[raylad]

This treatment does not in fact prevent HIV infection. It prevents infected cells from producing viable virus particles.

Because of this, it seems very likely that if any patient being treated with this drug ever discontinued it, they could develop HIV quickly from cells that were already infected in their body that had been suppressed from producing virus particles but were no longer suppressed.

I was not able to find, in a little searching, any study at all on whether cells infected during treatment survive or are somehow cleared by the immune system or undergo apoptosis. Without this information it seems highly irresponsible to claim that this is a method of preventing HIV infection.

[JumpCrisscross]

> This treatment does not in fact prevent HIV infection. It prevents infected cells from producing viable virus particles

Lenacapavir interferes "with multiple essential steps of the viral lifecycle, including capsid-mediated nuclear uptake of HIV-1 proviral DNA (by blocking nuclear import proteins binding to capsid), virus assembly and release (by interfering with Gag/Gag-Pol functioning, reducing production of capsid protein subunits), and capsid core formation (by disrupting the rate of capsid subunit association, leading to malformed capsids)" [1].

For comparison, tenofovir diphosphate (from Descovy) "inhibits the activity of HIV reverse transcriptase and causes DNA chain termination after getting incorporated into the viral DNA" [2].

Descovy thus works at stage 3 (reverse transcription); Lenacapavir works at stages 3 (integration), 6 (assembly) and 7 (budding) [3].

> it seems very likely that if any patient being treated with this drug ever discontinued it, they could develop HIV quickly from cells that were already infected in their body

HIV-uninhibted T cells should be fine clearing these out. IT would be more surprising to see the cells stick around after having been infected.

[1] https://dailymed.nlm.nih.gov/dailymed/drugInfo.cfm?setid=e56...

[2] https://www.clinicaltrialsarena.com/projects/descovy-emtrici...

[3] https://hivinfo.nih.gov/understanding-hiv/fact-sheets/hiv-li...

[raylad]

The references you provided are prescribing information and to other drugs which actually are anti-retroviral.

You did not provide any reference showing that cells that are actually infected but inhibited from producing virus through late stage assembly inhibitors are effectively eliminated by the immune system.

[JumpCrisscross]

> references you provided are prescribing information and to other drugs which actually are anti-retroviral

The first reference is for literally this drug.

> did not provide any reference showing that cells that are actually infected but inhibited from producing virus through late stage assembly inhibitors are effectively eliminated by the immune system

I did not because this is the normal function of the immune system. The extraordinary claim, yours, is that these cells will somehow get missed by the immune system.

[raylad]

Right. It’s prescribing information.

As per whether infected cells that don’t display any evidence of virus on their surfaces would somehow be detected and killed or would undergo apoptosis, that might happen but I don’t find any evidence that it does.

[roywiggins]

PrEP is not new, surely if this was common there would be studies showing everyone going off PrEP suddenly testing positive at enormous rates?

[raylad]

The existing PrEP drugs work differently.

Cabotegravir is an integrase strand transfer inhibitor. This means it blocks the HIV's enzyme integrase, thereby preventing its genome from being integrated into the human cells' DNA.

Emtricitabine is an analogue of cytidine. The drug works by inhibiting reverse transcriptase, the enzyme that copies HIV RNA into new viral DNA.

Both of these drugs actually prevent infection.

[mike_hearn]

The problems are bigger than that. The trials don't attempt to show impact on AIDS itself. Biomarker studies like this have a long history of going wrong due to statistical or theory related problems.

[roywiggins]

HIV isn't a biomarker, it's the cause of AIDS. People without detectable HIV don't develop AIDS.

People with HIV and on ARVs don't develop AIDS either, and any study that watched people contract HIV but didn't provide their participants with ARVs would be both unethical and pointless.

[mike_hearn]

By definition anything that isn't the actual disease is a biomarker proxy for it. What actually matters is disease.

> People without detectable HIV don't develop AIDS.

An AIDS diagnosis requires the presence of HIV so your statement is a tautology (not your fault). If we rephrase to what you meant, that people without detectable HIV don't develop AIDS or any identical set of symptoms, then actually they do but when it happens it goes by a different name (ICL, idiopathic CD4 T lymphocytopenia).

ICL is what they call AIDS that appears in HIV negative people and is essentially ignored by the public health community, as it's not supposed to exist.

[JumpCrisscross]

> what they call AIDS that appears in HIV negative people and is essentially ignored by the public health community, as it's not supposed to exist

And people who test negative for influenza often show flu-like symptoms, must be a conspiracy.

[roywiggins]

why should anyone care whether a drug that targets HIV has any effect on medical conditions that aren't caused by HIV? you wouldn't expect it to!

[mike_hearn]

They care because they think the claim that AIDS is caused by HIV is wrong, and that AIDS/ICL are in reality the same thing with a shared root cause.

The claim of a viral cause came from Team Fauci in the 90s, who we now know are all pathological liars who happily conspire with each other for their own ends. We can read the Slack logs where they arrange their conspiracies, even. Back then there were renegade virologists and journalists who claimed there was a coverup by virologists in progress, and the inventor of the PCR test agreed with them, but they were ignored because people thought scientists were ideal people who would never do things like that. That was wrong, so the prior for there being a COVID style problem back then too should be strong.

It's reasonable to disagree with that perspective, of course. You can point to pieces of evidence, other people can debate them. It's not reasonable to be like JumpCrisscross and simply roll your eyes at claims of medical malfeasance anymore - that's a severe case of non-memo-getting at this point. A rational person should default to assuming anything involving Fauci and virologists is unreliable. When Nobel-prize winning scientists and journalists speak up and provide a great deal of detail on an alleged conspiracy, priors should then get stronger (and they did). When Pharma companies do tests that implicitly claim to cure AIDS but don't actually test that claim, they should get stronger still.

Or you can be like JumpCrisscross and continue eye-rolling at anyone who has lost trust in the institutions. Don't be like that!

[roywiggins]

More than a million Americans are on PrEP. If any of them are contracting AIDS while HIV-negative, we would have noticed by now.

[John23832]

That’s because aids, the subsequent syndrome derived from hiv infection, wasn’t the target of the study?