Why the new HIV PrEP guidelines from the UK are so exciting

Simon Collins and Holger Sweers

In June 2025, a major update to PrEP guidelines was published in the UK. [1]

This based on more than 150 new references since the previous guidelines in 2018.

The guidelines are mainly about oral PrEP but also cover injectable formulations. An easy-to-read community guide is also online. [2]

PrEP is available free in the UK.

Why is the 2025 update so important?
What is PrEP?
How does PrEP work?
10 main changes in the 2025 guidelines?What happens after starting with a double dose?Where do the active drugs go to in your body?
BOX 1: What are PBMCs?
Why are doses needed after sex if the double dose is so good?
Is PrEP more effective for different types of sex?
Does PrEP work for trans and non-binary people?
Does PrEP work if the risk is from injecting drug use?
Why is PrEP research difficult?
What were the main studies that led to the new changes?
What about injectable PrEP?
BOX 2: Stages of infection
Which are the main PrEP guidelines?
Why are there differences between guidelines?
Why did the i-Base booklet include these changes 18 months earlier?
BOX 3: PrEP timeline?
How can I access PrEP in Germany?
Links
References

Why is the 2025 update so important?

A lot has happened in the seven years since the first PrEP guidelines were produced in the UK. This includes a new understanding of how PrEP works.

For example, the 2025 guidelines have a new perspective on sex and gender.

The new guidelines aim to broaden access and awareness to anyone who can benefit from PrEP. They also make PrEP easier to take for everyone. This includes cisgender women and people who are transgender or non-binary, and people who inject drugs.

What is PrEP?

PrEP stands for Pre-Exposure Prophylaxis. For HIV, this means taking PrEP before sex to reduce the risk of infection. HIV PrEP also needs to be taken after sex to make sure this protection lasts for several days.

PrEP is highly effective. It is more effective than using condoms even if your partner is HIV positive and not on treatment.

Most PrEP involves taking oral pills. However, new long-acting injections are also discussed.

How does PrEP work?

PrEP works by blocking the very early stages of HIV infection. Having good levels of these drugs before sex means PrEP can work straight away if it is needed. PrEP also needs to be taken after sex because infection might take several days.

When taken as prescribed, PrEP is more than 99% effective. However, even if dosing isn’t quite exact it can still work very well. Taking some PrEP, especially when starting with a double dose, is always better than no PrEP.

We also discuss below how the details of how PrEP works are more complex. This is complicated but also exciting and involves different types of studies.

10 main changes in the UK guidelines

These 10 main changes will make PrEP easier to access and use.

1. Wider access to PrEP

“The benefits of PrEP are rapid and substantial. Therefore, with only uncommon exceptions, PrEP should be initiated in people who request it…”

The guidelines recommend making PrEP easier to access.

They say that everyone who could benefit from PrEP should have the choice to use it. This is whatever your gender, sex or sexuality. Previous guidelines involved having to be at high risk.

The new guidelines also want more people to know about PrEP. A new 10-page section looks at how to make access more equitable.

2. Everyone can start with a double dose: protection in two hours.

The new guidelines recommend that everyone starts PrEP with a double dose (two pills).

This will give protection within two hours.

Up until now, some people were told they needed to take daily PrEP for a week. Some guidelines still recommended this – or even longer.

3. Adherence for daily PrEP is now less strict.

Anyone taking daily PrEP can now be more relaxed about adherence. So long as four doses are taken every week, protection will be very high.

This was always known for cisgender gay and bisexual men. New studies shows this applies to cisgender women too. This supports TTSS doing – taking PrEP on Tuesdays, Thursdays, Saturdays and Sundays.

Previous guidelines said cisgender women, and transgender and non-binary people needed to take 6 or 7 doses every week.

The more relaxed dosing also covers HIV risks from injecting drugs.

4. Everyone can now use event-based dosing.

Event-based dosing involves only taking PrEP when you want protection. This uses either 2:1:1 or 2:7 dosing, depending on your situation.

Cisgender men can use 2:1:1 dosing. Start with a double dose (2 to 24 hours before sex). Then take daily PrEP (single pills) for two days after sex. If you continue having sex for more days, continue taking PrEP on those days too. Then continue for two days afterwards. This dosing can be used by anyone if the only risk is either receptive anal sex or any insertive sex.

Cisgender women and people who are trans and/or non-binary are generally recommended to use 2:7 dosing. Start with a double dose (2 to 24 hours before sex). Then take daily PrEP for seven days after you last have sex. The longer dosing is a cautious approach because PrEP levels are lower in vaginal tissue and don’t last for as long.

Event-based PrEP using 2:7 dosing is also recommended if the risk of HIV is related to injecting drug use.

5. How to start and stop PrEP.

The 2025 guidelines now refer more to starting and stopping PrEP rather than being on daily or event-based PrEP.

Starting PrEP involves the double dose.

Stopping involves daily PrEP for 2 or 7 days after the last potential risk (see above).

6. TD/FTC and TAF/FTC can be used in the same ways.

Two different versions of oral PrEP use different versions of tenofovir. These are TD/FTC and the newer but less used TAF/FTC.

TD is tenofovir disoproxil. TAF is tenofovir alafenamide. FTC is emtricitabine. Because of the much higher cost, TAF/FTC in the UK is limited to people who are not able to use TD/FTC.

The guidelines now say both versions can be used in the same ways.

7. Practical information about dosing

The guidelines include lots of practical information about taking PrEP.

For example, if oral PrEP makes you feel nauseous, try taking it with food. Or separate the initial double dose by a few hours, so long as both doses are still at least two hours before sex.

Food can also help boost PrEP if you are late with a dose. Food increases levels of TD, so will help you reach drug levels more quickly.

Other situations are discussed, including after bariatric or other surgeries.

8. Updated evidence

The 2025 guidelines carefully review every aspect of PrEP research. This covers efficacy, safety, adherence, monitoring, pregnancy, drug interactions, different populations, access and pricing.

Roughly 150 of the 230 referenced studies were published since the previous version of the guidelines.

Some of these studies were published several years ago. This is frustrating because people could have benefitted much earlier. Even when guidelines are generally good, they need to be updated when new information becomes avaiable.

9. How PrEP works: drug levels in cells vs genital and rectal tissue.

“The evidence in totality suggests that drug levels in PBMCs play the major role in protection.”

The guidelines include an interesting and important discussion about how PrEP works.

For over 15 years, researchers worried that good drug levels in vaginal, rectal or penile genital tissue were essential. This led to dosing recommendations that depended on sex, gender, sexuality and risk.

Newer research shows that drug levels inside immune cells (PBMCs) are likely to be more important, and the new guidelines agree. These cells are not affected by sex, gender, sexuality or HIV risk. They are throughout the body which covers the HIV risk from sex and injecting drugs.

The latest research shows that adherence explains the results from earlier clinical studies, rather than biological differences in different tissues.

The new guidelines are still cautious though on this point. This is why 2:7 dosing is still included.

10. Future PrEP and injectable PrEP

Other versions of PrEP are also discussed.

This includes injectable PrEP and a vaginal dapivirine ring. Information about this ring is included to cover people who have been using this in other countries.

What happens after starting with a double dose?

Everyone can now start oral PrEP with a double dose (two pills). This is exciting. It makes it easier to have spontaneous sex.

The double dose gets PrEP drugs to protective levels after only two hours. Before this, cisgender women were told they needed to take daily pills for seven days before protection, or even longer.

The double dose also achieves higher drug levels than single doses and it keep levels higher for longer. For example, after 2:1:1 dosing, drug levels will stay high for 4 days in vaginal tissue, for 7 days in PBMCs and for 12 days in rectal tissue.

This is why event-based dosing uses either 2:1:1 or 2:7 dosing depending on the setting.

Some researchers think that everyone should get the same benefit from 2:1:1 dosing, but this is an area that needs more research.

Where do the active drugs go to in your body?

Oral PrEP is absorbed from your stomach into your bloodstream. This takes the drugs throughout your body.

Each drug is then absorbed differently.

FTC reaches high levels in vaginal tissue within 30 minutes.
Tenofovir disoproxil (TD) takes about 24 hours to reach protective levels in rectal tissue. These are 10 times higher compared to vaginal tissue.
TD never reaches high levels in vaginal tissue.
Both PrEP drugs reach high levels in immune cells called PBMCs.

Once inside the cells, both PrEP drugs need to go through another process before they can be active. They are generally absorbed quickly and take longer to be filtered out.

The differences between vaginal and rectal tissue led to different recommendations based on whether the risk was from receptive vaginal or rectal sex. This is now much less important.

The 2025 guidelines now explain PrEP efficacy by the drug levels in PBMCs. This includes CD4 cells that HIV targets in order to establish infection. This is important because drug levels inside cells are not affected by sex, sexuality or gender.

Just like other drugs, the active chemicals are then broken down as waste products and filtered out through your kidneys and liver. Drug levels in urine can be a research test for people were taking PrEP.

BOX 1: PBMCs

PBMC stands for peripheral blood mononuclear cell.

These are white blood cells (WBC, lymphocytes), monocytes, and dendritic cells. The WBCs include CD4 and CD8 T cells, B cells, and NK cells.

Approximately two-thirds of PBMCs are CD4 cells and one third are CD8 cells.

Why are doses needed after sex if the double dose is so good?

Early studies in animals showed that PrEP is much more effective when given both before and after exposure to HIV. Although these didn’t include testing a double dose, drug levels still drop in some people after 24 hours.

PrEP is also needed after sex because it might take several days for an infection to be cleared. If HIV has infected some immune cells, the cells take a day or two to die.

Keeping drug levels high for a few more days will stop new cells becoming infected.

Is PrEP more effective for different types of sex?

No, this doesn’t seem to be the case. Even though the risk of HIV transmission can vary depending on the type of sex, PrEP is just as effective for all types of sex.

Does PrEP work for trans and non-binary people?

Yes. The guidelines recommend 2:7 dosing is for trans and non-binary people.

Start with a double dose 24 to 2 hours before any risk and continue daily PrEP for seven days afterwards. However, if the only risk is from receptive anal sex, 2:1:1 dosing can be used.

The guidelines stress that there are no significant drug interactions between PrEP and gender affirming hormones. Trans men are now being actively recruited in PrEP studies because they were previously excluded.

PrEP should still be just as effective in trans men but getting this data is important.

Does PrEP work if the risk is from injecting drug use?

Yes. If the risk is from injecting drug use, 2:7 dosing is recommended.

Start with a double dose 24 to 2 hours before any risk and continue daily PrEP for seven days afterwards.

Why is PrEP research difficult?

PrEP research is difficult because of the time needed to know whether or not someone is HIV positive. It involves trying to explain events that usually happened months earlier.

Even in a study, most people don’t find out they are HIV positive until several months after they had sex. This also means not knowing for certain how many days someone took PrEP in that week.
If drug levels are only tested after a positive test result these levels are just used as a marker for adherence much earlier. Even the best studies involve these estimated guesses.
HIV is a low-risk virus – usually much lower than 1 in 100 (<1%). This means that if 100 people all have sex without a condom, only one person might become positive, even if no-one used condoms. The relatively low risk means PrEP studies need to enrol thousands of participants and then run for several years.
Any new versions of PrEP need to be tested against oral PrEP rather than a placebo, which would be unethical.

What were the main studies that led to the new changes?

Although there were more than 150 new studies, several key studies supported the new dosing and adherence recommendations.

These include studies measuring and/or predicting drugs levels with different doses. Also, in specific populations including women, transgender women and people who inject drugs. [1–4]

One of the modelling studies in 2023 showed how drug levels in PBMCs explained the results from large PrEP studies better than drug levels in tissue. [5]

Results from a very large observational study showed that taking four daily doses a week provided high levels of protection in women. [6]

What about injectable PrEP?

Two new versions of PrEP can be given by injections.

These are long-acting injections that are only given every two or six months. However, even though they are popular, they are priced much higher that oral PrEP. This means very few people are so far able to access them.

Other cautions include how long injectable PrEP stay in your body. For example, if you decide to stop PrEP or if there are interactions with other drug.

Cabotegravir-LA (CAB-LA) is given by injection into the buttock muscle every two months. It was approved as PrEP in the UK and the EU in 2023. However, availability and access to cabotegravir-LA in the UK is still being decided.

Lenacapavir is given by an injection just under the skin every six months. It was approved in the US in June 2025 and decisions the UK and Europe, with decisions expected in the next few months.

The main advantages of injections are that fewer doses are needed over the year. This might mean PrEP becomes available for people who don’t want to take pills or who often miss doses. Although oral PrEP is just as effective if taken as prescribed, injections reduce this dependence on adherence.

BOX 2: Stages of HIV infection?

There are many stages to HIV infection.

HIV first has to cross physical barriers to get into your body. For example, getting across genital tissue to get into the blood stream.
Once in the blood HIV start to infect immune cells. It then travel to a lymph node where it replicates. This might take a couple of hours or it might take a bit longer.
HIV then makes many copies of itself inside the lymph nodes.
As the lymph nodes swells with more and more HIV being produced, the lymph node finally bursts sending virus to all parts of the body.

PrEP works so well during stages one and two, that infection is stopped before stage 4 is reached.

Which are the main PrEP guidelines?

i-Base mainly uses the UK (BASHH/BHIVA) and European (EACS) guidelines. [1, 9]

We also refer to US guidelines (IAS-USA and the CDC) and WHO guidelines (produced for low- and middle-income countries). [10, 11, 12, 13]

Many other countries produce national guidelines including Australia, France, Germany, South Africa and Spain.

Why are there differences between guidelines?

Although all guidelines are based on the same research, some guideline panels interpret study results differently.

For example, US guidelines produced by IAS-USA (2024) included 2:1:1 dosing for gay and bisexual men and have done this since 2018. IAS-USA also recommends PrEP should be easy to access for anyone who is sexually active or who might benefit, including anyone using recreational drugs.

However, the latest US CDC guidelines from 2024 still do not recommend event-based dosing for anyone. They also say that daily PrEP needs to be taken for 7 days or 21 days, before protection is reached, for receptive rectal or vaginal sex, respectively.

EACS guidelines in 2024 also included that everyone can start with a double dose. Although 2:7 dosing was included as a way for cisgender women and transgender and non-binary people to start and stop PrEP, they didn’t specifically refer to this as event-based dosing.

The timeline for reviewing new evidence and for updating each guideline also varies. If a document is only updated every five years, and the update takes several years, guidelines can technically already be out of date on the day they are published.

Although some guidelines are updated every year or two, some PrEP and PEP guidelines are only updated every five years or longer. For example, US CDC guidelines on PEP published in May 2025 hadn’t been updated since 2016.

Sometimes guidelines are restricted to how a drug has originally been approved. Part of this is financial and bureaucratic. Once daily PrEP was approved in the US, there was no commercial interest for manufacturers to get a lower dose approved.

Some guidelines (including the UK, US HHS and WHO) involve a very structured and formal approach to reviewing evidence that takes much longer whereas others (including IAS-USA and EACS) are less structured and easier to update.

Why did the i-Base booklet include these changes 18 months earlier?

i-Base usually reports latest research when it is first presented. This will always be before it is included in treatment guidelines.

When we updated the community booklet in 2024 we expected the UK guidelines to come out at the same time.

i-Base was also very lucky to have the support of leading researchers from the guidelines panel working on the community guide. Community HIV groups have always worked in this way. The first UK Guide to PrEP was produced two years before the first UK guidelines.

The timeline for PrEP below shows how long PrEP took to be developed.

These few dates show that PrEP was not a research priority for public health. Most of the leading doctors and public health scientists did not want to look at anything other than condoms – even though condoms were clearly not effective for everyone.

PrEP research was led by independent researchers and driven by community demand.

Box 3: Brief PrEP timeline

1994 – The first animal studies showed that tenofovir could be 100% effective if taken both before and after sex.

2001 – Tenofovir was approved as an HIV treatment in the US.

2008 – The international i-PrEX study enrolled the first participants in gay and bisexual men and transgender women. Results were presented in 2010.

2012 – Daily oral PrEP was approved in the US. The European Medicines Agency (EMA) made the inappropriate decision that PrEP was not a priority in the EU. This was because they worried people might stop using condoms and it delayed access to PrEP in Europe.

2014 – French/Canadian IPERGAY results show 2:1:1 dosing was effective.

2016 – Oral PrEP approved in Europe.

2023 – CAB-LA approved as PrEP in Europe.

2025 – Lenacapavir approved in the USA, with a list price of $28,000 a year. The decision in Europe is expected soon.

Simon Collins edits and compiles the UK Guide to PrEP. This has been updated every year since 2016. He is a community activist with HIV i-Base which he co-founded in April 2000.

References

BASHH/BHIVA. Guidelines for PrEP (2025).
Community guide to PrEP in the UK (2025).
https://i-base.info/uk-guide-to-prep/
Cottrell ML et al. A translational pharmacology approach to predicting outcomes of preexposure prophylaxis against HIV in men and women using tenofovir disoproxil fumarate with or without emtricitabine. J Infect Dis. 2016 Jul 1;214(1):55-64. doi: 10.1093/infdis/jiw077. Epub 2016 Feb 24.
Thurman AR et al. Safety and pharmacokinetics of a tenofovir alafenamide fumarate-emtricitabine based oral antiretroviral regimen for prevention of HIV acquisition in women: a randomized controlled trial. EClinicalMedicine 2021; 36: 100893.
ncbi.nlm.nih.gov/26917574
Garrett KL et al. A pharmacokinetic/pharmacodynamic model to predict effective HIV prophylaxis dosing strategies for people who inject drugs. J Pharmacol Exp Ther. 2018 Nov;367(2):245-251. doi: 10.1124/jpet.118.251009. Epub 2018. (27 August 2018).
ncbi.nlm.nih.gov/30150483
Cespedes MS et al. (2024) Gender affirming hormones do not affect the exposure and efficacy of F/TDF or F/TAF for HIV preexposure prophylaxis: a subgroup analysis from the DISCOVER trial Transgender Health 9:1 46–52 DOI: 10.1089/trgh.2022.0048.
liebertpub.com/doi/full/10.1089/trgh.2022.0048
Zhang L et al. Model-based predictions of protective HIV pre-exposure prophylaxis adherence levels in cisgender women. Nat Med. 2023 Nov;29(11):2753-2762. doi: 10.1038/s41591-023-02615-x. (13 November 2023).
ncbi.nlm.nih.gov/pmc/articles/PMC10667095
Marrazzo J et al. HIV Preexposure Prophylaxis With Emtricitabine and Tenofovir Disoproxil Fumarate Among Cisgender Women. JAMA. doi:10.1001/jama.2024.0464. (1 March 2024).
com/journals/jama/fullarticle/2816036
European AIDS Clinical Society (EACS). EACS guidelines (2024)
https://eacs.sanfordguide.com/eacs-part1/art/eacs-pre-exposure-prophylaxis
IAS-USA PrEP guidelines (December 2024).
https://www.iasusa.org/2024/12/01/the-2024-ias-usa-hiv-treatment-and-prevention-guidelines-are-now-published/
US CDC guidelines (February 2025)
https://www.cdc.gov/hivnexus/hcp/prep/index.html
Consolidated guidelines on HIV prevention, testing, treatment, service delivery and monitoring: recommendations for a public health approach. (2021).
https://www.who.int/publications/i/item/9789240031593
Consolidated guidelines on HIV, viral hepatitis and STI prevention, diagnosis, treatment and care for key populations (2022).
https://www.who.int/publications/i/item/9789240052390