How should I prescribe HIV pre‑exposure prophylaxis (PrEP) for an HIV‑negative patient, including dosing, baseline laboratory testing, monitoring schedule, and alternative regimens for renal impairment or event‑driven use?

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Last updated: September 17, 2026 • View editorial policy

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PrEP Prescription Protocol

Daily oral TDF/FTC (tenofovir disoproxil fumarate/emtricitabine) remains the recommended first-line PrEP regimen for all populations at risk of HIV exposure, with initiation using a double dose followed by single daily tablets, and monitoring every 3 months for HIV, renal function, and sexually transmitted infections 1.

Who Should Receive PrEP

PrEP should be offered to all sexually active persons requesting it, without requiring specific behavioral criteria or screening tools 1. Priority populations include:

  • Cisgender men, transgender persons, and nonbinary persons who have sex with cisgender men
  • Young adults and adolescents up to age 24
  • Persons who inject drugs or have substance use disorders
  • Anyone with an STI in the past year
  • Individuals reporting transactional sex
  • Partners of persons from high HIV incidence regions 1

Baseline Requirements Before Starting PrEP

Mandatory Testing

  • HIV testing: Confirm HIV-negative status before initiating PrEP. Defer patients with signs/symptoms of acute HIV infection (fever, headache, muscle soreness, sore throat, rash, swollen lymph nodes) until proven HIV-negative 2
  • Renal function: Obtain baseline creatinine and estimated glomerular filtration rate (eGFR) 3
  • Hepatitis B serology: Screen for HBV infection 2
  • STI screening: Test for other sexually transmitted infections 3
  • Pregnancy testing: For women of childbearing potential 2

Clinical Assessment

Obtain complete medical history including:

  • Chronic diseases (viral hepatitis, renal insufficiency, osteoporosis)
  • Current medications
  • Substance use (methamphetamine, GHB/GBL, alcohol, opioids)
  • Pregnancy plans for women 2

Dosing Regimens

Daily Oral PrEP (All Populations)

  • Initiation: Double dose of TDF/FTC on day 1, then one tablet daily thereafter 1
  • Discontinuation timing:
    • For rectal exposures: Continue until 2 doses after last sexual activity
    • For vaginal/neovaginal/"front-hole" exposures: Continue until at least 7 days after last sexual activity 1
  • Minimum effective dosing: 4 or more doses per week provides high-level protection for both rectal and vaginal exposures; 2 or more doses per week provides 79-88% reduction for rectal exposures 1

On-Demand (2-1-1) PrEP

Recommended only for cisgender men and others having planned receptive anal sex (NOT for vaginal/neovaginal exposures) 1:

  • 2 tablets: 2-24 hours before sexual activity
  • 1 tablet: 24 hours after the first dose
  • 1 tablet: 48 hours after the first dose (24 hours after the second dose)
  • If additional sexual activity occurs, continue daily dosing until 2 doses after last activity 1
  • Important caveat: For transgender women using gender-affirming hormone therapy, administer TDF/FTC with food when using 2-1-1 dosing 1

The ANRS PREVENIR study demonstrated equivalent effectiveness between daily and on-demand PrEP in MSM, with HIV incidence of 1.1 cases per 1000 person-years for both regimens 4.

Monitoring Schedule

Every 3 Months

  • HIV testing: Mandatory at each visit 1, 3
  • Renal function monitoring: Creatinine and eGFR 3
  • STI screening: Test for sexually transmitted infections 3
  • Adherence assessment: Self-report and counseling 4
  • Prescription refills: Limit to ≤90-day supply 5

Adherence Monitoring

Self-reported adherence should be assessed at each visit. Tenofovir diphosphate concentrations in dried blood spots can provide objective adherence data when available 4.

Management of Renal Impairment

Baseline eGFR <60 mL/min/1.73 m²

TDF/FTC is contraindicated in patients with eGFR <60 mL/min/1.73 m² 6, 7. For these patients:

  • Consider alternative PrEP formulations (non-TDF-based regimens)
  • 16% of PrEP users with eGFR <60 required non-TDF/FTC formulations 7

eGFR 60-65 mL/min/1.73 m²

If renal impairment develops during PrEP (eGFR <65 mL/min/1.73 m²):

  • Repeat testing to confirm (median follow-up time: 42 days) 6
  • Review and stop nephrotoxic supplements or recreational drugs 7
  • If impairment persists or worsens, discontinue TDF/FTC 6
  • Consider alternative PrEP formulations

Real-world data shows that among 35,724 PrEP users, only 361 (1%) developed eGFR <60, and most required only conservative management with repeat sampling and cessation of supplements/recreational drugs 7.

Special Populations

Pregnancy and Breastfeeding

  • TDF/FTC daily oral PrEP is the recommended regimen for pregnant or breast/chest feeding individuals 1
  • Long-acting cabotegravir has growing safety data and can be used safely in pregnancy and breastfeeding 1

Persons Who Inject Drugs

  • Daily oral TDF/FTC is recommended 1
  • Integrate with medications for opioid use disorder and syringe service programs 1

Counseling Requirements

At each visit, counsel patients on:

  • PrEP is not 100% effective against HIV
  • PrEP does not prevent other STIs
  • Adherence is critical for efficacy
  • Condoms remain recommended for all penetrative sex acts 2
  • Discuss ongoing need for PrEP based on risk behaviors 1

Common Pitfalls to Avoid

  1. Prescribing >90-day supplies: Limits monitoring opportunities and increases risk of undetected HIV seroconversion or renal toxicity 5

  2. Inadequate HIV monitoring: HIV testing must occur every 3 months. Infectious disease specialists demonstrate better adherence to monitoring protocols than primary care providers (OR 1.81 for follow-up HIV monitoring) 5

  3. Using on-demand PrEP for vaginal exposures: The 2-1-1 regimen is only validated for receptive anal sex in cisgender men 1

  4. Continuing PrEP with persistent renal impairment: Three of six cases with non-resolving impairment required PrEP cessation, with one subsequent HIV infection reported 6

  5. Inadequate baseline HIV testing: Starting PrEP during unrecognized acute HIV infection can lead to drug resistance. Modeling studies show that confirming HIV-negative status at initiation reduces resistance by >90% 8

  6. Ignoring hepatitis B status: HBV reactivation is a risk when discontinuing TDF/FTC in HBV-positive individuals 8

References

2
Guideline

taiwan guideline on oral pre-exposure prophylaxis for hiv prevention - 2018 update.

Journal of Microbiology, Immunology and Infection, 2020

3
Research

Prescribing pre-exposure prophylaxis for HIV.

Australian prescriber, 2020

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This information is intended for healthcare professionals. Any medical decision-making should rely on clinical judgment and independently verified information. The content provided herein does not replace professional discretion and should be considered supplementary to established clinical guidelines. Healthcare providers should verify all information against primary literature and current practice standards before application in patient care. Dr.Oracle assumes no liability for clinical decisions based on this content.