Human Immunodeficiency Virus - HIV

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 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

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 1,2 Combined Antibodies with Reflex to HIV-1 Confirmation by Western Blot 0051160 Method: Enzyme Immunoassay/Western Blot	Screen for presence of HIV infection Screen for antibodies against HIV-1 and HIV-2
Human Immunodeficiency Virus 1 Antibody, Confirmation 0020284 Method: Western Blot	Confirmation after positive rapid point of care test If screening test is repeatedly reactive, the laboratory automatically performs Western Blot	Do not use for blood donor screening, associated re-entry protocols or for screening human cell, cellular and tissue-based products (HCT/P)
Lymphocyte Subset Panel 1 - CD4 Absolute Count Only 0095854 Method: Flow Cytometry	Monitor treatment efficacy Determine T-cell (CD4) levels to establish decision points for initiating P. jiroveci prophylaxis, antiviral therapy Order concurrently with HIV viral load monitoring tests		Other lymphocyte panels are available; see list of additional tests available
Human Immunodeficiency Virus 1, Genotyping 0055670 Method: Reverse Transcription Polymerase Chain Reaction/DNA Sequencing	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	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
Human Immunodeficiency Virus 1 RNA Quantitative Real-Time PCR 0055598 Method: Real-Time Polymerase Chain Reaction	Use in conjunction with clinical presentation as indicator of disease prognosis Use as aid in assessing viral response to antiretroviral treatment	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
Human Immunodeficiency Virus 1 RNA Quantitative bDNA 0020466 Method: Branched Chain DNA	Use with clinical presentation as indicator of disease prognosis Use as aid in assessing viral response to antiretroviral treatment	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
Human Immunodeficiency Virus 1 DNA PCR, Qualitative 0093061 Method: Polymerase Chain Reaction	Detects HIV-1 proviral DNA in infants (before 48 hours, 1-2 months and 3-6 months of age)	Do not use umbilical cord blood due to contamination with mother’s blood
Human Immunodeficiency Virus 2 Antibody with Reflex to Confirmation 0051250 Method: Enzyme Immunoassay/Immunoblot	Screen for presence of HIV-2 infection in patient with epidemiologic link to Africa		Repeatedly reactive EIA results will be confirmed by immunoblot

Additional Tests Available

Click the plus sign to expand the table of additional tests.

Test Name and Number	Comments
Human Immunodeficiency Virus 2 Antibody Confirmation by Immunoblot 0093272 Method: Immunoblot	Confirm positive screening results
Human Immunodeficiency Virus 1 Antibody with Reflex to Confirmation by Western Blot 0051154 Method: Enzyme Immunoassay/Western Blot	Screen for presence of HIV-1 infection
Human Immunodeficiency Virus1 RNA Quantitative Real-Time PCR with Reflex to Genotyping 0051660 Method: Real-Time Polymerase Chain Reaction	Panel test 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 Human Immunodeficiency Virus 1 Genotyping 0051664 Method: Branched Chain DNA/Genotyping	Panel test Use with clinical presentation as an indicator of disease prognosis and assess viral response to antiretroviral treatment
Lymphocyte Subset Panel 2 - CD4 Percent & Absolute 0095885 Method: Flow Cytometry
Lymphocyte Subset Panel 3 - T-Cell Subsets (CD4 & CD8), Absolute Counts Only 0095853 Method: Flow Cytometry
Lymphocyte Subset Panel 4 - T-Cell Subsets Percent & Absolute, Whole Blood 0095950 Method: Flow Cytometry
Lymphocyte Subset Panel 5 - Total Lymphocyte Enumeration 0095892 Method: Flow Cytometry
Lymphocyte Subset Panel 6 - Total Lymphocyte Enumeration with CD45RA & CD45RO 0095862 Method: Flow Cytometry
Erythropoietin 0050227 Method: Chemiluminescent Immunoassay
HLA-B*5701 Genotyping 2002429 Method: Polymerase Chain Reaction/Fluorescence Monitoring	Determine susceptibility to Abacavir hypersensitivity