eMedicine Specialties > Infectious Diseases > HIV

Early Symptomatic HIV Infection: Differential Diagnoses & Workup

Author: Robert J Carpenter, DO, Fellow in Infectious Diseases, Infectious Diseases Clinic, Naval Medical Center San Diego
Coauthor(s): Braden R Hale, MD, MPH, Assistant Clinical Professor, Department of Internal Medicine, University of California at San Diego; Consulting Staff, Department of Internal Medicine, Division of Infectious Diseases, Naval Medical Center at San Diego; Kirk M Chan-Tack, MD, Fellow, Division of Infectious Disease, University of Maryland School of Medicine; John Bartlett, MD, Chief of Division of Infectious Diseases, Chief of HIV Care Service, Professor, Department of Internal Medicine, Johns Hopkins University School of Medicine
Contributor Information and Disclosures

Updated: Jun 9, 2009

Differential Diagnoses

Other Problems to Be Considered

Retroviral syndrome

Influenza
Infectious mononucleosis
Toxoplasmosis
Rubella
Secondary syphilis
Drug reaction
Disseminated gonococcal infection
Acute viral hepatitis

Persistent generalized lymphadenopathy

CD4 cell counts greater than 200 cells/µL - Adenopathic form of Kaposi sarcoma (KS)
CD4 cell counts less than 200 cells/µL - Adenopathic form of KS, lymphoma, mycobacterial infection, toxoplasmosis, systemic fungal infection, bacillary angiomatosis

Oral lesions

CD4 cell counts greater than 200/µL - Thrush, hairy leukoplakia, aphthous ulcers, herpes simplex, herpes zoster
CD4 cell counts less than 200/µL - Thrush, hairy leukoplakia, aphthous ulcers, herpes simplex, herpes zoster, cytomegalovirus (CMV) infection, KS

Miscellaneous

All other causes of anemia
All other causes of thrombocytopenia
All other causes of meningitis

Acute inflammatory demyelinating polyneuropathy

Guillain-Barré syndrome
Lambert-Eaton syndrome
Botulism
Myasthenia gravis

Mononeuritis multiplex

Diabetes mellitus
Vitamin B-12 deficiency
Adverse effects of metronidazole (Flagyl) or dapsone

Workup

Laboratory Studies

  • Patients with suspected acute human immunodeficiency virus (HIV) infection should undergo serum testing for HIV antibody and HIV antigen using HIV nucleic acid amplification, HIV p24 antigen, or PCR for viral load. Beware of false-positive HIV viral load test results (<15,000 RNA copies/mL blood).6,4
  • Persistent generalized lymphadenopathy: This is diagnosed clinically. Lymph node biopsy is not indicated in patients with early-stage HIV disease unless the patient has signs and symptoms of systemic illness (eg, fever, weight loss) or enlarged, fixed, or coalescent lymph nodes. A serologic diagnosis of acute EBV or CMV mononucleosis should be considered.
  • Thrush: This is diagnosed based on clinical appearance or examination of a scraping for pseudohyphal elements. Culturing is of no value because throat cultures are positive for Candida in most patients with HIV infection, even those without thrush. See Thrush for more details.
  • Oral hairy leukoplakia: This is typically diagnosed based on clinical appearance. Biopsy tissue findings reveal epithelial hyperplasia with protruding hairs and minimal inflammation. EBV can be visualized with electron microscopy, immunofluorescence, or Southern blot analysis. See Hairy Leukoplakia for more details.
  • Aphthous ulcers: These are diagnosed clinically. Examination of biopsy tissue reveals nonspecific inflammation and is not diagnostic. The primary role for biopsy is when aphthous ulcers are difficult to distinguish from HSV lesions. See Aphthous Stomatitis for more details.
  • Herpes simplex virus: Viral culture is the criterion standard for diagnosis. Viral PCR of intralesional fluid is also highly sensitive. Direct fluorescent antigen (DFA) is also a useful and generally rapidly available test that yields good sensitivity and specificity. Tzanck preparation (ie, Giemsa stain of vesicle contents) may reveal multinucleated giant cells and intranuclear inclusions specific for HSV or VZV, but the sensitivity is low. See Herpes Simplex for more details.
  • Varicella-zoster virus: Viral culture is the criterion standard for diagnosis. DFA is also a useful and generally rapidly available test with good sensitivity and specificity. Results from a Tzanck preparation (ie, Giemsa stain of vesicle contents) may reveal multinucleated giant cells and intranuclear inclusions specific for HSV or VZV, but the sensitivity is low. See Herpes Zoster for more details.
  • Anemia: A thorough evaluation is essential to exclude all other causes of anemia, especially any correctable causes. In addition to the workup detailed in Anemia, measuring the serum erythropoietin (EPO) level can help distinguish between bone marrow damage (ie, normal EPO level) and inflammatory anemia (ie, low EPO level).
  • Thrombocytopenia: A thorough evaluation is essential to exclude all other causes of thrombocytopenia (eg, see Thrombotic Thrombocytopenic Purpura), such as drug toxicity, lymphoma, fungal infection, and mycobacterial infection. Bone marrow examination generally reveals a normal or increased number of megakaryocytes.
  • Elevated transaminases: Acute viral hepatitis A, B, and C should be excluded with appropriate serologic testing.
  • Neurologic: A lumbar puncture is an important element of the evaluation in patients with HIV infection who have neurologic abnormalities. A lumbar puncture is most helpful in the diagnosis of opportunistic infections.
    • Aseptic meningitis or encephalitis: Cerebrospinal fluid examination reveals lymphocytic pleocytosis, an elevated protein level, and a normal glucose level.
    • Acute inflammatory demyelinating polyneuropathy: Cerebrospinal fluid examination reveals pleocytosis and increased protein levels. A peripheral nerve biopsy reveals findings of a perivascular infiltrate, suggesting an autoimmune etiology. Electromyography (EMG) findings reveal demyelination.
    • Myopathy: Serial creatine kinase levels are useful for monitoring the course of HIV myopathy. EMG is a sensitive diagnostic test in patients with HIV myopathy. The most common finding after muscle biopsy is scattered myofiber degeneration with occasional inflammatory infiltrates. Other pathological findings include nemaline rod bodies, cytoplasmic bodies, and mitochondrial abnormalities.

Other Tests

  • Electromyography
    • The finding in acute inflammatory demyelinating polyneuropathy is demyelination.
    • EMG is also useful for evaluating mononeuritis multiplex; results generally reveal multifocal axonal neuropathy.
    • EMG is a sensitive test for the evaluation of HIV myopathy.

Procedures

  • Acute inflammatory demyelinating polyneuropathy - Peripheral nerve biopsy
  • Mononeuritis multiplex - Nerve biopsy
  • Myopathy - Muscle biopsy
  • Meningitis/encephalitis - Lumbar puncture and CSF analysis

Histologic Findings

  • Thrush: Microscopic examination of a lesion scraping shows pseudohyphal elements.
  • Oral hairy leukoplakia: Biopsy tissue reveals epithelial hyperplasia with protruding hairs and minimal inflammation. EBV can be visualized with electron microscopy, immunofluorescence, or Southern blot analysis.
  • HSV and VZV: Tzanck preparation (ie, Giemsa stain of vesicle contents) may reveal multinucleated giant cells and intranuclear inclusions specific for HSV or VZV.
  • Thrombocytopenia: Bone marrow examination generally reveals a normal or increased number of megakaryocytes.
  • Acute inflammatory demyelinating polyneuropathy: Peripheral nerve biopsy reveals a perivascular infiltrate suggestive of an autoimmune etiology.
  • Mononeuritis multiplex: Biopsy of nerve tissue reveals inflammation and vasculitis. In some cases, CMV inclusions have been found.
  • Myopathy: The most common muscle biopsy finding is scattered myofiber degeneration with occasional inflammatory infiltrates. Other pathological findings include nemaline rod bodies, cytoplasmic bodies, and mitochondrial abnormalities.

More on Early Symptomatic HIV Infection

Overview: Early Symptomatic HIV Infection
Differential Diagnoses & Workup: Early Symptomatic HIV Infection
Treatment & Medication: Early Symptomatic HIV Infection
Follow-up: Early Symptomatic HIV Infection
References

References

  1. Pilcher CD, Eron JJ Jr, Galvin S, Gay C, Cohen MS. Acute HIV revisited: new opportunities for treatment and prevention. J Clin Invest. Apr 2004;113(7):937-45. [Medline].

  2. Zetola NM, Pilcher CD. Diagnosis and management of acute HIV infection. Infect Dis Clin North Am. Mar 2007;21(1):19-48, vii. [Medline].

  3. Truong HM, Grant RM, McFarland W, Kellogg T, Kent C, Louie B. Routine surveillance for the detection of acute and recent HIV infections and transmission of antiretroviral resistance. AIDS. Nov 14 2006;20(17):2193-7. [Medline].

  4. Pilcher CD, Fiscus SA, Nguyen TQ, Foust E, Wolf L, Williams D. Detection of acute infections during HIV testing in North Carolina. N Engl J Med. May 5 2005;352(18):1873-83. [Medline].

  5. Bettaieb A, Fromont P, Louache F, et al. Presence of cross-reactive antibody between human immunodeficiency virus (HIV) and platelet glycoproteins in HIV-related immune thrombocytopenic purpura. Blood. Jul 1 1992;80(1):162-9. [Medline].

  6. Mylonakis E, Paliou M, Lally M, et al. Laboratory testing for infection with the human immunodeficiency virus: established and novel approaches. Am J Med. Nov 2000;109(7):568-76. [Medline].

  7. Streeck H, Jessen H, Alter G, Teigen N, Waring MT, Jessen A. Immunological and virological impact of highly active antiretroviral therapy initiated during acute HIV-1 infection. J Infect Dis. Sep 15 2006;194(6):734-9. [Medline].

  8. Hecht FM, Wang L, Collier A, Little S, Markowitz M, Margolick J. A multicenter observational study of the potential benefits of initiating combination antiretroviral therapy during acute HIV infection. J Infect Dis. Sep 15 2006;194(6):725-33. [Medline].

  9. Fidler S, Fox J, Touloumi G, Pantazis N, Porter K, Babiker A. Slower CD4 cell decline following cessation of a 3 month course of HAART in primary HIV infection: findings from an observational cohort. AIDS. Jun 19 2007;21(10):1283-91. [Medline].

  10. Strategies for Management of Antiretroviral Therapy (SMART) Study Group, Emery S, Neuhaus JA, Phillips AN, Babiker A, Cohen CJ, et al. Major clinical outcomes in antiretroviral therapy (ART)-naive participants and in those not receiving ART at baseline in the SMART study. J Infect Dis. Apr 15 2008;197(8):1133-44. [Medline].

  11. US Department of Health and Human Services. National Institutes of Health. NIH News. Starting Antiretroviral Therapy Earlier Yields Better Clinical Outcomes. June 8, 2009. [Full Text].

  12. Aberg JA, Gallant JE, Anderson J, et al. Primary care guidelines for the management of persons infected with human immunodeficiency virus: recommendations of the HIV Medicine Association of the Infectious Diseases Society of America. Clin Infect Dis. Sep 1 2004;39(5):609-29. [Medline].

Further Reading

Keywords

early symptomatic HIV infection, acute HIV infection, acute retroviral syndrome, HIV seroconversion illness, HIV seroconversion syndrome, immune reconstitution inflammatory syndrome, human immunodeficiency virus, HIV, viral infection, immunologic impairment, immunocompromise, pre-acquired immune deficiency syndrome, pre-AIDS, thrush, oral hairy leukoplakia, herpes simplex virus, HSV, varicella-zoster virus, VZV, shingles, herpes zoster, thrombocytopenia, acute inflammatory demyelinating polyneuropathy, mononeuritis multiplex, myopathy, persistent generalized lymphadenopathy, PGL, oral lesions, anemia, aseptic meningitis, aphthous ulcers

Contributor Information and Disclosures

Author

Robert J Carpenter, DO, Fellow in Infectious Diseases, Infectious Diseases Clinic, Naval Medical Center San Diego
Robert J Carpenter, DO is a member of the following medical societies: American College of Osteopathic Internists, American College of Physicians, American Osteopathic Association, and Infectious Diseases Society of America
Disclosure: Nothing to disclose.

Coauthor(s)

Braden R Hale, MD, MPH, Assistant Clinical Professor, Department of Internal Medicine, University of California at San Diego; Consulting Staff, Department of Internal Medicine, Division of Infectious Diseases, Naval Medical Center at San Diego
Braden R Hale, MD, MPH is a member of the following medical societies: Alpha Omega Alpha, American College of Physicians, Armed Forces Infectious Diseases Society, and Infectious Diseases Society of America
Disclosure: Nothing to disclose.

Kirk M Chan-Tack, MD, Fellow, Division of Infectious Disease, University of Maryland School of Medicine
Kirk M Chan-Tack, MD is a member of the following medical societies: American College of Physicians, American Medical Association, Christian Medical & Dental Society, Physicians for Social Responsibility, and Southern Medical Association
Disclosure: Nothing to disclose.

John Bartlett, MD, Chief of Division of Infectious Diseases, Chief of HIV Care Service, Professor, Department of Internal Medicine, Johns Hopkins University School of Medicine
John Bartlett, MD is a member of the following medical societies: Alpha Omega Alpha, American College of Clinical Pharmacology, American College of Physicians, American Society for Microbiology, American Society of Tropical Medicine and Hygiene, American Thoracic Society, American Venereal Disease Association, Association of American Physicians, Infectious Diseases Society of America, and Society of Critical Care Medicine
Disclosure: Nothing to disclose.

Medical Editor

Fred A Lopez, MD, Associate Professor and Vice Chair, Department of Medicine, Assistant Dean for Student Affairs, Louisiana State University School of Medicine
Fred A Lopez, MD is a member of the following medical societies: Alpha Omega Alpha, American College of Physicians-American Society of Internal Medicine, Infectious Diseases Society of America, and Louisiana State Medical Society
Disclosure: Nothing to disclose.

Pharmacy Editor

Francisco Talavera, PharmD, PhD, Senior Pharmacy Editor, eMedicine
Disclosure: Nothing to disclose.

Managing Editor

Joseph F John Jr, MD, FACP, FIDSA, FSHEA, Clinical Professor of Medicine, Molecular Genetics and Microbiology, Medical University of South Carolina; Associate Chief of Staff for Education, Ralph H Johnson Veterans Affairs Medical Center
Disclosure: BioMerieux Honoraria Review panel membership; Cubist Honoraria Review panel membership; Pfizer Honoraria Speaking and teaching; Merck Stock dividends stock holdings

CME Editor

Eleftherios Mylonakis, MD, Clinical and Research Fellow, Department of Internal Medicine, Division of Infectious Diseases, Massachusetts General Hospital
Eleftherios Mylonakis, MD is a member of the following medical societies: American Association for the Advancement of Science, American College of Physicians, American Society for Microbiology, and Infectious Diseases Society of America
Disclosure: Nothing to disclose.

Chief Editor

Ronald A Greenfield, MD, Professor, Department of Internal Medicine, Section of Infectious Diseases, University of Oklahoma College of Medicine
Ronald A Greenfield, MD is a member of the following medical societies: American College of Physicians, American Federation for Medical Research, American Society for Microbiology, Central Society for Clinical Research, Infectious Diseases Society of America, Medical Mycology Society of the Americas, Phi Beta Kappa, Southern Society for Clinical Investigation, and Southwestern Association of Clinical Microbiology
Disclosure: Pfizer Honoraria Speaking and teaching; Gilead Honoraria Speaking and teaching; Ortho McNeil Honoraria Speaking and teaching; Wyeth Honoraria Speaking and teaching; Abbott Honoraria Speaking and teaching; Astellas Honoraria Speaking and teaching; Cubist  Speaking and teaching

 
 
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