What is Pre-Exposure Prophylaxis (PREP), when is it indicated, what are the associated risks, and what blood tests and medications, such as tenofovir disoproxil fumarate (TDF) and emtricitabine (FTC), are required prior to initiation in Canada?

Pre-Exposure Prophylaxis (PrEP) for HIV Prevention

Daily oral tenofovir disoproxil fumarate/emtricitabine (TDF/FTC) is the first-line PrEP medication in Canada, providing substantial protection against HIV acquisition when taken consistently. 1, 2

What is PrEP?

PrEP is a prevention strategy where HIV-negative individuals at high risk of HIV acquisition take antiretroviral medication daily (or event-driven) to reduce their risk of infection. 1, 2 When used as prescribed, PrEP reduces HIV acquisition risk by 44-75% depending on the population and adherence levels. 3, 4

Indications for PrEP

PrEP should be discussed with all sexually active adults and adolescents, and anyone who injects drugs. 1, 2 Specific high-risk populations include:

• Men who have sex with men (MSM) with condomless anal intercourse in the past 6 months 1, 5
• Transgender women with similar risk behaviors 1
• Serodiscordant couples (one partner HIV-positive, one HIV-negative) 1, 4
• Heterosexual individuals with multiple partners, inconsistent condom use, or partners from high HIV prevalence areas 1
• People who inject drugs sharing needles or injection equipment 1
• Individuals with recent sexually transmitted infections 1
• Sex workers or those trading sex for money, goods, or services 1

Medications Used in Canada

First-Line: TDF/FTC (Truvada)

Daily oral TDF 300mg/FTC 200mg is the recommended PrEP regimen for all at-risk populations. 1, 2 This combination has the strongest evidence base across all risk groups. 6, 3

Dosing specifics:

• For MSM: Start with a double dose (2 tablets) on day 1, then one tablet daily; continue for 2 days after last sexual exposure when stopping 1, 5
• For vaginal/frontal exposures: One tablet daily; continue for 7 days after last sexual exposure when stopping 1, 2
• Event-driven "2-1-1" dosing (2 tablets 2-24 hours before sex, 1 tablet 24 hours later, 1 tablet 48 hours after first dose) is an option for MSM only 1

Alternative: TAF/FTC (Descovy)

TAF/FTC is recommended specifically for MSM with creatinine clearance 30-60 mL/min, osteopenia, osteoporosis, or high risk for these conditions. 1, 5, 7

Critical limitation: TAF/FTC is NOT approved for cisgender women or event-driven dosing. 5, 7

Blood Tests Required Prior to Initiation

Before starting PrEP, the following tests are mandatory: 1, 5, 2

• HIV testing: Combination antigen-antibody assay (4th generation test) within 7 days of starting 1, 5
  • If acute HIV suspected (high-risk exposure, flu-like symptoms), add HIV RNA testing 1
• Serum creatinine and estimated creatinine clearance: Do NOT start TDF-based PrEP if <60 mL/min 1, 5, 8
• Hepatitis B surface antigen (HBsAg): Essential due to risk of hepatic flares upon discontinuation if HBV-positive 1, 5, 8
• Hepatitis C antibody 5, 2
• STI screening: Gonorrhea and chlamydia testing at all potentially exposed sites (urogenital, rectal, pharyngeal) 5, 2
• Pregnancy test for individuals of childbearing potential 2

Same-day PrEP initiation is reasonable: Asymptomatic individuals who are HIV-negative by rapid assay can start TDF/FTC immediately without awaiting baseline lab results, though testing should still be performed. 1

Ongoing Monitoring Schedule

Every 3 months (quarterly): 1, 5

• HIV testing with combination antigen-antibody assay
• Three-site STI screening (rectal, pharyngeal, urogenital) for gonorrhea and chlamydia
• PrEP prescriptions should not exceed 90 days without HIV testing 1, 2

Every 6-12 months: 5, 2

• Serum creatinine and estimated glomerular filtration rate (eGFR)

More frequent renal monitoring (every 3-6 months) is required for: 5

• Patients >50 years old
• Those taking medications for hypertension or diabetes
• Baseline eGFR <90 mL/min

Annually (or more frequently if high-risk): 1

• Hepatitis C serology (more frequent for people who inject drugs or those with elevated transaminases)

One-month follow-up visit is recommended after initiation to assess adherence, tolerability, and ensure absence of HIV seroconversion. 1

Risks and Adverse Effects

Common Adverse Effects

Gastrointestinal symptoms are most common: mild to moderate nausea, vomiting, and diarrhea, typically resolving within the first month. 9, 3

Serious Safety Concerns

Renal toxicity: 8, 9

• Glomerular dysfunction may occur, particularly in individuals >50 years
• Usually reversible upon discontinuation
• Contraindicated if creatinine clearance <60 mL/min 1, 5, 8
• Avoid concurrent nephrotoxic drugs 8

Bone mineral density (BMD) decreases: 8, 9

• Consider BMD assessment in patients with history of pathologic fracture or osteoporosis risk factors
• TAF/FTC preferred over TDF/FTC for those with bone concerns 5, 7

Hepatitis B flares: 8

• Severe acute exacerbations can occur when discontinuing TDF/FTC in chronic HBV carriers
• Monitor hepatic function closely for several months after stopping
• Risk of hepatic decompensation, particularly with cirrhosis 5

Lactic acidosis/hepatic steatosis: Rare but serious; discontinue if symptoms develop. 8

Important Caveats

PrEP is not fail-safe: Seroconversion despite excellent adherence has been reported in cases of high viral inoculum or viral resistance. 1 Adherence is central to efficacy - the benefit of PrEP is highly dependent on consistent use. 6, 4

Risk compensation concerns: Condom use should still be encouraged for all genital contact to prevent STIs, as PrEP does not protect against other infections. 1

Avoid interruptions in PrEP delivery: Insurance lapses, incarceration, or relocation have been associated with seroconversions. 1

Special Considerations

If HIV infection occurs during PrEP: 1, 5

• Stop PrEP immediately and perform confirmatory HIV RNA and genotype testing
• Resistance (typically M184V/I mutation) can occur if PrEP initiated during undiagnosed acute HIV infection
• Start fully suppressive antiretroviral therapy immediately with a boosted protease inhibitor or dolutegravir added to TDF/FTC while awaiting results

Pregnancy and breastfeeding: 1, 2

• Daily TDF/FTC is safe and recommended during pregnancy and breastfeeding
• Do not withhold PrEP from pregnant or breastfeeding individuals at risk

Transition from PEP to PrEP: 1

• For individuals completing 28-day post-exposure prophylaxis who remain at ongoing risk, seamlessly transition to PrEP after negative 4th generation HIV test