By Marie Rosenthal, MS
A single HIV viral load test processed by a laboratory may not reliably detect HIV among some people taking long-acting, injectable cabotegravir (CAB-LA; Apretude, ViiV Healthcare) for HIV pre-exposure prophylaxis (PrEP) because of an increased likelihood of false-positive results, according to a study presented at AIDS 2024 in Munich, Germany (abstract OAE0406LB).
Colorized transmission electron micrograph of multiple HIV-1 virus particles (green) budding from a cell projection from an H9 cell (burgundy). Image captured at the NIAID Integrated Research Facility in Fort Detrick, Maryland. Credit: NIAID
Patients who take PrEP are tested routinely to assure they do not acquire HIV. In the United States, people who take oral PrEP can use point-of-care tests that detect HIV antibodies. However, U.S. public health officials recommend people taking CAB-LA for PrEP to receive an RNA test processed by a laboratory. In this instance, a second viral load test with a new blood sample may discriminate true-positive from false-positive results, according to the study chair Raphael Landovitz, MD, a professor of medicine in the Division of Infectious Diseases at the David Geffen School of Medicine at the University of California, Los Angeles.
However, Dr. Landovitz told Infectious Disease Special Edition: “For all other regions—and also for the U.S.—the message is: Don't include it [viral loads] in testing algorithms in the first place, except for before starting CAB-LA or perhaps after a six-month hiatus before restarting.”
In this latest study, which was an extension of the HPTN 083 studies, researchers compared the accuracy of viral load test results in patients taking CAB-LA for PrEP and found them lacking.
“We have previously presented the primary blinded and unblinded results from HPTN 083 of the two pivotal studies of long-acting injectable cabotegravir for HIV pre-exposure prophylaxis or PrEP,” Dr. Landovitz said. “That study found superiority of CAB-LA compared with daily oral FTC/TDF [emtricitabine-tenofovir disoproxil fumarate] for HIV PrEP in cisgender men and transgender women who have sex with men leading to global regulatory approvals.”
The original study also identified “long-acting early viral inhibition” (LIVI) syndrome, the phenomenon in which long-acting PrEP agents delay detection of new HIV infections—data he presented at CROI 2023—because viral replication was suppressed.
“The ongoing open-label extension [study] of CAB-LA in the HPTN 083 study aimed to prospectively evaluate site performed RNA testing in addition to the previously implemented site-based testing algorithm at all visits for the early detection of HIV infection in this setting of CAB-LA use,” Dr. Landovitz explained.
In this multi-country trial, sites performed rapid testing, antigen/antibody (Ag/Ab) testing and HIV RNA testing at every study visit (27,335 visits). The researchers followed 2,620 men who have sex with men (MSM) as well as transgender women who have sex with men from the original study population.
Twenty-nine people acquired HIV during this extension trial. In five of those 29 participants, HIV was first identified by an isolated positive viral load test result. Of these five, two had received CAB-LA in the previous six months, while three had not received CAB-LA for more than six months. The remaining 24 participants had multiple positive tests that identified the presence of HIV.
Twenty-three other participants had an isolated positive viral load test result, but 22 were later found to be HIV negative in confirmatory testing. One person’s status could not be determined at the time of analysis.
“Interestingly, of the 22 false-positive test results among the 26,528 testing events, these results were disproportionately concentrated among nine of the 43 sites,” Dr. Landovitz said. “The distribution of the nine sites at which false-positive results were concentrated represented a range of geographies, exhaustive QA [quality assurance] and QC [quality control] evaluations of the nine sites, laboratory processes, and performance did not identify a source of these false-positive results.”
A single positive viral load test had a 9.1% positive predictive value in study participants whose last CAB-LA injection was within six months and a 60% positive predictive value in participants whose last CAB-LA injection had been more than six months ago, according to Dr. Landovitz.
However, a second confirmatory viral load test with a new blood sample had a positive predictive value of 100%, regardless of when the patients received their last CAB-LA injection.
“Happily, none of these participants who experienced a delay because of the false-positive isolated RNA test results has shown evidence of HIV acquisition to date.
“We conclude from this preliminary analysis that a single HIV positive RNA test done at study sites performed poorly for detecting HIV infection setting of CAB-LA PrEP, RNA testing performed better absent CAB-LA exposures in the past,” Dr. Landovitz said.
