Single Viral Load Test May Yield False Positives for Long-Acting PrEP Users

On July 23, 2024, a key study presented at the International AIDS Conference (AIDS 2024) in Munich, Germany, revealed that a single laboratory-based HIV viral load test used by U.S. clinicians for people on long-acting, injectable cabotegravir (CAB-LA) HIV pre-exposure prophylaxis (PrEP) often produced false-positive results. This study underscores the need for a secondary confirmatory test to accurately detect HIV.

Dr. Jeanne Marrazzo, director of the National Institute of Allergy and Infectious Diseases (NIAID), highlighted that the findings expose significant performance gaps in the current U.S. HIV testing protocol for CAB-LA PrEP. CAB-LA is a highly effective HIV prevention method administered via injections every two months, necessitating regular HIV status monitoring to detect any potential infection promptly.

In the United States, individuals using oral PrEP can monitor their HIV status with rapid point-of-care tests and self-tests that detect HIV antibodies, besides laboratory-based methods. However, for CAB-LA PrEP, the FDA and CDC recommend a laboratory-based viral load test to detect HIV genetic material. This recommendation is due to CAB-LA’s ability to lower HIV antibody levels to the extent that antibody-based tests might fail to detect them.

To enhance the U.S. CAB-LA PrEP HIV testing algorithm, researchers assessed the accuracy of viral load tests in an extension of a large CAB-LA PrEP efficacy study. This study included 2,620 gay, bisexual, and other men who have sex with men, as well as transgender women who have sex with men. During the study, 29 participants were diagnosed with HIV. For five of these participants (17.2%), an isolated positive viral load test was the first indication of HIV. Among these five, two had received CAB-LA in the previous six months, while three had not received the injection for over six months. The remaining 24 participants had multiple positive tests confirming HIV presence.

Additionally, 23 other participants had initially isolated positive viral load tests but were later confirmed HIV-negative upon further testing. This result indicates that a single positive viral load test has a 9.1% likelihood of being accurate in identifying HIV for individuals who had their last CAB-LA injection within six months, and a 60% likelihood for those who had their injection over six months ago. However, the positive predictive value increased to 100% when a second confirmatory viral load test with a new blood sample was conducted.

Dr. Raphael Landovitz, study chair and professor at the David Geffen School of Medicine at UCLA, emphasized the challenges and psychological distress caused by false-positive results. These results can lead to unnecessary interruptions in PrEP use, potentially increasing vulnerability to HIV. The study suggests that while these false positives are concerning, they need to be weighed against the benefits of early HIV detection.

Previous analyses of this study had shown that combinations of two antibody-based tests had positive predictive values between 83% and 100% for those on CAB-LA PrEP. According to the researchers, these findings contribute to understanding the performance of current HIV testing tools, aiding the optimization and global implementation of CAB-LA PrEP.

The open-label extension study received support from NIAID, ViiV Healthcare, Gilead Sciences, Inc., and the NIH-funded HIV Prevention Trials Network (HPTN). The study continues to inform HIV prevention policies and practices globally.