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.
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.
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.
That is a matter of opinion. How much time do you think it takes to swallow a pill?
Here's another example of a pill that needs to be taken every day, at approximately the same time of day: https://www.plannedparenthood.org/learn/birth-control/birth-...
From this article on that pill,
> 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 :)
Having a shot like this be widely available will be an important stepping stone for eradicating HIV.
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).
So not as well? Is there a biological reason for this?
Also, is it typical to do such studies on single genders rather than on a mix of humans?
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.
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.
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.
It's still about a dollar a day, which is a lot of money for the most needy.
Now? You don't keep up on your immunisations? Ever seen an old person's medicine cabinet?
- 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.
https://ourworldindata.org/hiv-aids
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.
Receptive vaginal sex: 0.08% (1 transmission per 1,250 exposures)
Insertive vaginal sex: 0.04% (1 transmission per 2,500 exposures)
Receptive anal sex: 1.4% (1 transmission per 71 exposures.)
Insertive anal sex: 0.11% (1 transmission per 909 exposures)
[1] https://stanfordhealthcare.org/medical-conditions/sexual-and...
https://www.cdc.gov/hiv-data/nhss/estimated-hiv-incidence-an...
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...
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.
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.
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.
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").
The $40k+ price is the cost of the 2x pa injectable form. This is a relatively newer treatment and not widespread.
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.
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.
If only we had an institution with the aim of pursuing the long-term interests of the collective.
The OP article covered Mexico which remains closer to the US in outcomes being heavily male-gendered.
https://www.unaids.org/en/regionscountries/countries/mexico
https://www.statista.com/statistics/941203/distribution-indi...
* condom use is much lower in sub-Saharan Africa
* polygamy, specifically a man with multiple wives, is also more common in sub-Saharan Africa
This is already possible by DOTS.
In India it did wonders
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)
For a sexually transmitted disease? Harder than you'd expect, considering people are reticent about their private lives.
> short-course
This needs to be continued forever, as far as I understand.
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.
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.
https://www.unaids.org/en/resources/infographics/girls-and-w....
https://www.hiv.gov/hiv-basics/overview/data-and-trends/glob...
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 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.
> 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.
And people who test negative for influenza often show flu-like symptoms, must be a conspiracy.
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!
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?
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?
The meds are always next to bed, and a pouch with meds for when I travel, plus a set of them in my backpack in case I sleep out of home.
When I was in a relationship and we lived separately, I had two sets - one on my place, another in my gf’s place.
It’s a bit like “how do you manage to brush your teeth daily if you have a chaotic routine”.
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.
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.
AIDS is a syndrome, what a sufferer dies from is specific diseases they become vulnerable to. Go back to the 90s and you can find doctors claiming they were pressured not to report suspected cases of AIDS in people who were HIV- but rather to report them as individual unrelated cases of the specific diseases they contracted, or as ICL and so on. The people who aggregate the data decide who dies of what.
Nevertheless you do have to remember to pack them, and you need to regularly replenish your stocks. I'm guessing that this replenishing happens at least as often as every 6 months, which is how often you need to arrange the injection in question. By the sounds of it you do a lot of travelling, so you may need to anticipate cases where you are away at the time you would normally replenish stocks.
> you resupply as you would at home
How does that happen? You notice how many pills are left in the bottle, and make a note to order more when it's getting low? Or immediately make an order there and then?
I know I'm being really pedantic, but I'm trying to illustrate why many people would perceive daily pill-taking to be strictly more labour-intensive than a 6-monthly injection.
What order? Order? I go to the grocery store from time to time. I also go to the pharmacy. When I do, I buy things I require. It's literally that simple. I do the same with any other type of food, or supply I need.
Why aren't you asking me if I have trouble buying butter, toothpaste, salt, pepper? I see I'm getting low, and I buy. Done. Super simple.
Literally, the entire planet seems to do it mostly this way.
That doesn't move me away from my hunch that the jab is more convenient for many. Studies show that around 30% of people faily to brush the recommended twice a day.
As you say though, the shot may not be everyone's preference, but it will be great for many.
[0] https://www.ada.org/resources/research/health-policy-institu...
I feel you don't have young kids then. Jumping on you, bleeding, having a nightmare, making possibly-chocking-sounds, running away with your pills, vomiting on the floor, etc. will definitely take priority over whatever you thought you were going to do after waking up. And that doesn't even touch on people with executive functions issues. Or the 1-2yo period where the time you officially wake up may be often a very fuzzy concept. (You mean the 5am wake-up, the 5.45 one, or the getting up after not falling asleep)
It's literally all the same thing. I wake up. I do wake up stuff. If there's some disturbance, some emergency, I still have to go to the bathroom, drink, and yes take vitamins eventually.
It's insanely simple beyond all belief. You just need to form a habit, that's all. "Take vitamins when first drinking water in the morning", or coffee, or whatever. Done. Done forever.
I get that my above statements baffle some people. As I said before, I don't get why.
You gotta pee? You __know__ you have to pee, unless you automatically relieve yourself, and if that's the case, that's quite abnormal.
I feel like this is one of those situations where you need to realize that some people - and on this issue, the research says *most people* are not like you. They are different. It really, truly can be as simple as that. Recognizing that people are different and have different needs and struggles is difficult for a lot of people, but still very important.
Think of it like ADHD. The solution for a person with ADHD is not "just use more alarms" or "just get good".
If you're asking in general, then the statistics show this is a problem in general population. Regardless of the specific reasons for it, people can't take daily pills perfectly on schedule.
"Compliance to antihypertensive treatment was found in only 15% of the patients." (https://pubmed.ncbi.nlm.nih.gov/15942423/)
"In the treatment of HIV and AIDS, adherence to antiretroviral agents varies between 37% and 83% depending on the drug under study (10, 11) and the demographic characteristics of patient populations" (https://iris.who.int/bitstream/handle/10665/42682/9?sequence...)
When you look at this as a population overview and you say you're got a routine and have a 100% compliance rate - you are the anomaly! But that also means your "just do ..." does not generalise for multiple reasons.
No, you're just desperately hoping to imagine a scenario that might make it difficult to take a pill with a one-minute take-it-now-or-die window. You're crazy, and you should try to refrain from arguing like that.
The only one of the things you mentioned that could even take priority over a scheduled pill is choking, though you should know that choking doesn't make a sound -- the whole problem with choking is that it blocks airflow -- so if the kid is making sounds, they're not choking. If your kid runs away with your pills, first, that implies that you keep them somewhere your kid can get them (?!), and second, catch them and take the pills back.
Most of what you mentioned is random nonsense that wouldn't even interfere with you. If a little kid jumps into you while you're swallowing a pill, you can just... keep swallowing. If they throw up on the floor, there's nothing time-sensitive about that in any way.
> I feel you don't have young kids then.
I don't, but then again, I have a brother and sister who were born when I was 16. I seem to have more relevant experience than you do. Learn to tell the difference between an emergency and a nothing.
There are plenty of things kids - especially young kids - will do that require you to push tasks back. Like a vomit, poo, or spillage situation needing immediate attention. Or throwing a tantrum if you try to bring them back upstairs where the pills are (thus waking everyone else up). Not to mention that it can be exhausting if they're not sleeping well - which can be half the time - and it's tough to remember every little thing when you're exhausted.
> If you drank so much that it rendered you unconscious ... that's not exactly an unavoidable necessity of life
You asked "how much time does it take to swallow a pill". The convenience of that depends on people's lifestyles. Lots of people will wake up at 7am in the week, go out and have a few drinks on Friday/Saturday, and wake up whenever/wherever they wake up the next day. That is not an extreme situation. It's a great freedom to dynamically adapt when you go to bed and when you wake up. Requiring a change to that lifestyle is hardly evidence that something is trivially simple.
What's more convenient and likely to be followed: a 6-monthly jab or a daily pill?
Is it possible to remember to do something everyday?That is because you know and she knows that the vitamins are unimportant.
> 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?
What's being asked here was "do you have days where you won't bother to take your medicine". And my point was, as a diabetic... no, I don't. I do it every day at pretty much the same time. And I expect most people could do exactly the same. Having children or wanting to stay out late drinking doesn't change that.
That being said, I 100% that I would prefer one shot every 6 months, if that was an option (I take 2 shots per day at the same times, and then 2-8 more over the course of the day)