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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, currently there is only 1 FDA-approved supplemental (confirmatory) HIV-2 serologic assay for clinical use in the United States. Interpretation of visible band patterns is complicated due to the significant cross-reactivity between HIV-1 and HIV-2 antibodies in this assay.
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
Negative results for HIV-2 antibodies usually indicate absence of 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-2 infection. If acute or early HIV-2 infection is suspected, detection of HIV-2 DNA/RNA RNA (FHV2Q / HIV-2 DNA/RNA Qualitative Real-Time PCR) is recommended, based on patient’s clinical and epidemiologic exposure history.
Positive HIV-2 antibody results indicate the presence of HIV-2 infection. Verification of a first-time positive test result is recommended for the diagnosis of HIV-2 infection, by submitting a plasma specimen for HIV-2 DNA/RNA (FHV2Q).
Indeterminate results HIV-2 antibodies indicate either very early HIV-2 infection (in individuals with risk factors) or 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-2 infection, plasma specimens should be submitted for detection of HIV-2 DNA/RNA (FHV2Q), depending on the epidemiologic exposure history.
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 (FHV2Q / HIV-2 DNA/RNA Qualitative Real-Time PCR) 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.
Individuals at risk for HIV-2 infection with indeterminate or negative HIV-2 antibody supplemental test results should be retested in 2 to 4 weeks. Repeat testing may be performed with HIV-2 serologic testing (HIV2M / HIV-2 Antibody Screen, Serum), or qualitative HIV-2 DNA/RNA (FHV2Q).
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 DNA/RNA (FHV2Q).
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 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
3. 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
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6. 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