PrEP with tenofovir is (only) ~49% effective?

[skinster]

Came across of a piece of scientific news today, it kinda tripped my attention. I understand the demographic in the study below is injecting drug (ab)users first, and PrEP for HIV is only a secondary criteria, and that it is not a combo pill used as suggested farther below:

Study - "Antiretroviral prophylaxis for HIV infection in injecting drug users in Bangkok, Thailand (the Bangkok Tenofovir Study)" http://www.thelancet.com/journals/lancet/article/PIIS0140-6736(13)61127-7/fulltext

But in light of effectiveness on HIV side alone, what number is realistic (for lack of a better word) if one had to examine relevant info from multiple sources? Is it 49%, 44%, or 90%, as stated in a span of 1 paragraph in CDC fact sheet for PrEP, August 2012:

"Research among Men Who Have Sex with Men

In November 2010, the multinational iPrEx study showed that a once-daily pill containing tenofovir plus emtricitabine was safe and provided an average of 44 percent additional protection against HIV infection among men who have sex with men (MSM) who were also provided with a comprehensive package of prevention services. These services included provision of condoms, monthly HIV testing, counseling to reduce risk behavior and encourage adherence to the daily pill regimen, and management of other sexually transmitted infections.

The level of protection varied widely depending on how consistently participants used PrEP, with significantly greater levels of protection among those who adhered well to the daily dosing regimen. Among MSM with detectable levels of the medication in their blood, the risk of HIV acquisition was reduced by more than 90 percent."

Has anyone come across stats on the matter? As 100% difference between different methods is just not very assuring to me - "level of protection varied widely...". Am I misreading it?

[bearbandit]

The first paragraph only goes as far as counselling to encourage daily dosing, while the second goes on to imply good adherence, which in the UK is gauged at 97% - missing one pill per month. I don't think you are misreading it as different foods affect absorption. The usual window for effective absorption of most HIV drugs is one or two hours (ie take it at nine and the next dose must come between seven and eleven to maintain active levels in the blood, even though the half life is longer than that).

I recently saw similar juggling of figures about the effectiveness of condoms, normally quoted at 96%, whereas a new report was of the opinion that condoms prevented about 40% of infections in the late eighties. Sounds like garbage, but... At a recent HIV training weekend I was on, working in teams we had to list, in correct order, the twenty steps needed for successful condom usage. Nobody could; and that's stone cold sober working mode rather than desperate "c'mon man, I gotta have it" mode.

Side effects: while it's true that embitracine (FTC) has a relatively low side effect profile, tenofovir can be vicious and its damage permanent. There are a number of minerals and vitamins my kidneys piss away instead of recycling and despite massive doses of calcium and vitamin D, I've been unable to go back to the weights and still walk very slowly with a stick. We're finding these effects as little as three to six years after starting tenofovir as a therapeutic drug.

I think it best to look at Truvada PrEP as proof that PrEP is possible, but these are the wrong drugs, and more needs to be done on the psychology of PrEP especially. If I were neg, given the choice between PrEP and wrapping it, I'd go for the rubber or take my chances without drugs. I'll bet the drug companies have noticed that their therapeutic licences for FTC and tenofovir, as well as Truvada, are about to run out. How nice for them to have to organise a new patent for an old drug...

[skinster]

Thanks, bandit. First-hand info and experience trumps anything else one can read, hands down.

I've come across diet needs and guidance with other medications before, the idea of different absorption rates or reduced/enhanced effect is not foreign to me. Going back to the abstract from the study, I believe it was done as an ambulatory. So who knows if there were any individual diet deficiencies promoting weaker immune system/inflammation in this or that user which could have also skewed resulting infection rate. Math is a wonderful tool to confuse medicinally unaccustomed.

CDC material is also listing different prevention rate for heterosexual and homosexual subjects. Must be one bigoted pill, lol. I wonder if it has anything to do with involved sex practices that result in infection.

But along that path you are very much correct saying that side effects may be more damaging then not. And as with any major impact drug these days, effects are traversing multiple body systems at once - you're saving one and bashing more-than-one other at the same time. Cancer drugs and regiments seem to have the same pattern - if not frequently and closely monitored, they could reverse the action or clog other organs to a point of failure. Who'd wish for that? The study mentions it, but I don't recall seeing similar warnings or recommendations in PrEP promo materials. Your personal physician may not cover all angles due to other constraints during one's visit and probably won't push for specifically-adjusted bloodwork all that often either. Drug Co's will happily sell you any garbage as medicine as many recalls have shown. And common laymen's opinion is that it's next-to-wonderpill protective umbrella because you'd instinctively want to see that 90% number going all the way to a 100. That's what makes me even more cautious than not considering. And I am still of the opinion to take my chances without it.

Thanks for sharing. Feel better.

[rawTOP]

I'm on PrEP. It's only effective when it's in your system and the studies have been marred by the fact that many of the guys in the study don't take their pills. Most of the guys in the studies who became infected did not have the meds in their system when they came in reporting symptoms of initial infection. When you're healthy it just doesn't seem important to take meds I guess.

Regression models (not actual studies) suggest 90+% efficacy when you take PrEP daily.

I've written about this and other PrEP stuff on my blog...

http://www.rawtop.com/blog/tag/prep

[TattPig]

"CDC material is also listing different prevention rate for heterosexual and homosexual subjects. Must be one bigoted pill, lol. I wonder if it has anything to do with involved sex practices that result in infection."

The risk of HIV transmission in receptive anal sex is 18 times higher than traditional sex. That probably accounts for the different prevention rate, all other things being equal.

[Guest bbian7000]

"CDC material is also listing different prevention rate for heterosexual and homosexual subjects. Must be one bigoted pill, lol. I wonder if it has anything to do with involved sex practices that result in infection."

The risk of HIV transmission in receptive anal sex is 18 times higher than traditional sex. That probably accounts for the different prevention rate, all other things being equal.

Further to this fact, i believe it is because the rectum, like much of the GI-Tract, have CD4+ t-cell present MALTs (mucosa associated lymphatic tissue). Hence receptive anal intercourse poses more risk. Sex (M/F) Does not change this fact drastically if at all.

[bearbandit]

Two things worry me in particular: the first is the three month spacing of kidney work-ups. My January workup showed nothing unusual. I didn't get my April results because I was busy hallucinating (lack of potassium in my brain) in a trauma ward having wrecked £2000 worth of bike and snapped my softened ankle in the process. Three months between workups is too long: you don't notice the side effects coming on and they can come on fast. The second is that the side effects of tenofovir are not necessarily reversible on cessation. If they were I wouldn't be taking all these supplements, walking with a stick and so on. I'm not saying don't, but I am saying for fuck's sake be careful.

[TattPig]

I'm not sure what the concern is about tenofovir as PrEP. Besides the other problems mentioned about the study, it was conducted between 3 and 8 years ago--almost ancient history, given the rate of progress.

Plus, I have never heard anyone advocating Tenofovir by itself for PrEP. The only drug anyone ever mentions is Truvada, which contains tenofovir in combination with emtricitabine. Such combos are common, and the 1-2 punch is always more effective. The side effects that Bearbandit mentions are still a concern, but Truvada is remarkably effective for PrEP.

[bearbandit]

Plus, I have never heard anyone advocating Tenofovir by itself for PrEP. The only drug anyone ever mentions is Truvada, which contains tenofovir in combination with emtricitabine. Such combos are common, and the 1-2 punch is always more effective. The side effects that Bearbandit mentions are still a concern, but Truvada is remarkably effective for PrEP.

Sorry for my lack of clarity: I used to take tenofovir and FTC and different times of day in order to manage the side effects better and so tend to think of them separately (I'm still taking FTC, along with darunavir/ritonavir and raltegravir). I was essentially taking Truvada, but its components instead of the single pill. I don't doubt the efficacy of Truvada for PrEP, but I think the protocols for managing any combination containing tenofovir, in the light of what we're seeing here, aren't sufficient.

[wood]

Two things worry me in particular: the first is the three month spacing of kidney work-ups. My January workup showed nothing unusual. I didn't get my April results because I was busy hallucinating (lack of potassium in my brain) in a trauma ward having wrecked £2000 worth of bike and snapped my softened ankle in the process. Three months between workups is too long: you don't notice the side effects coming on and they can come on fast. The second is that the side effects of tenofovir are not necessarily reversible on cessation. If they were I wouldn't be taking all these supplements, walking with a stick and so on. I'm not saying don't, but I am saying for fuck's sake be careful.

Bearbandit, First of all thank you very much for your input on this, I always enjoy a good discussion.

Heres my main issue with your arguments. No one is doubting that is some cases PrEP with Truvada can be dangerous, However the statistical models, and experience with the drug show that the risk of kidney and liver problems are relatively low. That does not mean they are non-existent. That being said I am trying to look at the argument for and against PrEP in a logical and fact based way. Right now the way I see it is that people are continuing to have unprotected sex, and while condoms are one good way at prevention they certainly do not cover all different behaviors. Additionally PrEP with Truvada when taken correctly has shown to be 99% effective.

HIV infection rates in the US and many other developed countries have become very stagnant, and are not going down, because simply people are not following what is regarded as safer sex. IMO, PrEP is a good way to reduce those infections among high risk adults. It is far from perfect, but if you are a high risk person, isnt taking a medication to prevent infection for a potentially shorter amount of time better than taking medication for a lifetime? I think that many people in here forget that HIV is a LIFETIME illness, not a "bug or gift" It is something that will kill you if you dont take lifetime medication. With that in mind I think that PrEP is a good option for any people at high risk.

[Guest JizzDumpWI]

FWIW, my ID doc is doing first labs at 4 weeks, second round at 13 weeks and then every 13 weeks (or so afterwards); unless he begins to see some anomalies he is concerned with. I am trusting of his judgement on my own PrEP treatment; but appreciate bearbandits experience and will definitely be pressing my doc on those points at least up to the 6 month point.

[whoai]

I don't quite understand people that both want to be on PrEP and then don't take the pills regularly. Rawtop pointed out something important "When you're healthy it just doesn't seem important to take meds I guess." There are a lot of conditions that require long-term treatment but if you cease taking your drugs they don't immediately make you feel sick. High blood pressure is a good example. Taking BP medication can keep you healthy but not taking it (depending on the type) may not immediately have any obvious negative effect as high BP is often without any symptoms. "Compliance" as doctors call it can be pretty bad even for otherwise life threatening conditions (such as people not taking their antibiotics once the symptoms subside and getting a resistant strain).