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Truvada protects users from HIV with a 99% success rate
September 26, 2013 1:21 PM   Subscribe

"Not enough gay men realize there’s an HIV-prevention pill."
posted by showbiz_liz (44 comments total) 11 users marked this as a favorite

 
so does foot cream
posted by robbyrobs at 1:29 PM on September 26, 2013


From the Out article:

Those findings, which HIV specialists had been keenly awaiting for several years, were enough to make Dr. John talk to his own doctor and start the regimen himself. “I don’t want to become HIV-positive,” he says. “But I don’t love using condoms.” Sexually active with multiple partners, Dr. John admits he avoided condoms about 20% of the time. He was tired of stressing constantly over whether he’d gotten HIV. “Even if my sex was relatively safe, I would have long periods where I’d be freaked out that something had happened.”

Contrasted with the FDA press announcement:

Truvada’s safety and efficacy for PrEP were demonstrated in two large, randomized, double-blind, placebo-controlled clinical trials. The iPrEx trial evaluated Truvada in 2,499 HIV-negative men or transgender women who have sex with men and with evidence of high risk behavior for HIV infection, such as inconsistent or no condom use during sex with a partner of positive or unknown HIV status, a high number of sex partners, and exchange of sex for commodities. Results showed Truvada was effective in reducing the risk of HIV infection by 42 percent compared with placebo in this population. Efficacy was strongly correlated with drug adherence in this trial.


I am finding it hard to find concrete evidence for the 99% success rate. Can anyone help?
posted by hal_c_on at 1:32 PM on September 26, 2013 [6 favorites]


Treatment is 1200 dollars a month, so it's not exactly for everyone. Rich urban gay dudes in NYC who love barebacking? Sure. Another weapon in the arsenal for Africa? Not so much.
posted by Joakim Ziegler at 1:33 PM on September 26, 2013 [12 favorites]


Presumably 42% is typical use and 99% is perfect use, based on the correlation between efficacy and drug adherence?
posted by Kadin2048 at 1:34 PM on September 26, 2013 [1 favorite]


Joakim: There's a generic version made in India which is much cheaper. Presumably any country that doesn't kowtow to US pharma patents can just get that version, which won't be $1200/mo.
posted by Kadin2048 at 1:35 PM on September 26, 2013 [3 favorites]


Presumably 42% is typical use and 99% is perfect use, based on the correlation between efficacy and drug adherence?

Presumably that is incorrect. I can't see anything that actually says there is a 99% rate of success based on the trials.

This drug DOES seem to work based on the data. But lets not forget that people who are desperate for help will CLING to these percentages like nobody's business. This number should be backed up.
posted by hal_c_on at 1:35 PM on September 26, 2013 [2 favorites]


In isolation, a "99% success rate" means nothing - is that per act, per person-year, ...? I could buy that it was 99% effective per act, if only because the risk per act of getting HIV is so small already, but of course that's misleading since most people have sex more than once.
posted by en forme de poire at 1:38 PM on September 26, 2013 [2 favorites]


Why PrEP may do more harm than good
posted by roomthreeseventeen at 1:41 PM on September 26, 2013 [1 favorite]


“Even if my sex was relatively safe, I would have long periods where I’d be freaked out that something had happened.”
It's a troupe to make fun of Americans for their fetishizing of a pill to fix whatever their ills are, both medical conditions and self-inflicted ills.
posted by k5.user at 1:41 PM on September 26, 2013


hal_c_on: Out got the stats wrong.
"Truvada®, provides 99% protection against HIV infection in MSM, when taken seven days a week."
It reduces your odds below 1% of contracting HIV. It does not reduce your odds by 99%.
Link to the full text of the article is at the bottom of the PR piece I linked. Money quote from the full paper:
Among the 100 subjects with emergent HIV infection, 36 occurred in the FTC–TDF group, and 64 occurred in the placebo group, representing a relative reduction of 44% in incidence in the modified intention-to-treat population (95% confidence interval [CI], 15 to 63; P=0.005) After adjustment for the difference in age between the two groups, the efficacy was 43% (95% CI, 14 to 62).
posted by agentofselection at 1:43 PM on September 26, 2013 [2 favorites]


Syphalis and gohnerrra are still a thing, everybody. And getting more resistant to antibiotics every day.
posted by Gin and Comics at 1:43 PM on September 26, 2013 [11 favorites]


The description of the documents in the court ruling also implies collusion, suggesting the FDA worked with Gilead on what to say to get their unfavorable drug trial results spun in such a way that the FDA deemed them sufficient to approve the drug for expanded use of Truvada as an HIV prevention pill for pre-exposure prophylaxis (PrEP) in uninfected individuals.

Ugh. I'm gonna be sick.
posted by hal_c_on at 1:47 PM on September 26, 2013 [3 favorites]


Part of the reason I'm leery of PrEP is resistance. I think it's a good idea for serodiscordant couples (med jargon for a couple where one person is HIV+ and one is HIV-); I'm not sure it's a great idea for the general population. Not that they don't deserve protection, but if HIV out-evolves the very limited number of drugs we have, there isn't a lot to fall back on and then the HIV+ population could be really screwed over. The FDA report does say that Gilead is required to monitor for resistance in a somewhat intelligent way, which is good - but I'm not totally sure it's enough.

As far as "fetishizing of a pill" goes - first of all, this is about epidemiology and trying to achieve the result we want with the tools we have. In malaria, we have bed nets and antimalarials; here we have Truvada and condoms. Using antimalarials is hardly "fetishizing a pill." Second, I also don't understand the cultural meme that barebacking isn't that big a deal - though full disclosure, I seem to be way out in the tail of sexual caution among my cohort. But if barebacking persists despite decades of moralizing from basically every authority in the world, a snide remark about personal responsibility can hardly be expected to do anything either. (Besides impart a comforting rush of superiority, anyway.)
posted by en forme de poire at 1:52 PM on September 26, 2013 [9 favorites]


In isolation, a "99% success rate" means nothing - is that per act, per person-year
The study followed people for a median period of 1.2 years. While they were being followed, 1.2% of the placebo group got HIV, while 0.7% of the drug group got HIV.
posted by agentofselection at 1:53 PM on September 26, 2013


The proper use for these drugs is to protect the partners of HIV-positive patients, ideally as a back-up to barrier protection. Using antiretrovirals (or antivirals, or antibiotics) as prophylaxis in healthy individuals is short-sighted in the extreme, particularly in those whose risk stems primarily from a personal distaste for safe sex.
posted by dephlogisticated at 2:09 PM on September 26, 2013 [1 favorite]


The study followed people for a median period of 1.2 years. While they were being followed, 1.2% of the placebo group got HIV, while 0.7% of the drug group got HIV.

What the? Calling that a 99% effectiveness is completely misleading!
posted by Justinian at 2:12 PM on September 26, 2013


The study followed people for a median period of 1.2 years. While they were being followed, 1.2% of the placebo group got HIV, while 0.7% of the drug group got HIV.

It seems (roughly) like a coin flip, where unprotected sex that would have infected you would still get you infected, even on the Truvada. Cutting the odds by 40% doesn't seem like much of a replacement for condoms.
posted by Blazecock Pileon at 2:16 PM on September 26, 2013


I might be missing something, but it seems like if that's how you're doing math, not taking Truvada already has has a 98.8% success rate.
posted by the jam at 2:17 PM on September 26, 2013 [4 favorites]


The 99% effectiveness in a subset of men who had enough Truvada in their blood to demonstrate that they were taking PrEP as directed comes from a presentation by the lead researcher, Bob Grant, at the Conference on Retroviruses and Opportunistic Infections (CROI) in March 2013.
posted by hworth at 2:19 PM on September 26, 2013


Exactly; it's not clear to me that the moderate protective effect would be enough to overcome the almost certainly more cavalier attitudes towards protection that would be engendered by a false sense of security from taking it.
posted by Justinian at 2:19 PM on September 26, 2013


"Truvada®, provides 99% protection against HIV infection in MSM, when taken seven days a week."

Wow. What an incredibly, dangerously misleading statistic. Per the efficacy study, doing nothing at all "provides 98% protection."

The actual efficacy, a 43% absolute reduction in risk, is not very comforting. Even considering the absolute numbers, .7% in 1.2 years is still kind of high. That's about a 5.5% risk over 10 years, more than 1 in 20. People's risk aversion varies, of course, but I wouldn't want to roll that die.

I expect the actual risk will be higher in practice, since some people using Truvada may be more inclined not to use a condom, to have more sex, or to have sex with more partners. It could even be that people taking Truvada in the real world will have higher infection rates than those that don't use it. It wouldn't take much to tip .7% to over 1.2%
posted by jedicus at 2:20 PM on September 26, 2013 [2 favorites]


Drug-resistant gonorrhea may be sort of a derail because nobody's talking about prophylactic antibiotics for gonorrhea, but it is an interesting/terrifying story in its own right. One big difference is that drug resistance may be occurring because of unprotected oral sex. Gonorrhea in the genitals is usually easy to knock out before it has time to become resistant. But if you treat it when you also have pharyngeal gonorrhea (the symptoms of which are often pretty subtle or even absent), your pharynx gets a much lower dose of antibiotics and the treatment often stops before it is eliminated. This is basically exactly what you would do if you wanted to select for a drug-resistant gonorrhea strain.
posted by en forme de poire at 2:21 PM on September 26, 2013 [5 favorites]


BP: The reduction is statistically significant, so I would argue with calling it a coin flip. That said, statistically significant doesn't have to mean large--it just means you got a big enough sample size. Based on that study it is safe to say the drug really did protect some people who would otherwise have contracted HIV. It just didn't protect all of them, or even half of them.
posted by agentofselection at 2:23 PM on September 26, 2013 [1 favorite]


Among the gay men in the iPrex study who had enough detectable Truvada in their blood to demonstrate daily use, there were ZERO transmissions of HIV. Because of the size and duration of this study, the protection rate can only be categorized as 99%.
posted by hworth at 2:26 PM on September 26, 2013


Based on that study it is safe to say the drug really did protect some people who would otherwise have contracted HIV. It just didn't protect all of them, or even half of them.

I'm not disagreeing with the numbers being statistically significant. I'm disagreeing with the takeaway that Gilead would have its customers leave with (and to spread by word of mouth, so as to drive sales), namely that the drug provides anywhere near the kind of protection that condoms provide. The article itself shows a photograph of a condom wrapper ripped open to reveal a pill. To me, that presentation seems misleading, or at least not an accurate representation of the risk presented in the actual figures.
posted by Blazecock Pileon at 2:29 PM on September 26, 2013


The proper use for these drugs is to protect the partners of HIV-positive patients, ideally as a back-up to barrier protection.

Yes, I agree with this. PrEP (and ideally PrEP + "condoms every time") makes a lot of sense if you are HIV- and in an LTR with a person who is HIV+.

The compliance thing makes me nervous. It's great that it's potentially very effective in people who are good at taking their medicine on schedule, but if so many people are only partially compliant (which makes sense -- my impression is that HIV meds are sort of a pain in the butt to keep track of, and I'd imagine this is even worse without the urgency of treating an actual infection), that is also creating a good environment for selection - weak or intermittent concentrations of drugs are not your friend in treating infection.
posted by en forme de poire at 2:32 PM on September 26, 2013


Hworth's contention is that the protection if you take the treatment correctly is nearly universal and that the folks who were infected while in the Truvada group were not careful about taking their medication as evidenced by their blood titers.
posted by Justinian at 2:33 PM on September 26, 2013 [1 favorite]


Condom champions might want to check out the stats from this presentation also from this year's CROI. 70% reduced risk from self-reported 100% condom use compared with those who said they never used condoms. However, the majority of gay men report significantly less than 100% condom use, and this intermittent use of condoms offers no risk reduction compared with those who said they never used condoms.

50,000 people contracted HIV last year in the US. We need new prevention tools because what we are doing is not working. PrEP is one new tool. Treatment as Prevention (getting all HIV+ folks on medication) is another. Folks are also working on vaccines - both functional and preventative as well as topic microbicides. It is not the 1980s, condom only prevention is not enough. And, luckily, researchers have been working diligently to find those alternatives.
posted by hworth at 2:38 PM on September 26, 2013


hworth, I totally agree with your point about needing new prevention tools beyond condoms alone, but I'm concerned some applications of PrEP might be at the expense of the ability to effectively treat HIV+ people. Are there materials out there that address these concerns more specifically?
posted by en forme de poire at 2:55 PM on September 26, 2013 [1 favorite]


As to cost, Truvada is on the formulary of every major pharmacy insurance plan in the US. And, since the FDA approved a label change for Truvada in July 2012, doctor's prescribing Truvada as PrEP are prescribing it as directed. A number of national organizations have been tracking insurance companies and PrEP. Up until now, they have not identified any insurance company that has denied coverage for Truvada as PrEP prescription. In addition, Gilead offers a $200 co-pay card (regardless of income) that covers the 1st $200 of your Truvada co-pay each month. For many, many people (and more after Jan. 1 when ACA is implemented), this means that Truvada incurs zero monthly out of pocket expenses. If your insurance co-pays for top tier medication is more than $200, you would need to pay the difference each month. Truvada as PrEP is also covered by Medicaid and Medicare. If you have no insurance, and earn under 400% of the Federal Poverty Level, Gilead will pay 100% of the cost of your prescription.
posted by hworth at 2:59 PM on September 26, 2013 [2 favorites]


en forme de poire, To my knowledge no HIV treatment moneys are being directed toward PrEP. I don't know how PrEP would negatively impact the ability to effectively treat HIV+ folks. The US has significantly underfunded treatment efforts (see the ADAP Waiting Lists in many states), but saying prevention funding for PrEP is causing that is like saying paying for bridge construction is negatively impacting HIV treatment moneys. The two things just aren't related.

Is there another way besides $$$ that you imagine PrEP having a detrimental effect on treatment?
posted by hworth at 3:03 PM on September 26, 2013


Sorry, yeah, I meant increasing resistance to Truvada, not money. I agree with what you're saying about the budget for treatment.

Also, I thought this (from the 2nd article) was interesting:
Then again, there is the argument that being on PrEP actually makes people safer because it raises their consciousness about their health. The iPrEX study found that participants reported decreased anal sex and increased condom use...
I can definitely see how regular contact with a sexual health professional would be beneficial here. That's definitely one area where stigma could be contributing to HIV infection by making people more reticent to see a health professional. Personally, I know I barely talked about sex with my doctor before I explicitly found a gay-friendly clinic; just keeping the line of communication definitely made me safer (for one thing, they were able to evaluate my risk of meningitis and vaccinate me during the NYC outbreak). And being repeatedly asked about sexual history in a non-threatening, non-accusatory way did make it easier for me to bring up concerns that I had.
posted by en forme de poire at 3:07 PM on September 26, 2013


On the subject of resistance, this recent paper by Abbas et al. suggests that unmanaged use of Truvada could end up being problematic:

Third, PrEP alone results in low prevalence of drug resistance; high PrEP adherence leads to fewer infections and less opportunity for acquired resistance, while low adherence leads to predominantly wild-type breakthrough infections because of low drug pressure for emergence of acquired resistance...

Our model projects a low prevalence of drug resistance from PrEP. Highly effective PrEP results in few breakthrough infections and a chance for emergence of acquired resistance. By contrast, poorly effective PrEP fails to protect from acquisition of wild-type HIV but also fails to exert selective pressure for emergence of acquired resistance. Both of these phenomena have been observed in recent PrEP trials [1, 2]. However, drug resistance from PrEP at the population level could rise with inappropriate PrEP use among those with undiagnosed HIV infection. While this increase is modest from inappropriate PrEP use during the preseroconversion phase of acute infection, it becomes more pronounced with inappropriate use among persons with established HIV. The latter may be of concern in potential situations of unsupervised PrEP use (eg, black-market drugs and drug sharing [49]) or inaccurate HIV testing [50].

posted by Blazecock Pileon at 3:14 PM on September 26, 2013


en forme de poire, Despite the article by Dr. Abbas quoted above, I believe resistance is a red herring when talking about effective implementation of PrEP. Besides no evidence of resistance developing in any of the trials, the very process of developing resistance requires actively replicating virus. Before starting PrEP, folks need to have a confirmatory HIV negative result (not just an antibody test). If PrEP is taken as directed, HIV can not establish a foothold in the immune system. No virus = no resistance. To continue on PrEP, folks need to be retested every three months. If someone was found to have seroconverted since their last test, PrEP would be discontinued. The resistance typically develops after the founder/transmission virus begins to mutate. So, there is the possibility that someone might take not enough Truvada to get the protective effect, but just enough to develop a resistance after the transmission/founder has taken root. And, all of that would have to happen in the 3 month window before their next PrEP appointment.

Not impossible, but I think less likely than the typical path to resistance development - HIV+ individual stops taking meds after a period of viral suppression because of change in life circumstance, mental health, or attitude.

Now, for folks getting a party pack or using black market PrEP, resistance is definitely a concern. However, that is already happening. Effective implementation of PrEP as a widely accepted prevention tool should actually decrease the prevalence of black market PrEP and thus reduce the risk of population level resistance.

The real key is no virus = no resistance. If PrEP is as effective as the studies seem to demonstrate those taking PrEP as directed will not have replicating virus and so will not be able to have resistant mutations develop.
posted by hworth at 3:24 PM on September 26, 2013


40% transmission reduction is great from an epidemiological standpoint (nnt ~2? Sweet!), though the absolute risk reduction leads a little to be desired from the individual standpoint. I worry about an inverted placebo effect, where knowledge of a placebo group influenced all participants' behavior. It would be interesting to see transmission comparison against a matched, untreated cohort. Still, from a public health standpoint this is potentially very good, in the sense that you could (possibly) have 40% less new cases, not to mention less downstream transmission, etc. If a vaccine were this effective it would probably be rolled out. Granted, this is not: it must be taken regularly, may not be well-tolerated, etc.
posted by monocyte at 4:04 PM on September 26, 2013 [2 favorites]


monocyte, the 40% reduction was for all people assigned to the experimental arm of the iPrex study, EVEN IF THEY REPORTED NEVER TAKING THE STUDY DRUG. If they reported taking the drug, the reduction was 77%. If there was detectable drug in their blood, the reduction was 92%. And, if the level of drug in their blood was consistent with daily use, the reduction was 99%. If the reduction of risk among those taking the drug as directed was only 40%, I would have no use for it either.
posted by hworth at 4:14 PM on September 26, 2013 [1 favorite]


The study followed people for a median period of 1.2 years. While they were being followed, 1.2% of the placebo group got HIV, while 0.7% of the drug group got HIV.

er...can someone explain to me how it's ethical to give subjects a placebo in place of an HIV-prevention drug?
posted by threeants at 5:47 PM on September 26, 2013


can someone explain to me how it's ethical to give subjects a placebo in place of an HIV-prevention drug?

The study is what let us know it was an effective HIV-prevention drug. So, there was no ethical concern. Participants in both arms of the study knew that they might be getting placebo. The standard of HIV prevention at the start of the study was harm reduction counseling and condoms. Both arms of the study got that standard of care.
posted by hworth at 5:52 PM on September 26, 2013


Also, often in a study like this, as soon as you have adequate data to strongly support the new drug's efficacy, you stop thes tudy, so no one else is given the placebo once you're convinced the new drug is better. Sometimes arrangements are made in a case like this where the placebo group can get the real drug at thus point.

The exact ethical safeguards vary, but thus general setup is a routine type of trial that Institutional Review Boards review and approve all the time.
posted by Stacey at 7:41 PM on September 26, 2013


er...can someone explain to me how it's ethical to give subjects a placebo in place of an HIV-prevention drug?


The control arm of a study has to match the standard of care. The current standard of care for men who have sex with men who don't have evidence of recent exposure to HIV is education and advocating condom use. This kind of study is exactly what's needed before advocating a high-level change to the standard of care. IMO it's irresponsible to advocate millions of dollars in healthcare expenditure and pretty powerful chemotherapy without comparing the actual effectiveness.

Generally, the ethical justification is that if they weren't in the study, they'd be receiving the standard of care anyway (i.e. placebo + education) so they are no worse off. I feel like there's a snappy 'principle of xxx' for this but it's on the tip of my tongue.

The Declaration of Helsinki is the major worldwide ethical startpoint for research ethics, placebo is addressed in Article 32.
---

I don't think anyone's linked to the actual study as published in the NEJM we're all talking about - Preexposure Chemoprophylaxis for HIV Prevention in Men Who Have Sex with Men, looks like open access.

---

I've only had brief exposure to HIV clinics, but compliance with these meds when people actually have HIV is terrible, I can only imagine how bad it would be for prophylaxis.

(I have been astonished - no matter what condition you're thinking surely they'll take the meds for that, there's someone who doesn't take their meds).
posted by chiquitita at 9:32 PM on September 26, 2013


hworth, yeah, that scenario is basically exactly what I was thinking about - person is in the window period and contracts HIV, virus gets weak/intermittent exposure to Truvada, selection happens. I think the fact that it didn't happen in the trials isn't surprising, but also doesn't mean much because the populations were so small (small from an evo-bio standpoint, I get that the sample size was totally sufficient for what they wanted to show).

Black market PrEP does change the calculus (and the modeling appears to back that up). On top of that, by making legitimate PrEP more widely available you're also increasing the level of care and follow-up, etc. And if the risk reduction is really 99% with daily compliance, that's awesome - and probably knowing that would affect the compliance. On the other hand, as chiquitita says, taking drugs on a regular and continued schedule is something that a lot of people are not very good at, even if they are on board with the reason.

Thanks for being so patient and thorough with your commentary btw.
posted by en forme de poire at 10:40 PM on September 26, 2013


en forme de poire, They can not be in the window period when they begin PrEP because a confirmatory (protein, viral load, western blot) HIV test is used, not just an antibody test. (Well, these have a window period, as well, but it is days, not months.) It is a potential problem, but as chiquitita says many, many people living with HIV are not compliant/adherent and pose a much greater risk of developing and transmitting a Truvada resistant form of HIV.

Here is the issue with compliance/adherence. If you stop taking PrEP or miss doses, there are no inherent negative consequences the way there are when you stop a medication that is treating a disease. The negative consequences come if you participate in risk behaviors as if you were taking your meds. The analogy is birth control. If you are a female taking oral contraceptives and you miss doses, there are no inherent negative consequences to that. The negative consequences only come if you have vaginal sex with a man and expect to be protected against pregnancy. If you are not taking your birth control pills, you need to use another method to prevent pregnancy. If you are not taking your PrEP, you need to use another method to protect against HIV infection.

Education is key. You know the last time you missed a dose of the meds. If you missed a dose within the last 10 days, then you have decreased the efficacy of PrEP. At that point, you need to rethink your calculus of risk. If you have stopped using condoms, you may choose to start again. Or, you may choose to not engage in anal sex until you have had 14 days of continuous PrEP.

And, as someone who has worked with hundreds of people living with HIV/AIDS, I agree with chiquitita that adherence to med regimens is not always among those folks. However, they are looking at a lifetime of meds and medication fatigue is real. For the vast majority of people who will be on PrEP, it will not be lifetime of usage. Most folks have periods in their lives when they are more at risk than other times. I am not on PrEP currently because my husband and I have a sexually monogamous relationship. We have been together six years and got tested for HIV and STDs together every three months for the first 18 months after deciding to be monogamous. If PrEP had been available the last time I was single, I would definitely have been on it, despite a personal history of 100% condom use for anal sex since 1983.
posted by hworth at 4:18 AM on September 27, 2013


Okay, i'm a woman, and i'm prejudiced, based on my experience of men, but: ANYTHING THAT MAKES MEN EVEN LESS WILLING TO USE CONDOMS IS A BAD THING

there's a "No" that women say to men during sex that is treated as a yes that gets far too little attention: "No, i will not have sex without a condom".

To me, if you don't really know me well and you don't expect to use a condom, you're just showing you have no self respect. Just saying. (Or common sense, but sensible people can be kind of annoying with how they're always right, so i don't mind idiocy in a man, whereas if a man doesn't respect himself then his having sex with you is not much of compliment, so it's kind of offputting.)

I guess i sound harsh. Take this as proof of how repeated irritation can turn you over-bitter on a topic.
posted by maiamaia at 10:01 AM on September 28, 2013 [1 favorite]


or as my friend said, "No, i don't want to have sex with everybody you've had sex with in the past." Or, refusing to use a condom is like saying "Babes, i probably have half the STIs known to man." Perhaps hygiene obsession is an important trait to match on.
posted by maiamaia at 10:02 AM on September 28, 2013 [1 favorite]


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