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 Content

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

Human Immunodeficiency Virus in Adults Testing Algorithm

Human Immunodeficiency Virus in Infants Testing Algorithm

Immunodeficiency Evaluation for Chronic Infections in Adults and Older Children Testing Algorithm

Immunodeficiency Evaluation for Chronic Infections in Infants and Children Testing Algorithm

  • 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

Indications for Laboratory Testing

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

Additional Tests Available

Human Immunodeficiency Virus Type 1 (HIV-1) Antibody, Confirmation by Western Blot, with Reflex to HIV-2 Antibody 0020698
Method: Qualitative Western Blot/Qualitative Enzyme-Linked Immunosorbent Assay/Qualitative Immunoassay

Comments

Order only if patient is positive (repeatedly reactive) for combined HIV-1 and HIV-2 antibody screen

Reflex pattern – if HIV-1 antibody, confirmation by Western blot is indeterminate, negative or has non-specific staining, then HIV-2 antibody by ELISA with reflex to HIV-2 supplemental will be added

Human Immunodeficiency Virus 1 (HIV-1) by Quantitative PCR with Reflex to HIV-1 Genotype by Sequencing 2002689
Method: Quantitative Polymerase Chain Reaction/Sequencing

Comments

Use with clinical presentation as an indicator of disease prognosis and assess viral response to antiretroviral treatment

Reflex pattern – if Human Immunodeficiency Virus 1 by Quantitative PCR result is greater than or equal to 3.0 log copies/mL, then HIV-1 Genotype by Sequencing will be added

Limit of quantification for the HIV-1 by Quantitative PCR assay is 1.3 log copies/mL (20 copies/mL)

Lymphocyte Subset Panel 2 - CD4  Percent and Absolute 0095885
Method: Quantitative Flow Cytometry

Comments

Absolute CD4 count is sufficient for routine HIV monitoring

Panel includes – %CD4, absolute CD4, lymphocyte subset panel 2 information

Lymphocyte Subset Panel 3 - T-Cell Subsets (CD4 and CD8), Absolute Counts Only 0095853
Method: Quantitative Flow Cytometry

Comments

Absolute CD4 count is sufficient for routine HIV monitoring

Panel includes – absolute CD3, absolute CD4, absolute CD8, absolute CD4:CD8 ratio, lymphocyte subset panel 3 information

Lymphocyte Subset Panel 4 - T-Cell Subsets Percent and Absolute, Whole Blood 0095950
Method: Quantitative Flow Cytometry

Comments

Absolute CD4 count is sufficient for routine HIV monitoring

Panel includes – %CD3, %CD4, %CD8, absolute CD3, absolute CD4, absolute CD8, CD4:CD8 ratio, lymphocyte subset panel 4 information

HLA-B*57:01 for Abacavir Sensitivity 2002429
Method: Polymerase Chain Reaction/Fluorescence Monitoring

Comments

Identifies individuals at risk for abacavir sulfate hypersensitivity reaction (ABC HSR) prior to therapeutic treatment

Screening prior to reinitiation of treatment in individuals who have previously tolerated abacavir but whose HLA-B*57:01 status is unknown

Clinical sensitivity/specificity – for immunologically confirmed ABC HSR, 98% and 99%, respectively

Analytical sensitivity/specificity – 99% for prediction of HLA-B*57:01 carrier status by SNP rs2395029 genotyping

Diagnostic errors can occur due to rare sequence variations

Rare recombination events between HCP5 SNP rs2395029 and HLA-B*57:01 may occur

Nongenetic factors that may affect drug sensitivity are not identified

Testing for a genetic variant associated with ABC HSR does not replace the need for therapeutic drug or other clinical monitoring

CD4+ T-Cell Recent Thymic Emigrants (RTEs) 2010179
Method: Quantitative Flow Cytometry

Comments

Assesses thymic function in suspected severe combined immunodeficiency (SCID), DiGeorge syndrome and other T-cell immune deficiency disorders

Evaluates immune reconstitution during highly active antiviral therapy (HAART) in HIV patients and post chemotherapy and hematopoietic cell transplant

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]

HIV infection: detection, counseling, and referral. In: Sexually transmitted diseases treatment guidelines, 2010. Centers for Disease Control and Prevention. 1993 (Revised 2010 December). NGC: 008229

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 V, 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 D, 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

General References

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

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

Cohen M, Shaw G, McMichael A, Haynes B. Acute HIV-1 Infection. N Engl J Med. 2011; 364(20): 1943-54. PubMed

Cornett J, Kirn T. 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 C, Vullo V. The role of HIV-DNA testing in clinical practice. New Microbiol. 2010; 33(1): 1-11. PubMed

O'Conell R, Peel S. 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 V, Jaimes F, Delgado J, Rugeles C, Usuga X, Zapata W, Castaño M, Boasso A, Shearer G, Rugeles M. 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 H, Gray P, Storer T, Calof O, Woodhouse L, Singh A, Padero C, Mac R, Sinha-Hikim I, Shen R, Dzekov J, Dzekov C, Kushnir M, Rockwood A, Meikle A, Lee M, Hays R, 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 M, Mallory M, Wilson A, Dooley S, Hillyard D. 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 G, Slev P, 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 M, Hackett J, Holzmayer V, Hillyard D. 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 M, Konnick E, Phansalkar A, Hillyard D. 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 M, Wilson A, Hillyard D. 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 M, Perkins S, 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 N, Cataño J, Delgado J, Rugeles M, Montoya C. 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 S, Yee M, La'ulu S, Tosiello L, Straseski J. Multiple macroenzymes in a patient with AIDS: diagnosis using ultrafiltration. Am J Clin Pathol. 2014; 142(2): 266-8. PubMed

Medical Reviewers

Last Update: January 2016