Stopping PrEP: difference between Tops and Bottoms?

[hungry_hole]

A guy I know was on PrEP for a couple of years but, because he's now in a relationship, he doesn't get too many opportunities for anon sex and didn't make sense for him to take a daily pill. Also the Pandemic.

He sometimes goes on business trips for weeks at a time and he wants to have some anon sex while he's away. His doctor suggested he start taking PrEP a week before the first sexual encounter and take daily PrEP until, 30 days for bottoms, and 7 days for tops after the last sexual contact.

I have never heard of bottoms having to continue on PrEP longer than tops. Can anybody shed some light on this?

[justsexnowatl]

I haven't heard of this one.  I believe Prep "on demand" is a somewhat common method outside of the US and would use way less pills.  2 pills 2-24 hours ahead of sex then 1 pill each of the next 2 days.

[Guygonebad]

3 minutes ago, justsexnowatl said:

I haven't heard of this one.  I believe Prep "on demand" is a somewhat common method outside of the US and would use way less pills.  2 pills 2-24 hours ahead of sex then 1 pill each of the next 2 days.

Yes…SF promotes this method…2-1-1 as described by @justsexnowatl. Go to SF Aids foundation to learn more.

[fskn]

The US CDC guidelines lay out research-based PrEP regimens and say which patients they are suitable for.

An intermittent or "2-1-1" Truvada regimen, in patients for whom research supports its use, reduces to daily use if the person is having sex every day. However, the tail of that regimen remains one pill every day up to and including 2 days after the last sexual encounter — not 7 or 30 days. [See pp. 55–56.]

The CDC guidelines have this to say (about straightforward daily Truvada or Descovy; "2-1-1" Truvada is a separate matter):

"Protection from HIV infection will wane over 7–10 days after ceasing daily PrEP use." [p. 46]

Concentrations of PrEP drugs (note that Truvada and Descovy, the most common PrEP products, each contain two drugs) vary in different parts of the body. More is know about rectal tissue, and more is known about Truvada than about Descovy or Apretude (the new 2-month injectable for PrEP).

"The time from initiation of daily PrEP use to maximal protection against HIV infection is unknown. It has been shown that the pharmacokinetics of TDF and FTC [FTC is the drug common to Truvada and Descovy] vary by tissue but there is not scientific consensus on what tissue-specific intracellular concentrations are protective [...]

"Data from exploratory F/TDF [the distinct drug in Truvada] pharmacokinetic studies suggest that maximum intracellular concentrations of TFV-DP, the active form of tenofovir, are reached in blood PMBCs after approximately 7 days of daily oral dosing, in rectal tissue at approximately 7 days, and in cervicovaginal tissues at approximately 20 days.

"F/TAF [the distinct drug in Descovy] pharmacokinetic study data related to potential time to tissue-specific maximum concentrations are not yet available, so the time from initiation of daily F/TAF for PrEP to maximal tissue protection from HIV infection is not known.

"Data is not available for either F/TDF or F/TAF PrEP in penile tissues susceptible to HIV infection to inform considerations of time to protection for male insertive sex partners." [pp. 42–43]

And for the new injectable:

"No data are yet available from clinical trials in men or women to estimate the time from initiation of CAB injections to maximal protection against HIV acquisition." [p. 54]

[think before following links] https://www.cdc.gov/hiv/pdf/risk/prep/cdc-hiv-prep-guidelines-2021.pdf

Each patient should discuss with a medical professional, especially if there is a variance from the CDC guidelines.

Edited April 30, 2022 by fskn
Clarity

[BootmanLA]

While I agree that the original medical advice was overkill, there's some common sense behind the notion of longer PrEP duration for bottoms. It's well documented that bottoms face higher risk from an HIV+ top than tops face from an HIV+ bottom.

[RubberAustria]

17 hours ago, justsexnowatl said:

I believe Prep "on demand" is a somewhat common method outside of the US

Yes. Here in good old Europe it is common. There exist studies from several countries. I also use „Prep“ on demand. On weekends and holidays. 

[Guest]

Tell him to talk to his doctors.

[valldelxeno]

On 5/1/2022 at 6:13 AM, BootmanLA said:

While I agree that the original medical advice was overkill, there's some common sense behind the notion of longer PrEP duration for bottoms. It's well documented that bottoms face higher risk from an HIV+ top than tops face from an HIV+ bottom.

I don't think PrEP for more or less time is to do with likelihood of catching it or not, but to do with effective viral load. 

As I understand it, viral load in acute infection is proportional to the viral load of the person who gave it to them. Following this logic, more copies of the virus get into a bottom's bloodstream than into a top's bloodstream (which would explain why tops are more likely to clear the system of the virus entirely) and so generally speaking a top will need less of the medication to ensure a system clear of HIV compared to a bottom 

[fskn]

16 minutes ago, valldelxeno said:

I don't think PrEP for more or less time is to do with likelihood of catching it or not, but to do with effective viral load. 

As I understand it, viral load in acute infection is proportional to the viral load of the person who gave it to them. Following this logic, more copies of the virus get into a bottom's bloodstream than into a top's bloodstream (which would explain why tops are more likely to clear the system of the virus entirely) and so generally speaking a top will need less of the medication to ensure a system clear of HIV compared to a bottom 

The real issue, for which there is some empirical evidence, is that it takes different amounts of time for drugs to concentrate in different body tissues.

For example, we know that it takes many extra days of daily Truvada use for peak tenofovir levels to be reached in the vagina than in the rectum. (We still have incomplete data about concentration in penile tissues.)

But despite knowing how long it takes to achieve peak concentration in a given part of the body, we still don't know exactly what minimum concentration is needed for protection, in humans. A minimum therapeutic concentration is a best guess.

It's probably less than peak concentration. Otherwise, when experiments with intermittent or "2-1-1" Truvada PrEP were conducted in large groups of gay men, a 2-pill loading dose taken as late as 2 hours before sex would not have prevented HIV infections.

This is why research is done on large groups of people, under more-or-less realistic conditions in the field, and why final-phase trials focus on calculating rates of infection/illness in a group, not solely on measuring drug concentrations in body parts.

Edited May 4, 2022 by fskn

[valldelxeno]

11 minutes ago, fskn said:

The real issue, for which there is some empirical evidence, is that it takes different amounts of time for drugs to concentrate in different body tissues.

For example, we know that it takes many extra days of daily Truvada use for peak tenofovir levels to be reached in the vagina than in the rectum. (We still have incomplete data about concentration in penile tissues.)

But despite knowing how long it takes to achieve peak concentration in a given part of the body, we still don't know exactly what minimum concentration is needed for protection, in humans. A minimum therapeutic concentration is a best guess.

It's probably less than peak concentration. Otherwise, when experiments with intermittent or "2-1-1" Truvada PrEP were conducted in large groups of gay men, a 2-pill loading dose taken as late as 2 hours before sex would not have prevented HIV infections.

This is why research is done on large groups of people, under more-or-less realistic conditions in the field, and why final-phase trials focus on calculating rates of infection/illness in a group, not solely on measuring drug concentrations in body parts.

Wouldn't this be more to do with how long *before* sex you need to be on it though? If we're talking about 7 to 28 days after sex, presumably the virus has found its way through the rectal/penile tissues and is in the bloodstream by that point 

[BootmanLA]

51 minutes ago, valldelxeno said:

Wouldn't this be more to do with how long *before* sex you need to be on it though? If we're talking about 7 to 28 days after sex, presumably the virus has found its way through the rectal/penile tissues and is in the bloodstream by that point 

Yes and no. There's a difference between the virus being inserted into your system, and the virus being able to actively reproduce within your system, and the virus can continue to exist (it's not "living") within your system for a period before it breaks down and can no longer infect. The point of PrEP is to prime your body's cells with the ability to prevent HIV from replicating in your system until it naturally breaks down and is no longer a threat.

So both the amount of time the drug has to build up in your system before infection AND how long it remains in your system after infection are both relevant. If the penile/vaginal tissues have sufficient drug levels at the time of sex, they may be able to prevent the virus from ever entering your bloodstream to find other cells through which to replicate. But if it does reach the bloodstream, it's also important to keep priming the pump, so to speak, with additional drug levels (the day after and day after that doses, at a minimum) that continue to block replication by the virus.

[fskn]

1 hour ago, valldelxeno said:

Wouldn't this be more to do with how long *before* sex you need to be on it though? If we're talking about 7 to 28 days after sex, presumably the virus has found its way through the rectal/penile tissues and is in the bloodstream by that point 

Indeed, loading is more important.

In the case of intermittent or "2-1-1" Truvada dosing, though, a two-day, one pill per day tail after the last sexual encounter is required for protection from that sexual encounter.

For the new PrEP injectable, the tail is also significant, but in a different sense. Although long-acting Cabotegravir remains in the body for many months, concentrations drop below (not precisely known) therapeutic levels after about two months, meaning that switching to oral PrEP is essential if people want to be protected when they have sex more than 2 months after stopping injections.

Edited May 5, 2022 by fskn

[valldelxeno]

33 minutes ago, BootmanLA said:

Yes and no. There's a difference between the virus being inserted into your system, and the virus being able to actively reproduce within your system, and the virus can continue to exist (it's not "living") within your system for a period before it breaks down and can no longer infect. The point of PrEP is to prime your body's cells with the ability to prevent HIV from replicating in your system until it naturally breaks down and is no longer a threat.

So both the amount of time the drug has to build up in your system before infection AND how long it remains in your system after infection are both relevant. If the penile/vaginal tissues have sufficient drug levels at the time of sex, they may be able to prevent the virus from ever entering your bloodstream to find other cells through which to replicate. But if it does reach the bloodstream, it's also important to keep priming the pump, so to speak, with additional drug levels (the day after and day after that doses, at a minimum) that continue to block replication by the virus.

I'm not expert by any means so maybe I'm just misunderstanding your explanation, but based on what you're saying I would be under the impression that PrEP was a vaccine - albeit one that has to be taken repeatedly - if I didn't know otherwise. 

My understanding was that PrEP hangs out in your bloodstream and in other tissues such as the rectum, where it is ready to prevent virus replication, while the immune system deals with it somehow. But I wasn't aware of any interaction as such between PrEP and cells, as it just consists of reverse transcriptase inhibitors 

[BootmanLA]

1 hour ago, valldelxeno said:

I'm not expert by any means so maybe I'm just misunderstanding your explanation, but based on what you're saying I would be under the impression that PrEP was a vaccine - albeit one that has to be taken repeatedly - if I didn't know otherwise. 

My understanding was that PrEP hangs out in your bloodstream and in other tissues such as the rectum, where it is ready to prevent virus replication, while the immune system deals with it somehow. But I wasn't aware of any interaction as such between PrEP and cells, as it just consists of reverse transcriptase inhibitors 

I may not have explained my point clearly.

Your own response, though, touches on what I mean: it's not that PrEP enters any cells, but it does build up a barrier TO infecting certain cells, and that can take place either within the bloodstream or within certain types of tissue, specifically mucosal tissue, found in the vagina and rectum. PrEP, in other words, definitely enters certain tissues, even if it doesn't exactly enter the cells within the tissue. 

As I'm sure you know, HIV replicates by invading a cell, coopting the cell's reproductive capabilities, and using them to produce more virus particles. So in that context, PrEP exists to disrupt that interaction between the cell and the virus, and that's what I was referring to: as long as there's sufficient PrEP in your system, the virus particles can't enter your system, and eventually they're filtered out or break down.

The thing about mucosal tissues is probably what explains why taking PrEP longer (after sex) may be more important for a bottom than a top. There aren't nearly as many points of entry (via the bloodstream or mucosal tissues) on a cock as there are in a rectum. If a top's on PrEP and has sex with an HIV+ bottom, infection by the virus is not only prevented by the PrEP, but he's likely to be at risk only until his next urination or so. A bottom, on the other hand, may have active virus trying to invade through his rectal mucosal tissues for a good while, hence the need to keep the level of PrEP high in his system for a longer period.

[viking8x6]

OK, a couple of points here.

One, the 2-1-1 on-demand dosing for PrEP has been experimentally verified to be effective for bottoms. Therefore, a 2-day tail (plus however long it takes for the drug concentration to drop in the body)  is sufficient to protect from infection.  Therefore 28 days (or even 7) are not necessary. QED.

Two [warning, science ahead!] the drugs (reverse transcriptase inhibitors) in PrEP do indeed go into the cells, and they must do so significantly *before* the HIV virus in order to protect that cell from infection. They must enter the cells because that is where the viral RNA is unpacked and transcribed into DNA - the first step in replication, and the one that RTIs prevent. They must do so early because the dosed forms of the drug are not the ones that inhibit the process - they must first be deprotected (from the chemical modification that protects them and allows them to be absorbed by the body) and then have a couple of phosphate groups added by body enzymes before they are in the form that binds to the viral enzyme and prevents it from working. All that takes some time.