How do tests for drugs like this get conducted?
"Here's a shot, go have sex with people with HIV"? I hope the young women conducting the trials were compensated sufficiently for the risk taken, especially those who contracted HIV during the period.
"Here's a shot, go have sex with people with HIV"? I hope the young women conducting the trials were compensated sufficiently for the risk taken, especially those who contracted HIV during the period.
Normally, some percentage of the population will get HIV in any given year. So what you do is give a bunch of people the shot and track them long term. You count how many got HIV after N years, compared to what would be expected in a normal population.
Nobody is exposed to HIV as part of the study, that exposure would come through the participants living their ordinary lives.
But paying people to be studied tends to be effective.
But I don't think the particular aspect of "making sure you have enough participants" interacts very much with ethics. Especially when the failure state in question is an honest failure to attract them.
In that case, someone at high risk for HIV infection could be prevented from getting treatment because of the study protocol. The ethical solution, which the authors of the study chose, was to provide the highest standard of care as the placebo - in this case it was Truvada.
Since the treatment was actually even more effective than the existing standard of care, it was a home run success. Their conclusion is even stronger than it would be if they used a non pharmaceutical placebo, so in retrospect their decision was clearly correct.
In this case the study cites that as being unethical due to the high prevalence of HIV in the target population. So the actual trial gave some people the shot, and some other people the known-working daily pills as a control.
Poking around, it's my understanding that double blind procedure only covers treatment allocation--that is, who gets the placebo or not--and does not exclude general experiment communication to patients. I imagine trial communication is something generic along the lines of "We're running a novel drug trial, help us gather more data for $50/shot."
As a South African, I appreciate that we're also the most unequal country in the world (by Gini coef). So, some of what was going on in my mind as I read the Bloomberg piece, was:
* did they choose people at random, because the high HIV rate is obviously skewed towards vulnerable groups (think a young woman who's financially dependent on her boyfriend, who has multiple partners)
* just because the HIV rate is prevalent, doesn't mean that young sexually active people would have multiple partners, so how do they account for situations where we were sexually active, but with 1 or safe partners
* condoms are freely available in clinics and often public toilets, and we've generally gone past the fear of asking for them. So how does safe sex affect their study
[0] https://www.wits.ac.za/news/latest-news/opinion/2024/2024-04....
They chose around 5000 people; they randomized them to either try the new shot, or one of two existing PREP drugs.
Of the 2000 people in the lenacapavir group, 0 got HIV, while dozens got HIV in the existing PREP groups.
When you have that many people and shuffle them, the groups end up pretty similar. You'd have to be really unlucky to get all the promiscuous people in the PREP groups.
PREP is already pretty effective; to have such a crushing result over PREP is a breakthrough.
It is in their interest to ... fudge the truth a little.
Now pfizer did this a different time by removing 2/3rds of the treatment group, and only counting "infections" if they occurred after all doses/boosters were administered. If you compare actual results to what pfizer published and claimed, you see that it was 7 infections in the placebo group and over 100 in the test group. they claimed <7 in the treatment group (i don't think it was 0, but it was like 2), and 7 in the placebo, saying "see, reduced infections by 80%!" Well, yeah, if you don't count infections and remove 2/3rds of the people who would have counted as infections possibly.
which means, and you don't even have to squint very hard, that the vaccine was actually increasing the chances of infection.
A lot of us are completely burned out and therefore wary on multinationals, regardless of their vertical. Pharma has a lot to answer for. Nestle has a lot to answer for. Chevron (et al) have a lot to answer for.
https://www.nejm.org/doi/full/10.1056/NEJMoa2034577#t2
Yes, the primary endpoint shown in here was comparing 7 days after dose 2 of the vaccine to 7 days after dose 2 of the placebo group. (table 2):
https://www.nejm.org/cms/10.1056/NEJMoa2034577/asset/619bcb1...
However, figure 3 breaks down the efficacy vs. time, and it shows no effect like he describes:
https://www.nejm.org/cms/10.1056/NEJMoa2034577/asset/fe40d07...
Instead, the vaccine and control groups were about the same until roughly day 10-12 after the first dose, and then dramatically diverged (though not as decisively as after dose 2).
I never made the statement that this was their South Africa (or africa) study. It isn't difficult to find the CEO of Pfizer saying their vaccine was "100% effective" in africa on twitter (there was a video, as well). that was my first claim.
Then i said "Now pfizer did this a different time ..."
edit: the source eludes me because i originally saw it on my cellphone in a video (the paper) and the bullet points were being read by an asian female. I failed to bookmark/save the video, and i have a hard time chasing down research that is this controversial without a DOI or PMC due to the ... tens of thousands of papers containing the same keywords.
I'm not claiming it's "buried" or "being kept from us" or anything conspiratorial, but it never got any play on mainstream media and would obviously get shadowbanned on any large site with funding from pfizer (et al) because of the "fact checkers want you to know that the vaccine has been proven safe and effective!" modal.
this has the 2/3rds participants excluded https://www.fda.gov/media/159195/download
but i am done for today, i have to crack some hydrogeology textbooks so i hope this stays up so i have my own reference for the next time i mention this
> The trial involved about 5,300 women and female adolescents ages 16 to 25 in South Africa and Uganda, some of whom who received Gilead lenacapavir, and others who received older once-daily drugs from Gilead, including Truvada or Descovy.
Not to mention a superficial understanding of how drug trials are conducted would exclude that method.
As I skim TFA, they say nobody who got the shot ended up getting HIV, which would be statistical anomaly for the population they tested.
They're not comparing the new treatment to nothing. They're comparing it to existing treatments.
> The shot was also superior to once-daily Truvada, another Gilead drug that is used for HIV prevention.
That's good news. As I understand it the existing treatments were already very good. And these injections are only once per year.
Probably quite a bit. The trial used the same dose of lenacapavir as what's used for maintenance in HIV patients; it's quite possible that less is needed to prevent infection in a healthy patient. Unfortunately, there's really no safe/ethical way for them to test lower doses.
It's like giving police officers new buller-proof vests, and then none of them getting in the firing line. You can't say that your vests are more efficient than other vests if they technically didn't get tested.
So, my thinking was how they ensure that all test groups are sexually exposed to other people with HIV, for the trial to be effective.
Think about it like studies on which cars perform better in crashes. They don't need to have people drive more wrecklessly to determine if the car is safer. They just need to look at the expected risk compared to the outcomes of the people who drive that car. They are already doing the risky thing.
They don't. Some people will organically have sex with people with HIV, and some will not. Your study just needs to recruit enough participants that it is likely some will. Your study absolutely does not tell people to deliberately have sex with HIV+ partners.
1: https://www.youtube.com/watch?v=-IffpoUQpDc&pp=ygUUdGhlIHZpY...
This was in South Africa. You might as conclude on life in America based on observations in Caracas.
This is explicitly referred to as a risk factor in the study, although they say "gender-based violence"