How long does it take PreP to work for Tops?

[SirBillybob]

2 hours ago, pubic_assistance said:

I am confused by this question.

WHY would efficacy be different for a top than a bottom ? 🤔

I 'get' that the bottom is taking a BIG load of virus, while the top is somewhat less likely to have virus sneak in, but it only takes ONE little virus to start an HIV infection ....so to me whether top or bottom, you need the same protection. 

I think he was asking whether there’s a relationship between sexual position and number of days of PrEP pre-loading to confer equivalent pharmacological protection among the categories within the sexual position variable. This is a complex question because anatomical sites vary according to infection susceptibility and the degrees of drug concentrations and time on drug required to shut down replicating virus within mucosal tissue. So technically, there’s a theoretical basis for assuming less risk based on insertive sexual position, given receptive anal is 10-fold riskier than insertive anal, that itself compensates for the sub-optimal drug concentrations associated with sexual activity prematurity undertaken within the arbitrary, ie, 7 day, preloading rule of thumb. But this is really getting into the weeds and the guidance wouldn’t be easily packaged or consumable with this level of stratification detail. The risk arising from deviating from the 7-day preloading guidance may be mitigated by an impromptu transition to the 2 of 2-1-1. In fact, some guidance entities are happy with getting into the weeds on logistical tailored bilateral transitioning options between the two conventional uptake models. 

That said, efficacy isn’t the exact term as efficacy is calculated statistically from research cohorts and comparing two or more samples not representative of any one unique sexual interaction. Condom use also occurs among PrEP research subjects and may make the key difference for breakthrough infections that would otherwise have occurred. Undocumented condom use is a behavioural factor that supports efficacy confidence intervals as much as does the imperative of acknowledging statistical power and conceding less than the absolute efficacy metric. 

The all-it-takes idea regarding that low virion quantity that escapes prophylaxis is relevant enough to structure the guidance equally across the sexual position categorical variable. Where PrEP is researched and position assessed there are relatively few tops that aren’t sides. If all or most were exclusive tops the research cohort would have to be increased to astronomical numbers in order to achieve adequate sample power for meaningful statistical analysis of efficacy. The greater the background incidence of the thing the intervention aims to prevent the greater the reliability of the effectiveness result. Paradoxically, though, the value of 100% is that it can never be. 

Edited June 8 by SirBillybob

[pubic_assistance]

7 hours ago, SirBillybob said:

That said, efficacy isn’t the exact term as efficacy is calculated statistically from research cohorts and comparing two or more samples not representative of any one unique sexual interaction.

Well...thats my point. 

Its clear that risk is higher for a bottom than a top. BUT when it comes to the question - which is: How many days does a top need to take PreP v.s. a bottom. It seems to me that the dosage has nothing to do with your sexual position. The Russian Roulette quality of risk in a top barebacking, seems to be the only variable. Day of infection vs. efficacy of saturation in the blood stream is therefore the same for both. 

Edited June 9 by pubic_assistance
punctuation

[SirBillybob]

2 hours ago, pubic_assistance said:

Well...thats my point. 

Its clear that risk is higher for a bottom than a top. BUT when it comes to the question - which is: How many days does a top need to take PreP v.s. a bottom. It seems to me that the dosage has nothing to do with your sexual position. The Russian Roulette quality of risk in a top barebacking, seems to be the only variable. Day of infection vs. efficacy of saturation in the blood stream is therefore the same for both. 

Right, negative event (target) probability is key. Drug concentration is on a gradient. Some is better than none, yet inferior to the estimated ideal. At any degree of drug concentration the intent for the bottom is that not one ball representing the target be pulled from the bingo bin. The intent for the top is that not one ball representing the target in a collective of 12 bingo bins be pulled from any of the dozen bins. The risk for the non-PrEP top approaches the risk of the optimal PrEP bottom. The risk cannot be the same based on position alone. It depends on number of encounters. Because number of anticipated encounters isn’t considered in the estimate of efficacy it makes sense for both tops and bottoms to pursue optimal drug concentrations for prophylaxis. Like many things, the answer is “It depends”, but the simplest answer is for all sexual positions to acquire the benefit from the pharmacodynamics research that governs best practices. 

Added to this is the notion that event risk does not reset to the same probability following each successive avoidance of the negative target. The probability of the event avoidance must be subject to an exponent representing the cumulative number of occasions in which the negative event is potentiated. All things equal, each successive encounter poses greater risk even if negative event escape accrues. 

My hundreds of unprotected sexual encounters between 1981 and 1985 mean I am at greater risk for HIV infection now compared to today’s chap on his first or tenth encounter, what have you, all other factors equal. Nothing to do with age or wear & tear. When it comes to probability, a debt in one way or the  other is always owed at the multiple threshold. 

Edited June 9 by SirBillybob

[pubic_assistance]

37 minutes ago, SirBillybob said:

My hundreds of unprotected sexual encounters between 1981 and 1985 mean I am at greater risk for HIV infection now compared to today’s chap on his first or tenth encounter.

Wow. 

You were definitely blessed.

I grew up in the late 80s with condoms being absolutely mandatory for sex with anyone...and I wasnt even sleeping with men back then. 

You definitley dodged a lot of bullets there by being a top.

But this reinforces my opinion. Maximium efficacy of PreP is the same for tops and bottoms. Its just that tops arent as in the same hi risk position as a bottom.

[SirBillybob]

1 hour ago, pubic_assistance said:

Maximium efficacy of PreP is the same for tops and bottoms. It’s just that tops arent as in the same hi risk position as a bottom.

Well not exactly, in purist inferential statistics terms. The metric of efficacy when stratifying the two risk categories is unknown for each separately because, as you say, the risk probability differs. Research evaluating PrEP effectiveness, that is, percentage of infections prevented that would occur without the intervention, would need to compare tops with tops or bottoms with bottoms. That won’t happen as it was always going to be logistically impossible and is now unethical given prevention is incontrovertible.

Furthermore, a position risk distinction is not made and the categories are combined when the pharmacokinetics of time to drug concentrations correlated with protection are studied. Like I’ve suggested, in the context of not establishing whether PrEP is more effective for one versus the other position it’s best to treat them the same as opposed to implying that gaming the risk variables is valid and safe.

[pubic_assistance]

8 hours ago, SirBillybob said:

Well not exactly, in purist inferential statistics terms.

I don't agree with that assessment. I understand your point about the DATA being skewed, but my point is not about numbers and data but just logic. We know that tops CAN be infected. MY point is that ANYONE who is infected, whether top or bottom, likely needs the same degree of protection, because an infection is an infection. Whether you have a huge load up your ass, or a few cells in your urethra. 

[SirBillybob]

2 hours ago, pubic_assistance said:

I don't agree with that assessment. I understand your point about the DATA being skewed, but my point is not about numbers and data but just logic. We know that tops CAN be infected. MY point is that ANYONE who is infected, whether top or bottom, likely needs the same degree of protection, because an infection is an infection. Whether you have a huge load up your ass, or a few cells in your urethra. 

Yes, for zero risk to override relative risk, one oriented to risk elimination and the other to risk reduction. Risk elimination nullifies the concept of difference in need or requirement, and there’s no call to triage, because as you suggest one spark is the necessary and sufficient condition for infection. In that sense need is absolute. Need is not always absolute in retrospect. There are far more situations of non-infection resulting from unprotected sexual intercourse with a partner with unsuppressed viral load than situations of infection culminating from same. 

The guidance target is risk elimination and errs on the side of caution, but the statistical analysis reports risk reduction. 100% protection, say, no poz sexual partners, also renders the position risk difference moot. Otherwise, protection is on a gradient and condoms are recommended to supplement PrEP.

Injection drug users need the same degree of protection as anybody to prevent HIV but cannot acquire enough through PrEP. We know that for sure but not for sure whether bottoms on PrEP are more likely to be infected. We push condom supplementation without making the distinction between top and bottom because the bottom cannot be protected without the top protected. Symbiosis. It’s the same intervention although logically a bottom on PrEP is more likely to be infected because pre-PrEP the risk difference is clinically significant. The condom intervention is applied differently, a difference in the life trajectory of the product necessitating negotiation, unlike for PrEP if uptake is uniform. 

PEP would be offered equally to a top and bottom, all else equal. They need the same degree of post-exposure intervention to escape seroconversion.  If they asked about risk without the PEP uptake it would be a disservice to withhold the estimated difference while at the same time you push equal access. You might be more worried about a bottom taking a pass on the intervention. A top discontinuing PEP at 3 weeks might be less worrisome than the bottom doing so. But there’s no reason to adjust the resources as you might for different sizes of fire.

This isn’t to say that PrEP resources aren’t ever allocated according to risk difference since females have 2-fold risk. The need is the same because sex is symbiotic. 

Edited June 9 by SirBillybob

[Guest]

I dont wanna make another thread, so please dont mind me for asking for but I'm considering switching to Prep on-demand. It just makes more sense for my lifestyle (feast or famine). But I am scared. I read a few studies and TBF, it just seems like too good to be true.

I tend to plan things ahead of time, so being consistent is not a problem. It's 2-1-1. How did we go from need to taker it daily for 7 days or 14 days at one point before it works to 2-1-1 giving relatively the same protection.

Something feels off (don't mean to sound conspiratorial).

Could someone who uses 2-1-1 frequently/properly please enlighten me on its efficacy and any medical insights they have from on-hand experience?> Ty

 

[SirBillybob]

Well, since you understandably wish feedback from consumers … 

I have only used on-demand since commencing PrEP about 7 years ago. The grade of evidence for protection is strong, see attached for the randomized control trial results that underpin on-demand legitimacy. In contrast to daily PrEP the strength of recommendation is weak. That difference is not based on efficacy. Rather, there is no placebo control research evaluating efficacy among those using PrEP sporadically due to being sexually active sporadically, that is, like you and me.

What happened in the on-demand trial is that participants did not take PrEP daily but took on average about 15 doses monthly and that was close to the average monthly uptake (4 doses weekly) in studies of daily (intended to be daily adherence) PrEP. They planned for sexual activity quite frequently irrespective of having it or not. That also may account for the higher rate of renal adverse events than would occur for sporadic 2-1-1 users.

Personally I do not conflate the two-pronged strong/weak versus strong/strong with one being better. It’s all in the reasonable tailoring. The difference is an artefact of the inability to logistically and ethically design research in which more accurate effectiveness across all sexual activity frequency groups could be calculated. It would have taken too long to follow and evaluate for infrequent users because background HIV incidence is too low compared to flu, coronavirus, other STIs, etc. Any study of efficacy requires a relatively poor outcome for some participants. 

The protectiveness of on-demand in gold standard research is also superior to the findings of retrospective research of the daily regimen.

That said, I haven’t not used a condom for anal insertive or receptive in 40 years. I don’t consider PrEP as TGTBT since the probability of HIV infection over extremely long life periods of risky sexual activity is elevated and the trade-off is higher vulnerability to other STIs. 

Regarding dose loading, some guideline entities for daily PrEP are now stating 2 doses just as in on-demand, or the option of 7-day but inserting a one-time 2-dose uptake as in on-demand if the abstinence is not possible to sustain for the week. 

Edited June 16 by SirBillybob