Norm of Acquired Immune Deficiency Syndrome (AIDS) Evaluation Battery
Negative AIDS battery, nonreactive.
Antigen Detection by Serology. Negative for HIV antigens.
Antibody Detection. Negative for HIV antibodies.
|Lymphocyte Subset Enumeration
|OKT-4 cells (CD4)
|(<170 nmol/L, SI units)
Usage of Acquired Immune Deficiency Syndrome (AIDS) Evaluation Battery
Used often in combination with cultures and for confirmation of opportunistic infection to help diagnose acquired immune deficiency syndrome (AIDS).
Description of Acquired Immune Deficiency Syndrome (AIDS) Evaluation Battery
AIDS is caused by human immunodeficiency virus (HIV), a cytoplasmic retrovirus of the human T-cell leukemia and lymphoma virus family that reproduces and infects, even when antibodies against the virus are present. There are several strains. All attack a subgroup of T lymphocytes known as “helper” T cells, which are important in cell-mediated immunity. AIDS causes immunosuppression and susceptibility to infection with opportunistic organisms such as Pneumocystis carinii, Candida albicans, Cryptococcus neoformans, Mycobacterium, Toxoplasma gondii, Cryptosporidium, and herpes simplex. The predominant modes of transmission of HIV are believed to be (1) direct contact between the blood of an uninfected person and the blood of an infected person and (2) sexual and body fluid transmission. The incubation period may be as short as 6 days and as long as several years.
HIV is now the leading cause of death in men 25–40 years of age, the sixth leading cause of death worldwide in adolescent males 15–24 years, and the fourth leading cause of death in women 25–44 years. It is estimated that 42 million people worldwide, including 980,000 North Americans, are HIV infected (WHO, 2002). In 2002 3.1 million people died of HIV/AIDS and AIDS-related diseases.
A person may be infected with the human immunodeficiency virus for several years without becoming symptomatic when the virus enters a nonreplicating latent period. When the virus begins actively replicating, the person may develop AIDS. At 2–6 weeks after infection, clients may develop a viral-like illness consisting of fever, sweats, fatigue, malaise, lymphadenopathy, sore throat, and sometimes splenomegaly. Clients may remain asymptomatic for months to years, depending on the progression of the disease.
In 1993 the CDC expanded the AIDS surveillance case definition to include all HIV-infected persons who have <200 CD4+ T lymphocytes/μL or a CD4+ T-lymphocyte percentage of total lymphocytes <14. This expansion includes the addition of three clinical conditions: pulmonary tuberculosis, recurrent pneumonia, and invasive cervical cancer. As the number of CD4+ T lymphocytes decreases, the risk and severity of opportunistic illnesses increase. Measures of CD4+ T lymphocytes are used to guide clinical and therapeutic management of HIV-infected persons. Antimicrobial prophylaxis and antiretroviral therapies have been shown to be most effective within certain levels of immune dysfunction.
The AIDS evaluation battery results are not usually performed unless a rapid screening test is preliminarily positive (see OraQuick rapid HIV tests—Specimen ). The tests in this battery are often considered with other diagnostic tests for opportunistic infection such as body fluid culture and cytology, central nervous system tomography, bronchoscopy, and biopsy to complete the clinical picture description before diagnosis is made. The AIDS evaluation battery comprises the following tests: blood and body fluid cultures, antigen detection by serology, antibody detection, confirmatory antibody detection methods, and tests for immunologic status evaluation and beta2-microglobulin. No test that by itself confirms HIV infection has yet been developed.
Blood and body fluid cultures have been found to show positive results in some persons soon after infection with HIV. Although difficult to do, isolation of HIV has been accomplished in concentrated peripheral blood lymphocytes and body fluids. However, a negative result does not rule out infection (see Blood culture—Blood ; Body fluid, Routine—Culture ).
Antigen detection by serology methods may be positive for the viral antigen (frequently p24 core protein, HIV core antigen) from 1–2 weeks up to about 1 month after infection with the virus. The antigen is detectable during acute (initial) infection, undetectable as the virus becomes latent, and again detectable as the infection progresses. The enzyme-linked immunosorbent assay (ELISA) is used for screening for HIV. Detection of HIV antibody by ELISA must be confirmed by Western blot. Alternative diagnosis may be made by viral culture, by antigen detection, or by HIV DNA or RNA polymerase chain reaction (PCR). Quantitative virology using quantitative RNA PCR or branched-chain DNA (bDNA) has become a popular method to access viral load in staging clients or for therapeutic monitoring. Maternal antibodies may be present in infants until 18 months of age; therefore CD4 counts, viral culture, or PCR followed by antibody detection after 18 months must be performed to diagnose HIV in infants.
Studies indicate that the frequency of false-positive tests in a low-prevalence population with both the ELISA and Western blot is about 0.0007%, and the frequency of false-negative results in a high-prevalence population is about 0.3%. The usual cause of false-negative tests is testing in the time between transmission and seroconversion, a period that rarely lasts longer than 3 months. When the results are positive, it is recommended that repeat testing be done for those with no likely risk factors, and those who report positive results from an anonymous test site. Periodic tests are suggested for clients with negative results who continue to practice high-risk behaviors.
Confirmatory antibody detection methods include the Western blot, immunofluorescence, radioimmunoprecipitation, and ELISA tests that detect antibodies to genetically engineered HIV proteins. The Western blot and immunofluorescence methods have similar sensitivities. Immunofluorescence results are obtained more quickly but are less reliable than those of the Western blot. Radioimmunofluorescence is more sensitive than the Western blot but is not widely used because of the technical difficulty of the procedure. Newer ELISA tests are able to pinpoint the specific HIV antibody present in serum when one incubates the serum first with specific HIV proteins and then a tagged, anti-immunoglobulin enzyme and measures the amount of substrate hydrolyzed by the antigen-antibody reaction.
Quantitative testing for HIV p24 antigen may provide a surrogate marker for disease progression: however, this antigen usually disappears from the blood during the asymptomatic phase. The PCR for the detection of HIV DNA or RNA has been extensively used in the research setting and proven extremely valuable.
A few alternative detection methods are actively being studied. Two home test kits for HIV detection (Direct Access Diagnostics and ChemTrak) are under review by the FDA. There are currently two FDA-licensed rapid tests: SUDS (Murex) and Recombigen latex agglutination assay (Cambridge Biotech). These tests are attractive for use in areas such as emergency departments, autopsy areas, and STD clinics.
Tests for immunologic status evaluation include lymphocyte subset enumeration, T-lymphocyte and B-lymphocyte subset assays, and skin tests with known antigens for persons with infections such as Candida or mumps; these often demonstrate normal results until the later stages of infection. As T-lymphocyte helper cells (OKT-4 cells) become infected by the human immunodeficiency virus, their numbers decrease. Levels of suppressor T cells (OKT-8 cells) may remain normal or increase as virus activity progresses. Lymphocyte counts decrease as immune function decreases. False-negative results from known antigen skin tests indicate that the client's immune function is compromised.
Beta2-microglobulin is an amino acid peptide component of lymphocyte HLA complexes that increases in the serum in inflammatory conditions and when lymphocyte turnover increases, as when T-lymphocyte helper (OKT-4) cells are attacked by HIV. Rising levels may also be caused by conditions other than HIV. Although beta2-microglobulin levels usually rise with HIV infection, the levels do not always correlate with the stages of the infection (see Beta2-microglobulin — Blood and 24-hour urine).
CD4+ T-lymphocyte test results alone should not be used as a surrogate marker for HIV or AIDS. A low CD4+ T-lymphocyte count without a positive HIV test result will not be reportable, since other conditions may be the cause. Health care providers must ensure that persons who have a CD4+ T-lymphocyte count of <200/μL are HIV-infected before initiating treatment for HIV disease.
Professional Considerations of Acquired Immune Deficiency Syndrome (AIDS) Evaluation Battery
Consent form IS required because of area-specific legal regulations. Testing should be voluntary with appropriate counseling before and after informed consent.
- Clarify the type of tube needed for lymphocyte subset enumeration if the Becton Dickinson Immunocytology Systems method is not used.
- Tube: Red topped, red/gray topped, gold topped, or lavender topped.
- Antigen detection by serology, antibody detection, and confirmatory antibody detection method: Draw a 5-mL venous blood sample.
- Lymphocyte subset enumeration (Becton Dickinson Immunocytology Systems method): Completely fill two lavender-topped tubes with venous blood. Label one tube for complete blood count and the other tube for lymphocyte subset enumeration.
- Beta2-microglobulin: Draw a 10-mL venous blood sample in a lavender-topped tube.
- Either leave reusable equipment in the client's room or dispose of the equipment in the room.
Client and Family Teaching
- Explain the purpose of the test, the procedure for collection, and the results to the client.
- Two days are required for the Western blot.
- Assess client understanding of safe sex practices and provide counseling as needed.
- CDC National AIDS hotline: 1-800-342-AIDS.
Factors That Affect Results
- Antibody results may be negative up to 35 months after infection because of viral latency.
- False-positive ELISA results may be caused by HLA antibody reaction with specific proteins in certain test kits. False-negative ELISA results may occur in a small proportion of clients with HIV-1 infection and in some children infected with HIV in utero.
- Falsely depressed lymphocyte counts may be caused by steroids and general anesthetics.
- Beta2-microglobulin results are invalidated if the person has undergone a scan involving the administration of radioactive dyes within 1 week before the test.
- Legal restrictions exist and vary regarding HIV testing and reporting of results.
- Demonstration of homogeneous B or T lymphocytes is helpful in prognosis and therapeutic planning of malignant lymphoproliferative disorders.
- In a recent study at the National Institute of Allergy and Infectious Diseases, in a small number of HIV-infected clients, infusions of an immune system protein significantly increased levels of the infection-fighting white blood cells normally destroyed during HIV infection.
- Begin antiretroviral therapy before CD4 cells drop below 200/μL.
- Progression of cytomegalovirus retinitis occurs in 17% with low CD4 cell count.
- The Genie assay is faster, less costly, and yields fewer indeterminate results in detecting HIV-1 antibodies than the Western blot method.
- Miller V et al. (2002) showed that independent predictors to progression include CD4 <50 cells/mm3, Pneumocystis carinii pneumonia prophylaxis, low hemoglobin levels, and high virus load.
- Total viral load can sometimes be assessed to help monitor the impact of treatment.
- HIV testing should be performed at baseline, 4, 12, and 24 weeks.
- See also T- and B-lymphocyte subset assay—Blood ; Beta2-microglobulin—Blood and 24-hour urine ; Oral mucosal transudate—Specimen ; and OraQuick rapid HIV test—Specimen.