Comment by criticaltinker | Hacker News Reader

Comment by criticaltinker | Hacker News Reader

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Ivermectin used in a single-drug treatment regime has not shown significant benefits in a number of RCTs. However there is promising evidence of significant benefits when Ivermectin is used as part of a multi-drug treatment regime [1].

Since the beginning of the pandemic many front-line doctors have been combining multi-drug treatment regimes with early (in the symptomatic phase) treatment to successfully reduce hospitalization and death [2][3][4][5][6].

[1] Ivermectin in combination with doxycycline for treating COVID-19 symptoms: a randomized trial https://pubmed.ncbi.nlm.nih.gov/33983065/

[2] Multifaceted highly targeted sequential multidrug treatment of early ambulatory high-risk SARS-CoV-2 infection (COVID-19) https://scholarlycommons.henryford.com/cgi/viewcontent.cgi?a...

[3] Timing of Antiviral Treatment Initiation is Critical to Reduce SARS-CoV-2 Viral Load https://ascpt.onlinelibrary.wiley.com/doi/pdf/10.1002/psp4.1...

[4] Clinical outcomes after early ambulatory multidrug therapy for high-risk SARS-CoV-2 (COVID-19) infection https://rcm.imrpress.com/EN/article/downloadArticleFile.do?a...

[5] Early multidrug treatment of SARS-CoV-2 infection (COVID-19) and reduced mortality among nursing home (or outpatient/ambulatory) residents https://www.sciencedirect.com/science/article/abs/pii/S03069...

[6] Multidrug treatment for COVID-19 https://www.jstage.jst.go.jp/article/ddt/advpub/0/advpub_202...

You have, say, 10 different drugs you might use along with Ivermectin in a "multi-drug regime". From these 10 drugs, you can generate 10-choose-4 = 5040 different 4-drug regimes. As many as you please, effectively.

Assuming Ivermectin is useless, and your study is p95, how many false positives do you expect to get?

Unlike drawing a card from a deck, you don't need to choose drugs randomly. You can use existing safety and efficacy profiles to narrow the search - and in the case of SARS-CoV-2 you're likely looking for combinations of categories, e.g. antiviral, corticosteroid, and antithrombotic.

I agree though, the search space can explode quickly. Assuming Ivermectin is useless might be fair given the lackluster benefits seen in RCTs using it in single-drug regime. P95 is 2 sigma - typically in RCTs you'd be looking for stronger statistical significance, to reduce the risk of false positives as you allude to.

You certainly have a valid point, but hopefully you agree that it doesn't need to stop us from continuing to evaluate treatments using existing and widely available medicines.

[7] Favorable outcome on viral load and culture viability using Ivermectin in early treatment of non-hospitalized patients with mild COVID-19 – A double-blind, randomized placebo-controlled trial https://www.medrxiv.org/content/10.1101/2021.05.31.21258081v..., https://www.jpost.com/health-science/israeli-scientist-says-...

Ivermectin has shown some antiviral activity in a number of credible studies, but it is by no means a miracle cure. As the virus is bound to mutate and potentially evade the current vaccines (according to none other than Pfizer CEO), developing treatments, even if imperfect, as a second line of defense, must be a very high priority.

IF ivermectin were an actually useful treatment (huge IF), and it were actually deployed at scale, you would see an immediate rise in ivermectin resistant virus. Antivirals are very different from vaccines. They hit one target at one place in on specific binding mode, and it is easy to mutate so that the antiviral doesn't work. A vaccine produces a different repertoire of antibodies in every single person. No single mutation or even group of mutations affects the immune response in the same way from one person to another. It's bad luck that delta got so "lucky" in its enhanced transmissibility, but the vaccines are still effective against delta. An antiviral will not be effective against the next variant that comes after the antiviral is launched. Vaccines are the answer. If we need a slightly tweaked new booster for delta or lambda or whatever is next, I'm getting that and staying away from ivermectin et al.

Are you making a blanket statement that no antiviral treatment can possibly exist for long? I am not an expert, but Tamiflu is a widely available influenza antiviral.

Please make a comprehension effort: I am not suggesting that Ivermectin is some sort of miracle cure. I'm simply saying that I would sleep much better at night knowing that if the mRNA vaccines are evaded through evolution (they are narrower than natural immunity), there is a secondary line of defense, ideally with multiple alternative treatments. Whether these are Ivermectin (unlikely given the data so far), fluvoxamine (recently touted in the press), remdesevir, a derivative or something completely new, I don't know.

Edit. I looked up Tamiflu on Wikipedia, https://en.wikipedia.org/wiki/Oseltamivir. Alas, there are reasons to believe it not a miracle cure either.

> A 2014 Cochrane Review concluded that oseltamivir does not reduce hospitalizations, and that there is no evidence of reduction in complications of influenza.[9] Two meta-analyses have concluded that benefits in those who are otherwise healthy do not outweigh its risks.[10][11] They also found little evidence regarding whether treatment changes the risk of hospitalization or death in high risk populations.

I mean, anything is possible. Death rays from mars could strike me down tomorrow at 10 am. But it is certainly unlikely that a given antiviral would be effective for long. Tamiflu is very much widely available, but it is not really deployed (administered) at scale. At peak, and now down >50%, tamiflu sales were about 1B. Even if tamiflu were $1 a dose (it's not), we are talking about a very very small portion of the global influenza patients having taken it. So yes I think that, if tamiflu were a strong protection against severe flu (it's not) and it were deployed at scale (never has never was), its usefulness would not last long.

Scenario: X suffers a breakthrough infection and is hospitalized. Doctors estimate a ventilator may be necessary in a couple days. Would you X have access to a last minute post-infection treatment, even imperfect, or just resign yourself to the likely tragic outcome?

(Also, Tamiflu apparently doesn't work. Ugh...)

So "moving the goalposts" is a strategy that anti-vaxxers have been known to employ to try to stay relevant.

The first posts about Ivermectin claimed it itself was a miracle drug. One major retraction later, apparently now it only works when taken with hydroxychloroquine, or whatever new drug cocktail is supposed to make it work.

When that's disproven, it will be it needs to be taken 6 months before infection or whatever new drug needs to be taken, and the goal posts keep getting pushed back.

What's worse is this style of "dying-on-your-hill" argumentation prevents people from actually getting the vaccine. It's more important to be right these days, then for people to be vaccinated.

Just take the vaccine already.

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