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, 3
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. 2, 3, 4
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 3, 5
- Maximum protection is achieved within 24 hours of the double-dose initiation 3
- When stopping PrEP, continue for 2 days after the last at-risk exposure 3
For all other populations (cisgender women, transgender women, heterosexual individuals, people who inject drugs):
- Take once daily without loading dose 3, 6
- Maximum protection requires approximately 7 days of daily dosing 3, 5
- When stopping PrEP, continue for 7 days after the last at-risk exposure 3, 6
- 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 3, 6
Alternative On-Demand Dosing (MSM Only)
On-demand "2-1-1" dosing is an acceptable alternative for MSM only with planned receptive anal intercourse: 2, 3, 5
- 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 2
- This regimen is not recommended for vaginal or neovaginal exposures 2
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. 4, 7 The efficacy is highly adherence-dependent, with 92% reduction in HIV acquisition when drug levels are detectable versus only 44% with suboptimal adherence. 3, 5, 4
Single-agent TDF alone has shown efficacy in heterosexual couples and people who inject drugs, but TDF/FTC combination remains the recommended standard. 1, 8, 7 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. 7
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). 3, 5
Pre-Initiation Requirements
Before prescribing TDF/FTC for PrEP, the following tests are mandatory: 3, 5
- Combined HIV antibody and antigen testing to confirm HIV-seronegative status 1, 3
- HIV RNA testing if acute HIV infection is suspected 1
- Serum creatinine and estimated creatinine clearance 1, 3, 5
- Hepatitis B surface antigen (HBsAg) 1, 3, 5
- Hepatitis C antibody 3, 5
- Nucleic acid amplification testing for gonorrhea and chlamydia 3, 5
- Syphilis testing 3
- Pregnancy test for individuals of childbearing potential 3, 5
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. 3, 5
Monitoring Schedule
During PrEP use, the following monitoring is required: 1, 3, 5
- HIV testing every 3 months (with additional testing at 1 month after initiation) 1, 3, 5
- STI screening every 3 months 1, 3, 5
- Pregnancy testing every 3 months for individuals of childbearing potential 3, 5
- 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, 3
- 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, 6
Special Populations
Pregnant and breastfeeding individuals:
- TDF/FTC can be safely continued during pregnancy and breastfeeding with no documented adverse fetal effects 3, 6, 5
- This is the preferred regimen in these populations 2, 3, 5
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 3, 5
- Close monitoring with ALT/AST testing is required after discontinuation 5
Critical Adherence Counseling
Enhanced adherence counseling is essential at every PrEP visit to assess and troubleshoot barriers to adherence. 1, 3 This is particularly important for adolescents and women, given the adherence-dependent efficacy. 3, 5 Each visit should reinforce that PrEP does not prevent other sexually transmitted infections, and condoms remain recommended for STI prevention. 3, 6
Common Pitfalls to Avoid
Do not prescribe PrEP without confirming HIV-negative status with combination antigen-antibody testing. 1, 3 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. 4
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. 2, 3
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. 5