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Chances of PREP failing?


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Guest JizzDumpWI

Remote. Truvada changes a protein in your body HIV needs to infect, not the virus. That said, Truvada is to prevent HIV-1 infection. It does not matter the strain...

Some reading for you... WIKI on different HIV types here.

Reading on how Truvada prevents infection here.

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Guest beezee

This is not true. The strain is very relevant. It's very possible that Truvada will fail to prevent infection with HIV resistant to both components of Truvada. Such resistance exists (t69i) but isn't very common (maybe less than 1% of guys) .

More commonly resistance is to one component of Truvada, eg the common M184V mutation makes the FTC part of Truvada 300x weaker.

As usual there isn't any human data on how well PrEP protects you from PrEP-resistant strains. You folk taking it are the guineapigs.

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Guest JizzDumpWI

It isn't going after the virus beezee. PrEP works by blocking the action of a protein that HIV-1 needs to infect the body

Has little to do with the specific virus.

Edited by JizzDumpWI
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Guest JizzDumpWI

When I read the articles, NRTI's action is different post infection than pre infection. So explain more of what you mean... If you're never infected, it prevents it. Post infection, it is part of the solution which is why Truvada on its own for HIV poz people can lead to serious consequences.

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More commonly resistance is to one component of Truvada, eg the common M184V mutation makes the FTC part of Truvada 300x weaker.

I had read somewhere that HIV who is resistant to Truvada is not particularly virulent, so it's unlikely that those resistant strains will be the ones that will initiate the infection. In that context, Truvada would also work even if the individual had some mutation that was resistant to FTC.

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Guest JizzDumpWI

HIV2 less aggressive and much less common. I have found no studies about Truvada and HIV2 - and don't know if there is an active study or planned not. What I do read suggests that Truvada would probably be effective, but until this is studied, the only valid statement is "I don't know". As a guy on PrEP I am not terribly worried... In the synopsis of studies I've read TasP for HIV2 has also not been studied. Poz1956 and Bearbandit might have better access to details about HV2...

It is always a good idea to talk with your sex partners and get to know them.

You are right that HIV2 seems to be less aggressive. But it always makes sense to be reasonably careful.

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I find sometime people are irrational around HIV. They want 100% certainty that they can't become Poz. Nothing we do has zero risk. A condom could break with a "thinks he's Neg" guy, you could slip in the shower, or get hit by a truck on your way to work. If you're scared that PrEP won't protect you from HIV 2, then you must be terrified of Typhoid, Dengue Fever, Malaria, and millions of other diseases that are almost never seen in North America.

HIV2 is somewhat common in west Africa. I'm sure there have been some rare cases in North America, with people who brought it back from overseas. There hasn't been enough to generate any warnings about clusters of it in the developed world. HIV 1, Subtype C is the most common version seen in Africa. The HIV we're seeing in the developed world is HIV 1, Subtype B

** Warning - Science Lesson Ahead **

All the HIV drugs work by interfering with some part of the virus duplication process. What has made HIV so tricky, is that when it does reproduce, there are a lot of mutations. It is a strand of RNA (1/2 of a DNA double helix). Because of that, there is a greater chance of errors in reproduction. In uncontrolled HIV, Billions of copies are produced every day, which creates many opportunities for viral mutations.

After the virus injects itself into the CD4 cell, the Reverse Transcriptase enzyme creates a complementary strand of RNA, and glues it together with the original, making a strand of DNA, which gets passed on to the next step of reproduction. Most mutations happen here. All of Nucleoside, Nucleotide, and Non-Nucleoside Reverse Transcriptase Inhibitors interfere with this step, in slightly different ways.

In the early days, when only one antiretroviral drug was used, that natural tendency to mutate led to the virus becoming resistant to a drug within a few months. It is one of the most classic cases of Darwinian biology you will find -- Mutations occur during reproduction, a trait from one mutation proves useful (ie resistance to the drug), the survivors reproduce, and become the dominant species. The virus 'evolved' in that person to use Reverse Transcriptase in a different way. (Of course a virus isn't actually alive - so evolve might be too strong of a word)

People with HIV now get (at least) a three drug regime. Usually two from one class, and a third from a different class of drugs. While the first line combinations of choice are changing, most people start with two from the NRTI class (both drugs in Truvada are from that category), and one from a different class (NNRTI, PI, II). For example in my case, I take two NRTIs and one NNRTI all of which are aimed at blocking HIV's ability to use Reverse Transcrptase.

Truvada as PrEP uses two NRTI's to block that early step in viral replication. If an HIV exposure occurres it is unlikely that the virus would be able to reproduce itself efficiently enough for the new host to become HIV+. The viral copies from that initial exposure, and the few that were able to reproduce, are eventually "die" of old age, or are destroyed by body's own defences. That's how both PEP an PrEP work.

** HIV Reproduction Lesson End -- PrEP Resistance Lesson Begin **

Now to the OP's original question. Yes, exposure to a strain of HIV that is resistant to both drugs in Truvada is possible. The fear of that strain developing and spreading is one of the arguments PrEP nay sayers shout. We aren't seeing a lot of new HIV infections that are multi-drug resistant. We are seeing some, but not enough that doctors are worried. There are enough drugs now, that we have many options to treat a multi-drug resistant strain, with other ARVs that will inhibit the virus. In fact, it is common practice to test for drug resistance before starting an Poz guy on antiretrovirals.

Lets look at what would need to happen for you to catch a Truvada resistant strain.

Say a guy started on PrEP after testing Negative, but he was in the window period, and it doesn't show up on the test. While he bought the PrEP, and started taking it, but doesn't take it every day. He only takes it one or two days a week - weekend disco dosing. There's some drug in his system, and it is inhibiting some HIV replication, but not enough drug to do a very good job of it. The virus mutates, and by random chance comes up with a version that avoids the way BOTH of the drugs in Truvada inhibit Reverse Transcriptase. It could also happen with a Poz guy who was very bad with his three drug regime (assuming his ARVs included both drugs in Truvada).

Now he'd have to screw you after he developed a very high viral load before his next set of tests - assuming he goes for them, because he's not taking the drugs right. Or perhaps he dinks some guy who catches the Truvada resistant strain. That guy grows one of those window period ten million viral loads, and he fucks you - a good PrEP user. He gives you one of those dry, nasty, hard fucks that draws blood and is sure to Poz you. Or maybe it's gentle tender and loving, but unlucky you rolls snake eyes in that 1 in 71 chances per exposure, and you get infected. We also have to assume that his virus hasn't started to mutate back to its original wild type.

Those are an awful lot very special circumstances that would all have to line up just perfectly for PrEP to fail you because of a Truvada resistant strain. The chances of that are WAY WAY less than the already quite small chance of you catching any other strain of HIV 1 Subtype B while on PrEP.

I'm sure if there was something making the rounds that's resistant to both drugs in Truvada there would be bells ringing, sirens going off, and red lights flashing, in every HIV clinic, and phone calls being made to every doctor who prescribes PrEP.

If you're going to be fret about things with that small of a chance happening, you shouldn't be playing bare - period.

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HIV2 is somewhat common in west Africa. I'm sure there have been some rare cases in North America, with people who brought it back from overseas.

Those are an awful lot very special circumstances that would all have to line up just perfectly for PrEP to fail you because of a Truvada resistant strain. The chances of that are WAY WAY less than the already quite small chance of you catching any other strain of HIV 1 Subtype B while on PrEP.

I'm sure if there was something making the rounds that's resistant to both drugs in Truvada there would be bells ringing, sirens going off, and red lights flashing, in every HIV clinic, and phone calls being made to every doctor who prescribes PrEP.

If you're going to be fret about things with that small of a chance happening, you shouldn't be playing bare - period.

Does HIV2 require any different treatment from HIV1?

Anyway this post was correct, in theory the stars can align and you can get infected, PrEP is NOT 100% effective, If you want 100% effective you should not be having sex, or be in a completely monogamous relationship, and those hardly exist.

The biggest cause of PrEP failure is, and I bet will continue to be compliance with the medication. you want it to work, DONT EVER MISS A DAY. For me, I want PrEP to work so in the 8 months or so I have missed exactly twice, and that was in the first month before I got used to it. I have never missed since then.

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Guest JizzDumpWI

I will ask my ID doc at the coming ARCW (AIDS Resource Center Wisconsin) event at end of the month... There isn't much in the way of good data on HIV2 online but I k now he would know...

Wood I agree. While there is some thinking that every other day would work, compliance becomes a challenge. I know there are alternative dosing studies out there. PrEP though differs from PEP by developing an effective blood level as that virus enters your bloodstream from rough fucking and as a result is working on that first virus division. I will remain open to options as they become available; but for now I am on PrEP for it to work and so take it every day. What I did change was obsessing the hour.. I take mine with breakfast. If that is at 5am or 10am, it's all good...

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I will ask my ID doc at the coming ARCW (AIDS Resource Center Wisconsin) event at end of the month... There isn't much in the way of good data on HIV2 online but I k now he would know...

Wood I agree. While there is some thinking that every other day would work, compliance becomes a challenge. I know there are alternative dosing studies out there. PrEP though differs from PEP by developing an effective blood level as that virus enters your bloodstream from rough fucking and as a result is working on that first virus division. I will remain open to options as they become available; but for now I am on PrEP for it to work and so take it every day. What I did change was obsessing the hour.. I take mine with breakfast. If that is at 5am or 10am, it's all good...

Yeah I hope there is an alternative in the next few years. I know injections every 10 weeks are being investigated now, and that would be pretty awesome, especially if it could eventually be done in a pharmacy like a flu shot.

I agree on the timing. I used to be a nazi about trying to take it at exactly the same time everyday, and then I realized I was going a bit overboard. I normally take mine around 2 after a late lunch, but if it happens to be 11am or 6pm every so often I cant freak out about that.

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Guest JizzDumpWI

Poz1956, thanks. Interesting article. This seems to suggest Truvada is likely effective against HIV2 as well, but that has not been studied...

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