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    Clinical Pathology
    H180-A EUH
    Atlanta, GA 30322
    404 712-5721 Phone

    For an expert Pathology consultation,
    or to send a specimen, call:

    1-404-712-5947

    Pathology Faculty Photo

    Angela M Caliendo, MD, PhD

    Molecular Diagnostics
    Microbiology

    Professor
    Pathology & Laboratory Medicine


    Other Appointments/Positions

    Associate Professor, Medicine, Emory University School of Medicine, Atlanta, GA

    Medical Director of Clinical Microbiology and Molecular Diagnostics, Emory University Hospital, Atlanta

    Attending Physician, Infectious Diseases Division, Emory University Hospital, Atlanta

    Director, Emory Medical Laboratories, Emory University and Crawford Long Hospitals, Atlanta

    Director, Clinical Pathology, Department of Pathology and Laboratory Medicine, Emory University School of Medicine, Atlanta

    Vice Chair, Clinical Pathology, Department of Pathology and Laboratory Medicine, Emory University School of Medicine, Atlanta

    Executive Committee, Department of Pathology, Emory University, Atlanta

    Infectious Diseases Division Executive Committee, Emory University School of Medicine, Atlanta, GA

    Director, Medical Microbiology Fellowship, Department of Pathology, Emory University Hospital, Atlanta, GA


    Pathology Division(s):
    Clinical Pathology
    Experimental Pathology


    Email Address:
    acalien@emory.edu


    Education:

    BS   Grove City College, Grove City, PA (Biology), - 1978

      Kent State University, Kent, OH (Biochemistry), - 1979

    PhD   Case Western Reserve University, Cleveland, OH (Biochemistry) Advisor: Mulchand S. Patel, PhD, - 1983

    MD   Case Western Reserve University School of Medicine, Cleveland, OH, - 1987

    Residency   Internal Medicine Internship and Residency, Brigham and Womens Hospital, Boston, MA, 1987 - 1990

    Fellowship   Infectious Diseases Fellowship, Massachusetts General Hospital, Boston, MA, 1990 - 1994



    Research Interests:

    - Studies of HIV in the female genital tract
    In collaboration with Dr. Susan Cu-Uvin at Brown University, we are evaluating HIV-1 RNA burden and the development of antiretroviral resistance in the plasma and cervical secretions of HIV-1 seropositive women. The goal of these studies is to determine how viral load levels and resistance profiles differ in the female genital tract and plasma compartments. This work has implications for both vertical and heterosexual transmission of HIV-1.


    - Development and evaluation of molecular testing for Infectious Diseases
    My research laboratory has been actively involved in the development and clinical evaluation of molecular tests for the diagnosis and monitoring of infectious diseases. These studies focus on both the analytical and clinical performance of the tests.


    - Co-Director of Virology and Drug Discovery Core for the Emory Center for AIDS Research (CFAR)
    The preclinical and clinical virology laboratories provide support to investigators studying HIV by providing a range of molecular testing for the detection and monitoring of SIV, HIV-1, HIV-2, CMV, HCV, and sexually transmitted diseases. This testing supports investigators at Emory as well as those associated with other CFAR centers across the United States. The Core is also involved with training investigators in molecular methods.



    Clinical Focus:

    I am Vice Chair and Director of Clinical Pathology and Emory Medical Laboratories, as well as the Medical Director of the Clinical Microbiology and Molecular Diagnostics laboratories, and an Attending Physician for Infectious Diseases at Emory University Hospital.


    Honors / Awards:

    AnnaLee Boyett Award, In recognition of outstanding support to the Department of Pathology Residency Training Program, Department of Pathology and Laboratory Medicine, Emory University School of Medicine., 2006

    Emory University Attending Teaching Award, Department of Medicine, Emory University School of Medicine, 2003

    Outstanding Editorial Board Member, Journal of Clinical Microbiology, 2003

    Emory University Attending Teaching Award, Department of Medicine, Emory University School of Medicine, 2002

    Golden Apple Teaching Award, Department of Pathology and Laboratory Medicine, Emory University School of Medicine, 2001

    ASM Foundation for Microbiology Lecturer, American Society for Microbiology, 1999

    Outstanding Speaker Award, American Association for Clinical Chemistry, 1999

    Faculty Prize for Excellence in Teaching Clinical Pathology Residents, Massachusetts General Hospital, 1997

    Alpha Omega Alpha, Case Western Reserve University School of Medicine, 1987

    American College of Physicians, Ohio Chapter - Award to the Outstanding Student Entering Internal Medicine, 1987

    Magna Cum Laude, Grove City College, Grove City, PA, 1978

    Specialty Boards:

    1990 Diplomate Internal Medicine, American Board of Internal Medicine


    1992 Diplomate Infectious Diseases, American Board of Internal Medicine


    2002 Diplomate Recertification, Infectious Diseases, American Board of Internal Medicine


    Selected Publications:

    Published and Accepted Research Articles -

    Hill CE, Harris SB, Culler EE, Zimring JC, Nolte FS, and Caliendo AM. Comparison of a laboratory-developed real-time PCR assay with a LightCycler commercial assay for the quantification of Epstein Barr Virus DNA. American Journal of Clinical Pathology 2006;125:665-671.


    Caliendo AM, Valsamakis A, Zhou Y, Yen-Lieberman B, Andersen J, Young S, Ferreira-Gonzalez A, Tsongalis GJ, Pyles R, Bremer JW, and Lurain, NS. Multi-Laboratory Comparison of Hepatitis C Viral Load Assays. J Clin Micro 2006;44:1726-1732.


    Crosby RA, Salazar LF, DiClemente RJ, Yarber WL, Caliendo AM, Staples-Horne M. Accounting for failures may improve precision: Evidence supporting improved validity of self-reported condom use. Sexually Transmitted Diseases. 2005;32:513-515.


    Newstein M, Losikoff P, Caliendo A, Ingersoll J, Kurpewski J, Hanley D, Cerezo J, Ramratnam B, Cu-Uvin S. Prevalence and persistence of nonnucleoside reverse transcriptase inhibitor mutations in the femal genital tract. [Letter] JAIDS. 2005;38:364-6.


    Roback, J.D., Caliendo, A.M., Newman, J.L., Sgan, S., Saakadze, N., Gillespie, T.W., Lane, T.A., Kurtzberg, J., and Hillyer, C.D. (2005) Comparison of CMV PCR and serology for screening umbilical cord blood components. Transfusion. 2005;45:172-1728.


    Caliendo AM, Jordan JA, Green, AM, Ingersoll J, Wingood GM, and DiClemente RJ. Real-Time PCR Provides Improved Detection of Trichomonas vaginalis Infection Compared to Culture Using Self-Collected Vaginal Swabs. Infectious Diseases in Obstetrics and Gynecology. 2005;13:145-150.


    Hill C, Green A, Ingersoll J, Easley K, Nolte F, and Caliendo AM. Assessment of agreement between the AMPLICOR HIV-1 MONITOR test version 1.0 and 1.5. Journal of Clinical Microbiology. 2004; 42(1):286-289.


    Kessler AT, Kourtis AP, and Caliendo AM. Vascular graft infection due to Pasteurella multocida. Infection. 2004; 32(2):122-123.


    Caliendo AM, Ingersoll J, Green AM, Nolte FS, Easley KA. Comparison of the sensitivity and viral load values between the AMPLICOR HIV-1 MONITOR version 1.0 and 1.5 tests. Journal of Clinical Microbiology. 2004. 42 (11):5392-5393.


    Crosby R, Salazar LF, DiClemente RJ, Yarber WL, Caliendo AM, and Staples-Horne M. Health risk factors among detained adolescent females. American Journal of Preventive Medicine. 2004;27:404-410.


    Borucki M, Spritzler J, Asmuth D, Gnann J, Hirsch MS, Nokta M, Aweeka F, Nadler PI, Sattler F, Alston B, Nevin TT, Owens S, Waterman K, Hubbard L, Caliendo AM, Pollard RB and the AACTG 266 Team. A phase II, double-masked, randomized, placebo-controlled evaluation of a human monoclonal anti-cytomegalovirus antibody (MLS-109) in combination with standard therapy versus standard therapy alone in the treatment of AIDS patients with cytomegalovirus retinitis. Antiviral Research. 2004;64:103-111.


    Barbeau JM, Goforth J, Caliendo AM, and Nolte FS. Performance characteristics of a quantitative, TaqMan Hepatitis C virus RNA analyte specific reagent. Journal of Clinical Microbiology. 2004;42(8):3739-3746.


    Nolte FS, Green AM, Fiebelkorn KR, Caliendo AM, Sturchio C, Grunwald A, and Healy M. Clinical evaluation of two methods for genotyping hepatitis C virus based on analysis of the 5' noncoding region. Journal of Clinical Microbiology. 2003; 41: 1558-1564.


    Caliendo A, Yen-Lieberman B, Baptista J, Andersen J, Crumpacker C, Schuurman R, Spector S, Bremer J, and Lurain N. Comparison of molecular tests for detection and quantification of cell-associated cytomegalovirus DNA. Journal of Clinical Microbiology. 2003; 41:3509-3513.


    Zimmer SM, Caliendo AM, Thigpen MC, and Somani J. Failure of linezolid treatment for enterococcal endocarditis. Clinical Infectious Diseases. 2003; 37: e29-30.


    De Pasquale MP, Leigh Brown AJ, Cu-Uvin S, Allega-Ingersoll J, Caliendo AM, Sutton L, Donahue S, and D'Aquila RT. Differences in HIV-1 pol sequences from female genital tract and blood during antiretroviral therapy. JAIDS. 2003; 34(1):37-44.


    Lee BG, Fiebelkorn KR, Caliendo AM, and Nolte F. Development and verification of an automated sample processing protocol for quantitation of human immunodeficiency virus type 1 RNA in plasma. Journal of Clinical Microbiology. 2003; 41(5): 2062-2067.


    Culler EE, Caliendo AM, and Nolte F. Reproducibility of positive test results in the BDProbeTec ET system for detection of Chlamydia trachomatis and Neisseria gonorrhoeae. Journal of Clinical Microbiology. 2003; 41(8): 3911-3914.


    Harwell JI, Flanigan TP, Mitty JA, Macalino GE, Caliendo AM, Ingersoll J, Stenzel MS, Carpenter CCJ, and Cu-Uvin S. Directly observed antiretroviral therapy to reduce genital tract and plasma HIV-1 RNA in women with poor adherence. AIDS. 2003; 17 (13): 1990-1993.


    Natividad-Villanueva GU, Santiago E, Manalastas RM, Jr. Brown HW, Ingersoll J, Caliendo AM, Mayer KH, and Cu-Uvin S. Human immunodeficiency virus in plasma and cervicovaginal secretions in Filipino women. International Journal of STD & AIDS. 2003; 14(12):826-9.


    Erice A, Tierney C, Hirsch M, and Caliendo AM. Weinberg A. Kendall MA. Polsky B. AIDS Clinical Trials Group Protocol 360 Study Team. Cytomegalovirus (CMV) and human immunodeficiency virus (HIV) burden, CMV end-organ disease, and survival in subjects with advanced HIV infection (AIDS Clinical Trials Group Protocol 360). Clinical Infectious Diseases. 2003; 37(4):567-78.


    Humar A, Kumar D, Caliendo AM, Moussa G, Ashi-Sulaiman A, Levy G, and Mazzulli T. Clinical impact of human herpesvirus 6 infection after liver transplantation. Transplantation. 2002; 73:599-604.


    Humar A, Kumar D, Raboud J, Caliendo AM, Moussa G, Levy G, and Mazzulli T. Interactions between cytomegalovirus, human herpesvirus-6, and the recurrence of hepatitis C after liver transplantation. American Journal of Transplantation. 2002; 2(5):461-6.


    Caliendo AM, St. George K, Allega J, Bullotta AC, Gilbane L, and Rinaldo CR. Distinguishing cytomegalovirus (CMV) infection and disease with CMV nucleic acid assays. Journal of Clinical Microbiology. 2002; 40:1581-1586.


    Simko JP, Caliendo AM, Hogle K, and Versalovic J. Differences in CSF laboratory findings in patients with DNA-positive meningitis and encephalitis. Clinical Infectious Diseases. 2002; 35: 414-419.


    Fiebelkorn KR, Lee BG, Hill CE, Caliendo AM, and Nolte FS. Clinical evaluation of an automated nucleic acid isolation system. Clinical Chemistry. 2002; 48(9): 1613-1615.


    Humar A, Dumar, D, Boivin, G, and Caliendo A. Cytomegalovirus (CMV) viral load kinetics to predict recurrent disease in solid organ transplant patients with CMV disease. Journal of Infectious Diseases. 2002; 186 (6): 829-833.


    Langston AA, Redei I, Caliendo AM, Somani J, Hutcherson D, Lonial S, Bucur S, Cherry J, Allen A, and Waller EK. Development of drug-resistant herpes simplex virus infection after haploidentical hematopoietic progenitor cell transplantation. Blood. 2002; 99(3): 1085-1088.


    Caliendo AM, Schuurman R, Yen-Liebermann B, Spector SA, Andersen J, Manjiry R, Crumpacker C, Lurain N, and Erice A, for the CMV Working Group Complications of HIV Disease RAC, AIDS Clinical Trials Group (ACTG). Comparison of quantitative and qualitative PCR assays for CMV DNA in plasma. Journal of Clinical Microbiology. 2001; 39:1334-1338.


    CuUvin S, Hogan JW, Caliendo A, Harwell J, Mayer K, and Carpenter CCJ. Association between bacterial vaginosis and expression of HIV-1 RNA in the female genital tract. Clinical Infectious Diseases. 2001; 33(6):894-896.


    Witt DJ, Kemper M, Stead A, Ginocchio CC, and Caliendo AM. Relationship of incremental specimen volumes and enhanced detection of human immunodeficiency virus type-1 RNA with nucleic acid amplification technology. Journal of Clinical Microbiology. 2000; 38: 85-89.


    Cu-Uvin S, Caliendo AM, Reinnert S, Chang A, Juliano-Remollino C, Flanigan TP, Mayer KH, and Carpenter CCJ. Effect of highly active antiretroviral therapy on cervicovaginal HIV-1 RNA. AIDS. 2000; 14:415-421.


    Caliendo AM, St. George K, Kao S-Y, Allega J, Tan B, LaFontaine R, Bui L, and Rinaldo CR. Quantitative CMV PCR in Plasma as Compared with CMV Antigenemia: Clinical Utility of the Prototype AMPLICOR CMV MONITOR Test in Transplant Recipients. Journal of Clinical Microbiology. 2000; 38:2122-2127.


    Fitzgerald DW, Behets F, Caliendo A, Roberfroid D, Lucet C, Fitzgerald JW, and Kuykens L. Economic hardship and sexually transmitted diseases in Haiti's rural Artibonite Valley. American Journal of Tropical Medicine & Hygiene. 2000; 62:496-501.


    Witt DJ, Kemper M, Stead A, Sillekens P, Ginocchio CC, Espy MJ, Paya CV, Smith TF, Roeles F, and Caliendo AM. Analytical performance and clinical utility of a nucleic acid sequenced-based amplification assay for detection of cytomegalovirus infection. Journal of Clinical Microbiology. 2000; 38:3994-3999.


    Shacklett BL, Cu-Uvin S, Beadle TJ, Pace CA, Fast NM, Donahue SM, Caliendo AM, Flanigan TP, Carpenter CCJ, and Nixon DF. Quantification of HIV-1-specificT-cell responses at the mucosal cervicovaginal surface. AIDS. 2000; 14:1911-1915.


    Akpek EK, Kent C, Jakobiec F, Caliendo AM, and Foster CS. Bilateral acute retinal necrosis caused by cytomegalovirus in an immunocompromised patient. American Journal of Ophthalmology. 1999; 127:93-5.


    Humar A, Gregson D, Caliendo AM, McGeer A, Malkan G, Krajden M, Corey P, Greig P, Walmsley S, Levy G, and Mazzulli T. Clinical utility of quantitative cytomegalovirus viral load determination for predicting cytomegalovirus disease in liver transplant recipients. Transplantation. 1999; 68:1305-1311.


    Murphy RL, Gulick RM, DeGruttola V, D'Aquila RT, Eron JJ, Sommadossi J-P, Currier JS, Smeaton L, Frank I, Caliendo AM, Gerber JG, Tung R, and Kuritzkes DR, for the AIDS Clinical Trials Group 347 Study Team. Treatment with amprenavir alone or amprenavir with zidovudine and lamivudine in adults with human immunodeficiency virus infection. Journal of Infectious Diseases. 1999; 179:808-16.


    Tashima KT, Caliendo AM, Ahmad M, Gormley JM, Fiske WD, Brennan JM, and Flanigan TP. Cerebrospinal fluid (CSF) human immunodeficiency virus type 1 (HIV-1) suppression and efavirenz drug concentrations in HIV-1 infected patients receiving combination therapy. Journal of Infectious Diseases. 1999; 180:862-4.


    Mani I, Cao H, Hom D, Johnson JL, Mugerwa RD, Travers KU, Caliendo AM, Walker BD, and Kanki PJ. Plasma RNA viral load as measured by the bDNA and NASBA assays of HIV-1 subtypes A and D in Uganda. JAIDS Journal of Acquired Immune Deficiency Syndromes. 1999; 22(2):208-209.


    Ahmad M, Tashima KT, Caliendo AM, and Flanigan TP. Cerebrospinal fluid and plasma HIV-1 RNA stability at 4oC. AIDS. 1999; 13:1281-1282.


    Caliendo AM, Hewitt PL, Allega JM, Keen A, Ruoff KL, and Ferraro MJ. Performance of a PCR assay for the detection of Pneumocystis carinii from respiratory specimens. Journal of Clinical Microbiology. 1998; 36:979-982.


    Cu Uvin S Caliendo AM, Reinert, Mayer KH, Flanigan TP, and Carpenter CC. HIV-1 n the female genital tract and the effect of antiretroviral therapy [Letter]. AIDS. 1998; 12:826-7.


    Farrar DJ, Cu Uvin S, Caliendo AM, Costello SF, Murphy DM, Flanigan TP, Mayer KH, and Carpenter CCJ. Detection of HIV-1 RNA in vaginal secretions of HIV-1-seropositive women who have undergone hysterectomy [Letter]. AIDS. 1997; 11:1296-1297.


    Rosenberg ES, Billingsley JM, Caliendo AM, Boswell SL, Sax P, Kalams SA, Walker BD. Vigorous HIV-1-specific CD4+ T cell responses associated with control of viremia. Science. 1997; 278:1447-1450


    Hass J, Jernick SL, Scardina J, Teruya J, Caliendo AM, and Ruoff KL. Colonization of skin by Helcococcus kunzii. Journal of Clinical Microbiology. 1997; 35:2759-2761.


    Cu Uvin S and Caliendo AM. Cervicovaginal human immuno-deficiency virus secretion and plasma viral load in human immuno-deficiency virus-seropositive women. Obstetrics & Gynecology. 1997; 90:739-743.


    Farrar DJ, Cu Uvin S, Caliendo AM, Costello SF, Murphy DM, Flanigan TP, Mayer KH, and Carpenter CCJ. Detection of HIV-1 RNA in vaginal secretions of HIV-1-seropositive women who have undergone hysterectomy [Letter]. AIDS. 1997; 11:1296-1297.


    Caliendo AM, Savara A, An D, DeVore KM, Kaplan JC, and DAquila RT. Effects of zidovudine-selected HIV-1 reverse transcriptase amino acid substitutions on processive DNA synthesis and viral replication. Journal of Virology. 1996; 70:2146-2153.


    Harrer T, Harrer E, Kalams SA, Elbeik T, Feinberg M, Cao Y, Ho DD, Tilahun Y, Caliendo AM, Johnson RP, Buchbinder S, and Walker BD. Strong cytotoxic T cells and weak neutralizing antibodies responses in a subset of persons with stable non-progressing HIV type 1 infection. AIDS Research & Human Retroviruses. 1996; 12:585-592.


    Manion DJ, Vibhagool A, Chou T-C, Kaplan J, Caliendo AM, and Hirsch MS. Susceptibility of human cytomegalovirus (HCMV) to 2-drug combinations in vitro. Antiviral Therapy. 1996; 1:237-245.


    Caliendo AM, Jordan CD, and Ruoff KL. Helcococcus, a new genus of catalase-negative, gram positive cocci isolated from clinical specimens. Journal of Clinical Microbiology. 1995; 33:1638-1639.


    Zhang D, Caliendo AM, Eron JJ, DeVore KM, Kaplan JC, Hirsch MS, and D'Aquila RT. Resistance to 2', 3-dideoxycytidine conferred by a mutation in codon 65 of human immunodeficiency virus type 1 reverse transcriptase. Antimicrobial Agents & Chemotherapy. 1994; 38:282-287.


    Eron JJ, Chow Y-K, Caliendo AM, Videler J, DeVore K, Cooley TC, Liebman H, Kaplan J, Hirsch MS, and D'Aquila RT. Pol mutations conferring zidovudine and didanosine resistance with different effects in vitro yield multiply resistant human immunodeficiency virus type 1 isolates in vivo. Antimicrobial Agents & Chemotherapy. 1993; 37:1480-1487


    Ho L, Javed AA, Pepin RA, Thekkumkara TJ, Raefsky C, Mole JE, Caliendo AM, Kwon MS, Kerr DS, and Patel MS. Identification of A cDNA Clone for the B-Subunit of the Pyruvate Dehydrogenase Component of Human Pyruvate Dehydrogenase Complex. Biochemical and Biophysical Research Communications. 1988; 150:904-908.


    Haney PM, Estrin CR, Caliendo AM, and Patel MS. Precocious Induction of Hepatic Glucokinase and Malic Enzyme in Artificially Reared Rat Pups Fed a High-Carbohydrate Diet. Archives of Biochemistry and Biophysics. 1986; 244:787-794.


    Caliendo AM, and Patel MS. Insulin Receptors in Developing Rat Liver: Acquisition of Regulation in the Immediate Postnatal Period. Archives of Biochemistry and Biophysics. 1983; 227:552-561.


    Book Chapters -

    Caliendo, AM. Human Immunodeficiency Virus Type 1. In: Molecular Pathology and Clinical Practice. Submitted.


    Ferreira-Gonzalez, A and Caliendo, AM. Molecular Diagnostics of Viral Infections in Transplant Patients. In: Molecular Pathology and Clinical Practice. Submitted.


    Caliendo, AM and Nell S. Lurain. Cytomegalovirus. In: Molecular Diagnostics for the Clinical Laboratorian 2nd Edition. Eds. WB Coleman and GJ Tsongalis. Humana Press. pp. 473-482.


    Caliendo AM and Hill CE, Human Immunodeficiency Virus Type 1. In: Molecular Diagnostics for the Clinical Laboratorian 2nd Edition. Eds. WB Coleman and GJ Tsongalis. Humana Press. pp. 453-459.


    Ferreira-Gonzalez A, Versalovic J, Habeebu S, and Caliendo AM. Molecular Methods in Diagnosis and Monitoring of Infectious Diseases. In: Fundamentals of Molecular Diagnostics. Elsevier Science, DE Bruns, ER Ashwood, CA Burtis (eds). Submitted.


    Ferreira-Gonzalez, A and Caliendo, AM. Molecular Methods in Diagnosis and Monitoring of Infectious Diseases. In: Tietz Textbook of Clinical Chemistry and Molecular Diagnostics (4th Ed). Eds. Burtis, Ashwood, and Bruns. Elsevier Saunders. 2005.


    Hill, CE and Caliendo, AM. Viral Load Testing. In: Molecular Microbiology. Diagnostic Principles and Practice. 2004. 2nd Edition. Eds. DH Persing, FC Tenover, J Versalovic, Y-W Tang, ER Unger, DA Relman, TJ White. ASM Press. pp. 478-488.


    Caliendo, AM and Yen-Lieberman, B. Viral Genotyping. In: Molecular Microbiology. Diagnostic Principles and Practice. 2004. 2nd Edition. Eds. DH Persing, FC Tenover, J Versalovic, Y-W Tang, ER Unger, DA Relman, TJ White. ASM Press. pp. 489-500


    Nolte FS and Caliendo AM. Molecular Detection and Identification of Microorganisms. In: Manual of Clinical Microbiology. 2003. 8th Edition. Eds. EJ Baron, JH Jorgensen, MA Pfaller, RH Yolken, ASM Press. pp. 234-256.


    Books Edited and Written -

    Caliendo, AM. Section Editor, Infectious Diseases Section. In: Molecular Pathology and Clinical Practice. In Preparation.


    Caliendo, AM. Section Editor, Virology Section. In: Manual of Clinical Microbiology, 9th Edition. In Preparation.


    Other Publications -

    Henderson D. Caliendo AM. Antiretroviral rounds. A red herring? AIDS Clinical Care. 2000; 12(8):66-7.


    Rosenberg ES, Caliendo AM, and Walker BD. Acute HIV infection among patients tested for mononucleosis [Letter]. New England Journal of Medicine. 1999; 340:969.