Use of HIV-1/HIV-2 Differentiation Test Increases, HIV-2 Remains Rare in US

HIV-2 infections remain rare in the United States, but the CDC continues to recommend an HIV-1/HIV-2 differentiation test as a second step in testing.

Use of an HIV-1/HIV-2 differentiation test has increased since the US Centers for Disease Control and Prevention (CDC) began recommending it in 2014, but the number of confirmed cases of HIV-2 remained low, according to a recent report.

The CDC’s Morbidity and Mortality Weekly Report for January 24th featured an article that highlighted trends in the use of the test between 2010 and 2017, using data from CDC’s National HIV Surveillance System (NHSS).

During the study period, less than 0.03% of all HIV infections identified in the United States were HIV-2. The increased use of the second-step testing was associated with an increase in the number of false positive HIV-2 test results.

The CDC continues to recommend second-step testing with an antibody-based HIV-1/HIV-2 differentiation test.

“Although HIV-2 is rare, correct diagnosis is vital for ensuring correct clinical management,” the report noted. “Persons with HIV-2 who have an incorrect HIV-1 diagnosis and are treated with nonnucleoside reverse-transcriptase inhibitors, to which HIV-2 is intrinsically resistant, might fail to suppress an HIV-2 viral load.”

HIV-2 has been reported throughout the world, including 166 reported to CDC as cases of public health importance from 1987 to 2009, but most cases occur in West Africa.

The data included people tested with the Multispot HIV-1/HIV-2 Rapid Test and the Geenius HIV-1/HIV-2 Supplemental Assay but didn’t differentiate which of the 2 tests available during the study period were used.

Between 2010 and 2017, 327,700 cases of HIV were diagnosed in the United States, 198 (0.06%) of which were HIV-2. Among the HIV-2 cases, 102 were classified as monoinfections, 11 as dual HIV-1 and HIV-2 infections, and 85 as probable but unconfirmed HIV-2 infections.

The number of HIV-1/HIV-2 test results reported during the study period increased by an estimated 21.2% per year (95% confidence interval [CI] = 21.0—21.4). The number of confirmed HIV-2 cases increased by an estimated 12.0% per year (95% CI = 2.8–22.1) during that time, and the number of probable HIV-2 cases rose 11.4% per year (95% CI = 1.4–22.3). After the CDC began recommending the differentiation tests in 2014, their use continued to increase by an estimated 6.4% per year (95% CI = 6.2%–6.9%), but the number of confirmed or probable HIV-2 infections saw no significant change.

The differentiation tests resulted in 356 false-positive HIV-2 results, amounting to an estimated increase in false-positive reports of 18.8% per year (95% CI = 13.3—24.5) relative to all HIV diagnoses. But false-positive results decreased by 6.2% (95% CI = –10.7% to –1.5%) relative to those who received an HIV-1/HIV-2 differentiation test.

"In spite of widespread use of a test that distinguishes HIV-1 from HIV-2 as the second step in the CDC- Association of Public Health Laboratories (CDC/APHL) algorithm, there were few HIV-2 diagnoses in the United States," Anne Peruski, PhD, Epidemiologist in CDC’s Division for HIV/AIDS Prevention, told Contagion®. "This finding adds to existing evidence that it’s time to review the HIV diagnostic testing algorithm to determine if it should be updated and amended."

“CDC continues to recommend that laboratories follow the laboratory-based algorithm with the HIV-1/HIV-2 differentiation test as the second step,” the authors of the report noted. “However, updates to the laboratory-based testing algorithm merit consideration in the United States. This could include development of new [US Food and Drug Administration]-approved tests to reduce the time to HIV diagnosis and treatment, primarily for HIV-1, but in rare cases, for HIV-2.”

Improving testing is a key weapon in the fight against HIV. According to the CDC, an estimated 1 in 7 people living with HIV are unaware of their infection.

"Further work needs to be done to determine what types of tests should be included in an updated version of the recommended HIV testing algorithm and the order in which the tests should be performed," Peruski told Contagion®.

Universal screening could help identify transmission among individuals who might not seek testing, according to a recent study that examined universal screening programs in 2 emergency departments in San Diego. Another recent study found that passive venues have been successful in screening for HIV in San Diego County, California.

In November, the World Health Organization released new testing guidelines encouraging all countries to adopt a standard HIV testing strategy using 3 consecutive reactive tests to confirm a diagnosis, recommending use of self-tests, and emphasizing the importance of using social network-based HIV testing to reach at-risk individuals.