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Human immunodeficiency virus type 2 (HIV-2) is a lentivirus, a retrovirus in the same genus (Lentiviridae) as HIV-1. It was first isolated in 1986 in West Africa, where it is currently endemic. As of June 2010, CDC has reported a total of 166 cases that met the CDC case definition of HIV-2 infection in the United States. Most of these cases were found in the northeastern United States, and the majority had a West African origin or connection.
Compared to HIV-1 infection, HIV-2 infection is associated with slower rate of progression, low viral load (which may not be reliably measurable with current methods), slower rates of decline in CD4 cell count, and lower rates of transmission (sexually or vertically). Up to 95% of HIV-2-infected individuals are long-term nonprogressors, and individuals with undetectable HIV-2 viral load have similar survival rates as that of the uninfected population. However, HIV-2 does cause immunosuppression as well as AIDS with the same signs, symptoms, and opportunistic infections seen in HIV-1. Due to the rarity of HIV-2, there are scant data from controlled trials to inform management decisions.
Although there are several FDA-approved screening assays to detect both combined HIV-1 and HIV-2 antibodies or HIV-2 antibodies alone, there is currently no FDA-approved supplemental (confirmatory) HIV-2 serologic or molecular test in the United States. Interpretation of visible band patterns in supplemental HIV-2 antibody detection assays (eg, Western blot, line immunoblot) is complicated due to significant cross-reactivity between HIV-1 and HIV-2 antibodies in these assays.
Confirmation of the presence of HIV-2 antibodies in patients with repeatedly reactive combined HIV-1 and HIV-2 antibody or HIV-2 antibody-only screening test results
Diagnosis of HIV-2 infection
A negative HIV-2 antibody supplemental (confirmatory) test result indicates absence of HIV-2-specific antibodies. Such a result with either a reactive combined HIV-1 and HIV-2 antibody or HIV-2 antibody-only screening test result, in the absence of signs, symptoms, or risk factors for HIV infection, probably indicates a false-positive screening test result.
A positive HIV-2 antibody supplemental test result, following a reactive combined HIV-1 and HIV-2 antibody or HIV-2 antibody-only screening test result, indicates presence of HIV-2 infection, but it does not indicate the stage of disease. Positive results with this HIV-2 antibody line immunoblot assay are defined by band patterns showing presence of antibodies to HIV-2-specific envelope peptides (sgp105 and gp36), with or without antibodies to HIV-1 nonenvelope peptides (p17, p24, and p31), and absence of antibodies to HIV-1-specific envelope peptides (sgp120, gp41).
An indeterminate HIV-2 antibody supplemental test result indicates that the line immunoblot band pattern does not meet the criteria for a positive or negative test result. Such test results may be due to acute or early HIV-2 infection, presence of HIV-1-specific antibodies, or cross-reactivity with non-HIV antibodies. Individuals at risk for acute or early HIV infection should undergo nucleic acid testing (quantitative HIV-1 RNA, qualitative HIV-1 proviral DNA, and/or qualitative HIV-2 DNA/RNA). Alternatively, combined HIV-1 and HIV-2 antibody screening serologic testing could be repeated in 2 to 4 weeks. If no additional HIV-2 antibody line immunoblot bands develop during that time, the patient is considered not to be infected with HIV-2.
Certain line immunoblot band patterns indicate presence of HIV antibodies but cannot differentiate between HIV-1 and HIV-2 antibodies. Such cases may be due to HIV-1 infection or HIV-1 and HIV-2 coinfection. Additional tests for quantitative HIV-1 RNA, qualitative HIV-2 DNA/RNA, and/or quantitative HIV-2 RNA are recommended.
An ''unreadable'' HIV-2 antibody line immunoblot result indicates the presence of unusually strong, nonspecific reactivity of the strip background that obscures proper reading of the immunoblot bands. Such findings are usually due to nonspecific binding of non-HIV antibodies in patient's serum to the immunoblot bands. Patients with such unreadable results should be retested in 2 to 4 weeks as clinically indicated.
Negative HIV-2 antibody supplemental (confirmatory) test results does not exclude the possibility of acute or early (<60 days from time of exposure) HIV-2 infection. Individuals suspected of having acute or early HIV-2 infection should be tested for qualitative HIV-2 DNA/RNA or quantitative HIV-2 RNA.
The US Association of Public Health Laboratories recommends verification of all first-time positive supplemental test results for the definitive diagnosis of HIV infection. A second serum specimen should be obtained from the patient and submitted for repeat testing to verify all first-time positive test results.
Although a positive HIV-2 antibody supplemental test result indicates HIV-2 infection, a diagnosis of AIDS can only be made based on the case definition established by the CDC. In many US states, positive HIV-2 antibody supplemental test results are required to be reported to the state department of health.
High-risk individuals with reactive rapid HIV antibody tests, but negative combined HIV-1 and HIV-2 antibody screening test results, indeterminate or negative HIV-1 antibody Western blot results, and indeterminate or negative HIV-2 antibody supplemental test results, should be retested in 2 to 4 weeks. Repeat testing may be performed with either rapid HIV antibody or routine HIV-1/-2 antibody screening test, followed by HIV-1 antibody Western blot and HIV-2 antibody supplemental tests as needed.
Positive HIV-2 antibody supplemental test results in infants of <18 month old and born to HIV-2-infected mothers may indicate passive transfer of maternal HIV-2 antibodies. Serologic tests (screening or supplemental) cannot distinguish between active HIV-2 infection and passive transfer of maternal HIV-2 antibodies during the postnatal period (up to 18 months). Diagnosis of HIV-2 infection in newborns and infants of <18 months old should be made by consistently positive nucleic acid test results, such as the presence of HIV-2 RNA or HIV-2 proviral DNA.
This test should be ordered only on sera that are repeatedly reactive by FDA-licensed combined HIV-1 and HIV-2 screening serologic tests, HIV-2 antibody-only screening tests, or rapid HIV antibody tests.
This confirmatory assay should be ordered only on specimens that are reactive by an HIV-2 antibody screening immunoassay.
1. Campbell-Yesufu OT, Gandhi RT: Update on human immunodeficiency virus (HIV)-2 infection. 2011;52(6):780-787
2. Centers for Disease Control and Prevention: HIV-2 infection surveillance-United States, 1987-2009. 2011;60(29):985-988
3. New York State Department of Health AIDS Institute: Clinical guidelines-Human immunodeficiency virus type 2 (HIV-2). April 2012. Available from URL: http://www.hivguidelines.org/wp-content/uploads/human-immunodeficiency-virus-type-2-hiv-2-posted-04-02-2012.pdf
4. Bennett B, Branson B, Delaney K, et al: HIV testing algorithms: a status report. Association of Public Health Laboratories, April 2009. Available from URL: http://www.aphl.org/aphlprograms/infectious/hiv/Documents/ID_2009April_HIV-Testing-Algorithms-Status-Report.pdf