HIV Patients Treated Long-Term May Have False-Negative Tests

Daniel M. Keller, PhD

October 06, 2011

October 6, 2011 (Chicago, Illinois) — The loss of HIV-specific antibodies can lead to false-negative results on rapid HIV tests in children and adolescents after successful long-term antiretroviral therapy, according to results presented here at the 51st Interscience Conference on Antimicrobial Agents and Chemotherapy (ICAAC).

Ram Yogev, MD, medical director of pediatric and maternal HIV infection at Children's Memorial Hospital and professor of pediatric, adolescent, and maternal HIV infection at Northwestern University Feinberg School of Medicine in Chicago, Illinois, presented the findings.

Reports have documented the loss of HIV-specific antibodies in patients with late-stage disease because of the loss of immune function related to the disease.

Dr. Yogev hypothesized that patients who have been successfully treated with highly active antiretroviral therapy (HAART) for prolonged periods and who have highly suppressed viral loads (defined as the absence of detectable virus in the blood) sero-revert to apparently negative HIV status on rapid HIV tests. Such tests are used throughout the world, mainly in clinics and doctors' offices, for diagnostic and screening purposes.

He used 5 commercially available rapid HIV assay kits, all approved by the US Food and Drug Administration, to test multiple plasma samples from 25 HIV-infected adolescents receiving HAART who had undetectable viral loads for 67 to 157 months (Trinity Uni-Gold Recombigen HIV-1, OraQuick ADVANCE HIV-1/2, Reveal G3 HIV-1, Clearview HIV-1/2 STAT-PAK, and Clearview COMPLETE HIV-1/2).

Samples tested were from a periodwhen the virus was detectable in each patient. Samples were obtained at least twice within 7 to 13 years of achieving full viral load suppression. The test results were compared with results from standard laboratory-based antibody tests, which are generally more sensitive.

Dr. Yogev reported that of the 309 tests (80 samples from 25 patients) performed from May 2009 to March 2011, 38 (12.3%) tested negative on all 5 rapid HIV tests.

Only some of the test kits yielded false-negative results for samples from patients who were virally suppressed for as little as 9 years. The frequency of false-negative results from some kits increased with the duration of viral suppression. Similarly, the number of different brands of kits giving false-negative results rose with the length of viral suppression.

When the rapid tests were compared with a laboratory-based enzyme-linked immunoassay (EIA) for HIV antibodies (which were all positive), the loss of signal on the rapid tests was highly correlated with the loss of the HIV-specific antibody, as expressed by the reciprocal antibody titer.

On the basis of his findings, Dr. Yogev advised clinicians to be aware that HIV-infected children and adolescents with highly suppressed viral loads might have a slow but persistent loss of HIV-specific antibodies, which could give false-negative results on rapid HIV antibody tests.

Rapid HIV antibody tests are not as sensitive as laboratory-based ones, Dr. Yogev warned, adding that the loss of circulating antibodies could eventually lead to signal loss on the more sensitive tests as well.

Vincent Racaniello, PhD, professor of microbiology and immunology at Columbia University School of Medicine in New York City, told Medscape Medical News that after being treated for a number of years, a person could test negative. "That would be a problem because they're not really negative, and they could donate blood or do other at-risk activities that could transmit infections."

Dr. Racaniello predicted that as rapid tests improve, the issue of false-negative results will diminish.

If antibody levels are so low that they could be missed even by 1 laboratory test, a number of different laboratory tests could be preformed to increase the possibility of detecting true antibody positivity. Such blood tests (e.g., enzyme-linked immunosorbent assays, Western blot assays, and nucleic acid testing) use different methods to look for HIV antigens.

The research was privately funded. Dr. Yogev and Dr. Racaniello have disclosed no relevant financial relationships.

51st Interscience Conference on Antimicrobial Agents and Chemotherapy (ICAAC): Abstract H1-1402. Presented September 19, 2011.


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