Some rapid hepatitis C tests have high false-negative rate in people with HIV

Approximately 9% of hepatitis C infections in HIV-positive individuals are missed by some rapid hepatitis C testing assays, US investigators report in the September 15^th edition of the Journal of Infectious Diseases.

Three rapid tests were evaluated in the study. The OraSure assay had a very low rate of false-negative results. However, the two remaining assays had an overall false negative rate of 8.5% in HIV-positive patients, a significantly higher rate than that observed in HIV-negative patients.

Although the confidence intervals were wide and the estimate of the false-negative rate therefore imprecise, the investigators say that further evaluation is needed in a larger HIV-positive population.

However, overall the rapid assays performed well, having a sensitivity of between 87% and 96% and a specificity of almost 100%.

“Anti-HCV [antibody hepatitis C virus] rapid assays could be implemented in many settings,” suggest the investigators, “hard-to-reach, high-risk populations, such as persons who inject drugs, are unlikely to be screened for anti-HCV using conventional testing, and when they are, they are less likely to return for their results.”

It is estimated that between 50% to 70% of the US’s 3.2 million hepatitis C infections are undiagnosed.

Guidelines recommend routine antibody testing for patients at high risk of hepatitis C. However, many hepatitis C-infected individuals belong to marginalised or hard-to-reach populations who do not access conventional testing services.

Rapid antibody tests are incorporated into HIV screening services and research indicates that individuals receive their HIV test results more often when they have a rapid test rather than a conventional test (83-100% vs. 43-84%).

Investigators therefore evaluated three rapid hepatitis C antibody tests capable of delivering a result in less than 40 minutes.

The Chembio DPP HCV Test screens for hepatitis C using whole blood, serum, plasma, or oral fluid. The time required to perform the assay is between 15 and 30 minutes.

The Multiplo Rapid HIV/HCV (MedMira) Antibody test uses whole blood, serum or plasma samples and can deliver a result within three minutes.

The OraQuick HCV Rapid Antibody Test can detect antibodies using blood samples from a finger stick, oral fluid collected using a swab, or whole blood, serum or plasma obtained using a conventional blood test. This assay has been licensed in the US.

Using 1100 stored blood samples obtained from injecting drug users between 1997 and 1999 the investigators evaluated the reliability of the three assays.

Just under than half the samples (49.7%) were positive for hepatitis C antibodies and the remaining 50.3% were negative.

Performance of the rapid tests was compared against the standard antibody screening assay and the Centers for Disease Control (CDC) testing algorithm.

Compared to standard antibody screening, the rapid assays had a sensitivity of between 87% and 98%, and their specificity ranged from 99.6% to 99.8%.

Sensitivity of Orasure (97.8%) was significantly higher than both Chembio (96.2%, p = 0.012) and MedMira (87%, p < 0.01).

Using the CDC testing approach, sensitivity ranged from 88% to 99% and the specificity between 99.5% and 99.8%. Once again, sensitivity was higher for OraSure (99.3%) compared to Chembio (97.8%, p = 0.021) and MedMira (88%, p < 0.001).

Rates of false positives and false negatives varied between the assays and reference approaches.

Chembio had 0.2% false positives and between 2.2% and 3.9% false negatives.

The rate of false positives using MedMira was 0.2%, with between 11.7% and13.4% being false negative.

OraSure had between 0.4% and 0.6% with a false positive result and 0.7% to 2.2% had a false-negative result.

Infection with HIV was significantly associated with false results for both the Chembio (p < 0.01) and MedMira (p < 0.01) assays, but not OraSure.

“Controlling for all other variables, specimens from HIV-positive persons were 11 times more likely to have a false result than those from HIV-negative persons using the Chembio test, and 4 times more likely using the MedMira test,” write the authors.

However, they note “the sample of HIV-positive specimens (both anti-HCV positive and negative) was small (n = 43), and the associated estimates imprecise.”

They suggest, “anti-HCV rapid assays need to be evaluated using an HIV-positive specimen panel to establish and expected proportion of false-negative results. Also, demonstration projects should be conducted to see how these assays would be implemented in HIV settings.”