I see these in the court document linked in the child comment, which looks like it's the same case, but not in the (archive version of the) Bloomberg article.
All 55 of those infections were observed in trial participants randomised to the tenofovir/emtracitabine groups. There were no infections in the lenacapavir group.
The site also indicated that "Adherence to F/TAF and F/TDF was low" which means those that got infected most likely weren't taking their pills on a daily basis, unfortunately.
It's not hard to find groups of society where expose to HIV is very high, which are the ideal groups to study. Many people in these groups see contracting HIV as inevitable and do not fear it as you would expect, as it is not seen as a shame or death as as it was around the late 80s.
There subculture of people are people who actively try to transmit / contract HIV, often at so called "biohazard parties".
So I won't tell you to keep reading like others (which you should), but these studies don't work by some research scientist having an HIV+ blood IV at the ready with some "you might notice a little prick" trope, they offer these medications to people that are already in high-risk groups and are conducting activities that make them the most likely demographic to obtain or transmit HIV. Folks like promiscuous homosexuals, prostitutes, drug addicts (risk of sharing needles), and focus groups like that.
I think this study was just young African women in a high incidence area. They basically picked the most likely place in the world a person would get it
"Lenacapavir works by binding directly to the interface between HIV-1 viral capsid protein (p24) subunits in capsid hexamers, interfering with essential steps of viral replication, including capsid-mediated nuclear uptake of HIV-1 proviral DNA, virus assembly and release, production of capsid protein subunits, and capsid core formation[1]... It functions by binding to the hydrophobic pocket formed by two neighboring protein subunits in the capsid shell. This bond stabilizes the capsid structure and inhibits the functional disassembly of the capsid in infected cells.[2]"
In other words, it prevents the virus' protein shell (capsid) from being built properly, which in turn prevents the virus from properly opening ("uncoating") once it enters a host cell.
> It functions by binding to the hydrophobic pocket formed by two neighboring protein subunits in the capsid shell
That's entirely cool to me, it operates by exploiting an "incidental construction feature" of the capsid and not targeting any specific feature in and of itself?
It's HIV itself that "knows" where the nucleus is and is actively trying to get there once it's inside your cell. It does this by walking itself along your cell's microtubial network. It would be fascinating if it wasn't so deadly.
by preventing viral capsid assembly, as noted in the article.
Once bound to the P24 capsid protein, the drug also interferes with other stages of the virus’ lifecycle[1]:
>Lenacapavir is a multistage, selective inhibitor of HIV-1 capsid function that directly binds to the interface between capsid protein (p24) subunits in hexamers. Surface plasmon resonance sensorgrams showed dose-dependent and saturable binding of lenacapavir to cross-linked wild-type capsid hexamer with an equilibrium binding constant (KD) of 1.4 nM. Lenacapavir inhibits HIV-1 replication by interfering 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).
Apple should have written it themselves. It's embarrassing that they didn't. Nonprofit Linux distros with one-millionth the resources manage to write package managers and run repos, and then with MacOS, Apple gives you diddly-squat.
Back in the day Apple marketed macOS as a serious Unix system for scientists and engineers boasting about NASA’s use of it.
I think if Apple aspired to lockdown general purpose computing they would push the ipad pro range with more models and slowly kill off the Mac but they’re not doing that.
> IMO, it's just counter to what Apple aspires MacOS to be.
Every OS wants to be attractive to developers. Apple has a long history of underdelivering this core proposition. To me it's an odd situation to reason about - look at Apple's dev conferences and then look at what it's like on the ground in dev's reality.
Please don't. It would be a resource hog SwiftUI monstrosity like the new Settings app. And while they are at it, they would probably introduce the 46353th bespoke feature into the Swift language too, because why not?
It would be (or at least have) a command-line utility like rpm, npm, apt, or pacman. That's necessary for it to integrate well with various installation scripts. So you wouldn't have to use a UI at all, especially if it's bad.
* Apple has no aversion to Ruby, and on the contrary has multiple developers pushing for it. They themselves had MacRuby, a project that allowed one to create Mac OS X (at the time) applications with Ruby.¹
* The reason there’s even an Xcode command line tools package available officially from Apple is because of Homebrew. A third-party made it first by extracting the necessary bits and then Apple officially supported it.²
* There’s a liaison between Homebrew and Apple, who helped during the Intel to Apple Silicon transition.³
Wrong. MacPorts started as official DarwinPorts, supported by Apple. It became independent later. It is a proper ports package manager.
Homebrew would have a good head start, because it can use a better language, ruby. But it blew its chances with many questionable choices, they are just amateurs. But as always, worse is better.
I thought it was clear from my comment that I was suggesting Apple would do it better. Think of how useful something like apt, npm, or pip is, and then realize that MacOS has no in-house equivalent.
I think saying it's the new binary is closer to the truth. You can't reproduce it, but you can use it. In this new version, you can even nudge it a bit to do something a little different.
New stuff, so probably not good to force old words, with known meanings, onto new stuff.
> The model is more akin to a python script than a compiled C binary.
No, I completely disagree. Python is near pseudo-text source. Source exists for the specific purpose of being easily and completely understood, by humans, because it's for and from humans. You can turn a python calculator into a web server, because it can be split and separated at any point, because it can be completely understood at any point, and it's deterministic at every point.
A model cannot be understood by a human. It isn't meant to be. It's meant to be used, very close to as is. You can't fundamentally change the model, or dissect it, you can only nudge it in a direction, with the force of that nudge being proportional to the money you can burn, along with hope that it turns out how you want.
That's why I say it's closer to a binary: more of a black box you can use. You can't easily make a binary do something fundamentally different without changing the source. You can't easily see into that black box, or even know what it will do without trying. You can only nudge it to act a little differently, or use it as part of a workflow. (decompilation tools aside ;))
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