This is incredibly exciting! The main method available for PrEP, in the United States, at least, is a daily pill. I think (I don't know) there is a monthly shot, too.
Daily pills take a lot of time investment; monthly shots are better; but once every 6 months is awesome! Especially in circumstances where it might be difficult to guarantee a daily pill or even a monthly shot.
There is a generic daily pill (Truvada), a more expensive one (Descovy) and an every two months shot (Apretude.)
Apretude has lower efficacy than Descovy or Truvada, but once you factor in human error in taking a daily pill regimen, it is more even. Human error is a significant factor since the current treatment protocols say if you’re not sure whether or not to take it, it is safer to skip than to accidentally double the dose.
Seen these on commercial, I wish they stop with commercial for meds. Depressing asf, keep reminding me of my mortality while I’m trying to relax and enjoy a moment
I was talking about med ads in general, and yes I don’t need to be reminded humans can get stds from unprotected sex, nor I think that is a place for it
Every gay person I know, myself included, is on prep. From the VP at a Fortune 500 on down to a coffeeshop barista. Cost is not an issue, at least not in the United States.
Pretty much exactly what you expect given than promiscuity is not taboo in the gay community.
All in all, HIV just isn't a problem anymore. It's on the same sort of threat scale as any other STD. Even if you're infected, you just continue taking PrEP (technically PEP) for the rest of your life and that's about it. Normal life expectancy and not much other health complications for most people with consistent treatment.
It's frankly nuts that we don't make preventative medicine for transmissable diseases free in the rich world. It's so obviously in the collective interest to reduce prevalence.
There have been many failed attempts at developing suppressive, curative and preventative medicine against HIV over the decades, and not all of that was funded by charities or government grants that don't expect repayment - especially not the later stage trials.
Isn’t that the starting price? Insurance and countries can buy in bulk and bring it down. Then overtime doesn’t the price come down due to competition from generics?
Generics aren't possible in markets where the patent holder enforces their rights. The article is about how Gilead will allow certain poverty ridden countries to access the drug without the need to pay a licensing cost (i.e. they can receive a "generic").
Am I wrong in thinking this is a huge development? Maybe one of the most important stories for public health this decade?
AIDS kills more people than malaria, and preventing malaria has long been viewed as one of the lowest hanging fruits in public health.
Hoping for eradication is too much with the limited immunity duration, but if we can mass produce a vaccine - even if it has to be administered twice a year - this could save millions of lives over the course of a decade.
You need to be in the same place, at the same time, every day, and always have them with you, continually. You also need to keep them dry and at room temperature all the time, so no leaving them in your car.
> But people aren’t perfect and it’s easy to forget or miss pills — so in reality the pill is about 93% effective. That means about 7 out of 100 pill users get pregnant each year.
You mess up and you have HIV for life. It's better to have something that provides more stable protection :)
DOTS is effective for TB because it’s a time-limited treatment (usually 4 months for drug susceptible strains of TB) and is only relevant for treating infected individuals
DOTS wouldn’t be feasible for a prophylactic treatment like this as the number of participants would be huge and the treatment period is indefinite (ie: the patient’s lifespan)
I know from experience that I'm not able to take a vitamin D pill every day in the winter months to combat winter depression. It's actually kinda difficult to build habits like that, and I'd have to remember to bring it with me wherever I may go and stay for a couple of days.
I think I got monthly vitamin D supplements a while ago. Since the body stores it it was feasible to just take one large dose once a month. (however overdosing is still a possibility ; definitely never take a monthly pill daily).
Thanks. I just realized I can just take small handfuls from time to time. I should have been taking it daily but, likely because I don't care for it, I only remember to do so about twice a month.
I find such things inordinately simple. I wake, stretch, urinate, go take my vitamins and drink two glasses of water. A third follows me to my current home office, where I process emails, alerts, whatever may be.
I find the best time to triage overnight emails is when I'm not quite awake yet to realise I'm doing it. Less pain that way.
The key is it being part of a routine, and the easiest is a part of the wake routine. At least for me. Which is why I find human variance interesting.
Meanwhile scheduling something 6+ months out (a doctor's appointment, or maybe at a pharmacy) for a shot is quite difficult to keep on time. I have to schedule, I have to keep free, I have to keep it in my mental space (calendars on phones help, but still...).
I literally don't know what part of the planet I will be on in a week. How on Earth could I know where to schedule such a thing, months or even weeks in advance?
Yet I bet for the parent poster, scheduling things like this is a breeze. Wild. Totally incomprehensible for me, as maybe it being easy for me to daily schedule is for them?
How do you ensure that you always have a sufficient stock of vitamins either you, despite being in a different part of the world on a weekly basis?
Do you have kids, if so how do you deal with frequent disruptions to the morning routine? Do you not have days where you just need to get up and go e.g. to catch a flight, get to a meeting, take a kid to school, or because you stayed up late and got drunk, etc... and taking vitamins took a back seat?
I don't have much issue with buying vitamins, because I take them with me. Just as I take toothpaste, etc. If I am there long enough to need more vitamins, it is in the same category as needing more toothpaste, and you resupply as you would at home.
No kids. I do have emergency paging and downed server / PROD to deal with 24/7, not the same as kids, but wake-disrupting all the same.
There is rarely something urgent enough to prevent urinating in the morning, and being thirsty after waking up is typcially a no go either. If prod is down maybe I'll eval first, but humans need out and in of water. I'm not going to urinate on the floor, and I'm not going to sit dehydrated and parched mouth for long either.
So wake, urinate, drink and vitamins are in that too.
My vitamins are in the bathroom, and it takes less than 10 seconds to consume them.
> Do you have kids, if so how do you deal with frequent disruptions to the morning routine? Do you not have days where you just need to get up and go e.g. to catch a flight, get to a meeting, take a kid to school, or because you stayed up late and got drunk, etc... and taking vitamins took a back seat?
This is crazy. You deal with the morning routine by taking your pills when the alarm goes off, because there's nothing the kids can be doing that won't wait for that.
Flying, driving, and driving are exactly the same. Take your pill when the alarm goes off.
If you drank so much that it rendered you unconscious through the time you needed to take your pill, the solution is "don't do that". That's not exactly an unavoidable necessity of life.
Of course it's easier to get a shot than to take individual pills, I think people would universally agree on that.
Also with prep, since you have to continue dosing 2 days after last activity you get awkward situations where you left it at home or get distracted by life events.
I think this is more common because most people do event based dosing rather than continuous (which would form a habit of taking it every day).
When you're trying to limit the variables on a study, yes. HIV reception between men and women has many differences so it can be better to limit your study and get twice as much data
- Women and girls make up the majority of HIV cases, especially in the developing world
- If you're estimating the effect in both men and women, you're reducing your power to detect an effect in either group. If you have a limited budget, it's going to be hard to recruit, etc., you may well be better off powering your study for the group you think is going to be the most impactful, then going back. We saw this with the HPV vaccine - getting it going in the highest impact groups, and then going back later
- Preventing HIV in women also prevents maternal to child transmission
- "Men with HIV" are actually two different groups - men who have sex exclusively with women, and men who have sex with men. You then also need to power your study for both sub-groups.
That's inaccurate. The vast majority of all cases are in men. For instance in America only 22% of HIV+ people are women. Our World In Data has a map that shows this visually:
The only place this isn't true is sub-Saharan Africa. As there's no biological explanation for that discrepancy it's been hypothesized that it's because in Africa a lot of reported HIV cases are fraudulent, due to the large amount of AIDS/women specific foreign aid money and weak auditing standards.
The phrasing "majority of all cases, especially in the developing world" implies that it's true everywhere. Even putting that aside, it's only the bizarre situation in Africa makes the statement technically true. If we interpret it in the way it was meant to be interpreted then the statement isn't really true because everywhere that has reliable data shows the opposite: men get it the most.
I don't think the 'especially' has that implication when you consider the context of the article that we're commenting on. It's true that women and girls make up the majority of people living with HIV worldwide, and this is especially true of the developing world. On the other hand, your statement that "the vast majority of all cases are in men" is simply false. Depending on the interpretation of 'vast', it's arguably not even true in much of the West. For example, in the UK, about a third of people living with HIV are women; in the US it's about a quarter.
There's nothing 'bizarre' about the situation in Africa. People's sexual behaviour is different in different societies, and this can obviously influence how STIs are distributed among different groups in the population.
There is a societal reason; condom use and polygamy. Condom use is less common and polygamy more amongst straight people in sub saharan Africa.
There was also very prominent AIDS denialism up to the 2000s so there was a bunch of lost time leading to an explosion in infections; the most notable example being South African president Thabo Mbeki.
Penis in vagina. It's a specification. It's like "birthing parent", to be clear what hardware is being used.
Given that HIV infection rates are very variable (over an order of magnitude, sometimes two) by subpopulation, clarifications detailing what hardware is doing what are very necessary.
Here's a talk by someone from Gilead from a few years ago about how it works.[1] Back then they were still testing on animals.
It's amazing that a small-molecule drug can be that effective for six months. It's not a vaccine. It doesn't stimulate the immune system. Completely different mechanism. It's not a slow-release implanted thing, either.
That is what got me. How in the world does this drug have such a long life in the body? Can it bioaccumulate, and that's why it's only given every 6 months? If it can, are there effects that are not desirable?
Really cool. Is the mechanism already used for other diseases? Or is this a first-of-its-kind application that'll open the door to using the mechanism for others?
How does a shot that prevents HIV fit in with the current Republican project of killing women and exposing everyone else to unchecked disease? It seems we are working to cross purposes here.
During Covid the process chemists working on this, including my wife, and the group working on Remdesivir were the only ones not working from home at the Gilead's Edmonton facility.
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.
> 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.
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.
> 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.
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.
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.
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.
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.
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.
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!
Great news that it's so effective in women. Less great news is that availability to people who could use it the most is based on the whims of the drug maker.
At least for now, PrEP is available on most/all drug plans for free or very, very cheap, in the United States https://www.goodrx.com/truvada. No idea what happens when the ACA is further harmed.
And per the article,
> Drugmaker Gilead said it will allow cheap, generic versions to be sold in 120 poor countries with high HIV rates — mostly in Africa, Southeast Asia and the Caribbean.
So, the places that need it most will be able to get it for cheap. This is about as positive of a result as can be with how the modern world is currently laid out.
The people that need it the most in the countries that need it the most will likely be able to get it.
Daily pills take a lot of time investment; monthly shots are better; but once every 6 months is awesome! Especially in circumstances where it might be difficult to guarantee a daily pill or even a monthly shot.