Acute HIV Screening With Combo Assay Ups Diagnostic Yield

Use of an HIV antigen/antibody (Ag/Ab) combination assay increases the diagnostic yield by more than 10 percent compared with rapid HIV testing in a high-prevalence population, while pooled RNA testing further increases the diagnostic yield, according to a study published in the Feb. 16 issue of the Journal of the American Medical Association. Because rapid testing detected HIV infection in only 87 percent of HIV-infected participants, the authors say alternative strategies that can detect acute infection should be considered in high-prevalence, U.S. populations.

Acute HIV infection is defined as the interval between the appearance of HIV RNA and detection of HIV-specific antibodies and can be diagnosed with HIV RNA assays (the reference standard) or the p24 antigen. The U.S. Centers for Disease Control and Prevention (CDC) recommends an HIV diagnostic algorithm that uses HIV immunoassays that detect both the p24 antigen and anti-HIV antibody (fourth generation Ag/Ab combo assay) as the initial screening test. But, they are not as sensitive as pooled HIV RNA tests, which are not widely used because there is only one U.S. Food and Drug Administration-approved assay and the protocol is complex.

This prospective trial (September 2011 through October 2013) included seven sexually transmitted infection clinics and five community-based programs in New York, California, and North Carolina. All participants (median age, 29 years; seeking HIV testing, without previously known infection) with a negative rapid HIV test result were screened for acute HIV infection with an HIV Ag/Ab assay (index test) and a pooled HIV-1 RNA test (reference standard).

The researchers found that among 86,836 participants with complete test results, established HIV infection was diagnosed in 1.33 percent of participants and acute HIV infection was diagnosed in 0.19 percent. HIV Ag/Ab combination testing detected acute HIV infection in 134 of 168 participants (sensitivity, 79.8 percent; specificity, 99.9 percent; positive predictive value, 59.0 percent) versus HIV RNA testing which detected 164 of 168 participants (sensitivity, 97.6 percent; specificity, 100 percent; positive predictive value, 96.5 percent). HIV Ag/Ab testing detected 82 percent of acute HIV infections detectable by pooled HIV RNA testing. Compared with rapid HIV testing alone, HIV Ag/Ab combo testing increased the relative HIV diagnostic yield by 10.4 percent, while pooled HIV RNA testing increased the relative HIV diagnostic yield by 12.4 percent.

The authors, led by Philip Peters, M.D., from the CDC, suggest two scenarios for incorporating Ag/Ab combo testing into screening regimens. In one scenario, for patients with adequate contact information, laboratory- based Ag/Ab combination testing could replace the rapid HIV test for initial screening. In the second scenario, if rapid testing is negative, high-risk individuals could be offered an additional laboratory-based Ag/Ab testing to diagnose acute HIV infection potentially missed with rapid testing, although this approach would be unsuited to low–HIV prevalence populations due to the test's low positive predictive value.