What is the most common Pre-Exposure Prophylaxis (PrEP) medication to start?

Most Common PrEP Medication to Start

The most common and recommended first-line PrEP medication to start is tenofovir disoproxil fumarate/emtricitabine (TDF/FTC) 300mg/200mg taken once daily, which is the standard regimen for all populations at risk of HIV acquisition. 1, 2

Standard Regimen and Dosing

TDF/FTC (brand name Truvada, or generic equivalents) is the only FDA-approved oral PrEP regimen with proven efficacy exceeding 90% when adherence is maintained. 1, 2, 3

Population-Specific Initiation Strategies

For men who have sex with men (MSM):

• Initiate with a double dose (2 tablets) on day 1, then continue once daily thereafter to achieve maximal protection within 24 hours 2, 4
• Maximum protection is achieved within 24 hours of the double-dose initiation 2
• When stopping PrEP, continue for 2 days after the last at-risk exposure 2

For all other populations (cisgender women, transgender women, heterosexual individuals, people who inject drugs):

• Take once daily without loading dose 2, 5
• Maximum protection requires approximately 7 days of daily dosing 2, 4
• When stopping PrEP, continue for 7 days after the last at-risk exposure 2, 5
• Daily dosing is especially critical for women because tenofovir concentrates at 10-fold lower levels in vaginal tissue compared to rectal tissue, with faster clearance 2, 5

Alternative On-Demand Dosing (MSM Only)

On-demand "2-1-1" dosing is an acceptable alternative for MSM only with planned receptive anal intercourse: 1, 2, 4

• 2 tablets taken 2-24 hours before sex
• 1 tablet 24 hours after the first dose
• 1 tablet 48 hours after the first dose
• If additional sexual activity occurs, continue daily single dosing until 2 doses after the last activity 1
• This regimen is not recommended for vaginal or neovaginal exposures 1

Why TDF/FTC is the Standard

TDF/FTC has the strongest evidence base from multiple placebo-controlled randomized trials demonstrating significant HIV risk reduction in MSM, high-risk heterosexuals, and injection drug users. 3, 6 The efficacy is highly adherence-dependent, with 92% reduction in HIV acquisition when drug levels are detectable versus only 44% with suboptimal adherence. 2, 4, 3

Single-agent TDF alone has shown efficacy in heterosexual couples and people who inject drugs, but TDF/FTC combination remains the recommended standard. 1, 6 While one large trial found no significant difference between TDF alone versus TDF/FTC (hazard ratio 0.67,95% CI 0.39-1.17; p=0.16), the combination is preferred to minimize resistance risk if HIV infection occurs during PrEP use. 6

Medications NOT Recommended for PrEP

TDF/lamivudine, TAF/emtricitabine (as initial PrEP), and TDF alone are not recommended for PrEP. 1 TAF/FTC may be considered as an alternative only for specific populations with contraindications to TDF (creatinine clearance 30-60 mL/min, osteopenia/osteoporosis, or age >50 years in MSM). 2, 4

Pre-Initiation Requirements

Before prescribing TDF/FTC for PrEP, the following tests are mandatory: 2, 4

• Combined HIV antibody and antigen testing to confirm HIV-seronegative status 1, 2
• HIV RNA testing if acute HIV infection is suspected 1
• Serum creatinine and estimated creatinine clearance 1, 2, 4
• Hepatitis B surface antigen (HBsAg) 1, 2, 4
• Hepatitis C antibody 2, 4
• Nucleic acid amplification testing for gonorrhea and chlamydia 2, 4
• Syphilis testing 2
• Pregnancy test for individuals of childbearing potential 2, 4

These tests should not delay PrEP initiation once HIV-negative status is confirmed. 1

Contraindications

TDF-based PrEP is not recommended in persons with creatinine clearance below 60 mL/min/1.73m². 1 For these individuals, consider TAF/FTC as an alternative or address the underlying renal dysfunction before initiating PrEP. 2, 4

Monitoring Schedule

During PrEP use, the following monitoring is required: 1, 2, 4

• HIV testing every 3 months (with additional testing at 1 month after initiation) 1, 2, 4
• STI screening every 3 months 1, 2, 4
• Pregnancy testing every 3 months for individuals of childbearing potential 2, 4
• Creatinine measurement at least every 6 months, more frequently for patients >50 years, taking hypertension or diabetes medications, or with baseline creatinine clearance <90 mL/min 1, 2
• HCV serologic testing at least annually, more frequently in high-risk individuals 1

PrEP prescriptions should not exceed 90 days without interval HIV testing. 1, 5

Special Populations

Pregnant and breastfeeding individuals:

• TDF/FTC can be safely continued during pregnancy and breastfeeding with no documented adverse fetal effects 2, 5, 4
• This is the preferred regimen in these populations 1, 2, 4

Hepatitis B co-infection:

• For HBsAg-positive individuals, consider indefinite continuation or transition to hepatitis B treatment if stopping PrEP, as discontinuation can cause hepatitis flares 2, 4
• Close monitoring with ALT/AST testing is required after discontinuation 4

Critical Adherence Counseling

Enhanced adherence counseling is essential at every PrEP visit to assess and troubleshoot barriers to adherence. 1, 2 This is particularly important for adolescents and women, given the adherence-dependent efficacy. 2, 4 Each visit should reinforce that PrEP does not prevent other sexually transmitted infections, and condoms remain recommended for STI prevention. 2, 5

Common Pitfalls to Avoid

Do not prescribe PrEP without confirming HIV-negative status with combination antigen-antibody testing. 1, 2 Resistance to TDF/FTC is rare (<0.1%) but usually occurs when PrEP is inadvertently prescribed to individuals with undiagnosed acute HIV infection who have false-negative findings on HIV antibody/antigen testing. 3

Do not use on-demand dosing for vaginal or neovaginal exposures - only daily dosing provides adequate protection for these routes of exposure due to lower tissue drug concentrations. 1, 2

Do not abruptly discontinue TDF/FTC in HBsAg-positive individuals without transitioning to hepatitis B treatment or close monitoring, as this can precipitate acute hepatitis B flares or hepatic decompensation. 4