Human Immunodeficiency Virus - HIV

Key Points

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.

• HIV Clinical Symptoms by Stage

  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 to distinguish acute HIV from other viral illnesses Latency period without symptoms   Lasts 2-8 years Early chronic infection phase Persistent fever Diarrhea Adenopathy Chronic oral and cutaneous conditions End stage disease (AIDS) CD4+ <200 cells/µL Opportunistic infections – viral, bacterial, fungal Malignancies – Kaposi sarcoma, non-Hodgkin lymphoma (NHL), invasive cervical cancer, primary brain lymphoma Chronic metabolic complications – dyslipidemia, impaired glucose tolerance, lipodystrophy, wasting

  Indications for Laboratory Testing

  At-risk patients Symptoms of infection Recent exposure to HIV-infected individual History of high-risk behaviors Pregnancy Infant born to HIV-positive mother

  Guideline recommendations for HIV screening CDC, 2010 (endorsed by ACOG, ACP) All patients ages 13-64 years - in all health care settings Patients at high risk for HIV - annual screening Pregnant women - routine prenatal screening USPSTF, 2013 All adolescents and adults ages 15 to 65 years At-risk younger adolescents and older adults  Pregnant women - including those who present in labor who are untested and whose HIV status is unknown

  Recommended Laboratory Testing

  Recommended Laboratory Testing Refer to testing algorithms New CDC Proposed HIV Diagnostic Algorithm Human Immunodeficiency Virus in Adults Testing algorithm
  Rapid Screening Test (Point-of-Care)
  	Test Description Can be performed in point-of-care settings Provides results within minutes Limitation Not positive until 3-5 weeks after exposure Follow-up Refer to Human Immunodeficiency Virus in Adults Testing algorithm Preliminary positive results must be confirmed with Western blot
  4th Generation HIV-1, HIV-2 Antibody/p24 Antigen  Screen
  ARUP available test Human Immunodeficiency Virus (HIV) Combo Antigen/Antibody (HIV-1/O/2) by ELISA, with Reflex to HIV-1/HIV-2 Antibody Differentiation  2007980	Test Description 4th generation qualitative screen simultaneously detects HIV-1 p24 antigen and antibodies to HIV types 1 and 2 Discriminates between HIV-1 and HIV-2 antibodies Reflex Pattern If HIV-1,2 combo antigen/antibodies screen is repeatedly reactive, confirmation by antibody differentiation test (Multispot) is added This test reflects the multi-test algorithm proposed by the CDC and adopted by the Clinical Laboratory Standards Institute (CLSI) for diagnosis of HIV Follow-up Refer to CDC Proposed HIV Diagnostic Algorithm Indeterminate antibody differentiation testing requires HIV-1 NAAT testing using a separate specimen
  ARUP available test Human Immunodeficiency Virus (HIV) Combo Antigen/Antibody (HIV-1/O/2) by ELISA, with Reflex to HIV-1 Antibody Confirmation by Western Blot 2006526	Test Description 4th generation qualitative screen simultaneously detects HIV-1 p24 antigen and antibodies to HIV types 1 and 2 Antibody/antigen combination testing reduces diagnostic window by 5 to 7 days when compared to antibody only assay Reflex Pattern If HIV-1,2 combo antigen/antibody screen is repeatedly reactive, confirmation by Western blot is added Limitation Does not distinguish between the presence of HIV-1 p24 antigen, HIV-1 antibody, and HIV-2 antibody Follow-up Refer to the 4th Generation Antigen/Antibody Combo test section of the Human Immunodeficiency Virus in Adults Testing algorithm If Western blot confirmation is indeterminate or negative, proceed to NAAT (viral DNA) testing
  3rd Generation HIV-1, HIV-2 Antibody Screen
  ARUP available test Human Immunodeficiency Virus Types 1 and 2 (HIV-1, HIV-2) Antibodies with Reflex to HIV-1 Antibody Confirmation by Western Blot 2005377 Also available – HIV-1 only antibody screen with Western blot confirmation (Human Immunodeficiency Virus Type 1 [HIV-1] with Reflex to Human Immunodeficiency Virus Type 1 [HIV-1] Antibody Confirmation by Western Blot 2005375 )	Test Description Qualitative test detects antibodies to HIV types 1 and 2 Reflex Pattern If HIV-1,2 antibodies screen is repeatedly reactive, confirmation by Western blot is added Limitation Not positive until 3-5 weeks after exposure Follow-up Refer to the 3rd Generation Antibody Only Immunoassay section of the Human Immunodeficiency Virus in Adults Testing algorithm If Western blot confirmation is Indeterminate - repeat testing in 4 weeks Negative – consider HIV-2 testing, if clinically indicated
  Confirmation test
  Western blot ARUP available test Human Immunodeficiency Virus Type 1 (HIV-1) Antibody Confirmation by Western Blot 0020284	Test Description Confirms HIV after preliminary positive rapid point-of-care test or HIV type 1 antibody screen If Western blot confirmation is Indeterminate - repeat testing in 4 weeks Negative – consider HIV-2 testing, if clinically indicated
  Follow-up testing for confirmed HIV
  HIV Quantitative PCR ARUP available test Human Immunodeficiency Virus 1 RNA Quantitative Real-Time PCR 0055598	Test Description Quantitative test Use When 4th generation testing determines HIV is positive but type is unclear To determine and monitor therapy in confirmed HIV cases
  HIV Qualitative ARUP available test Human Immunodeficiency Virus 1, PCR, Qualitative 0093061	Test Description Qualitative test detects HIV-1 proviral DNA in infants For initially positive test, recommend repeat testing at 1-2 months and 3-6 months of age to confirm diagnosis
  CD4 Lymphocyte Counts ARUP available test Lymphocyte Subset Panel  1 – CD4 Absolute Count Only 0095854	Test Description Quantitative test Absolute CD4 count is sufficient for routine HIV monitoring Order concurrently with HIV viral load testing for monitoring treatment and disease

Diagnosis

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

• CDC revised recommendations for HIV testing of adults, adolescents, and pregnant women in health-care settings
• Refer to
  • Key Points section for clinical symptoms, indications for testing, and available laboratory tests
  • HIV testing algorithms section
    • HIV Testing in Adults Algorithm
    • New CDC Proposed HIV Diagnostic Algorithm
    • HIV Testing in Infants Algorithm
• Refer to Human Immunodeficiency Virus 1, Antiretroviral Drug Resistance Testing for antiretroviral drugs genotyping analysis
  • Resistance testing recommended for treatment-naïve patients prior to initiating therapy and in all patients with treatment failure

Differential Diagnosis

• Pharyngitis
  • Streptococcal disease, group A
  • Epstein-Barr virus
  • Neisseria gonorrhoeae
  • Head and neck cancer
  • Viral pharyngitis
• Flu-like illness
  • Influenza virus
  • Parainfluenza
  • Respiratory viruses
  • Hantavirus
• AIDS-presenting infection (recurrent)
  • Cervical cancer
  • Cytomegalovirus
  • Herpes simplex virus
  • Isospora belli
  • Kaposi sarcoma
  • Lymphoma
  • Mycobacterium tuberculosis
  • Pneumocystis jirovecii
  • Toxoplasma gondii
  • Disseminated fungal infection
    • Histoplasma
    • Coccidioides
    • Candidiasis

Screening

Monitoring

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 – ~47,500 new HIV infections in 2010 (CDC)
• 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

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: Qualitative Immunoblot
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
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

Diagnostic Algorithm

  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

  New CDC Proposed HIV Diagnostic Algorithm