The Problems with Long-Acting Injectables Continue to Mount

PrEP affects “HIV” test results in deceptive ways—who could have guessed?

This will be a short post, but it’s important to alert you to the following report out of the NIH:

An isolated viral load test may generate false positive results for people using long-acting PrEP

The long-acting PrEP under consideration in this report is cabotegravir, sold under the brand name Cabenuva for ARV, and as Apretude for PrEP. This is not to be confused with lenacapavir, the twice-yearly injectable that recently made a splash due to its “promising results.” Cabenuva has already been through the clinical trial process, and is administered either monthly or bimonthly.

Regardless, the headline is intriguing. Let’s see what the article tells us. As always, emphasis is added by me throughout.

A single laboratory-based HIV viral load test used by U.S. clinicians who provide people with long-acting, injectable cabotegravir (CAB-LA) HIV pre-exposure prophylaxis (PrEP) did not reliably detect HIV in a multi-country study. In the study, a single positive viral load test was frequently found to be a false positive result. However, a second viral load test with a new blood sample was able to distinguish true positive results from false positive results for all participants whose initial viral load test was positive.

Right out of the gate, this is confusing. My translation of this (intentionally?) confusingly worded paragraph is that “HIV” was not reliably detected in this study due to the propensity of a single “viral load” test to register a false positive. How do they distinguish between false and true positives, anyway?

Check out how Dr. Jeanne Marrazzo explains this conundrum:

“We are still learning how to optimize the package of services that accompany long-acting PrEP, including HIV testing,” said Jeanne Marrazzo, M.D., M.P.H., director of the National Institutes of Health’s (NIH) National Institute of Allergy and Infectious Diseases (NIAID). “The viral load testing findings observed in this study illuminate performance gaps in the current U.S. HIV testing algorithm for injectable cabotegravir PrEP.”

“Performance gaps in the testing algorithm” is a new euphemism on me, so points to them for that, I guess. Of course, Dr. Marrazzo can’t translate that to the truth, which is that we don’t actually know what the results of an “HIV” test even indicate.

Long-acting, injectable cabotegravir PrEP, known as CAB-LA, is a highly effective HIV prevention method, administered by intramuscular injection every two months. Routine HIV status monitoring is recommended for any form of PrEP to ensure that people can promptly be aware if they acquire HIV while taking PrEP drugs. In the United States, people taking oral PrEP can do this with point-of-care rapid tests and self-tests that detect HIV antibodies, or laboratory-based HIV testing. However, the Food and Drug Administration (FDA) and the Centers for Disease Control and Prevention (CDC) recommend that people starting or taking CAB-LA PrEP receive a laboratory-based viral load test that detects HIV genetic material(link is external) in the blood. This recommendation was made because CAB-LA can keep HIV antibodies at such low levels following acquisition that they might not be detected on an antibody-based test.

The implications of this are potentially enormous. Cabenuva can “keep HIV antibodies at such low levels following acquisition that they might not be detected on an antibody-based test”? Let me get this straight. An individual goes on Cabenuva for PrEP, “contracts ‘HIV’,” has no measurable antibody response, yet has a “measurable viral load” that, mysteriously, no antibody response was mounted to? Is this drug actually suppressing the antibody arm of the immune system? This is a really important question and one that must be answered. We know these drugs don’t actually suppress or prevent “HIV” infection—what are they actually doing to people’s bodies?

To better inform the U.S. CAB-LA PrEP HIV testing algorithm, researchers examined the accuracy of viral load test results in an open-label extension of a large CAB-LA PrEP efficacy study.

The open-label study extension followed 2,620 gay, bisexual, and other men who have sex with men as well as transgender women who have sex with men from the original study population. Twenty-nine participants acquired HIV during the study extension. In five of those 29 participants (17.2%), 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. Separately, 23 other participants had an isolated positive viral load test result, but 22 were later found to be HIV-negative in confirmatory testing, meaning their initial result was a false positive. One person’s status could not be determined at the time of analysis.

So much for PrEP failure being “rare.” And again, how do we tell a “true” from a “false” positive? That methodology is unclear.

These data indicate that a single positive viral load test alone had a 9.1% positive predictive value—that is, a 9.1% chance of being true HIV acquisition rather than a false positive—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. Notably, the positive predictive value increased to 100% when study participants had a second round of confirmatory viral load testing with a new blood sample, regardless of the timing of their last CAB-LA injection.

Let that sink in. A single positive viral load test has a less than 10% chance of being accurate in patients that received Cabenuva within six months, but in patients whose systems had a chance to clear Cabenuva, having received their injection more than six months prior to testing, the accuracy goes up to 60%? Again, there is something about this drug that is interfering with the tests, and we need more information as to what is happening, because these PrEP drugs are being given to millions of people who don’t have a hint of “HIV” related genetic material. What are they doing to people’s immune systems?

Finally, we conclude:

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,” said study chair Raphael Landovitz, M.D., professor of medicine in the Division of Infectious Diseases at the David Geffen School of Medicine at the University of California, Los Angeles. “These concerns need to be balanced against the anticipated benefits of slightly earlier HIV detection.”  

A false positive can result in “PrEP interruption”? If a patient on PrEP “seroconverts,” they take them off the medication that is supposed to treat the condition they just acquired? That can’t be the case. This whole setup is so ridiculous. And what would be the “anticipated benefits of slightly earlier HIV detection”? Given that, after “seroconversion,” one would presumably switch to an ARV regimen with all the same drugs they were given for PrEP, plus possibly an extra medication thrown on top of that, what would those benefits actually be? No one seems to be able to explain this.

Regardless, this study raises yet more concerns about the quality of these tests that aren’t testing for a virus, nor for any virus-specific antibodies. They’re saying the quiet parts out loud here—ARVs, used for “HIV” or for PrEP, are obviously interfering with the antibody arm of the immune system, at the very least; and the so-called “viral load” test throws false positives right, left and center. And these are the results of forty years of research; this is where we are in the year of our Lord 2024—again, forty years after both a cure and a vaccine had been promised “by 1986.”