[HN Gopher] Gilead shot prevents all HIV cases in trial
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Gilead shot prevents all HIV cases in trial
Author : toomuchtodo
Score : 242 points
Date : 2024-06-20 19:12 UTC (3 hours ago)
(HTM) web link (www.bloomberg.com)
(TXT) w3m dump (www.bloomberg.com)
| toomuchtodo wrote:
| https://archive.today/7cGmG
|
| Press release: https://www.gilead.com/news-and-press/press-
| room/press-relea...
| nevi-me wrote:
| 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.
| mmh0000 wrote:
| You give the shot to a group and you give no shot to another
| group. Then you compare rates of HIV contractions between the
| two groups.
| tupshin wrote:
| The summary text explicitly called out why that would be
| unethical in this case.
| asveikau wrote:
| They don't ask people to live their lives any differently
| than they would, nor do they expose anyone to HIV on
| purpose; they just track them assuming that x% of people
| get HIV in any given year. So they compare what X is for
| people who got the shot, vs those who did not.
|
| 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.
| smeej wrote:
| It's not "no shot," though. It's other existing, widely
| available forms of pre-exposure prophylaxis.
|
| They're not comparing the new treatment to _nothing._
| They 're comparing it to existing treatments.
| asveikau wrote:
| Oh, ok, I skimmed past this:
|
| > 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.
| duskwuff wrote:
| Twice a year, but yes. That's a huge benefit -- not only
| is it easier for patients to stay on the treatment, but
| it's likely to be a lot cheaper as well.
| jghn wrote:
| They're comparing against typical rates of infection over time.
| Svoka wrote:
| How does your mind even go there? Did you consider they just
| give shots and see how many of treated got infected in
| treatment vs control group?
| nevi-me wrote:
| People are sexually active at different rates over different
| times, I also assume that a 100 people having sex with each
| other, where none of them have HIV, would not contract it.
|
| 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.
| opprobium wrote:
| South Africa (study was in SA and Uganda) has an adult HIV
| prevalence of 18.3% and 210k new infections per year. It is
| easy to select a high risk group in which you would expect
| to see new HIV infections during the course of the study
| without intervention.
| imzadi wrote:
| They don't need to ensure that all test groups are exposed
| to people with HIV. There is already a known risk factor
| for the specific population. All they need to do is see if
| the people who received the medication had
| more/fewer/similar infection rates as those who didn't.
|
| 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.
| loeg wrote:
| > 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.
|
| 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.
| langcss wrote:
| I think it is like coin flips, do enough of them and the
| total heads or tails gets very predictable even though
| individual flips are not.
| dekhn wrote:
| Here's the study page. https://www.purposestudies.com/purpose1/
| and extensive details on clinicaltrials.gov
| https://clinicaltrials.gov/study/NCT04994509 It's double-blind
| so the patients do not know if they received the drug or an
| alternative. The investigators inform the patients of the risk
| and tell them to do what they would usually do. The
| participants must meet certain criteria including already being
| sexually active. The investigators would not tell the
| participants to be more sexually active, or active with more
| risky people than they normally would. The prevalence of HIV
| infection in the area is already fairly high so people are
| actively at risk already. I believe there was only very limited
| compensation.
| withinrafael wrote:
| I didn't think the question was unreasonable as some suggest
| and couldn't find an answer in any of the replies to you.
|
| 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."
| bee_rider wrote:
| I don't think the question is inherently unreasonable, but
| they asked it in a really flip and disrespectful way, and
| weirdly went with a very negative assumption. There's also a
| whole field of medical research ethics and, I guess, it is
| hard to believe that somebody could be not aware of that
| (then again, I guess everyone has to learn it at some point).
| nevi-me wrote:
| Yeah, I asked it in a negative way, probably because I hold
| the view that Africa is the dumping ground for unethical
| behaviour/products. Just 2 months ago we were outraged at
| Nestle putting sugar in baby foods [0] in Africa. We have 2
| kids, the eldest of which is addicted to sugar.
|
| 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....
| mlyle wrote:
| > So, some of what was going on in my mind as I read the
| Bloomberg piece, was: did they choose people at random
|
| 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.
| x0x0 wrote:
| It was literally answered directly in the article
|
| > _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.
| 3523582908 wrote:
| A while ago I watched this highly disturbing documentary
| produced by Vice about the prevalence of rape in the DRC as a
| weapon of war and terror against women. [1]. I have to imagine
| that this is involved, somehow.
|
| 1:
| https://www.youtube.com/watch?v=-IffpoUQpDc&pp=ygUUdGhlIHZpY...
| folli wrote:
| How so?
| JumpCrisscross wrote:
| > _the prevalence of rape in the DRC_
|
| This was in South Africa. You might as conclude on life in
| America based on observations in Caracas.
| asveikau wrote:
| As I understand it would go like this:
|
| 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.
| worldvoyageur wrote:
| From Gilead's press release:
|
| " PURPOSE 1, a Phase 3, double-blind, randomized study, is
| evaluating the safety and efficacy of twice-yearly, subcutaneous
| lenacapavir for pre-exposure prophylaxis (PrEP) and once-daily
| oral Descovy(r) (emtricitabine 200mg and tenofovir alafenamide
| 25mg; F/TAF) in more than 5,300 cisgender women and adolescent
| girls aged 16-25 across 25 sites in South Africa and three sites
| in Uganda. The drugs are being tested in parallel, with one group
| receiving twice-yearly lenacapavir and one group taking once-
| daily oral Descovy. Additionally, a third group was assigned
| once-daily oral Truvada. Study participants were randomized in a
| 2:2:1 ratio to lenacapavir, Descovy and Truvada, respectively.
| Because effective PrEP options already exist, there is broad
| consensus in the PrEP field that a placebo group would be
| unethical; thus, the trial used bHIV as the primary comparator
| and Truvada as a secondary comparator.
|
| There were 0 incident cases of HIV infection among 2,134 women in
| the lenacapavir group (incidence 0.00 per 100 person-years).
| There were 16 incident cases among 1,068 women in the Truvada
| group (incidence 1.69 per 100 person-years). The results
| demonstrated superiority of twice-yearly lenacapavir over bHIV
| (primary endpoint, incidence 2.41 per 100 person-years) and
| superiority of twice-yearly lenacapavir over once-daily Truvada
| (secondary endpoint), with p<0.0001 for both endpoints. In the
| trial, lenacapavir was generally well-tolerated and no
| significant or new safety concerns were identified.
|
| [...]
|
| Gilead expects results in late 2024/early 2025 from the program's
| other pivotal trial, PURPOSE 2, which is assessing twice-yearly
| lenacapavir for PrEP among cisgender men who have sex with men,
| transgender men, transgender women and gender non-binary
| individuals who have sex with partners assigned male at birth in
| Argentina, Brazil, Mexico, Peru, South Africa, Thailand and the
| United States. "
| levocardia wrote:
| This is a legitimately amazing result and a huge win against
| HIV. I hope it replicates in PURPOSE 2. Zero incident cases in
| an at-risk population is, frankly, fantastic, in a country
| where prevalence of HIV ranges from 12-27% depending on the
| province.
| hawk_ wrote:
| VaaS (Vaccine as a Service) suits Gilead as a business model,
| vfclists wrote:
| How come they use the phrase "cisgender women and adolescent
| girls aged 16-25"? Aren't 16 year old females "women"? Do they
| think the terms "cisgender" is that meaningful to Africans or
| that the term matters to Africans?
| devman0 wrote:
| I read that as cisgendered && (women || adolescent girls) &&
| (16 <= age <= 25). Basically 'cisgendered' and the age range
| are describing all study participants which which are all
| either women or adolescent girls which makes sense to me
| based on how I believe these trials are generally
| constructed.
| aetherspawn wrote:
| Well HIV is most common amongst homosexual populations, so it
| is just clarifying that they gave the drug to straight girls
| in the first trial.
| viraptor wrote:
| Cisgender doesn't mean straight. They may be homosexual,
| just not trans.
| frankvdwaal wrote:
| It says cisgendered, not straight, though.
| mandevil wrote:
| This prevalence is true in the US (and most Western
| countries I think, though not as certain), is definitely
| not true in Sub-Saharan Africa (where 75% of the world's
| HIV+ population lives). Women and girls are more likely to
| have it in Sub-Saharan Africa. See
| https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10126805/
| estimates that over 60% of all new infections in SSA are in
| women. Parts of that region the HIV+ prevalence rate is
| above 5%. That is why they are focused on testing that
| population in that region, they are the most at risk.
| senordevnyc wrote:
| Just going by the name, the "Gilead Shot" sounds like the last
| thing I'd want if I were a woman.
| Rediscover wrote:
| My thoughts too, biased by a Margaret Atwood novel:
|
| https://en.m.wikipedia.org/wiki/The_Handmaid%27s_Tale
| eindiran wrote:
| The Republic of Gilead is named for the biblical name
| "Gilead" for a region in Jordan[0]; the shot is presumably
| named for the Balm of Gilead[1], also named for biblical
| Gilead.
|
| [0] https://en.m.wikipedia.org/wiki/Gilead
|
| [1] https://en.m.wikipedia.org/wiki/Balm_of_Gilead
| duskwuff wrote:
| Gilead is the name of the pharmaceutical company, not the
| drug.
|
| The trade name of the drug is Sunlenca; the generic name is
| lenacapavir.
| mikeyouse wrote:
| And fwiw, the company Gilead is indeed named for the Balm
| of Gilead.
| kube-system wrote:
| Manufacturer names are frequently associated with their
| products.
|
| e.g. nobody says "did you get Comirnaty or Spikevax?
| bobthepanda wrote:
| Descovy and Truvada are already more commonly referred to
| by their marketing names than with Gilead's. Hard to see
| how this new shot would be different.
| janice1999 wrote:
| It might be a PR decision to encourage the name to hide the
| fact Gilead "Profited by Slow-Walking a Promising HIV Therapy".
| Profit before health.
|
| https://www.nytimes.com/2023/07/22/business/gilead-hiv-drug-...
| JumpCrisscross wrote:
| "For most people, experts say, the two tenofovir-based drugs
| -- the first known as T.D.F., the second called T.A.F. --
| offer roughly equal risks and benefits."
|
| Do we have an update on the case?
| MrLeap wrote:
| A childhood friend of mine died of AIDs related complications a
| few years ago. I hope this saves a lot of people.
| dekhn wrote:
| HIV/AIDS dominated my high school years; it was just starting
| to become known; the first reported US case was in 1981, and in
| 1983, the disease (AIDS) was traced to the virus (HIV). My
| biology class had a poster of all the things AIDS could present
| as (kaposi's sarcoma, etc). At the time HIV was effectively a
| death sentence and it really affected places like SF heavily.
|
| One of my main motivations in college and grad school was to
| work in drug discovery, specifically for HIV. At the time
| (~1995-2000) we were just starting to see positive results from
| protease inhibitors and reverse transcriptase inhibtors came
| somewhat later leading to the current "managment of HIV through
| HART" https://en.wikipedia.org/wiki/Management_of_HIV/AIDS
|
| All of this came slowly - decades between significant new
| technologies/improvements in treatment. many sources of
| infection such as blood transfusions are now much less risky
| (people in the 70s and 80s were getting hep C and HIV from
| blood taken from HIV-positive donors). And the disease presents
| very differently in the US vs. other areas such as Sub-Saharan
| africa. But with extensive effort, prevention has gotten better
| and treatments have gotten much better. If there are truly
| usable preventatives for at-risk populations, and those
| medications are affordable, it will be a huge boon to the
| recipients.
|
| Some interesting things to note:
|
| - there was a lot of controversy about the source of infection
| and a lot of people used this to criticize gay people and
| injected drug users.
|
| - one of the world's most famous virologists,
| https://en.wikipedia.org/wiki/Peter_Duesberg actively denied
| that HIV caused AIDS and instead thought it was transmitted by
| drug use. Note "Duesberg entered a long dispute with John
| Maddox, then-editor of the scientific journal Nature, demanding
| the right to rebut articles that HIV caused AIDS." which I
| think presages the current arguments about what scientists can
| say regarding the origins of COVID. The impact of his
| statements in South Africa was significant. From what I can
| tell he was completely off base and never made any truly
| convincing arguments for his position.
|
| - Fauci, of COVID fame, played a big role in getting NIH and
| the various AIDS community organzations working together and
| making large improvements to HIV/AIDS treatment. Before that,
| Fauci was heavily criticized by various LBGTQ orgs (see
| https://www.nytimes.com/2022/12/31/opinion/anthony-fauci-
| hiv...) "Larry Kramer, one of the group's founders, wrote an
| open letter to Dr. Fauci in The Village Voice calling him a
| murderer and comparing him to the Holocaust organizer Adolf
| Eichmann." Again, all this presages the later treatment of
| Fauci by various political groups during COVID. I often think
| back to Fauci during HIV/AIDS while reflecting on the current
| situation around COVID and I think we got lucky to find
| somebody like him, even if he said a few dumb things, and we'll
| be lucky if any public servants are willing to take up his role
| in the future.
|
| - modern gene therapy often uses variants on HIV as the vector.
| That's right: it's so good at getting into cells and modifying
| the genome, that we use it as the preferred method. it took
| quite some time before the vectors were made safe enough
| (https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5152689/)
| mrmetanoia wrote:
| One of my in-laws is a full on Fox news nut, but has a rare
| condition that he received treatments for as part of an NIH
| study that did him a world of good and Fauci was one of the
| doctors that worked on it, as a result the bits of nuttery he
| didn't buy into were attempts to discredit Fauci or anti-vax
| stuff. Oddly it didn't pull into question any other beliefs
| he picked up from that station.
| YeGoblynQueenne wrote:
| >> one of the world's most famous virologists,
| https://en.wikipedia.org/wiki/Peter_Duesberg actively denied
| that HIV caused AIDS and instead thought it was transmitted
| by drug use.
|
| I'm curious about his claim that retroviruses (retrovirii?)
| must be harmless to survive and multiply. What is the
| mainstream consensus on this?
|
| To be clear: I know next to nothing about viruses (virii? I
| mean I don't even know how to call them) and I have no idea
| whether it really supports Peter Duesberg's claims about AIDS
| in general. I'm just wondering whether he's pointed out an
| interesting peculiarity of HIV that is not further
| investigated by others for fear of being accused of
| denialism.
|
| Scientists can get very like that.
|
| >> (...) the current arguments about what scientists can say
| regarding the origins of COVID.
|
| It reminded me most about John Ioannidi's polemic against the
| way COVID was dealt with, rather than its origin. Ioannidis
| is a leading epidemiologist so he had to be taken seriously,
| although of course his opinion was rejected by most everyone
| else.
| musha68k wrote:
| Amazing. I guess SARS-CoV-2 is much less stable in comparison to
| HIV?
|
| Higher mutation rate and other shifts vs broadly neutralizing
| antibodies? Anyways, it would be nice to fully "solve" COVID-19
| as it's still wreaking havoc somewhat silently (?)
|
| I also wonder when or if we'll see therapeutic vaccines against
| either of these and more sooner than later?
|
| Each time I only briefly start staring into the abyss that is
| "wetware" I'm gladly returning to our comparatively trivial
| (self-inflicted) complexity in the world of software / computing.
| frankus wrote:
| I'm not sure if taking e.g. Paxlovid as pre-exposure
| prophylaxis has been studied, but my guess is that the side
| effects from the drug are worse in the long run than the
| disease itself (especially if the seriousness can be blunted
| via vaccination).
|
| Since people don't spontaneously recover from HIV infection,
| and the PrEP drugs have relatively few side-effects, the
| tradeoff is more favorable.
| ds_opseeker wrote:
| In the long run, the side effect of HIV is death due to total
| collapse of the immune system.
| worstspotgain wrote:
| Turns out you can do Covid PrEP with just Neosporin in your
| nose. It works for other pathogens too:
|
| https://www.pnas.org/doi/10.1073/pnas.2319566121
|
| In case you're wondering, this paper is 100% legit, see e.g.
| the bio for the big-shot author:
| https://en.wikipedia.org/wiki/Akiko_Iwasaki
|
| No clue if this _easy trick_ would induce immune escape if a
| large number of people started using it. I guess it 's a good
| time to get in on the ground floor.
| Fomite wrote:
| HIV is notoriously unstable - RNA viruses don't contain any
| error checking during replication. Which is one reason HIV
| drugs, including those one, are almost always used in
| combination.
| uiberto wrote:
| coronaviruses are also RNA viruses, fwiw
| worstspotgain wrote:
| There are several variant-resistant pan-Covid/pan-
| Sarbecovirus/etc. vaccines under development [1], including one
| by the US Army [2].
|
| Vaccines are notoriously slow to develop, perfect, and test for
| safety and efficacy. The original Covid mRNA vaccines were
| developed at breakneck speeds as far as vaccines go.
| Unfortunately, much of the funding has since dried up.
|
| In fact, it's HIV that's much harder to develop a vaccine for.
| HIV vaccine research has been going on for 40 years and hasn't
| really had any candidates that went beyond "plausible" until
| recently.
|
| [1] https://www.nature.com/articles/s41423-023-01116-8
|
| [2]
| https://mrdc.health.mil/index.cfm/media/news_releases/2021/p...
| opprobium wrote:
| This injection isn't a vaccine, it's an anti-viral drug being
| used as pre-exposure prophylaxis. The first approval of this
| approach was in 2012, but using an oral pill with a short half-
| life taken daily.
|
| That drug is still in use and also highly effective, the new
| improvement is to provide the same approach with a longer
| acting injected drug. One reason there has been great interest
| in this, despite the already effective oral PREP, is that there
| are thought to be socio-behavior advantages for cases like
| women in Africa as in this study. For example: the woman does
| not have to keep a supply of daily pills that a partner can
| find. Also possibly improved adherence with no missed doses.
|
| The drug itself is not thought to be more biologically
| effective than the oral drugs, which are basically already at
| close to 100% effective assuming the patient actually takes
| them as scheduled.
| Lammy wrote:
| Relevant Bill Hicks (1989) :)
| https://www.youtube.com/watch?v=lxjyg5dTx6k
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