A new study presented at the 2024 International AIDS Conference (AIDS 2024) reveals that isolated viral load tests may generate false positive results for individuals using long-acting injectable cabotegravir (CAB-LA) for HIV pre-exposure prophylaxis (PrEP). The multi-country study found that a single positive viral load test frequently resulted in a false positive, potentially impacting the reliability of HIV detection in this population. However, a second viral load test using a new blood sample effectively differentiated true positives from false positives.
Jeanne Marrazzo, M.D., M.P.H., director of the National Institutes of Health’s (NIH) National Institute of Allergy and Infectious Diseases (NIAID), stated, “We are still learning how to optimize the package of services that accompany long-acting PrEP, including HIV testing.” She added that the study's findings highlight performance gaps in the current U.S. HIV testing algorithm for injectable cabotegravir PrEP.
Implications of False Positives
CAB-LA is a highly effective HIV prevention method administered via intramuscular injection every two months. Routine HIV status monitoring is crucial to ensure prompt awareness of HIV acquisition while on PrEP. In the United States, while oral PrEP users can utilize point-of-care rapid tests and self-tests, the FDA and CDC recommend laboratory-based viral load tests for those on CAB-LA PrEP. This recommendation stems from CAB-LA's ability to suppress HIV antibodies to levels undetectable by antibody-based tests.
To assess the accuracy of viral load tests in CAB-LA PrEP users, researchers analyzed data from an open-label extension of a large CAB-LA PrEP efficacy study. The study followed 2,620 participants, including gay, bisexual, and other men who have sex with men, as well as transgender women who have sex with men. Among the 29 participants who acquired HIV during the study extension, five (17.2%) were initially identified through an isolated positive viral load test. Two of these five had received CAB-LA within the previous six months, while three had not received CAB-LA for over six months. Additionally, 23 other participants had an isolated positive viral load test, but 22 were later confirmed HIV-negative, indicating a false positive. The HIV status of one participant could not be determined at the time of analysis.
The data indicated that a single positive viral load test alone had a 9.1% positive predictive value in participants whose last CAB-LA injection was within six months, and a 60% positive predictive value in participants whose last CAB-LA injection was more than six months ago. Importantly, the positive predictive value increased to 100% when participants underwent a second confirmatory viral load test with a new blood sample, regardless of the timing of their last CAB-LA injection.
Expert Commentary
Raphael Landovitz, M.D., professor of medicine at the David Geffen School of Medicine at UCLA and study chair, emphasized the potential negative consequences of false positives: “A false positive can result in PrEP interruptions that create potential vulnerability to HIV acquisition, and more importantly causes profound psychological distress while a person awaits confirmatory results from a second test.” He noted that these concerns must be balanced against the benefits of earlier HIV detection.
Previous analyses from this study demonstrated that combinations of two antibody-based tests had positive predictive values between 83-100% in participants receiving CAB-LA PrEP. The authors suggest that these findings contribute to a better understanding of the performance of available HIV testing tools, which can optimize CAB-LA PrEP implementation and global scale-up. The global NIAID-supported CAB-LA studies continue to inform HIV prevention policy and practice.
