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What is PrEP?

Pre-Exposure Prophylaxis (PrEP) is the use of HIV medication by someone who is HIV-negative, in advance of a potential exposure to HIV, with the aim of preventing HIV infection. When taken daily, PrEP can significantly decrease the likelihood of an HIV infection occurring.

The medication most commonly used as PrEP is emtricitabine/tenofovir disoproxil fumarate (TDF/FTC). Originally manufactured by Gilead Sciences under the brand name Truvada, Health Canada has recently approved several generic versions of TDF/FTC as well.

How does PrEP work?

PrEP prevents HIV infection by preventing the virus from making copies of itself, limiting the ability of HIV to spread from cell to cell. Because of this, it is much more difficult for the virus to multiply and establish an infection within the body.

For PrEP to stop this multiplication from occurring, there must be adequate concentration of the drug in the body when the virus first enters. Therefore, PrEP should be taken daily as prescribed to generate sufficient levels of the drug within the blood and in tissues which are most likely to come into contact with the virus such as rectal and genital tissues.

The time taken to reach these levels is not certain, however there are estimates for how long (or how many doses) it can take PrEP to reach maximum drug concentration levels within certain tissues:

  • Seven doses to reach maximum drug concentration in rectal tissues (for receptive anal sex)

  • Twenty doses to reach maximum concentration in vaginal (or frontal hole) tissues (for receptive vaginal or frontal sex).

  • Twenty doses to reach maximum concentration as it relates to preventing HIV infection through injection drug use.

  • There is insufficient data to establish exactly when maximum concentration is reached in penile tissues (for insertive anal or vaginal/frontal sex).

Proof that PrEP Works

Several studies have demonstrated that PrEP is a highly effective method of reducing the risk of HIV infection amongst men who have sex with men (MSM), transgender women, heterosexual men and women, and people who inject drugs.

The iPrEx clinical trial conducted in 2010 showed that when PrEP is taken daily, there is a 92% reduction in the risk of HIV infection amongst MSM and transgender women. These findings prompted additional open-label studies (PROUD & IPERGAY) which both reported a relative risk reduction of 86% (and here). Together these studies confirmed that PrEP is as effective as traditional HIV prevention options like condoms.

The efficacy of PrEP has also been studied in heterosexual populations with a high risk of HIV exposure. The PARTNERS trial, conducted with heterosexual serodiscordant couples, showed PrEP to be highly effective, reducing the risk of HIV infection by 90% when there were detectable levels of TDF/FTC in the blood.

It is important to note the reference to “detectable” levels of PrEP in the blood. A common theme amongst PrEP studies is that the level of HIV risk reduction individuals experienced was directly related to drug adherence, or how often they took the drug. Those who took the drug daily (or at a high adherence of 4-7 pills/week) experienced a higher risk reduction than those who took the pill less frequently. 

Because of this it is important that PrEP is taken as prescribed to ensure maximum HIV prevention benefit. Fortunately, as the benefits of PrEP have become more well-known, recent demonstration projects and real-world PrEP use data have indicated very high levels of adherence amongst populations at an elevated risk of HIV infection.

[Note: Although PrEP has been demonstrated to be nearly 100% effective at preventing HIV infection amongst those who take the medication daily as prescribed, there have been a handful of HIV infections amongst individuals demonstrated to be highly adherent to PrEP. Most of these occurrences appear to be related to a rare circumstance wherein the strain of HIV someone is infected with is resistant to the drugs present in PrEP (TDF/FTC). You can read more about these cases here, here, and here.]

What about Side Effects?

Although PrEP is generally well tolerated, some users have reported side effects. These include:

  • Nausea and headache

  • Reduced bone mineral density

  • Impaired kidney function

 

Some people experience mild symptoms when starting PrEP, with <10% reporting nausea within the first month – known as “start-up syndrome.” After the first month, these symptoms generally disappear and are not experienced at higher rates than amongst people taking a placebo.

Clinical trials also demonstrated that PrEP can have an impact on the bone density and kidney function of some users. Decreases in bone density were minor (~1%) and were not associated with an increased likelihood of bone fractures. Increases in the amount of serum creatinine, a molecule normally filtered by the kidneys, has also been reported as a side effect in up to 2% of HIV-negative individuals taking PrEP (and here). Although this is a mild side effect that generally requires no intervention, it may be more severe in individuals with pre-existing kidney conditions.

Your healthcare provider will monitor you for these side effects while on PrEP. Fortunately, these side effects are not generally long-term and usually resolve themselves after an individual stops taking PrEP.

Glossary

Generic: A generic drug is a medication created to be the same as an already marketed brand-name drug in dosage form, safety, strength, route of administration, quality, performance characteristics, and intended use.

Drug Concentration: The amount of a drug in a given volume of blood plasma, measured as the number of micrograms per milliliter

Frontal Sex: Some individuals, particularly trans men, may choose to refer to their front genitals as a front hole instead of a vagina. Therefore, the term frontal sex might be used instead of vaginal sex when discussing penetrative sex involving the front genitals.

Receptive vs. Insertive Sex: For penetrative sex (vaginal, frontal, or anal), if you are receiving your sexual partners body part, such as a penis, into one of your orifices then you are the receptive partner. Conversely, if you are inserting your body part into your sexual partner during penetrative sex, then you are considered the insertive partner.

Efficacy: Plainly speaking, a drug's efficacy speaks to the ability of a drug to produce the desired therapeutic effect; in short, its effectiveness.

 

Adherence: Medication adherence refers to the degree to which someone complies with or follows the advice or instructions of their healthcare provider as it relates to proper drug dosing. For example, if your healthcare provider instructs you to take one pill every day at the same time with food, if you follow that instruction, you would be considered highly adherent. On the other hand, if you take two pills, every third day, without eating, then you would likely be considered to demonstrate low adherence. 

 

Serodiscordant: Serodiscordant (or serodifferent, magentic, etc.) is a term used to describe a couple wherein one partner is HIV-positive and the other is HIV-negative.

 

Open-Label: Open-Label trials are studies wherein both the researchers and the participants are aware of the treatment that is being administered. 

Placebo: A placebo is a substance given to an individual to mimic the act of taking a medication, with no actual therapeutic effects. Placebos are commonly used in clinical studies and trials to demonstrate that the medication or intervention being studied produces a desired outcome.   

 

Bone Mineral Density: In addition to calcium, your bones are made up of a wide variety of minerals. The amounts of these minerals that are present determine the strength of your bones - the higher the density the less likely they are to break and vice versa. This information can be obtained from a number of non-invasive tests; however the most widely used method is a DXA test which uses X-rays to measure a specific bone or bones.

 

Serum Creatinine: Simply put, creatinine is a molecule that is commonly produced by your body and is filtered out of your blood by your kidneys. After filtration, creatinine is normally excreted in your urine along with other stuff your body doesn’t need at the moment. However, when the kidneys aren’t functioning correctly, the levels of creatinine in the blood can increase. Therefore, the levels of creatinine present in your blood (serum) can be used as an indirect indicator of your overall kidney health.