Clinical Background
Algorithm(s)
PDF algorithm(s) available at www.arupconsult.com.
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 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 Sooty Mangabeys.
Epidemiology
- Incidence - >5,000,000 annually infected worldwide
- Age - 18-30 years (peak)
- Sex - M>F
- Transmission
- Primarily via sexual contact (especially in men having sex with men)
- Parenterally and perinatally
- Tissue transplantation
- Blood-borne; not transmitted via saliva, insect vectors or household contacts
- Intravenous drug use
Organism
- Retroviridae family - includes HIV-1 and -2, and HTLV-1 and -2
- RNA single-stranded virus
- HIV-1 and HIV-2 are etiologic agents of acquired immunodeficiency syndrome (AIDS)
- HIV-1 accounts for the vast majority of all 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 to 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
- Resolves in a few days to a few weeks
- Clinical latency - absence of clinical symptoms; viremia symptoms have cleared
- AIDS - progression of HIV in treated or untreated patients
- CD4+ <2,000 cells/µL
- Opportunistic infections - viral, bacterial, fungal
- Malignancies - Kaposi sarcoma, non-Hodgkin lymphoma (NHL), invasive cervical cancer, primary brain NHL
- Chronic metabolic complications - dyslipidemia, impaired glucose tolerance, lipodystrophy
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
See Also
Refer to Human Immunodeficiency Virus at http://www.arupconsult.com for list of references
Diagnosis
- Indications for testing - routine HIV screening is currently recommended in all adult patients in the U.S.
- Early diagnosis is crucial to institute highly active antiretroviral therapy (HAART)
- Reduces risk of devastating complications of full-blown AIDS
- Prevents further spread of HIV
- Antibodies detected approximately 22 to 27 days after acute infection
- Laboratory testing
- Rapid screening tests are newly available as point-of-care testing (HIV 1/2 STAT-PAK™, Multispot HIV-1/HIV-2, OraQuick ADVANCE®, Reveal®, OraQuick Rapid HIV-1, SURE CHECK® HIV 1/2, Unigold Recombigen®)
- Overall sensitivity and specificity >99%
- Rapid tests are not positive for 3-5 weeks after exposure
- If not using rapid screening tests, initial testing should be HIV-1 and -2 antibody confirmed by Western Blot
- Requires 3-5 weeks after exposure for a positive test result
- Refer to HIV Testing in Adults and HIV Testing in Infants Testing Algorithms
- Refer to human immunodeficiency virus 1, antiretroviral drug resistance testing for antiretroviral drugs genotyping analysis
Tests generally appear in the order most useful for common clinical situations
| Test name: Human Immunodeficiency Virus 1,2 Combined Antibodies with Reflex to HIV-1 Confirmation by Western Blot |
| ARUP #: 0051160 |
| Methodology: Enzyme Immunoassay/Western Blot |
| Use: Screen for presence of HIV infection Screen for antibodies against HIV-1 and HIV-2 |
| Test name: Human Immunodeficiency Virus 1 Antibody, Confirmation |
| ARUP #: 0020284 |
| Methodology: Western Blot |
| Use: Confirmation after positive rapid point of care test If screening test is repeatedly reactive, the laboratory automatically performs Western Blot |
| Limitations: Do not use for blood donor screening, associated re-entry protocols or for screening human cell, cellular and tissue-based products (HCT/P) |
| Test name: Lymphocyte Subset Panel 1 - CD4 Absolute Count Only |
| ARUP #: 0095854 |
| Methodology: Flow Cytometry |
| Use: Determine T-cell (CD4) baseline levels to establish decision points for initiating P. jiroveci prophylaxis, antiviral therapy, and monitoring treatment efficacy Order concurrently with HIV viral load monitoring tests |
| Follow-up: Other lymphocyte panels are available; see list of additional tests available |
| Test name: Human Immunodeficiency Virus 1, Genotyping |
| ARUP #: 0055670 |
| Methodology: Reverse Transcription Polymerase Chain Reaction/DNA Sequencing |
| Use: Detect changes in the viral genome that are associated with drug resistance Use in conjunction with CD4 measurement to monitor treatment efficacy Test requires specimens with HIV-1 RNA plasma levels of >1,000 copies/mL |
| Limitations: Treatment failure can be caused by factors other than drug resistance; therefore, the interpretation of resistance genotyping results must be done in conjunction with other clinical and laboratory information Comparisons between assays performed in different laboratories are not recommended since no method standardization exists among HIV-1 drug resistance testing Results from different test methods/algorithms may provide different resistance interpretation Absence of resistance mutations does not rule out the presence of reservoirs of resistant viruses that cannot be detected by these tests Some 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 that are less than approximately 20% of the total population |
| Test name: Human Immunodeficiency Virus 1 RNA Quantitative Real-Time PCR |
| ARUP #: 0055598 |
| Methodology: Real-Time Polymerase Chain Reaction |
| Use: Use in conjunction with clinical presentation as indicator of disease prognosis Use as aid in assessing viral response to antiretroviral treatment |
| Limitations: An interpretation of "Not Detected" does not rule out the presence of inhibitors in the patient specimen or HIV-1 virus RNA concentrations below the level of detection of the assay |
| Test name: Human Immunodeficiency Virus 1 RNA Quantitative bDNA |
| ARUP #: 0020466 |
| Methodology: Branched Chain DNA |
| Use: Use with clinical presentation as indicator of disease prognosis Use as aid in assessing viral response to antiretroviral treatment |
| Limitations: An interpretation of "Not Detected" does not rule out the presence of inhibitors in the patient specimen or HIV-1 virus RNA concentrations below the level of detection of the assay; low positive values may occasionally be seen in specimens from patients who are uninfected |
| Test name: Human Immunodeficiency Virus 1 DNA PCR, Qualitative |
| ARUP #: 0093061 |
| Methodology: Polymerase Chain Reaction |
| Use: Detects HIV-1 proviral DNA in infants (before 48 hours, 1-2 months and 3-6 months of age) |
| Limitations: Do not use umbilical cord blood due to contamination with mother’s blood |
| Test name: Human Immunodeficiency Virus 2 Antibody with Reflex to Confirmation |
| ARUP #: 0051250 |
| Methodology: Enzyme Immunoassay/Immunoblot |
| Use: Screen for presence of HIV-2 infection in patient with epidemiologic link to Africa |
| Follow-up: Repeatedly reactive EIA results will be confirmed by immunoblot |
Additional Tests Available
| Test name: Human Immunodeficiency Virus 2 Antibody Confirmation by Immunoblot |
| ARUP #: 0093272 |
| Methodology: Immunoblot |
| Comments: Confirm positive screening results |
| Test name: Human Immunodeficiency Virus 1 Antibody with Reflex to Confirmation by Western Blot |
| ARUP #: 0051154 |
| Methodology: Enzyme Immunoassay/Western Blot |
| Comments: Screen for presence of HIV-1 infection |
| Test name: Human Immunodeficiency Virus 1 RNA Quantitative Real-Time PCR with Reflex to Genotype |
| ARUP #: 2002689 |
| Methodology: Real-Time Polymerase Chain Reaction |
| Comments: Panel test Use with clinical presentation as an indicator of disease prognosis and assess viral response to antiretroviral treatment |
| Test name: Human Immunodeficiency Virus 1 RNA Quantitative bDNA with Reflex to Genotype |
| ARUP #: 2002688 |
| Methodology: Branched Chain DNA/Genotyping |
| Comments: Panel test Use with clinical presentation as an indicator of disease prognosis and assess viral response to antiretroviral treatment |
| Test name: Lymphocyte Subset Panel 2 - CD4 Percent & Absolute |
| ARUP #: 0095885 |
| Methodology: Flow Cytometry |
| Comments: For routine HIV monitoring, the absolute CD4 count is sufficient |
| Test name: Lymphocyte Subset Panel 3 - T-Cell Subsets (CD4 & CD8), Absolute Counts Only |
| ARUP #: 0095853 |
| Methodology: Flow Cytometry |
| Comments: For routine HIV monitoring, the absolute CD4 count is sufficient |
| Test name: Lymphocyte Subset Panel 4 - T-Cell Subsets Percent & Absolute, Whole Blood |
| ARUP #: 0095950 |
| Methodology: Flow Cytometry |
| Comments: For routine HIV monitoring, the absolute CD4 count is sufficient |
| Test name: Lymphocyte Subset Panel 5 - Total Lymphocyte Enumeration |
| ARUP #: 0095892 |
| Methodology: Flow Cytometry |
| Comments: For routine HIV monitoring, the absolute CD4 count is sufficient |
| Test name: Lymphocyte Subset Panel 6 - Total Lymphocyte Enumeration with CD45RA & CD45RO |
| ARUP #: 0095862 |
| Methodology: Flow Cytometry |
| Comments: For routine HIV monitoring, the absolute CD4 count is sufficient |
| Test name: Erythropoietin |
| ARUP #: 0050227 |
| Methodology: Chemiluminescent Immunoassay |
| Comments: For routine HIV monitoring, the absolute CD4 count is sufficient |
| Test name: HLA-B*5701 Genotyping |
| ARUP #: 2002429 |
| Methodology: Polymerase Chain Reaction/Fluorescence Monitoring |
| Comments: Determine susceptibility to Abacavir hypersensitivity |
Medical Reviewers
Hillyard, David R., MD. Medical Director, Molecular Infectious Diseases at ARUP Laboratories; Professor of Pathology, University of Utah
Reimer , Larry G., MD. Medical Director, Microbiology, Veteran's Affairs Hospital; Professor of Pathology and Associate Dean for Curriculum and GME, University of Utah School of Medicine
Slev, Patricia R., PhD. Medical Director, Serological Hepatitis/Retrovirus at ARUP Laboratories; Assistant Professor of Pathology (Clinical), University of Utah
Comprehensive Review: November 2009
Last Update: February 2010 Screening
- Centers for Disease Control recommends
- 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
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
