Take Our Survey

Interpretive Handbook

Test 62421 :
HIV-1 and HIV-2 Antibody Confirmation and Differentiation, Serum

Clinical Information Discusses physiology, pathophysiology, and general clinical aspects, as they relate to a laboratory test

AIDS is caused by 2 known types of HIV. HIV type 1 (HIV-1) is found in patients with AIDS, AIDS-related complex, and asymptomatic infected individuals at high risk for AIDS. The virus is transmitted by sexual contact, by exposure to infected blood or blood products, or from an infected mother to her fetus or infant. HIV type 2 (HIV-2) infection is endemic only in West Africa, and it has been identified in individuals who had sexual relations with individuals from that geographic region. HIV-2 is similar to HIV-1 in viral morphology, overall genomic structure, and its ability to cause AIDS.

 

Antibodies against HIV-1 and HIV-2 are usually not detectable until 6 to 12 weeks following exposure and are almost always detectable by 12 months. They may fall to undetectable levels (ie, seroreversion) in the terminal stage of AIDS when the patient's immune system is severely depressed.

 

Routine serologic screening of patients at risk for HIV-1 or HIV-2 infection usually begins with a HIV-1/-2 antigen and/or antibody screening test, which may be performed by various FDA-approved assay methods, including rapid HIV antibody tests, enzyme immunoassays, chemiluminescent immunoassays. In testing algorithms that begin with these methods, supplemental or confirmatory testing should be requested only for specimens that are repeatedly reactive by these methods according to assay manufacturers' instructions for use.

Useful For Suggests clinical disorders or settings where the test may be helpful

Confirmation and differentiation of HIV-1 and HIV-2 antibodies in serum specimens that show reactive results with third- (HIV-1/-2 antibody only) and fourth- (HIV antigen and antibody) generation HIV serologic assays

Interpretation Provides information to assist in interpretation of the test results

Negative results for both HIV-1 and HIV-2 antibodies usually indicate the absence of HIV-1 and HIV-2 infection. However, in patients with reactive initial combined HIV-1/-2 antigen and antibody test results, such negative results do not rule-out acute or early HIV infection. If acute or early HIV infection is suspected, detection of HIV-1 RNA (HIVDQ / HIV-1 RNA Detection and Quantification, Plasma) and/or HIV-2 DNA/RNA (FHV2Q / HIV-2 DNA/RNA Qualitative Real-Time PCR) is recommended, based on patient’s clinical and epidemiologic exposure history.

 

Positive HIV-1 antibody, but negative HIV-2 antibody results, indicates the presence of HIV-1 infection. Together with reactive initial combined HIV-1/-2 antigen and antibody test results, individuals with such results are presumed to have HIV-1 infection. Verification of a first-time positive test result is recommended for the diagnosis of HIV-1 infection. Additional testing with a newly submitted plasma specimen for HIV-1 RNA (HIVDQ) is recommended to verify and confirm the diagnosis of HIV-1 infection prior to initiating antiretroviral treatment.

 

Positive HIV-1 antibody, but indeterminate HIV-2 antibody results, indicates the presence of HIV-1 infection, with probable cross-reactivity of HIV-1 antibodies with HIV-2 antigens on the assay strip. Verification of a first-time positive test result is recommended for the diagnosis of HIV-1 infection. Submit a plasma specimen for detection of HIV-1 RNA (HIVDQ). However, such result patterns may rarely indicate early HIV-2 infection (ie, HIV-2 coinfection) in HIV-1-infected individuals. For individuals at risk for HIV-2 infection (based on epidemiologic exposure history), a plasma specimen should be submitted also for HIV-2 DNA/RNA (FHV2Q).

 

Indeterminate HIV-1 antibody, but negative HIV-2 antibody results, suggest either very early HIV-1 infection (in individuals with risk factors) or the presence of nonspecific cross-reactivity between the patients' specimens and HIV-1 antigens on the assay strip. If patient has known risk factors for HIV-1 infection, a new specimen should be submitted for HIV-2 serologic testing (HIV2 / HIV-2 Antibody Evaluation, Serum or HIV2M / HIV-2 Antibody Screen, Serum) or HIV-2 DNA/RNA (FHV2Q).

 

Negative HIV-1 antibody, but indeterminate HIV-2 antibody results, suggests either very early HIV-2 infection (in individuals with risk factors) or presence of nonspecific cross-reactivity between the patients' specimens and HIV-2 antigens on the assay strip. If patient has known risk factors for HIV-2 infection (based on patient's clinical and epidemiologic history), a new specimen should be submitted for HIV-2 serologic testing (HIV2 or HIV2M) or HIV-2 DNA/RNA (FHV2Q).

 

Positive results for both HIV-1 and HIV-2 antibodies suggest probable the presence of HIV-1 and HIV-2 coinfection. However, such results may be rarely due to: a) HIV-1 infection with HIV-2 antibody cross-reactivity; or b) HIV-2 infection with HIV-1 antibody cross-reactivity (eg, absence of HIV-1 p24 and p31 bands). Verification of a first-time positive test result is recommended for the diagnosis of HIV infection. Based on patient's clinical and epidemiologic history, plasma specimens should be submitted for detection of HIV-1 RNA (HIVDQ) and/or HIV-2 DNA/RNA (FHV2Q).

                       

Indeterminate results for both HIV-1 and HIV-2 antibodies indicate either very early HIV infection (in individuals with risk factors) or the presence of nonspecific cross-reactivity between the patients' specimens and HIV antigens on the assay strip. Nonspecific cross-reactivity may be due to recent non-HIV infections, hypergammaglobulinemic states, connective tissue disorders, or pregnancy (alloantibodies). For individuals at risk for HIV infection, plasma specimens should be submitted for detection of HIV-1 RNA (HIVDQ) and/or HIV-2 DNA/RNA (FHV2Q), depending on the epidemiologic exposure history.

 

Negative HIV-1 antibody, but positive HIV-2 antibody results, indicates the presence of HIV-2 infection. Together with a reactive initial HIV-1/-2 antigen and antibody screening test results, individuals with such results are presumed to have HIV-2 infection. Additional testing with a newly submitted plasma specimen for HIV-2 DNA/RNA (FHV2Q) is recommended to verify and confirm the diagnosis of HIV-2 infection prior to initiating antiretroviral treatment.

 

Reactive HIV-1 antibody, but positive HIV-2 antibody results, usually indicates the presence of HIV-2 infection with HIV-1 antibody cross-reactivity (eg, presence of only HIV-1 gp41 and/or gp160 band). However, such results may be rarely due to HIV-1 and HIV-2 coinfection. Verification of a first-time positive test result is recommended for the diagnosis of HIV-2 infection, by submitting a new specimen for HIV-2 serologic testing (HIV2 or HIV2M) or a plasma specimen for HIV-2 DNA/RNA (FHV2Q). If the patient is at risk for HIV-1 infection (based on patient's clinical and epidemiologic history), a plasma specimen should be submitted also for detection of HIV-1 RNA (HIVDQ).

 

Indeterminate HIV-1 antibody, but positive HIV-2 antibody results, indicates the presence of HIV-2 infection, with probable cross-reactivity of HIV-2 antibodies with HIV-1 antigens on the assay strip. Verification of a first-time positive test result is recommended for the diagnosis of HIV-2 infection, by submitting a plasma specimen for (FHV2Q). However, such result patterns may rarely indicate early HIV-1 infection (ie, HIV-1 coinfection) in HIV-2-infected individuals. For individuals at risk for HIV-1 infection, (based on epidemiologic exposure history), plasma specimen should be submitted also for detection of HIV-1 RNA (HIVDQ).

 

See HIV Testing Algorithm (Fourth Generation Screening Assay) Including Follow-up of Reactive HIV Rapid Serologic Test Results in Special Instructions.

Cautions Discusses conditions that may cause diagnostic confusion, including improper specimen collection and handling, inappropriate test selection, and interfering substances

This test is not offered as a screening test for HIV infection in symptomatic or asymptomatic individuals. It is not to be used as a screening or confirmatory test for blood donor specimens.

 

This test is not offered for maternal or newborn HIV screening for specimens originating in New York State.

 

This test is not suitable for follow-up testing of patients with reactive results from any rapid HIV tests. These patients should be tested subsequently with laboratory-based HIV antigen and antibody combination immunoassays, such as HIVCO / HIV-1 and HIV-2 Antigen and Antibody Evaluation, Serum at Mayo Medical Laboratories, per the latest CDC recommended HIV testing algorithm.

 

A negative result for both HIV-1 and HIV-2 antibodies does not rule-out acute HIV infection. If acute HIV-1 infection is suspected, detection of HIV-1 RNA (HIVDQ / HIV-1 RNA Detection and Quantification, Plasma) is recommended. For patients at risk for HIV-2 infection (eg, having lived in West Africa or have sexual partners from West Africa), testing for HIV-2 DNA/RNA (FHV2Q / HIV-2 DNA/RNA Qualitative Real-Time PCR) is recommended.

 

All initially positive supplemental or confirmatory HIV test results should be verified by submitting a second specimen for repeat testing. Such positive HIV test results are required under laws in many states in the United States to be reported to the departments of health of the respective states where the patients reside.

 

Screening, supplemental, or confirmatory serologic tests for HIV-1 or HIV-2 antibodies cannot distinguish between active neonatal HIV infection and passive transfer of maternal HIV antibodies in infants during the postnatal period (up to 18 months). Diagnosis of HIV infection in newborns and infants up to 18 months should be made by virologic tests, such as detection of HIV RNA (HIVDQ / HIV-1 RNA Detection and Quantification, Plasma).

 

Participation in the recipients of HIV-1 vaccine (eg, participants in HIV-1 vaccine study trials) may develop vaccine-specific antibodies that may cross-react with this test and yield to the vaccine giving a positive, indeterminate, or unreadable HIV-1 antibody result, while they may or may not be infected with HIV-1.

 

Assay performance characteristics have not been established for the following specimen characteristics:

-Heat-inactivated specimens

-Cadaveric specimens

-Presence of particulate matter

Reference Values Describes reference intervals and additional information for interpretation of test results. May include intervals based on age and sex when appropriate. Intervals are Mayo-derived, unless otherwise designated. If an interpretive report is provided, the reference value field will state this.

Negative

 

See HIV Serologic Interpretive Guide in Special Instructions for further interpretive information.

Clinical References Provides recommendations for further in-depth reading of a clinical nature

1. Centers for Disease Control and Prevention and Association of Public Health Laboratories. Laboratory testing for the diagnosis of HIV infection: Updated recommendations. June 27, 2014. Available at: http://stacks.cdc.gov/view/cdc/23447

2. Malloch L, Kadivar K, Putz J, et al: Comparative evaluation of the Bio-Rad Geenius HIV-1/2 confirmatory assay and the Bio-Rad Multispot HIV-1/2 rapid test as an alternative differentiation assay for CLSI M53 algorithm-I. J Clin Virol 2013;58(suppl. 1):e85-e91

3. Montesinos I, Eykmans J, Delforge ML: Evaluation of the Bio-Rad Geenius HIV-1/2 test as confirmatory assay. J Clin Virol 2014;60:399-401

4. Mor O, Milequir F, Michaeli M, et al: Evaluation of the Bio-Rad Geenius HIV 1/2 assay as an alternative to the INNO-LIA HIV 1/2 assay for confirmation of HIV infection. J Clin Microbiol 2014;52:2677-2679

5. Abbate I, Pergola C, Pisciotta M, et al: Evaluation in a clinical setting of the performances of a new rapid confirmatory assay for HIV-1/2 serodiagnosis. J Clin Virol 2014;61:166-169


Key