What Is PrEP and How Does It Prevent HIV?

A medication that reduces the risk of HIV infection by up to 99 percent exists, has been available for over a decade, and is still being taken by only a fraction of the people who would benefit from it. Clinical data published in The Lancet confirmed that areas with the highest PrEP coverage saw a 38 percent decrease in new HIV diagnoses over a ten-year period. The treatment works. The gap between who has access to it and who is actually using it remains one of the most significant missed opportunities in preventive medicine today.

The Medication That Stops HIV Before It Ever Takes Hold

PrEP stands for pre-exposure prophylaxis. In plain language, it is a prescription medication taken by HIV-negative individuals to prevent HIV infection before any potential exposure occurs. Taken correctly and consistently, it builds a pharmacological barrier inside the body that blocks the virus from establishing itself in cells even when exposure does happen.

The concept behind PrEP is the same principle applied across preventive medicine broadly:

• Vaccines are administered before a pathogen is encountered
• Blood pressure medication is taken before a cardiac event occurs
• PrEP applies that same logic specifically to HIV prevention, and the evidence behind it is extensive

The formulations currently approved for use:

• Tenofovir disoproxil fumarate combined with emtricitabine, sold under the brand name Truvada and now available as a generic
• Tenofovir alafenamide combined with emtricitabine, sold as Descovy
• Cabotegravir, sold under the brand name Apretude, approved in 2024 as a long-acting injectable administered every two months rather than a daily pill (source)

What Actually Happens Inside the Body When PrEP Is Working?

Understanding how PrEP prevents HIV requires a brief look at how HIV infects in the first place.

• HIV uses proteins on the surface of CD4 T-cells to attach, enter, and insert its genetic material directly into the cell’s DNA
• Once inside, the infected cell becomes a replication facility, producing new copies of the virus that go on to infect surrounding cells
• Left uninterrupted, this process depletes the immune system progressively over years until it can no longer defend against infections a healthy body would clear without difficulty
• PrEP works by placing antiretroviral drugs inside the exact cells HIV targets before the virus ever arrives
• The active compounds, tenofovir and emtricitabine, are nucleoside reverse transcriptase inhibitors that block the enzyme HIV needs to convert its genetic material into a form that can integrate into human DNA
• Without that conversion the virus cannot replicate, and without replication infection cannot establish itself
• The protective effect comes from drug concentrations building up inside the cells themselves, not simply circulating in the bloodstream
• This is why consistent daily dosing is clinically essential, the drugs must be present at therapeutic levels inside the target cells at the exact moment of exposure
• Sporadic or inconsistent use drops those intracellular drug levels below the protective threshold and significantly reduces the effectiveness of PrEP

How Effective Is PrEP? What the Clinical Evidence Shows

The efficacy data behind PrEP is among the most compelling in preventive medicine.

The iPrEx Trial, Where the Evidence Started

The iPrEx trial, the landmark study that led to initial regulatory approval, found that daily oral PrEP reduced HIV acquisition among men who have sex with men and transgender women by 44 percent overall and by 92 percent among participants with detectable drug levels confirming consistent use. The real-world implication of that finding is significant: the gap between 44 and 92 percent was almost entirely explained by adherence.

The Partners PrEP Study, Proof It Works Across Populations

Subsequent trials confirmed and extended those results. The Partners PrEP study demonstrated a 75 percent reduction in HIV transmission among serodiscordant heterosexual couples using tenofovir alone and an 84 percent reduction with the combination formulation. Real-world observational data from clinic populations with confirmed high adherence consistently shows protection rates above 99 percent.

The HPTN 083 Trial, How Injectable PrEP Outperformed the Daily Pill

For the injectable formulation, the HPTN 083 trial found that long-acting cabotegravir was 66 percent more effective than daily oral tenofovir-emtricitabine in preventing HIV among men who have sex with men and transgender women, largely because the injectable format removes the adherence variable from the equation entirely. There is no daily pill to miss when the injection is administered every two months in a clinical setting.

The Three Forms of PrEP Available and How Each One Works

Daily Oral PrEP:

The original and most widely prescribed formulation. One tablet taken at the same time each day. Full protective drug levels in rectal tissue are reached within approximately seven days of consistent daily use. Protective levels in vaginal and cervical tissue take longer, with most clinical guidelines recommending twenty-one days of consistent use before relying on PrEP for receptive vaginal exposure. For individuals who can maintain daily adherence, this formulation has a well-established safety profile across fifteen-plus years of clinical use.

Daily Oral PrEP: 

Approved as an alternative to Truvada, Descovy uses a different formulation of tenofovir called tenofovir alafenamide, which delivers equivalent efficacy at a lower dose and with a more favourable kidney and bone safety profile in long-term use. Currently approved for use in men who have sex with men and transgender women. Not yet approved for use in cisgender women due to insufficient trial data in that population.

Long-Acting Injectable PrEP: 

Administered as an intramuscular injection every two months following an initial loading dose. Approved by Health Canada in 2024. The HPTN 083 and 084 trials established its superiority over daily oral PrEP in populations where adherence to daily dosing is a barrier. Clinic-administered rather than self-managed, which removes the daily adherence requirement and eliminates the risk of missed doses entirely.

How to Start PrEP  (The Steps From First Appointment to Full Protection)

Starting PrEP at Intrepid Health follows a structured clinical process. Here is exactly what that looks like:

• Initial Consultation 

A clinician reviews medical history, current medications, and assesses suitability for PrEP. This is a confidential clinical conversation, not a judgment about behaviour or lifestyle.

• Baseline Blood Work 

Before a prescription is issued, specific blood tests are required. These include an HIV test to confirm negative status, hepatitis B screening, kidney function tests including creatinine and estimated glomerular filtration rate, and screening for sexually transmitted infections including chlamydia, gonorrhoea, and syphilis.

• Prescription and Formulation Selection 

Based on blood work results, medical history, and the patient’s preference regarding daily pills versus injectable administration, the clinician selects the appropriate formulation and issues the prescription.

• Starting the Medication 

Daily oral PrEP begins immediately. Full protection for anal sex is reached at approximately seven days. Full protection for vaginal sex requires approximately twenty-one days of consistent use. Injectable PrEP begins with a loading dose followed by a second injection one month later, then continues on a two-monthly schedule.

• Three-Monthly Follow-Up 

PrEP requires ongoing clinical monitoring every three months. This includes an HIV test, kidney function assessment, STI screening, and a review of adherence and any side effects. These appointments are clinical requirements, not optional check-ins.

Who PrEP Is Prescribed For?

PrEP is prescribed to HIV-negative individuals who are at elevated risk of HIV acquisition. Clinical guidelines identify several groups for whom PrEP is particularly indicated:

• Men who have sex with men with multiple partners or inconsistent condom use
• Individuals in serodiscordant relationships, where one partner is HIV-positive
• Heterosexual individuals with multiple partners in high-prevalence settings
• People who inject drugs and share equipment
• Individuals who have had a recent sexually transmitted infection, as this significantly increases HIV susceptibility
• Those who have previously required post-exposure prophylaxis

The 2025 Canadian guideline update states that it is appropriate to prescribe PrEP to any adult or adolescent who requests it, and encourages clinicians to proactively assess HIV risk during routine health visits to identify patients who would benefit but have not yet been offered the option. (source)

PrEP is not a treatment for HIV. It cannot be used by individuals who are already HIV-positive, and it does not function as antiretroviral therapy.

What to Expect in the First Few Weeks on PrEP?

The most commonly reported side effects in the first weeks of daily oral PrEP are mild and temporary. Nausea, headache, fatigue, and occasional loose stools affect a proportion of new starters, typically resolving within two to four weeks as the body adjusts. These are the same class of side effects reported with most antiretroviral medications at initiation and rarely require discontinuation.

Kidney function is monitored at every three-monthly follow-up because tenofovir disoproxil fumarate carries a small risk of nephrotoxicity with long-term use in susceptible individuals. Descovy’s formulation was developed specifically to reduce this risk. Patients with pre-existing kidney conditions are assessed individually, and in most cases an appropriate formulation can still be identified.

Injectable PrEP carries its own tolerability profile. Injection site reactions including temporary pain, swelling, and warmth at the injection site are common and typically resolve within a week. Systemic side effects are less commonly reported with the injectable formulation than with the daily pill.

Long-term safety data across the clinical populations using PrEP since initial approval shows no significant cumulative health risks in individuals without pre-existing contraindications.

START PrEP AT INTREPID HEALTH

Protecting against HIV does not require waiting for a referral. Book a PrEP consultation at Intrepid Health directly.

Frequently Asked Questions

What is PrEP in simple terms?

PrEP is a prescription medication taken by HIV-negative people to prevent HIV infection. It works by keeping antiretroviral drugs at protective levels inside the cells that HIV targets, so that if exposure occurs, the virus cannot replicate and infection cannot establish itself. Taken correctly, it reduces the risk of HIV acquisition by up to 99 percent.

How long does PrEP take to start working?

For oral PrEP used before anal sex, protective drug levels in rectal tissue are reached after approximately seven days of consistent daily use. For vaginal sex, guidelines recommend twenty-one days of consistent use before relying on PrEP for protection. Injectable PrEP provides protection from the time of the initial loading dose, with the second injection given one month later and then every two months thereafter.

Does PrEP have side effects?

A proportion of people starting daily oral PrEP experience mild nausea, headache, or fatigue in the first two to four weeks. These side effects are temporary and resolve as the body adjusts in the majority of cases. Long-term serious side effects are rare. Kidney function and other markers are monitored every three months to ensure continued tolerability.

Does PrEP protect against other sexually transmitted infections?

No. PrEP prevents HIV specifically. It does not protect against chlamydia, gonorrhoea, syphilis, herpes, or any other sexually transmitted infection. Condoms are recommended alongside PrEP for broader sexual health protection, and STI screening is conducted at every three-monthly PrEP monitoring appointment.

What is the difference between daily PrEP and injectable PrEP?

Daily oral PrEP requires one tablet taken at the same time every day. Injectable PrEP, cabotegravir under the brand name Apretude, is administered as an intramuscular injection every two months at a clinic. The injectable formulation removes the daily adherence requirement and clinical trial data shows it outperforms daily oral PrEP in populations where missing doses is a practical concern.

What blood tests are needed before starting PrEP?

Before a PrEP prescription is issued, a clinician will require an HIV test confirming negative status, hepatitis B screening, kidney function blood work, and screening for common sexually transmitted infections. These tests are repeated every three months throughout the time a patient is on PrEP.