Human Immunodeficiency Virus - HIV

Diagnosis

Indications for Testing

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

Laboratory Testing

  • CDC recommendations for HIV testing
  • Rapid screening tests are available as point-of-care testing (HIV 1/2 STAT-PAK™, Multispot HIV-1/HIV-2, OraQuick ADVANCE®, Reveal G3®, Clearview® Complete HIV 1/2, Unigold Recombigen®)
    • Overall sensitivity and specificity >99%
    • Rapid tests are not positive until 3-5 weeks after exposure
    • Positive rapid tests should be confirmed with Western blot follow-up test
  • If not using rapid screening tests, initial testing should be HIV-1 and -2 antibodies confirmed by Western Blot
    • Requires 3-5 weeks after exposure for a positive test result
    • In patients at low risk for HIV-2, HIV-1 testing alone is sufficient
  • Fourth-generation combination antigen/antibody immunoassays detecting both p24 antigens and anti-HIV antibodies are available for use in the U.S.
    • Acute HIV infection should be considered in patients testing positive with a combined antigen/antibody screening immunoassay
    • PCR testing preferred over bDNA due to higher rate of false positives with bDNA
  • Refer to HIV Testing in Adults and HIV Testing in Infants algorithms
  • Refer to human immunodeficiency virus 1, antiretroviral drug resistance testing for antiretroviral drugs genotyping analysis
    • Resistance testing recommended in treatment-naïve patients prior to initiating therapy and in all patients with treatment failure

Differential Diagnosis

Screening

  • Centers for Disease Control recommendations (endorsed by ACOG, ACP)
    • HIV screening in all patients ages 13-64 who seek health care
    • Annual screening for high-risk patients
    • Routine screening as part of prenatal screen in pregnant females
  • AAFP and USPSTF do not recommend routine HIV testing in low-risk populations

Monitoring

  • Quantitative viral load and drug resistance testing allows for monitoring during treatment
  • The Public Health Service has recommended that T-helper cell (CD4) levels be monitored every 3-6 months in all HIV-infected persons

Clinical Background

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 – 22/100,000 (2006 U.S.)
  • 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
    • Approximately 30 billion virus particles produced in first weeks of infection

Clinical Presentation

  • Acute retroviral syndrome – fever, fatigue, rash, headache, lymphadenopathy, pharyngitis, myalgias, nausea, vomiting, diarrhea and night sweats
    • Develops 1-4 weeks after exposure
    • Symptoms are too vague and nonspecific to distinguish acute HIV from another viral illness unless high degree of clinical suspicion
  • Clinical latency – absence of clinical symptoms; viremia symptoms have cleared
  • AIDS – progression of HIV in treated or untreated patients

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
Test Name and Number Recommended Use Limitations Follow Up
Human Immunodeficiency Virus Types 1 and 2 (HIV-1, HIV-2) Antibodies with Reflex to Human Immunodeficiency Virus Type 1 (HIV-1) Antibody Confirmation by Western Blot 2005377
Method: Qualitative Chemiluminescent Immunoassay/Qualitative Western Blot

Screen for antibodies against HIV-1 and HIV-2

If test is reactive, confirmation will be made by Western Blot

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

Confirm HIV after positive rapid point-of-care test

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

Determine T-cell (CD4) baseline levels to establish decision points for initiating P. jiroveci prophylaxis, antiviral therapy, and for monitoring treatment efficacy

Order concurrently with HIV viral load monitoring

  

Other lymphocyte panels are available; see list of additional tests available, below
Human Immunodeficiency Virus 1 RNA Quantitative Real-Time PCR 0055598
Method: Quantitative Real-Time Polymerase Chain Reaction

Use in conjunction with clinical presentation as indicator of disease prognosis

Aids in assessing viral response to antiretroviral treatment

"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 RNA Quantitative bDNA 0020466
Method: Quantitative Branched Chain DNA

Use with clinical presentation as indicator of disease prognosis

Aids in assessing viral response to antiretroviral treatment

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

Low positive values may occasionally be seen in specimens from uninfected patients

  
Human Immunodeficiency Virus 1, PCR, Qualitative 0093061
Method: Qualitative Polymerase Chain Reaction

Detect HIV-1 proviral DNA in infants <48 hours old; repeat testing at 1-2 months and 3-6 months of age

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

  
Human Immunodeficiency Virus 2 Antibody with Reflex to Confirmation 0051250
Method: Qualitative Enzyme Immunoassay/Qualitative Immunoblot

Screen for HIV-2 infection in patient with epidemiologic link to Africa

  

Repeatedly reactive EIA results will be confirmed by immunoblot
Human Immunodeficiency Virus 1, Genotyping 0055670
Method: Reverse Transcription Polymerase Chain Reaction/Sequencing

Detect changes in the viral genome associated with drug resistance

Use in conjunction with CD4 measurement to monitor treatment efficacy

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 

Sequenced using the Viroseq™ HIV-1 Genotyping System; 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
 
 
Click the plus sign to expand the table of additional tests.
Test Name and NumberComments
Human Immunodeficiency Virus 2 Antibody Confirmation by Immunoblot 0093272
Method: Qualitative Immunoblot

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

Screen for presence of HIV-1 infection if HIV-1/HIV-2 combined antibody testing not available
Human Immunodeficiency Virus 1 RNA Quantitative Real-Time PCR with Reflex to Genotype 2002689
Method: Quantitative Real-Time Polymerase Chain Reaction/Sequencing

Panel includes Human Immunodeficiency Virus 1 RNA Quantitative Real-Time PCR and Human Immunodeficiency Virus 1, Genotyping

Use with clinical presentation as an indicator of disease prognosis and assess viral response to antiretroviral treatment
Human Immunodeficiency Virus 1 RNA Quantitative bDNA with Reflex to Genotype 2002688
Method: Quantitative Branched Chain DNA/Sequencing

Panel includes Human Immunodeficiency Virus 1 RNA Quantitative bDNA and Human Immunodeficiency Virus 1, Genotyping

Use with clinical presentation as an indicator of disease prognosis and assess viral response to antiretroviral treatment
Lymphocyte Subset Panel 2 - CD4  Percent and Absolute 0095885
Method: Quantitative Flow Cytometry

Absolute CD4 count is sufficient for routine HIV monitoring
Lymphocyte Subset Panel 3 - T-Cell Subsets (CD4 and CD8), Absolute Counts Only 0095853
Method: Quantitative Flow Cytometry
 Absolute CD4 count is sufficient for routine HIV monitoring
Lymphocyte Subset Panel 4 - T-Cell Subsets Percent and Absolute, Whole Blood 0095950
Method: Quantitative Flow Cytometry

Absolute CD4 count is sufficient for routine HIV monitoring
Lymphocyte Subset Panel 5 - Total Lymphocyte Enumeration 0095892
Method: Quantitative Flow Cytometry

Absolute CD4 count is sufficient for routine HIV monitoring
Lymphocyte Subset Panel 6 - Total Lymphocyte Enumeration with CD45RA and CD45RO 0095862
Method: Quantitative Flow Cytometry

Absolute CD4 count is sufficient for routine HIV monitoring
Erythropoietin 0050227
Method: Quantitative Chemiluminescent Immunoassay

Absolute CD4 count is sufficient for routine HIV monitoring
HLA-B*5701 Associated Variant Genotyping for Abacavir Sensitivity 2002429
Method: Polymerase Chain Reaction/Fluorescence Monitoring

Determine susceptibility to Abacavir hypersensitivity