Introduction

Human Immunodeficiency Virus (HIV) is a virus that attacks the cells that make up our immune system. This weakens the body’s ability to fight off everyday infections and diseases. HIV was first identified in the 1980s but was likely being passed between humans for some time before this.¹

For those who contracted HIV in the 1980s, it was commonly a death sentence, with most infected people going on to develop Acquired Immunodeficiency Syndrome (AIDS). However, these days, millions of people worldwide are living with HIV and are able to lead normal lives. This is possible due to the development of antiretroviral medications, which fight the HIV virus These medications stop HIV both progressing to AIDS and from being passed on to others.²

If an individual with HIV has a detectable viral load, their infection can be passed on to others through body fluids, including blood, semen, vaginal fluid, anal mucus and breast milk. Activities such as sex (anal or vaginal), sharing drug injecting equipment and sharing sex toys all carry a theoretical risk of acquiring HIV. Additionally, although rare in the UK, HIV can be passed from a mother to a baby during pregnancy or through coming into contact with contaminated blood (e.g. through blood transfusion).³

A class of medications known as pre-exposure prophylaxis (PrEP) can practically eliminate someone’s risk of contracting HIV in the first place. This article will explore everything you need to know about PrEP. 

What is pre-exposure prophylaxis (PrEP)?

PrEP is recommended for people who are at high risk of HIV infection, such as those with an HIV-positive partner, people who inject drugs, and those who have unprotected sex with partners of unknown HIV status. It involves these HIV-negative individuals taking medications known as antiretrovirals, commonly used to treat HIV. These antiretrovirals reduce their risk of contracting HIV in the first place. Usually, being on PrEP means taking a pill daily containing three medications tenofovir, disoproxil and emtricitabine.

PrEP works by ‘blocking’ HIV if it does enter a person’s body and has been shown to be highly effective. However, PrEP does not protect against other sexually transmitted infections (STIs) and is also not a substitute for other preventive measures such as condoms.⁴

Who should consider taking PrEP?

It is recommended that the following groups of people should consider taking PrEP: 

• People with an HIV-positive partner who has a detectable viral load
• People who do not always use condoms for sex and are having sex with those of unknown HIV status
• People with partners from regions of the world where the rate of HIV is much higher
• Men who have sex with men, especially if they have recently had another STI
• People who are transgender
• People using chemical sex drugs (e.g. GHB)⁵

What forms of PrEP are available?

There are currently a few forms of PrEP available. As mentioned above, perhaps the most common form of PrEP is a tablet that a person takes daily—usually containing a combination of the medications tenofovir, disoproxil, and emtricitabine. This is sometimes known by the brand name Truvada, but in the UK, a generic form is usually prescribed.

More recently, a second pill, available in branded (Descovy) and generic forms, has been approved for use. Descovy contains tenofovir, alafenamide and emtricitabine. 

In other countries, long-acting injectable PrEP and PrEP-releasing vaginal rings have been approved, but these are not yet available in the UK.⁵

Where can I get PrEP?

In the UK, PrEP is now available for free through sexual health clinics. As it stands, cannot get free PrEP direct from GPs or community pharmacies.⁵

Do I have to take PrEP every day?

The short answer is no, not necessarily. PrEP has been used in two different ways in clinical trials:

1. Taken regularly i.e. one tablet each day
2. Taken when needed according to sexual activity: two tablets should be taken 2 to 24 hours before sex, one tablet 24 hours later and a further tablet 48 hours after that. This is known as ‘2-1-1 dosing’, ‘event-based’ or ‘on-demand’ dosing

Choosing the right dosing for you and your individual circumstances is important. The specialist doctor or nurse at the sexual health clinic will discuss your needs and what is important to you. This will help you to arrive at the best option for yourself. Healthcare professionals will then explain how to take your PrEP properly when this preventative treatment is started.⁶

It is vital to remember, that whichever dosing regimen you choose, missing a dose of PrEP can put you at risk of contracting HIV, so it is important to take PrEP as advised. 

How effective is PrEP?

There have been numerous clinical trials studying the effectiveness of PrEP. 

One study showed that when PrEP is taken 2, 4 or 7 times a week, the estimated reduction in HIV risk is 76%, 90% and 99% respectively, whilst another showed that taking 2-3 tablets a week provided an 84% risk reduction.⁷ Furthermore, another study found that taking more than 4 doses provided a 100% reduction.⁸

A study, looking only at men who have sex with men using an on-demand dosing regimen, showed that this method resulted in an 86% reduction in new HIV infections. This is similar to the efficacy seen in daily dosing.⁹ On-demand dosing has not yet been investigated in other populations. Therefore, at the moment, it is not recommended that heterosexual men and women and transgender people use on-demand PrEP dosing regimens. 

Is it safe to take PrEP: what are the side effects?

Most people taking PrEP do not experience any side effects. Around 10% of people will experience gastrointestinal side effects such as: 

• Nausea
• Bloating 
• Diarrhoea 

A similar amount of people experience headaches. These symptoms tend to go away after about a month of taking PrEP. 

Some studies have shown that PrEP can affect the functioning of the kidneys, and reduce bone mineral density.^10,11,12

In clinical trials, a small decrease in kidney function has been demonstrated in people taking PrEP. However, this is seen to normalise after stopping the medication. People who already have lower kidney function may need to be seen by a kidney specialist to allow a full discussion of the risks and benefits of PrEP before they start taking it. 

Similarly, bone mineral density decreases in those taking PrEP, but also normalises after stopping the medication. This drop in bone density is most significant in those under 25 years of age, but again, bone mineral density returns to normal in these people after stopping PrEP. 

Who should not take PrEP? 

PrEP is not a treatment for people who already have HIV. If an individual tests positive for HIV, it is recommended that they should be referred to specialist HIV services immediately, so that they can be started on appropriate medication as soon as possible.

PrEP may possibly not be necessary if you have a partner who has HIV but it is being treated. People living with HIV who have been receiving treatment and have had an undetectable viral load for at least 6 months are not at risk of transmitting HIV through sex. This is sometimes known as ‘U=U’ or ‘undetectable equals untransmittable’. 

If you do need to take PrEP, to ensure PrEP is safe for you, you should tell the clinician at the sexual health clinic if you:

• Are allergic to any medication
• Have severe liver or kidney problems
• Are pregnant or breastfeeding
• Are immunocompromised
• Already have known HIV
• Have hepatitis⁶

Does PrEP require any monitoring?

The main monitoring recommendations for those taking PrEP are as follows: 

• Baseline HIV testing and retesting for HIV every three months 
• Baseline testing for bacterial sexually transmitted infections (STIs) such as chlamydia, gonorrhoea and syphilis, and hepatitis B and C
• Re-testing for bacterial STIs and hepatitis C every three months
• Baseline kidney function testing and follow-up kidney function testing in some groups of patients
• Urine pregnancy tests before starting treatment, after one month of treatment and then every three months⁶

Implications: looking forward

The impact of PrEP is huge. It has been shown to be able to reduce the incidence of HIV among its users by up to 99% when it is taken as prescribed. In countries with high PrEP uptake, huge drops in HIV diagnosis rates have been seen - for example, in the UK, HIV diagnosis rates fell by 35% between 2014 and 2018.¹³

Although PrEP is now readily available and accessible in the UK and many other countries, globally not enough people are taking PrEP to make a meaningful impact on HIV rates. Unfortunately, access to PrEP is concentrated in a fairly small number of countries.¹⁴

In the future, it is hoped that PrEP will not only be more accessible worldwide, but that further PrEP options, such as long-acting injectables and vaginal rings, will become more readily available. It is thought that options like this will improve adherence to medication protocols and also that more options will allow more people to protect themselves against HIV infection. 

Summary

• Pre-exposure prophylaxis (PrEP) is a medication used to prevent HIV-negative individuals from being infected by HIV
• PrEP is recommended for certain people who are at increased risk of getting HIV
• PrEP is available in different forms in different countries
• In the UK, PrEP consists of taking a tablet daily or taking a tablet regime when required before sex and after the event
• Free PrEP is available in the UK through sexual health clinics, but not directly via GPs and community pharmacies. You can also buy it through private prescription services.
• It is strongly recommended to take PrEP according to the prescribed instructions to maximise its effectiveness
• Side effects of PrEP include nausea, diarrhoea and headaches
• People taking PrEP need to be monitored regularly to ensure that it remains a suitable treatment