News Roundup—lenacapavir isn’t so perfect; “Fact checking” “misinformation” about AIDS

Injectables affect bio markers in weird ways—who could have guessed?

Happy Monday! I have two articles to discuss with you today. The first is serious; the second one (unintentionally) is not.

Yesterday was World AIDS Day, and the Journal of the American Medical Association devoted several articles to “HIV,” with a focus on PrEP. I won’t cover each article, but you can check out Advances in Treatment and Prevention of HIV and Antiretroviral Drugs for Treatment and Prevention of HIV in Adults: 2024 Recommendations of the International Antiviral Society–USA Panel at the links provided. Today, I’d like to focus on this:

Is Lenacapavir Needed for Individuals Adherent to Daily Oral PrEP?

Right out of the gate, the title of this piece intrigues me. They’re talking about adding the long acting injectable onto daily PrEP pills to “increase effectiveness”—why would we want to add to the toxicities if PrEP is nearly 100% effective at “preventing seroconversion?” What could be the rationale for this? (Emphasis is mine throughout.)

In 2023, roughly 1.3 million people worldwide acquired HIV—3 times more than the target set for 2025.¹ Recently, the World Health Organization described interim results of the PURPOSE 2 trial, which evaluated long-acting injectable lenacapavir, an HIV-1 capsid inhibitor administered subcutaneously twice a year. The analysis showed that lenacapavir was 89% more effective than daily oral preexposure prophylaxis (PrEP) with emtricitabine/tenofovir disoproxil fumarate in preventing HIV among gender-diverse individuals who have sex with men. These findings are consistent with results from the PURPOSE 1 trial, which reported a 100% relative risk reduction in HIV incidence with lenacapavir among cisgender women.

So already, once we leave the “risk group” of biological women, Lenacapavir is already beginning to fail. However, for years now, we’ve been told that PrEP failures are “rare” because of oral PrEP’s incredible efficacy. Yet, according to these authors, adding lenacapavir to oral PrEP supposedly increases its (already claimed to be near perfect) effectiveness—how do they square that circle?

The comparison chart in the article is very interesting. It compares oral TDF/FTC, bimonthly cabotegravir, and twice yearly lenacapavir. The drugs are compared in the categories of efficacy, effective use (method of administration), adherence, generic formulation, and risks. This is a very interesting chart. Effectiveness is listed as follows:

1. TDF/FTC is claimed to be at least 90% effective, or “ possibly as high as 94-99%.”

2. Cabotegravir is claimed to be at least 90% effective, or “possibly as high as 92-95%.”

3. Lenacapavir is claimed to be at least 90% effective, or “possibly as high as 90-99%.”

These values, which have been obtained via statistical trickery involving measuring drug concentrations in dried blood spots, are statistically indistinguishable. In fact, the low value of 90% for lenacapavir is actually lower than the low value for either oral PrEP or cabotegravir. What on earth could be the motivation behind adding the injectable to oral PrEP? Returning to the chart, let’s check out the “risks” for each regimen. Here we go:

1. For TDF/FTC, the only risk listed is “high risk of nonadherence.” Put a pin in that; we’ll come back to it.

2. For cabotegravir, the risk listed is “breakthrough infections and LEVI (ultra sensitive RNA testing required).”

3. Again, for lenacapavir, the same risk of “breakthrough infections and LEVI (ultra sensitive RNA testing required).”

I think I know why they’d want to add the long acting injectable to oral PrEP—it’s to increase adherence. Of course it is. But I’m very curious about the risk of “breakthrough infections and LEVI” that would require “ultra sensitive RNA testing”—like using 45 PCR cycles to maybe try and find some genetic sequences that might be related to “HIV?” Just asking. And what is LEVI, exactly?

According to this article from the Conference on Retroviruses and Opportunistic Infections, LEVI is an acronym for “the long-acting early viral inhibition syndrome.” Allow the authors to explain what this syndrome is:

Infections that occurred within six months of CAB-LA exposure had clinical and laboratory features that were distinct from those usually seen in acute HIV infection and had minimal or no clinical symptoms. In most cases, viral replication was suppressed and antibody production was diminished/delayed for long periods. HIV DNA levels were undetectable or low in half of the cases where testing was performed. Seven infections occurred with no recent CAB exposure; these infections were detected using standard HIV testing algorithms. In contrast, detection of infection was delayed using standard HIV testing algorithms in 12 of 13 remaining cases. Major integrase strand transfer inhibitor (INSTI) resistance mutations were observed in seven cases. Delayed detection of infection in this setting led to inadvertent administration of CAB-LA to persons with undiagnosed infection in 11 cases.

They are discussing the twenty “infections” that occurred in the cabotegravir trial. What they’re saying here is that somehow, “HIV” infection occurred in patients taking cabotegravir for PrEP, despite no measurable viral load and no antibody production. What exactly are these drugs doing to people? This is not how antivirals are supposed to work, nor how an alleged viral infection is meant to respond. Something very strange is going on. I’ll be looking into LEVI in great detail in an upcoming post. However, we’re getting off course here. What were the actual results obtained for the addition of lenacapavir to oral PrEP? Well, apparently, if “adherence” is not an issue, there’s no point in adding on or switching an injectable medication (why do they only mention cabotegravir and not lenacapavir?):

Given these findings, individuals without adherence issues to oral PrEP may have minimal benefits from switching to long-acting cabotegravir, except for reasons of personal preference or convenience, assuming cost is not an issue.

Basically this is all about “retention in care:”

In addition to easier adherence associated with long-acting injectable treatments, the restarting process for participants who missed their scheduled injections (active or placebo) may have also contributed to the superior efficacy of long-acting injectable treatments compared with oral PrEP.

[…]

The low adherence to oral PrEP, potentially exacerbated by the lack of intervention, likely contributed to higher HIV risk in the oral PrEP groups. A more balanced comparison would involve providing objective adherence monitoring and restarting support for both long-acting injectable treatments and oral PrEP to ensure comparable levels of intervention across groups, thereby offering a clearer understanding of the true efficacy of each regimen.

I think we get the picture here. We’re really dialing up “adherence” and “retention in care” to 11 here. Let’s add even more monitoring—that won’t cause confusion (or ennui) at all. Regardless, the conclusion of this article is unsurprising. They give a tiny bit of lip service to the dangers of PrEP medications to kidney function, but mention no other toxicities. Also, they are careful to point out that you don’t really need to take PrEP forever—of course, they have to say that, because what perfectly healthy person would commit to a lifetime of toxic medication intended to treat a condition they don’t even have?

Recent advances in HIV prevention have expanded PrEP options, including more long-acting injectable treatments as well as the event-driven oral PrEP regimen. These options now offer more tailored and effective solutions to meet the diverse needs of individuals at risk for HIV. Importantly, PrEP is not a lifelong commitment; people should feel empowered to start, stop, or restart as their circumstances change. Oral PrEP continues to offer reliable protection when taken as directed, remaining both flexible and affordable. With the emergence of more effective options, additional routine or opportunistic testing may be helpful to assist clients—whose needs and preferences may evolve—in navigating their choices and identifying the best PrEP option for maximizing protection.

In summary: long acting injectables are not necessarily any more effective than oral PrEP, we don’t really know how to identify “infections” among patients on these injectable medications because they interfere with “viral replication” and antibody production, but we need these injectables because not enough patients are sufficiently adherent to oral PrEP, and we need to monitor these patients as much as possible in order to keep them in the system. Forty years after the announcement of “HIV” as the cause of AIDS, this is the best we’ve got. How depressing.

The second article I’d like to cover today, published by GLAAD, is much more lighthearted, though that was likely not its intent. Check this out:

FACT CHECK: Correcting the Record on HIV/AIDS Misinformation Online

There is less focus on “AIDS denialism” in this piece than you’d think; in fact, only the first two points mention HIV AIDS skepticism. Let’s run through their points of “misinformation:”

1. False claim: AIDS is caused by “party drugs.” Fact: Progression of the HIV virus causes AIDS. They don’t say how progression of “HIV” leads to AIDS, but perhaps saying it three times while twirling around and clicking your heels will make it so.

2. False claim: AZT killed more people than the virus itself. Fact: AZT did not kill anyone. It has saved many lives. Are they kidding us here?

3. Haitian immigrants are rapidly spreading HIV in Springfield, Ohio.
   Fact: There is no evidence that Haitian immigrants are causing HIV in Springfield, Ohio. Wait, what? I’d heard about eating the dogs and eating the cats, but Haitians spreading “HIV” is a real blast from the past—remember back in the beginning of AIDS when Haitians were considered a “risk group?”

4. False claim: Nicotine deters HIV.
   Fact: Nicotine is addictive, is linked to a variety of health issues, and does not deter HIV. Okay, this one is actually funny to me. Forget PrEP, let’s just chew some nicotine gum! Has anyone heard this one? I’d love to know.

5. False claim: HIV was added to COVID vaccines.
   Fact: HIV was not added to COVID vaccines. Anna Merlan is quoted: “As Anna Merlan writes for MIT Tech Review: “Widespread distrust of our public health system is reviving long-debunked ideas on HIV and AIDS — and energizing a broad movement that questions the foundations of disease prevention … One reason AIDS and covid denialists have been able to build similar and interlocking movements that inveigh against government science is that the early days of the two viruses were markedly similar: full of confusion, mystery, and skepticism.””

6. False Claim: Bill Gates inserted HIV into the Mpox vaccine.
   Fact: HIV was not added to the Mpox vaccine. I don’t know about you, but I had no idea that there were so many theories about “HIV” being added to vaccines. Also, I love how Gates is singled out personally.

7. False Claim: The US government is spending millions conducting HIV research on “transgender monkeys.”
   Fact: In 2022, the National Institute of Health (NIH) contracted a $477,121 study that looked at how hormone replacement therapy (HRT) may affect HIV treatment for trans women, where monkeys served as test subjects. Okay, this is getting ridiculous. Maybe that’s the point. They can’t refute the arguments of HIV AIDS skeptics, so they’re bringing out the most insane sounding ideas as a kind of smokescreen. We’re almost done. Thank God.

8. False Claims: Pete Buttigieg and Alicia Keys are HIV-positive.
   Fact: Alicia Keys and Pete Buttigieg do not have HIV. Wait, what? I can agree with their assessment though: “The falsehoods feed into existing racist and anti-LGBTQ stereotypes associated with HIV/AIDS.”

9. False Claims: Bleach, as well as other herbal remedies, can cure HIV/AIDS.
   Fact: There is currently no cure for HIV/AIDS. Who has ever claimed that bleach can magically make someone “HIV” negative? Donald Trump?

Well, that’s the end of that. I hope that provided a small amount of levity after the Lenacapavir article. As always, let me know what you think in the comments. Have you heard any of these points of misinformation?