Between 2010 and 2017, the use of an antibody-based HIV-1/HIV-2 differentiation test increased in the United States, but the number of confirmed HIV-2 diagnoses remained low at <.1%. These findings, based on data from the Centers for Disease Control and Prevention’s (CDC) National HIV Surveillance System, was published in its Morbidity and Mortality Weekly Report.

The use of the antibody-based differentiation test has been recommended by the CDC since 2014 as part of the laboratory-based algorithm to confirm both HIV-1 and -2 infections. Despite the use of the test steadily increasing throughout the study period, after 2014 the number of confirmed HIV-2 cases remained stable. This result, according to the investigators, is consistent with previous reports that HIV-2 remains a rare diagnosis in the United States.

As the number of HIV-1/HIV-2 differentiation test results increased over the study period, results also demonstrated an increase in the number of confirmed and probable HIV-2 infections by an estimated 12.0% per year (95% CI, 2.8%-22.1%) and 11.4% per year (95% CI, 1.4%-22.3%), respectively, during the study period. Further, the number of HIV-1 patients with a false positive HIV-2 diagnosis among cases that reported the use of the differentiation test decreased by 6.2% (95% CI, −10% to −1.5%). However, the number of people with a false-positive HIV-2 result via the use of the HIV-1/HIV-2 differentiation test was greater than the total combined number of confirmed and probable HIV-2 diagnoses.

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The investigators noted several limitations of the analysis. The definition used to define HIV-2 infection using test results entered into the Enhanced HIV/AIDS Reporting System was developed for use with surveillance data to report epidemiologic trends and identification of HIV type for patient management may require additional tests beyond the scope of this report. Also, for 33% of HIV-2 diagnoses, both probable and confirmed, with missing HIV-1 nucleic acid test results it was impossible to rule out the possibility of HIV-2 infection or identification of dual infection. Finally, the evidence of pregnancy in women with HIV is underreported and while this can result in underreporting of HIV-2, the likelihood of perinatal HIV-2 being recognized is increased by robust reporting of perinatal HIV.

While HIV-2 infections are rare, it is important that they be correctly diagnosed. Inaccurately diagnosed patients are treated with non-nucleoside reverse-transcriptase inhibitors, to which HIV-2 is intrinsically resistant. Furthermore, because there are no commercially available HIV-2 viral load tests, infection may not be recognized or require additional tests to determine HIV status.

The CDC continues to recommend that laboratories follow the laboratory-based algorithm with the HIV-1/HIV-2 differentiation test as the second step. They also recommended that the use of HIV-1 nucleic acid testing in the algorithm would likely distinguish the majority of HIV infection types in the United States. Follow-up testing of ambiguous samples after nucleic acid testing for HIV-1 is also recommended.

The investigators also concluded that updates to the laboratory-based testing algorithm in the United States merit consideration. Suggested updates included the development of US Food and Drug Administration-approved tests to reduce time to diagnosis and treatment, mainly for HIV-1 but in rare cases for HIV-2 as well.


Peruski AH, Wesolowski LG, Delaney KP, et al. Trends in HIV-2 diagnoses and use of the HIV-1/HIV-2 differentiation test – United States, 2010-2017. MMWR Morb Mortal Wkly Rep. 2020;69:63-66.