially not detecting
nonclade B virus, very early infection within the window period, and
lack of antibody production [7,8]. This case likely represents a rarely
reported case of seronegative HIV-1 infection despite chronic
infection [8]. Some patients do not develop humoral immunity to
HIV-1 despite evidence of HIV-1 infection. Surprisingly, only 25
cases have been published despite 35 million HIV patients identified
worldwide [9]. Most of these patients featured severe immunodeficiency, high-level viremia, rapid disease progression, possible
association with certain human leukocyte antigen type, and
infrequent seroconversion after HAART initiation. A more common
problem is acute HIV in which HIV antibody has not yet developed
[10]. Here, the fourth-generation HIV EIA was positive presumably
because it detects p24 HIV antigen as well as antibodies, unlike rapid
and third-generation HIV EIAs [11]. This case highlights the
importance of frontline providers to put all test results in the proper
clinical context and understand the limitations of all testing
methods. Clinical suspicion is a crucial aspect to interpreting
either a negative rapid HIV test or even laboratory-based EIAs and
supplemental tests with fourth-generation HIV EIA or nucleic acid
test may be necessary for accurate diagnosis. Settings that use the
rapid test must remain aware of the caveats to negative HIV tests and
be able to offer further testing if appropriate.
0735-6757/Published by Elsevier Inc.
Please cite this article as: Jindai K, et al, Human immunodeficiency virus testing pitfalls and clinical suspicion, Am J Emerg Med (2014),
http://dx.doi.org/10.1016/j.ajem.2014.04.017
2
K. Jindai et al. / American Journal of Emergency Medicine xxx (2014) xxx–xxx
Kazuaki Jindai, MD
Bethaney Kunzer, NP
The Section of Infectious Diseases
Department of Medicine
University of Wisconsin School of Medicine and Public Health
Madison, WI
Tam T. Van, PhD
Wisconsin State Laboratory of Hygiene
Madison, WI
Rob Striker, MD, PhD
The Section of Infectious Diseases
Department of Medicine
University of Wisconsin School of Medicine and Public Health
Madison, WI
W. S. Middleton Memorial Veteran’s Hospital
Madison, WI
E-mail address: [email protected]
http://dx.doi.org/10.1016/j.ajem.2014.04.017
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Please cite this article as: Jindai K, et al, Human immunodeficiency virus testing pitfalls and clinical suspicion, Am J Emerg Med (2014),
http://dx.doi.org/10.1016/j.ajem.2014.04.017