What are the recommended HIV pre-exposure prophylaxis (PrEP) options for individuals at high risk of HIV exposure?

HIV Pre-Exposure Prophylaxis Options

Daily oral tenofovir disoproxil fumarate/emtricitabine (TDF/FTC) 300mg/200mg once daily is the first-line PrEP regimen for all individuals at high risk of HIV acquisition, with proven efficacy exceeding 90% when adherence is maintained. 1, 2, 3

Primary PrEP Regimens

Standard Daily Oral PrEP

• TDF/FTC (Truvada) 300mg/200mg once daily is the gold-standard option with the strongest evidence (AIa rating) across all populations and exposure routes 4, 2, 3
• Efficacy exceeds 90% with maintained adherence, but drops to 44% with suboptimal adherence 1, 3
• This regimen is safe during pregnancy and breastfeeding with no documented adverse fetal effects 1, 2

Alternative Oral PrEP for Specific Populations

• TAF/FTC (Descovy) 25mg/200mg once daily is recommended for MSM and transgender women with creatinine clearance 30-60 mL/min, osteopenia, osteoporosis, or other bone/renal concerns 1, 5, 6
• TAF/FTC has demonstrated non-inferior efficacy to TDF/FTC with improved bone and renal safety profiles 6
• Critical caveat: TAF/FTC is NOT recommended for cisgender women due to insufficient efficacy data for vaginal exposure 2

Injectable Long-Acting PrEP

• Cabotegravir long-acting injectable every 8 weeks is an emerging option (pending full regulatory approval and availability) 5
• This provides an alternative for individuals who struggle with daily oral adherence 5

Population-Specific Dosing Strategies

Men Who Have Sex with Men (MSM)

• Daily regimen: Start with a double dose (2 tablets) on day 1, then one tablet daily thereafter to achieve maximal protection within 24 hours 1, 2, 5
• When stopping PrEP, continue for 2 days after the last at-risk exposure 1, 2
• On-demand "2-1-1" dosing (alternative for MSM only): 2 tablets taken 2-24 hours before sex, 1 tablet 24 hours after the first dose, and 1 tablet 48 hours after the first dose 4, 1, 2, 7
• The 2-1-1 regimen showed equivalent HIV incidence to daily dosing in the ANRS PREVENIR study (1.1 cases per 1000 person-years for both regimens) 7

Cisgender Women and Transgender Women

• Daily dosing is mandatory—on-demand dosing is NOT recommended for vaginal or neovaginal exposure 2, 5
• Maximum protection requires approximately 7 days of daily dosing (no loading dose) 1, 2
• When stopping PrEP, continue for 7 days after the last at-risk exposure 1, 5
• Daily dosing is critical because tenofovir concentrates at 10-fold lower levels in vaginal tissue compared to rectal tissue, with faster clearance 1

Injection Drug Users

• Daily TDF/FTC once daily without loading dose 1
• Continue for 7 days after last at-risk exposure 1

Pre-Initiation Testing Requirements

Before prescribing PrEP, the following tests are mandatory:

• HIV testing: Combined HIV antibody and antigen assay to confirm HIV-seronegative status; add HIV RNA testing if acute HIV is suspected 4, 2, 5
• Renal function: Serum creatinine level and estimated creatinine clearance (TDF-based PrEP is contraindicated if creatinine clearance <60 mL/min/1.73m²) 4, 2
• Hepatitis screening: Hepatitis B surface antigen (HBsAg) and hepatitis C IgG antibody 4, 2, 5
• STI screening: Nucleic acid amplification testing for gonorrhea and chlamydia (genital and extragenital sites), plus syphilis testing 1, 2, 5
• Pregnancy test for individuals of childbearing potential 1, 2, 5

Important: These tests should not delay PrEP initiation if HIV-negative status is confirmed 4

Monitoring Schedule During PrEP Use

Every 3 Months (Quarterly)

• HIV antibody/antigen testing (PrEP prescription should not exceed 90 days without interval HIV testing) 4, 2, 5
• Comprehensive STI screening 4, 2, 5
• Pregnancy testing for individuals of childbearing potential 2, 5
• Adherence assessment and troubleshooting barriers 4, 2

Additional Monitoring at 1 Month After Initiation

• Follow-up HIV testing to assess for acute infection and adherence support 4, 5

Renal Function Monitoring

• At 3 months after initiation, then every 6 months for most patients 4, 2
• More frequent monitoring (every 3 months) for patients with baseline creatinine clearance <90 mL/min, age >50 years, diabetes, or hypertension 4, 2, 5

Hepatitis C Screening

• At least annually, and more frequently if elevated transaminase levels or high-risk behaviors (e.g., people who inject drugs) 4, 2

Who Should Receive PrEP

PrEP should be discussed with all sexually active adults and adolescents, and anyone who injects drugs 1, 5

High-Risk Populations Include:

• MSM with condomless anal intercourse, multiple partners, or HIV-positive partner(s) 1, 2
• Transgender individuals engaging in condomless sex or with multiple partners 1, 2
• Heterosexual individuals with HIV-positive sexual partners or inconsistent condom use with partners of unknown HIV status 1, 2
• Individuals who inject drugs and share injection equipment 3
• Anyone requesting PrEP, without limiting access based on specific behavioral criteria 5

Critical Clinical Pitfalls to Avoid

Dosing Errors

• Never use on-demand (2-1-1) dosing for cisgender women or transgender women—daily dosing is mandatory for vaginal exposure 2
• Do not forget the 7-day lead-in period for women before maximal protection is achieved 1, 2

Contraindications and Drug Selection

• Do not prescribe TDF-based PrEP if creatinine clearance is <60 mL/min/1.73m² 4
• Do not use TDF/lamivudine, TAF/emtricitabine (for women), or TDF alone—these are not recommended for PrEP 4
• Do not use TAF/FTC as first-line for cisgender women due to insufficient efficacy data for vaginal exposure 2

HIV Testing and Resistance

• Never prescribe PrEP without confirming HIV-negative status—resistance can develop if prescribed during acute HIV infection 2, 3
• If HIV infection is confirmed during PrEP use, immediately start a recommended initial antiretroviral treatment regimen pending resistance testing 4, 2
• Resistance to TDF/FTC when used for PrEP is rare (<0.1%) but usually occurs when PrEP is inadvertently prescribed during undiagnosed acute HIV infection 3

Hepatitis B Co-infection

• For HBsAg-positive individuals, if PrEP is discontinued, consider indefinite continuation or transition to hepatitis B treatment, as discontinuation can cause hepatitis flares 1, 2

STI Prevention

• PrEP does not prevent other sexually transmitted infections—condoms remain essential for comprehensive STI prevention 1, 2
• Sexually transmitted infections are common among PrEP users and require quarterly screening 3

Adherence Counseling

• Enhanced adherence counseling is essential, particularly for adolescents and women, given the adherence-dependent efficacy 1
• Each PrEP visit should be used to assess and troubleshoot barriers to adherence 4, 2

Safety Profile

• Only 2% of people discontinue PrEP due to adverse effects (most commonly nausea, vomiting, diarrhea) 3, 7
• TDF/FTC is generally safe and well-tolerated across all populations 8, 3
• Long-term monitoring of renal function and bone mineral density is important since PrEP involves long-term administration to healthy individuals 8

Transition from PEP to PrEP

For individuals being treated with a 3-drug post-exposure prophylaxis (PEP) course who are likely to be at risk of ongoing exposure, a seamless transition from PEP to PrEP is recommended 4