Human Immunodeficiency Virus - HIV

Primary Authors: Reimer, Larry G., MD. Slev, Patricia R., PhD.

  • Key Points
  • Diagnosis
  • Algorithms
  • Screening
  • Monitoring
  • Background
  • Lab Tests
  • References
  • Related Topics
  • Videos

Human immunodeficiency virus (HIV) causes acquired immunodeficiency syndrome (AIDS). While therapy has become available to treat HIV infections, HIV remains a major public health problem, emphasizing the importance of continued diagnostic testing.

 

Indications for Testing

  • Symptomatic patients, those with recent exposure to HIV-infected individuals, infants born to HIV-infected mothers, pregnancy, or history of high-risk behaviors (intravenous drug use, multiple sexual partners, men having sex with men)

Laboratory Testing

Differential Diagnosis

  • Refer to Key Points section
  • Quantitative viral load – allows for monitoring during treatment
  • Drug resistance testing – allows for guided therapy decisions, particularly if patient response to therapy lessens
  • Public Health Service – T-helper cell (CD4) levels every 3-6 months in all HIV-infected persons

Human immunodeficiency virus 1 (HIV-1) is thought to have originated as a zoonotic transmission from simian immunodeficiency virus (SIV)-infected primates, while human immunodeficiency virus 2 (HIV-2) is thought to have originated as a zoonotic transmission from SIV-infected Sooty Mangabey monkeys.

Epidemiology

  • Incidence – ~50,000 new HIV infections per year (CDC, 2014)
  • Age – 18-30 years (peak)
  • Sex – M>F
  • Ethnicity – higher in African Americans
  • Transmission
    • Primarily via sexual contact (especially in men having sex with men)
    • Perinatally
    • Tissue transplantation
    • Blood-borne – not transmitted via saliva, insect vectors, or household contacts
    • Intravenous drug use

Organism

  • RNA single-stranded virus
  • Retroviridae family – includes HIV-1 and -2, and HTLV-1 and -2
  • HIV-1 and HIV-2 are etiologic agents of acquired immunodeficiency syndrome (AIDS)
    • HIV-1 accounts for the vast majority of HIV infections in the U.S.
      • Includes group M and at least 10 subtypes (A through J)
        • Group O (for outlier)
        • Group N (for non-M, non-O)
    • HIV-2 is endemic in West Africa and rarely seen in U.S.
      • Includes groups A through E

Pathophysiology

  • HIV localizes to the lymphoid organs
    • Infects the CD4+ helper cells and  T-cell lymphocytes
  • Viremia ensues post infection
  • Viral spread from local inoculation occurs quickly
    • ~30 billion virus particles produced in first weeks of infection

Clinical Presentation

  • Refer to Key Points section

Prevention

  • Can be prevented in 98% of infants of infected mothers by drug therapy during pregnancy, elective caesarian section, and refraining from breastfeeding
  • Use of condoms and needle exchange programs also reduce risk

Tests generally appear in the order most useful for common clinical situations. Click on number for test-specific information in the ARUP Laboratory Test Directory.

Human Immunodeficiency Virus (HIV) Combo Antigen/Antibody (HIV-1/O/2) by ELISA, Reflexive Panel 2012674
Method: Qualitative Enzyme-Linked Immunosorbent Assay/Qualitative Immunoassay/Quantitative Polymerase Chain Reaction

Human Immunodeficiency Virus (HIV) Combo Antigen/Antibody (HIV-1/O/2) by ELISA, with Reflex to HIV-1 Antibody Confirmation by Western Blot 2006526
Method: Qualitative Enzyme-Linked Immunosorbent Assay/Qualitative Western Blot

Limitations

Does not distinguish between the presence of HIV-1 p24 antigen, HIV-1 antibody, and HIV-2 antibody

Human Immunodeficiency Virus Types 1 and 2 (HIV-1, HIV-2) Antibodies by CIA with Reflex to HIV-1 Antibody Confirmation by Western Blot 2005377
Method: Qualitative Chemiluminescent Immunoassay/Qualitative Western Blot

Human Immunodeficiency Virus Type 1 (HIV-1) Antibody by CIA with Reflex to HIV-1 Antibody Confirmation by Western Blot 2005375
Method: Qualitative Chemiluminescent Immunoassay/Qualitative Western Blot

Human Immunodeficiency Virus Types 1 and 2 (HIV-1/2) Antibody Differentiation, Supplemental, with Reflex to HIV-1 Quantitative PCR 2012669
Method: Qualitative Immunoassay/Quantitative Polymerase Chain Reaction

Limitations

Test cannot be used as a rapid screen nor as a follow-up for a positive rapid screen

Human Immunodeficiency Virus Types 1 and 2 (HIV-1/2) Antibody Differentiation, Supplemental 2013107
Method: Qualitative Immunoassay

Human Immunodeficiency Virus Type 1 (HIV-1) Antibody Confirmation by Western Blot 0020284
Method: Qualitative Western Blot

Lymphocyte Subset Panel 1 - CD4 Absolute Count Only 0095854
Method: Quantitative Flow Cytometry

Follow Up

Other lymphocyte panels are available; see list of additional tests available below

Human Immunodeficiency Virus 1 by Quantitative PCR 0055598
Method: Quantitative Polymerase Chain Reaction

Limitations

"Not Detected" does not rule out the presence of inhibitors or HIV-1 virus RNA concentrations below the assay detection level

Human Immunodeficiency Virus 1 (HIV-1) by Qualitative PCR 0093061
Method: Qualitative Polymerase Chain Reaction

Limitations

Do not use umbilical cord blood due to contamination with maternal blood

Follow Up

Repeat testing at 1-2 mos and 3-6 mos

Human Immunodeficiency Virus Type 2 (HIV-2) Antibody by ELISA with Reflex to HIV-2 Supplemental 0051250
Method: Qualitative Enzyme Immunoassay/Qualitative Immunoassay

Human Immunodeficiency Virus 1, Genotype by Sequencing 0055670
Method: Reverse Transcription Polymerase Chain Reaction/Sequencing

Limitations

Because treatment failure can be caused by factors other than drug resistance, interpretation of resistance genotyping results must be made in conjunction with other clinical and laboratory information

Some insertions or deletions may be difficult to detect 

Absence of resistant mutations does not rule out possible reservoirs of resistant viruses undetectable by this assay

Specimens with HIV-1 RNA plasma levels <1,000 copies/mL may not provide adequate data due to polymorphisms in the priming areas of genome

Test does not detect HIV-1 populations <20% of the total population

Related Tests

Guidelines

ACOG Committee Opinion no 596: Committee on Gynecologic Practice: Routine human immunodeficiency virus screening. Obstet Gynecol. 2014; 123(5): 1137-9. PubMed

Branson B, Handsfield H, Lampe M, Janssen R, Taylor A, Lyss S, Clark J. Revised Recommendations for HIV Testing of Adults, Adolescents, and Pregnant Women in Health-Care Settings. 55(RR14);1-17. Centers for Disease Control and Prevention. Atlanta, GA [Last Reviewed Sep 2006; Accessed: Dec 2015]

Branson B, Owen S, Wesolowski L, et al. Laboratory Testing for the Diagnosis of HIV Infection: Updated Recommendations. Centers for Disease Control and Prevention. Atlanta, GA [Published June 27, 2014; Accessed: Nov 2015]

Human Immunodeficiency Virus (HIV) Infection: Screening. U.S. Preventive Services Task Force. Rockville, MD [Accessed: Nov 2015]

M53-A - Criteria for Laboratory Testing and Diagnosis of Human Immunodeficiency Virus Infection; Approved Guideline. Clinical and Laboratory Standards Institute. Wayne, PA [Accessed: Nov 2015]

Moyer VA, U.S. Preventive Services Task Force*. Screening for HIV: U.S. Preventive Services Task Force Recommendation Statement. Ann Intern Med. 2013; 159(1): 51-60. PubMed

Qaseem A, Snow V, Shekelle P, Hopkins R, Owens DK, Clinical Efficacy Assessment Subcommittee, American College of Physicians. Screening for HIV in health care settings: a guidance statement from the American College of Physicians and HIV Medicine Association. Ann Intern Med. 2009; 150(2): 125-31. PubMed

Workowski KA, Bolan GA, Centers for Disease Control and Prevention. Sexually transmitted diseases treatment guidelines, 2015 MMWR Recomm Rep. 2015; 64(RR-03): 1-137. PubMed

General References

Campbell-Yesufu OT, Gandhi RT. Update on human immunodeficiency virus (HIV)-2 infection. Clin Infect Dis. 2011; 52(6): 780-7. PubMed

Chu C, Selwyn PA. Diagnosis and initial management of acute HIV infection. Am Fam Physician. 2010; 81(10): 1239-44. PubMed

Cohen MS, Shaw GM, McMichael AJ, Haynes BF. Acute HIV-1 Infection. N Engl J Med. 2011; 364(20): 1943-54. PubMed

Cornett JKang, Kirn TJ. Laboratory diagnosis of HIV in adults: a review of current methods. Clin Infect Dis. 2013; 57(5): 712-8. PubMed

d'Ettorre G, Zaffiri L, Ceccarelli G, Mastroianni CM, Vullo V. The role of HIV-DNA testing in clinical practice. New Microbiol. 2010; 33(1): 1-11. PubMed

O'Conell RJ, Peel SA. Multispot HIV-1/HIV-2 Rapid Test: advantages over other rapid HIV tests. Expert Rev Mol Diagn. 2007; 7(5): 499-505. PubMed

References from the ARUP Institute for Clinical and Experimental Pathology®

Bedoya VInés, Jaimes FAlberto, Delgado JC, Rugeles C, Usuga X, Zapata W, Castaño MEugenia, Boasso A, Shearer G, Rugeles MTeresa. Fetal-maternal HLA-A and -B discordance is associated with placental RNase expression and anti-HIV-1 activity. Curr HIV Res. 2008; 6(4): 380-7. PubMed

Choi HH, Gray PB, Storer TW, Calof OM, Woodhouse L, Singh AB, Padero C, Mac RP, Sinha-Hikim I, Shen R, Dzekov J, Dzekov C, Kushnir MM, Rockwood AL, Meikle AW, Lee ML, Hays RD, Bhasin S. Effects of testosterone replacement in human immunodeficiency virus-infected women with weight loss. J Clin Endocrinol Metab. 2005; 90(3): 1531-41. PubMed

Ebbert MT W, Mallory MA, Wilson AR, Dooley SK, Hillyard DR. Application of a new informatics tool for contamination screening in the HIV sequencing laboratory. J Clin Virol. 2013; 57(3): 249-53. PubMed

Melis R, Lewis T, Millson A, Lyon E, McMillin GA, Slev PR, Swensen J. Copy number variation and incomplete linkage disequilibrium interfere with the HCP5 genotyping assay for abacavir hypersensitivity. Genet Test Mol Biomarkers. 2012; 16(9): 1111-4. PubMed

Pyne MT, Hackett J, Holzmayer V, Hillyard DR. Large-scale analysis of the prevalence and geographic distribution of HIV-1 non-B variants in the United States. J Clin Microbiol. 2013; 51(8): 2662-9. PubMed

Pyne MT, Konnick EQ, Phansalkar A, Hillyard DR. Evaluation of the Abbott investigational use only realtime HIV-1 assay and comparison to the Roche Amplicor HIV-1 monitor test, version 1.5. J Mol Diagn. 2009; 11(4): 347-54. PubMed

Pyne MT, Wilson A, Hillyard DR. Large-scale comparison of Roche Cobas AmpliPrep/Cobas TaqMan and Abbott RealTime HIV assays. J Virol Methods. 2012; 184(1-2): 106-8. PubMed

Salama ME, Perkins SL, Mariappan R. Images in HIV/AIDS. Primary bone marrow presentation of Epstein-Barr virus-driven HIV-associated Hodgkin lymphoma. AIDS Read. 2007; 17(12): 604-5. PubMed

Taborda NA, Cataño JC, Delgado JC, Rugeles MT, Montoya CJ. Higher SLPI expression, lower immune activation, and increased frequency of immune cells in a cohort of Colombian HIV-1 controllers. J Acquir Immune Defic Syndr. 2012; 60(1): 12-9. PubMed

Wyness SP, Yee MA, La'ulu SL, Tosiello L, Straseski JA. Multiple macroenzymes in a patient with AIDS: diagnosis using ultrafiltration. Am J Clin Pathol. 2014; 142(2): 266-8. PubMed

Medical Reviewers

Last Update: February 2016