Question

How to take PrEP: daily dosing and other options?

21 August 2015. Related: Access to treatment, All topics, HIV transmission, PrEP.

What are the differences between the ways that PrEP can be dosed?

Some websites and clinics say daily and some say there are options for taking it just when you have sex.

Which is best?

Answer

Answer: Simon Collins

Note: a new i-Base guide to PrEP is now available.
https://i-base.info/uk-guide-to-prep

……

Thanks for your questions – both important and current.

Even though there are currently no UK guidelines that discuss this, PrEP is already being widely used in different settings – including as an off-label street drug.

When used correctly, PrEP is highly effective and safe. But PrEP is a medicine and so also needs to be taken seriously.

• PrEP should only be used if you are HIV negative, and that this has been supported by a recent HIV test.
• PrEP also requires some simple monitoring tests to check that it is a good idea to use PrEP and that you are not getting side effects.

i-Base strongly recommends talking to a doctor at a sexual health clinic if you want to use PrEP. The information below is based on results from a wide range of research. The information is to be used in consultation with a doctor. 

PrEP in this article refers to tenofovir and emtricitabine in a single tablet. Please note the important differences for dosing depending on whether this is for vaginal sex or anal sex.

Daily PrEP

The research studies that led to the approval of PrEP in the US all used daily dosing.

The UK PROUD study also used daily dosing.

Daily dosing is therefore the only dosing strategy that has been proved in large trials.

This doesn’t mean that PrEP can’t be used in other ways. Especially as many people in the daily-dosing studies did not actually follow daily dosing. In fact, most people used less-than-daily dosing, and PrEP was still very effective.

So other ways of using PrEP might be just as effective. It just means there is very little evidence that proves this efficacy.

Before using anything other than daily dosing, it is important to understand what you need from PrEP, and also a little about how PrEP works.

Alternative dosing

Several studies have also looked at other ways of dosing PrEP.

Although these studies are important, these studies are generally too small to prove whether PrEP is effective. On the other hand, many of these smaller studies are reporting no infections when people are using PrEP with less frequent dosing.

Alternative ways to dose PrEP include:

• Reduced dosing. This is when PrEP is still taken regularly, but on a different schedule – for example, every other day, or taking PrEP four times a week.
• Event-based dosing. This is when PrEP is taken because you are going to have sex or are likely to have sex. Event-based dosing was used in the French IPERGAY study.

There are advantages and disadvantages to both approaches. Whether one of these is better for you will depend on your individual circumstances.

Individualising circumstances and dosing

In practice, there are many disadvantages of daily PrEP and this has driven the need for looking at alternative dosing.

Alternative dosing might even make PrEP more effective, because it becomes easier to match your individual need. And this in turn makes it easier to be adherent in taking PrEP.

So the question of dosing relates closely to your circumstances.

This includes:

• Your need in terms of likely risk – how often you have sex.
• Whether the times you have sex is fairly predictable – for example, knowing this is likely at the weekend or on a specific day in advance.
• The level of protection you want to get from PrEP – whether you want 100% protection or just to reduce the risk.
• Whether PrEP is to cover anal sex or vaginal sex.
• Whether cost is a factor in buying PrEP.

How often you have sex?

If you are likely to have sex every every week, or most weeks, or several times a week this would be a reason to choose a dosing that covers you all through the week and all through the month – for as long as you are taking PrEP.

If you want protection against HIV less frequently, for example once a month, this might be a reason to prefer event-based dosing.

This might be because you have sex less frequently or it might be because you generally use condoms but sometimes want to have sex without a condom.

Do you roughly know in advance when you might have sex?

If is it difficult to know when you are going to have sex – and this might be instant and spontaneous – then it might be more appropriate to use dosing that gives you protection 24 hours a day, seven days a week, 365 days a year.

If you have a good idea when you are likely to have sex, this might be a reason to used reduced or daily dosing.

For example, every Tuesday, or at the weekend, or for a one-off party, or when going on holiday or on your birthday…

What level of protection do you want from PrEP?

Part of the reason that PrEP is such an important option is that when used correctly it is virtually 100% effective. PrEP doesn’t just reduce your risk of HIV but cuts it to zero.

If this is the level of protection that you want – if you want to rely on PrEP to say negative – then it will affect how you use PrEP.

If you just want to reduce your risk, then the dosing choice becomes less important.

“Some PrEP” might always have some reduced risk compared to “no PrEP”.

But only using a little PrEP – certainly just one or two pills used wrongly or too late – might not provide any significant protection.

Whether PrEP is to cover vaginal or anal sex?

This is very important because the drugs in PrEP are absorbed different in vaginal compared to rectal tissue.

Tenofovir levels are 10 times higher in rectal tissue than vaginal tissue – and this is perhaps why tenofovir is so effective in studies in gay men.

If your risk is from vaginal sex (as the receptive partner, whether you are a women or trans man) then PrEP needs to be taken every day to reach the right drug levels.

This doesn’t mean that you have to be taking daily PrEP throughout the year. But it does mean that you probably need to take daily PrEP for a week before relying on protection. It also means continuing daily PrEP for as long as you want protection to continue.

Stopping PrEP is easy if your circumstances changes and you no longer need this level of protection. But you will need to allow for another lead-in period to get protection again in the future, each time you want this.

Although daily PrEP gives the best protection, missing an occasional dose is okay – i.e. 6-7 doses a week is likely to give similar protection to 7 doses a week.

If your risk is from anal sex (as the receptive partner) – whatever your gender – then taking 4 doses a week is likely to provide more than 95% protection, and perhaps close to 100% protection.

This is based on high level of tenofovir in rectal tissue. It is also based on tenofovir levels staying high for a day or two once the drug reaches the ideal level inside a cell.

The evidence for needing at least 4 doses a week for anal sex is based on results from the iPrEX study in gay men and transgender women.

This can mean taking PrEP every other day. It could also cover PrEP four days a week using a routine that you find easy to remember.

For example, Monday, Wednesday, Friday, Sunday if you have sex throughout the week.

Or Midweek, Friday, Saturday and Sunday, if you are more likely to have sex at the weekend.

In the PrEP efficacy studies, many people aimed to take daily PrEP but in practice only took four tablets a week.

Is cost a factor is getting PreP?

If you are buying PrEP privately, then cost might be an important factor.

If you are getting free prescriptions – either as part of a research study or as part of routine care – then there is no cost pressure on decide the dosing strategy.

If cost is an issue, this might be an important reason to use event-based dosing.

For example, a gay man wanting continual protection, every day, every week, that is close to 100%, could make a one month prescription of 30 tablets last for 6 to 8 weeks by using alternate dosing.

Someone who only wants protection to cover occasional risks for example once a month, could make a one month supply of 30 tablets cover 6 or more events.

This makes PrEP an option that is affordable for much larger percentage of people who could benefit for this option than are ever likely to get this prescribed on the NHS, while PrEP meds are still in patent.

Event-based dosing – IPERGAY and other studies

One of the most widely publicised ways of using event-based dosing, relates to a French and Canadian study called IPERGAY.

IPERGAY dosing

The dosing in IPERGAY involved:

• Taking a double dose of PrEP (2 tablets) before sex. This would ideally be the day before, but could be anywhere from 24 to 2 hours before.
• Taking another single dose (1 tablet) after sex – i.e. the same day.
• Taking another single dose (1 tablet) the following day.

This means taking four tablets if you had sex once in a week. This also means taking four tablets if you had sex lots of times if this was all on one day.

If this involved having sex on several days, then daily dosing was recommended, with a final dose the day after all this activity ended.

So to cover a period when you have sex on Friday, Saturday and Sunday, involves taking a double-dose on Thursday, single doses on Friday, Saturday and Sunday, and a final dose on Monday. This would involve taking six tablets altogether.

This level of protection is using virtually daily dosing and IPERGAY recommended not using more than seven doses in any one week.

Understanding this range of flexibility is important to understand the results from IPERGAY. This is because although event-based doing was being studied, most of the men used at least four doses a week – which produces >95% efficacy.

So although the overall results from IPERGAY showed that PrEP was highly effective, even the research say that it did;t provide evidence to show whether this dosing works for people who perhaps only had sex once a month.

On the other hand, no-one who was using once-monthly PrEP became HIV positive. It just means there were not enough people doing this to understand the actual level of protection.

Timing of the pre-sex dose

Part of the difficulty in providing information about the timing of the pre-sex dose, involves the limited data we have on this question.

This includes limited data on timing and limited date on the ideal drug levels that are needed to stop infection.

The pre-sex dose is definitely important. Animal studies showed that protection is significantly reduced if PrEP is only used after sex.

Timing before sex is also important because of the time it takes for PrEP drugs to be reach good levels in the part of your body where you need protection – especially inside cells in vaginal and rectal tissue.

The two drugs in PrEP – tenofovir and emtricitabine (FTC) – are absorbed differently and at different times.

Tenofovir

• Tenofovir is the main active drug in PrEP or rather it is the drug that we have the strongest evidence for protecting agains infection.
• Some PrEP studies showed similar efficacy with single drug tenofovir PrEP compared to dual drug tenofovir+FTC. Tenofovir is not approved in the US as PrEP as a single drug though because only the two-drug PrEP was submitted for approval.
• Tenofovir takes a longer time to be absorbed than FTC.
• Tenofovir takes up to 24 hours to reach good levels in rectal tissue.
• After 8 hours, tenofovir still isn’t detectable in rectal tissue.
• i-Base is not aware of any data that pins down when during the 8-24 hour period that tenofovir reaches rectal tissue – just that by 8 hours there is nothing and by 24 hours it is good.
• This means that taking PrEP the day before sex is likely to be better than relying on taking this just two hours before. If planning to rely on event-based dosing for infrequent use – i.e. less than weekly use – then there is a good reason to be cautious and start PrEP the day before.
• Once absorbed, tenofovir levels in vaginal tissue are ten time higher than in blood. Tenofovir levels in rectal tissue are 10-100 times higher than in vaginal tissue.

Emtricitabine (FTC)

• FTC is the second drug in PrEP. It is likely that using FTC adds to the protection but it is not clear by how much.
• There is limited data that FTC as a single drug on its own has some level of protections, but it is not as strong as tenofovir and the evidence is much less.
• FTC is more rapidly absorbed into both vaginal and rectal tissue.
• FTC is absorbed into rectal tissue within 30 minutes.
• This means that taking PrEP only two hours before sex will enable some level of protection in rectal tissue. This protection is likely to reduce the risk of HIV transmission compared to no PrEP, but not by 100%.

i-Base strongly recommends talking to a doctor at a sexual health clinic if you want to use PrEP. The information below is based on results from a wide range of research. The information is to be used in consultation with a doctor. 

A new i-Base guide to PrEP is now available that discusses dosing.
https://i-base.info/uk-guide-to-prep