What are the guidelines for pre-exposure prophylaxis (PrEP) for individuals at risk of Human Immunodeficiency Virus (HIV) exposure?

HIV Pre-Exposure Prophylaxis (PrEP) Guidelines

Daily oral tenofovir disoproxil fumarate/emtricitabine (TDF/FTC) 300mg/200mg is the standard first-line PrEP regimen for all populations at risk of HIV acquisition, with proven efficacy exceeding 90% when adherence is maintained. 1, 2

Who Should Receive PrEP

Men Who Have Sex with Men (MSM)

• Offer PrEP to MSM with any of the following risk factors: 3, 1
  • At least one episode of condomless anal intercourse (insertive or receptive) in the past 6 months 3
  • Multiple male sex partners (>5 partners in 6 months increases risk) 3
  • HIV-positive sex partner(s) 3
  • Recent sexually transmitted infection diagnosis 1
  • Methamphetamine or other stimulant use 3
  • Risk score ≥10 on validated assessment tools 3

Transgender Women

• Strongly recommend PrEP for transgender women engaging in condomless anal intercourse or with multiple partners, despite limited specific efficacy data in this population 3, 1

Heterosexual Men and Women

• Offer PrEP to heterosexual individuals with: 1, 4
  • HIV-positive sexual partner (serodiscordant couples) 1
  • Inconsistent condom use with partners of unknown HIV status 4
  • Recent bacterial STI diagnosis 4
  • HIV incidence >2% per year in their sexual network 4

People Who Inject Drugs

• Recommend PrEP for individuals who share injection equipment or have HIV-positive injection partners 1, 2

PrEP Regimen Selection

First-Line Options

For MSM and Transgender Women:

• TDF/FTC 300mg/200mg: Give 2 tablets on day 1, then 1 tablet daily thereafter 1, 2
• Continue daily dosing until 2 days after last receptive anal exposure 2
• Alternative - TAF/FTC: Use for those with creatinine clearance <60 mL/min, osteopenia/osteoporosis, or age >50 years 3, 1, 2, 5
• Alternative - Event-driven "2-1-1" dosing: 2 tablets 2-24 hours before sex, 1 tablet 24 hours after first dose, 1 tablet 48 hours after first dose (only for MSM with planned sexual activity) 3, 1, 2
• Injectable cabotegravir: Every 8 weeks (when available) 1, 2

For Cisgender Women:

• TDF/FTC 300mg/200mg: 1 tablet daily only (event-driven dosing NOT recommended due to inadequate vaginal tissue drug levels) 2, 4
• Requires minimum 7-day lead-in period before protection is achieved 4
• Continue daily dosing until 7 days after last vaginal exposure 2, 4

For People Who Inject Drugs:

• TDF/FTC 300mg/200mg: 1 tablet daily 1

Pre-Initiation Requirements

Mandatory Testing Before Starting PrEP

Perform all of the following tests before prescribing PrEP: 3, 1, 2, 4

• HIV testing: Combined antibody/antigen immunoassay (4th generation) 3, 1

  • Add HIV RNA testing if acute infection suspected (fever, rash, lymphadenopathy, or high-risk exposure within past 2-4 weeks) 3, 1
  • Critical pitfall: Never start PrEP if acute HIV infection cannot be ruled out, as this risks drug resistance 6

• Renal function: Serum creatinine with calculated creatinine clearance 3, 1, 2

  • Do not use TDF/FTC if creatinine clearance <60 mL/min 3

• Hepatitis B surface antigen (HBsAg): Essential because discontinuing TDF/FTC can cause hepatitis B flares in chronic carriers 3, 1, 2

• Hepatitis C antibody: Baseline testing required 3, 1, 2

• STI screening: Genital and extragenital (rectal, pharyngeal) testing for gonorrhea and chlamydia 1, 2, 4

• Pregnancy test: For all individuals of childbearing potential 2, 4

Tests That Should Not Delay PrEP Initiation

• Creatinine and HBsAg results should not prevent same-day PrEP start if clinical assessment suggests low risk 3

Monitoring Schedule During PrEP Use

At 1 Month After Initiation

• HIV antibody/antigen testing 3, 1, 2
• Assess adherence and side effects 3

Every 3 Months (Quarterly)

• HIV antibody/antigen testing (mandatory - never prescribe >90 days without HIV testing) 3, 1, 2
• STI screening (genital and extragenital sites based on sexual practices) 3, 1, 2, 4
• Pregnancy testing for individuals of childbearing potential 4
• Adherence counseling 3

Every 6 Months

• Creatinine clearance assessment 3, 1, 2
• Hepatitis C antibody testing (or more frequently if elevated transaminases or ongoing injection drug use) 3

More Frequent Monitoring Needed For:

• Age >50 years: Check creatinine every 3 months 3
• Baseline creatinine clearance <90 mL/min: Check every 3 months 3
• Diabetes or hypertension: Check creatinine every 3 months 3

Special Populations

Pregnancy and Breastfeeding

• Continue TDF/FTC during pregnancy - it is safe with no documented adverse fetal effects 2, 4
• TDF/FTC is the preferred regimen during pregnancy and breastfeeding 2, 4
• Do not discontinue PrEP in pregnant individuals at ongoing HIV risk 3

Chronic Hepatitis B

• Warning: If PrEP is discontinued in HBsAg-positive individuals, monitor closely for hepatitis flares with ALT/AST testing 3
• Consider indefinite continuation or transition to hepatitis B treatment if PrEP is stopped 3

Renal Impairment

• Use TAF/FTC instead of TDF/FTC for creatinine clearance 30-60 mL/min 1, 2, 5
• Do not use TDF/FTC if creatinine clearance <60 mL/min 3

Bone Health Concerns

• Use TAF/FTC instead of TDF/FTC for individuals with osteopenia, osteoporosis, or fracture history 1, 2, 5

Transitioning from PEP to PrEP

• For individuals completing post-exposure prophylaxis (PEP) who have ongoing HIV risk, transition immediately to PrEP after HIV testing at completion of the 28-day PEP course 3

Critical Pitfalls to Avoid

Acute HIV Infection at PrEP Initiation

• Most important pitfall: Starting PrEP during undiagnosed acute HIV infection leads to drug resistance 6
• Always obtain HIV RNA testing if symptoms suggest acute infection (fever, rash, pharyngitis, lymphadenopathy) even if antibody/antigen test is negative 3, 6
• Primary HIV infection in PrEP users presents with lower viral loads and fewer symptoms, making diagnosis more difficult 6

Inadequate Lead-In Time for Women

• Women require 7 days of daily TDF/FTC before vaginal tissue protection is adequate 2, 4
• Event-driven dosing does NOT work for vaginal exposures 2, 4

Prescribing Beyond 90 Days Without HIV Testing

• Never provide >90-day prescription without interval HIV testing 3, 2

Discontinuing PrEP in Hepatitis B Carriers

• Abrupt discontinuation can cause severe hepatitis B flares 3
• Monitor ALT/AST closely or transition to hepatitis B treatment 3

Inadequate STI Screening

• PrEP does not prevent other STIs - condoms remain essential 4, 7
• Screen all anatomic sites of exposure (rectal and pharyngeal, not just genital) 1, 2

Efficacy and Adherence

• PrEP efficacy exceeds 90% with detectable drug levels 3, 7, 8
• Efficacy is highly adherence-dependent: 44% reduction with suboptimal adherence vs. 92% with detectable drug levels 3
• Only 2% of users discontinue due to adverse effects 4, 7
• Common side effects (nausea, headache) are typically self-limited and resolve within weeks 4, 9