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Comment by dougmwne | Hacker News Reader

I have always heard that Truvada (prep) was extremely effective at preventing HIV infection. These new injectables are reported by the article to be 89% and 66% more effective at preventing transmission.

What is this based on? Was I misinformed about Truvada's effectiveness? Is this a decrease in an already very low chance of transmission? Or is this in comparison to people forgetting to take their daily pills vs a shot that a health care provider had record of administering?

It's currently common in the gay community for sexually active, healthy people to take Truvada proactively to protect against HIV because it's understood to be even more effective than condoms. If there is a better option or if the current option is not as effective as widely believed then standard of care should change.

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It is a decrease in already low transmission. For ethical reasons, the placebo group is not no treatment, but rather current standard of care.

I had to do some digging to find any source on the effectiveness on preventing transmission (the recent FDA approval is for post infection treatment).

The study I found is [0]. In a double blinded study of 4,600 participants, half were given the cabotegravir injection, and half were given the daily oral treatment. The study notes a "high level of adherence to oral therapy"; however, the actual numbers on adherence are:

> Adherence to oral FTC/TDF was high, based on a random subset sampling that detected tenofovir (> 0.31 ng/ml) in 87% of all samples tested.

I'm not qualified to say if this actually indicates 87% adherence, or if a fully compliant patient may get a negative result on that test.

The result of this study was that 50 particpants got HIV, of which 12 were on the injectable and 38 were on the oral.

By my calculation, this gives a relative effectiveness of (38-13)/38 = 68.4%, although the paper reports 69%.

[0] https://viivhealthcare.com/en-us/us-news/us-articles/2020/gl...

This is awesome, thank you! The likelihood of pill compliance does seem to be probably higher than normal since everyone had 2 month follow-up appointments for injections, plus presumably they knew they were being blood tested. This looks like a game changer for HIV prevention. 6 shots a year and you can have better protection than any other known method. To me it looks like this is something that should be rapidly adopted.

> It is a decrease in already low transmission. For ethical reasons, the placebo group is not no treatment, but rather current standard of care.

I see nothing wrong with sacrificing a few men, who consent and sign up and know the risk, for the far larger majority.

If better drugs can be developed that would serve millions by sacrificing a hundred consenting subjects that know they run this risk, that seems like an overall benefit to me.

It seems rather irrational to not be willing to do this. — It is fine if men die, so long as their blood not be on my hands directly, but only indirectly.

Yikes. There's absolutely no reason to do this. You get equally useful results by comparing to current standard of care, and that's the thing you ultimately need to measure for approval of a treatment for which existing treatments exist anyway (the FDA wouldn't approve a drug that's better than nothing but markedly worse than the current standard of care, so that's the benchmark).

Then why isn't it done as such in all instances?

It seems that whenever a perfect placebo be permissible, that is what is being used rather than the current standard of care.

Soldiers can be sent to their death for oil and other resources that benefit the larger majority? but this is “yikes”?, not a phrase I find to occur in conjunction with rational decisions often.

> Then why isn't it done as such in all instances?

It is. Control groups are no-treatment if no approved treatment exists, or current standard of care if there's an approved treatment. That's standard practice.

> It seems that whenever a perfect placebo be permissible, that is what is being used rather than the current standard of care.

If by "perfect placebo," you mean "no treatment," that's not correct, and is considered unethical.

> It is. Control groups are no-treatment if no approved treatment exists, or current standard of care if there's an approved treatment. That's standard practice.

I've read plenty of pharmaceutical trials where the control was a plain placebo, not the current standard of care, when it not involve a life threatening illness.

https://clinicaltrials.gov/ct2/show/NCT00061802

Clearly this antipsychotics trial does not evaluate the drug 's effectiveness against the current standard of care's, but against a placebo's.

> If by "perfect placebo," you mean "no treatment," that's not correct, and is considered unethical.

I mean giving them a drug that lacks an active ingredient but is otherwise not to the lay eye discriminatable from an effective drug.

And that is very much what is done in the case of the antipsychotics medicine I showed. So it's only unethical when human lives be at stake, apparently.

Cabotegravir is somewhat novel -- not a recompounding of current therapy with different pharmacokinetics.

Americans aren't going to develop an efficient approach that is not highly encumbered because the FDA stacks the deck against approval of efficient solutions in favor of whatever makes the most total profit. So you'll see that sort of thing approved overseas and we'll get it (or not) in a decade or maybe never.

Logistics-wise, it’s easier to get someone to come into the doctors for blood work every 3 months for testing (as required for prep) than once a month for a shot.

However, from reading the article, I do think there’s a convenience factor at play related to the struggles of taking pills daily.

Note though, the article mentioned a trial of _women_ where truvada and one-shot prevention effectiveness were compared and the one-shot was deemed 89% more effective.

A quick search explains _why_ this might be the case for women. Basically, it takes more truvada to get rid of the disease in vaginal and cervical tissue than it takes for rectal tissue.

Source: https://www.uspharmacist.com/article/why-do-women-need-highe...

Also, doctors have been recommending a different drug, Descovy, for prep instead of Truvada. This isn’t due to effectiveness but side effects I believe. I guess if one experienced side effects though, they would be less likely to continue taking the medicine.

I'm not sure about this one but subcutaneous and intramuscular injectables are pretty easy to self-administer. I self-inject once a week myself.

https://www.poz.com/drug/cabenuva seems to suggest it is intramuscular (administered in the buttocks, which is not hard to do by oneself) but requires a healthcare provider. Not sure why, there might be storage requirements and such.

I think people would rather prefer to take a pill than give themselves an injection. It doesn’t matter if it’s “easy” or not. There’s the “ick” or “ahhh needle” or “breaking skin” factor at play.

Even if you self-inject and find it easy, I’m sure you’re not saying it’s easier and less of a hassle than taking a pill lmao.

Depo-Provera (monthly injected contraceptive) is used by over 2 million women in the US.

Ok... and 10.6 million use birth control pills according to the CDC.

Also, just because something appears convenient doesn’t mean that it actually is.

Have you looked up how many women use one of those invasive contraceptive implants?

Technically, a woman only has to get a new implant once every 4 years+. But have you not read the horror stories about the implants becoming dislodged and causing internal bleeding and severe damage?

You seem to be implying that IUDs are much less popular than the pill. That is not the case. They are just behind the pill in popularity.

Also, people on PrEP already need to do regular bloodwork, so needles and appointments are already involved every few months. Doing an appointment every 2 months instead of every 3 and not needing to take a daily pill as well is a huge win in level of effort.

https://www.cdc.gov/nchs/data/databriefs/db327-h.pdf

“You seem to be implying that IUDs are much less popular than the pill. That is not the case. They are just behind the pill in popularity.”

Your first sentence makes no sense. You say that I’m implying that pills are more popular yet you confirm that indeed they are.

Unless, you’re saying that I was implying that they’re _heavily_ more popular, which is also not what I implied.

You’re completely missing the point. I’m gay and on prep myself for several years.

The grandfather post mentioned that 2 million people are doing an injection as if that implies that many people prefer that over pills.

I could write more and explain more but I’m tired of talking to so many morons for today.

I'm not quite sure what your point is. Mine was that millions of people choose from a variety of treatment options and that there's no clear evidence that a pill is vastly preferred to an injection or even some more invasive delivery method. I think my link about birth control usage just shows that the more options, the better. Presumably we'll cover the at-risk population better if there are more good options.

I think this is a wonderful thing and that we should spread the word when these new treatments are available so that more people know they have options if they like the sound of occasional injections but don't like daily pills or vice versa.

It is in fact much easier and less of a hassle (for me) than taking a pill everyday, which is what I used to do before I switched to injectables.

Injectables seemed scary right until the moment when I started taking them, after which they became a normal part of my life.

In what way is it easier besides you saying that it’s easier? You have a hard time swallowing pills I guess? Or do you remember to take injections more because they stand out more in your mind than pills do?

EDIT: Not sure why this is getting downvoted. Since when on HN is it acceptable for someone to say “I think this way so it must be a fact” without providing an explanation? Even when it comes to subjectivity, there’s an expectation that people share why they believe in their opinion, right?

I swear I dislike this site and the people who use it more and more every week.

I'm pretty sure that "easier" is a subjective determination. But no, I don't have a hard time swallowing pills. It's just that doing something once a week is easier than having to remember to do something everyday. The injections are also more effective for me, as they are here. And finally there's an aesthetic aspect to plunging a needle into one's muscle that I appreciate.

Yes, it’s subjective to some extent, hence why I asked in what way is it easier beside you just saying that it is? I left out “to you” but I thought the HN community was a bit smarter than that. Even if you had said “it’s easier to me. Full stop,” I still would have written the same reply...

All you said was “it’s easier” in your original point. You obviously felt the need to clarify yourself in your most recent comment. So clearly your first comment was lacking information. There was no reason to downvote me just because you felt my original comment made you look stupid.

FWIW, even though “easy” is subjective, there’s still a consensus to be considered. For example, finding piercing your skin with a needle to be an asthetically-pleasing act does not fit that consensus...

Something that _does_ fit the consensus is that taking a pill every day is a hassle.

Stop being facetious just to prove a point.

I did not downvote you, for the record. I thought your questions were useful and I hope I answered them to the best of my ability.

This pandemic has been hard on all of us. Take care.

? I’m not sure what the pandemic has to do with this.

I looked at your comment history and you say “in fact” without supporting your opinions _often_ to the point that I laughed.

Also, you edited your original comment which probably led to the downvotes.

I’m assuming you must also correlate the pandemic with your immaturity then.

It’s disgusting that I’m being downvoted when the main point in my great-great-grandfather post was explaining about the effectiveness of the trial mentioned in the article. Not whether some random Internet weirdo prefers to inject themself...

He edited his comment to say “(for me)” after I had replied.

Also, if you click damnyou@‘s comment history, you’ll clearly see that he loves using the phrase “in fact” without supporting his assumptions. I didn’t deserve to be downvoted.

My pronouns are they/them, thank you.

I edited my comment within a couple minutes of posting it. Sorry about the confusion.

You didn’t edit your comment minutes afterwards. It was at least 1 hour afterwards.

And sorry if you actually do prefer those gender terms. But honestly, it sounds like you’re just making shit up. I’m assuming you’re just a young white kid. I’ve met many of you in the tech industry who act like that. “Oh, I said something stupid and fucked up, let me pretend to be ‘woke’”. People like you exhaust me.

Wrong on every count, bucko. Not young, not white, no making it up.

Disgusting piece of shit. You deserve to die.

This pandemic really has been hard on all of us. Take care.

> Was I misinformed about Truvada's effectiveness?

No, effectively used Truvada works very well.

> Or is this in comparison to people forgetting to take their daily pills vs a shot that a health care provider had record of administering?

Probably almost certainly yes or it's just a small improvement at the margin.

Compliance is a big issue, as is price. In the US, Truvada's retail price is about $2,000 for a 30 day supply. Truvada costs about $40 in other countries.

Compliance is a huge issue because health insurance will do a lot to make you jump through huge hoops to get it. I have had prescriptions “disappear” into the CVS “specialty pharmacy” and you have to wait on the phone for hours for them to “find” it.

I helped my mom deal with 2 specialty pharmacies for some Parkinson's drugs she was taking. The drugs weren't available from other pharmacies (that CVS runs one of the largest specialty pharmacies can make this confusing, but normal CVS probably don't stock it if the prescription goes to their specialty pharmacy).

They present themselves as helping the patient navigate a complex drug, but in practice this just meant they had a bunch of questions to tick off each time you talked to them. Their outreach and phone tree were both pretty bad, clearly designed for high operator utilization and not customer service.

The article states,

"...abotegravir – a component of Cabenuva – was 89% more effective in preventing infection among women than Truvada"

That 89% when was compared to Truvada.

Do healthcare workers actively take Prep or is it administered within the 72 hour period after exposure?

Prep from what I understand can be hard on the body's organs and you will need to do a kidney function test every few months when on it

Truvada is commonly taken proactively by sexually active people in high risk categories. It is true that it has side effects, so the risk of those needs to be balanced against the risk of HIV exposure.

Yes I do know it is take by high risk sexually active people. But I was wondering about health workers themselves and in what health field exactly.

Truvada is PREP. PRE exposure prophylaxis.

PEP =/= PREP. PEP is after the fact treatment, there's more than just Truvada in that protocol.

PEP is typically much harder on the body than PREP.

Most every gay man I know takes PREP with few or no side effects.

The side effects are of the type where a small group of users will experience changes in kidney function, and you have to check for it, but the vast majority won't. The side effect profile for most people is very low.

I don't have stats, but Biktarvy has been advertised for PReP lately. Descovy is approved by the FDA for such use. The shot is around the same price (at list anyway) as some of the other treatments, so if it's even equally effective the convenience might win.

Biktarvy doesn't make any sense for PrEP, Descovy is emtricitabine and tenofovir alafenamide, Biktarvy is emtricitabine and tenofovir alafenamide plus an integrase inhibitor which just adds possible additional side effects and isn't necessary.

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