Introduction

Did you know that people at higher risk of exposure to Human Immunodeficiency virus (HIV) can take medicine to prevent the infection, before exposure? This article provides information about what pre-exposure prophylaxis is, and how it’s used in the global fight in HIV/AIDS prevention.

What does pre-exposure prophylaxis (PrEP) mean?

To support HIV-negative people at high risk (lifestyle or habits) of contact with the virus, and to prevent the development of the infection, these people can take antiviral medication, pre-exposure prophylaxis or “PrEP”.¹ This form of medication refers to the proactive use of HIV medicine.

What is the difference between pre-exposure and post-exposure prophylaxis (PEP)?

Both PrEP and PEP are treatment regimens designed to prevent the development of HIV infection. Their main difference is the timing: PrEP is taken before exposure, and PEP after possible exposure to the virus. Other differences include the types of medicine used, the duration of use and the categories of people usually offered this particular treatment regimen. 

Significance of PrEP in HIV/AIDS prevention

The global HIV epidemic has killed 32 million people so far, and 1.7 million new infections are recorded each year. In the past decade, highly effective and safe HIV prevention tools have been developed using antiretroviral medications in a two-pronged approach.² 

• As pre-exposure prophylaxis (PrEP) in uninfected persons to prevent infection  
• HIV treatment for persons living with HIV to eliminate infectiousness

In England,  the annual number of new HIV diagnoses steadily declined from 2014 to 2021.^{1 3} Men who have sex with men (MSM) represent the highest proportion of new HIV diagnoses (36% in 2021), this group has also experienced the greatest decline (–77%) between 2014 and 2021. This is believed to be due to a combination of HIV prevention strategies.

Mechanism of action

How does PrEP work?

PrEP works by stopping HIV from getting into the body and replicating (making copies of itself). Treating potential HIV exposure, by taking PrEP ensures enough of the drug can block the virus from taking hold. 

Types of PrEP medications

Oral PrEP (Tablets)

The most common PrEP regimen is in tablet form, containing the antiretroviral medicines tenofovir disoproxil and emtricitabine. Following a WHO recommendation in September 2015 for people at substantial risk of HIV infection to be offered tenofovir disoproxil fumarate (TDF) treatment as an additional preventative measure. This is the only form of treatment available in the UK, used as a daily medication or “on-demand” regimen, depending on the kind and frequency of sexual intercourse.

Vaginal ring 

WHO recommended in 2021, that the dapivirine vaginal ring could be offered to women at high risk as an additional preventative measure. 

Injectable

Long-acting injectable PreP containing cabotegravir (CAB-LA) is an additional prevention choice for people at high risk of HIV. The injection is usually administered every two months.

PrEP eligibility and considerations

Who is a candidate for pre-exposure prophylaxis?

Consider talking to someone about taking PrEP if you're HIV-negative and:⁴

• A man having condomless sex with men
• Have a partner (or ex-partner) with HIV
• Your partner (or ex-partner) originates from a country with high rates of HIV
• Have condomless sex with a partner(s) and are unsure of their HIV status
• A trans or non-binary person who regularly has condomless sex
• You exchange sex for money, drugs, shelter or another reason
• Injecting drugs

Who may not be eligible for PrEP?

PrEP can be used by most people over 16 years of age. It may sometimes be prescribed for people under 16 who are at risk of HIV. 

If you are considering PrEP, inform your doctor if:

• Have you ever had an allergic reaction to any medicine, especially tenofovir disoproxil or emtricitabine
• You have severe liver or kidney problems or are taking medicine that may affect your liver or kidneys
• You are pregnant or breastfeeding
• You have a weakened immune system (immunocompromised)
• Have hepatitis

Note that you may not need to take PrEP if:

• Your partner is HIV-positive, takes HIV medicine and has an undetectable viral load (the level of HIV in the body is too low to be detected by an HIV test)
• You always wear condoms when you're having sex

Screening and assessment

Before you start PrEP, you will be asked to take:

• HIV and other sexually transmitted infection tests – you'll have to do these regularly (e.g. every 3 months)
• Hepatitis B test
• Kidney function test – PrEP can reduce kidney function. It would be important to disclose any pre-existing kidney problems. If you are over 40 years of age or already have kidney function problems, you may need more regular kidney function tests

If there are concerns about any of these test results, your doctor may talk to you about starting, stopping or alternative PrEP treatment.

PrEP access

How can I get pre-exposure prophylaxis?

In the UK, PrEP can be obtained from dedicated sexual health or HIV clinics. 

PrEP Efficacy and effectiveness

Oral PrEP has been shown to reduce HIV seroconversion (development of antibodies in blood serum) by at least 86.8% compared to non-PrEP users among men who have sex with men⁵ increasing to up to 99% with strict adherence, and up to 75% reduction for serodiscordant (mixed sex) couples⁶ The studies of its efficacy in heterosexual women remains inconsistent.

Vaginal ring PrEP has shown 27% to 56% risk reduction in women having sex with men while injectable PrEP has at least a 66% reduction in HIV infection.

Factors affecting PrEP efficacy

PrEP adherence appears to be the single greatest factor affecting efficacy. A person is protected from HIV infection only if they have high enough levels of PrEP in the body, so it is important to take PrEP properly as prescribed. 

Stigma and discrimination surrounding PrEP use is an important factor in adherence and discontinuation of treatment, making advocacy and community engagement within high-risk populations invaluable. Undiagnosed HIV infection at PrEP initiation can also contribute to PrEP failure (and drug resistance.)

Real-world implementation and success stories

PrEP safety and side effects

Common side effects of PrEP

PrEP may cause side effects,¹ with the most common side effects going away after a few weeks.

Common side effects

Side effects may occur in 1 in 100 people.

• Nausea and, or vomiting: Eat simple meals, and avoid rich or spicy food.
  • Taking PrEP after eating or just before bed can help avoid feeling nauseous (sick) 
  • If required,  anti-sickness tablets. If you vomit within 1 hour of taking PrEP, take another tablet. If more than 1 hour has passed after taking PrEP, do not take another tablet.
• Bloating and indigestion: foods such as lentils, peas, beans and onions can exacerbate this effect.
  • Eat smaller meals, eat and drink slowly, and exercise regularly
  • Peppermint oil capsules or drinking peppermint tea can help, as can antacids for indigestion. 
• Diarrhoea: Drinking plenty of water in small frequent sips helps to avoid dehydration. It is important not to take any other medicines to treat diarrhoea without speaking to a pharmacist or doctor

If your severe diarrhoea lasts more than a few days, contact your clinic for advice.

• Feeling dizzy or weak: Sit or lie down until you feel better. Do not drive, cycle or use tools or machinery when feeling dizzy or weak. Do not drink alcohol, it may make you feel worse
• Insomnia (trouble sleeping): Daily PrEP, it’s better to take your tablet in the morning to avoid sleep problems at night

Serious side effects

Very few people taking PrEP have serious problems, which may include:

• PrEP can sometimes affect the kidneys, particularly in people aged 50 or above, especially if they already have kidney problems. This is why kidney tests are completed before and during treatment.
• PrEP can also affect bone health, particularly if you have bone mass density loss. But this is rare, and the risk stops once the medicine ceases

Serious allergic reaction

In rare cases, some people can have a serious allergic reaction (anaphylaxis) to PrEP. This manifests as:

• Swelling of the lips, mouth, throat or tongue happens suddenly
• Fast or shallow breathing or finding it difficult to breathe (wheezing/choking or gasping for air)
• Throat feeling tight or struggling to swallow
• Skin, tongue or lips turn blue, or grey (in black or brown-skinned people, this may be easier to see on the palms of the hands or soles of the feet)
• Confusion, drowsiness or dizziness
• Unresponsiveness after fainting
• Rash with swelling, itchiness, blistering or peeling

A serious allergic reaction may need immediate treatment in the hospital, it is important to call emergency services when this occurs.

Long-term safety considerations

As long as there are no concerns with the regular tests and their results, PrEP can be taken for a long time.

Summary

PrEP remains an integral part of the global multi-strategy prevention strategy to fight against HIV-AIDS disease. There are different types of PrEP, depending on the population risk being targeted. PrEP adherence remains the single most important factor identified as affecting PrEP efficacy. By improving PrEP access worldwide,  advocacy within at-risk populations, and the necessary support for PrEP users. Re-exposure prophylaxis, along with other strategies may be indispensable to the elimination of HIV-AIDS.