What is the recommended regimen for Pre-Exposure Prophylaxis (PrEP) for individuals at high risk of Human Immunodeficiency Virus (HIV) infection?

HIV Pre-Exposure Prophylaxis (PrEP) Recommendations

Daily oral tenofovir disoproxil fumarate/emtricitabine (TDF/FTC) 300mg/200mg as a single pill is the standard first-line PrEP regimen for all individuals at high risk of HIV infection. 1, 2

First-Line PrEP Regimens by Population

For Men Who Have Sex with Men (MSM)

• Start with a double dose (2 pills) of TDF/FTC on day one, then continue with one pill daily to achieve protective drug levels more quickly 1, 2
• Continue daily dosing until 2 doses after the last sexual activity for rectal exposures 1
• Alternative option: On-demand "2-1-1" dosing for cisgender men and transgender women having planned receptive anal sex (2 pills 2-24 hours before sex, 1 pill 24 hours after first dose, 1 pill 48 hours after first dose) 1, 2, 3
• Injectable cabotegravir every 8 weeks is an alternative for MSM and transgender women where available 1, 2

For Women (Cisgender and Transgender)

• Daily TDF/FTC is the only recommended regimen—on-demand dosing is NOT appropriate for women 4, 2
• Daily dosing is critical because tenofovir concentrates at 10-fold lower levels in vaginal tissue compared to rectal tissue, with faster clearance 4
• Continue dosing until at least 7 days after last sexual activity for vaginal, neovaginal, or "front-hole" exposures 1

For Individuals with Renal or Bone Health Concerns

• Daily tenofovir alafenamide/emtricitabine (TAF/FTC) is preferred for MSM and transgender women with or at risk for kidney dysfunction, osteopenia, or osteoporosis 1, 2, 5
• TAF/FTC has superior bone and renal safety profiles compared to TDF/FTC 5

Who Should Receive PrEP

PrEP should be discussed and offered to all sexually active persons requesting it, without limiting access based on specific behavioral criteria 1. Specific high-risk groups include:

• MSM with condomless anal sex in the past 6 months, multiple partners, or high-risk assessment scores 2
• Transgender women engaging in high-risk sexual behaviors 2
• HIV-serodiscordant couples where the HIV-positive partner is not consistently virally suppressed 4, 2
• People who inject drugs and share injection equipment 2
• Anyone using substances or requesting PrEP 1
• Populations with HIV incidence above 2% per year 4

Pre-Initiation Testing Requirements

Before starting PrEP, perform the following mandatory tests 1, 4, 2:

• Combined HIV antibody and antigen testing (add HIV RNA if acute infection suspected) 2, 6
• Serum creatinine level and estimated creatinine clearance 1, 4
• Hepatitis B surface antigen 1, 4, 2
• Hepatitis C IgG antibody 1, 4
• Genital and nongenital Neisseria gonorrhoeae and Chlamydia trachomatis testing by NAAT 1, 4, 2
• Pregnancy testing for individuals of childbearing potential 1, 4
• Hepatitis A antibody for MSM and people who inject drugs 2

Critical Pitfall to Avoid

Ruling out acute HIV infection before initiating PrEP is crucial—starting PrEP during undiagnosed acute infection can lead to drug resistance and complicate diagnosis, as PrEP prolongs seroconversion stages and reduces viral load peaks 6. If acute infection is suspected, add HIV RNA testing 2, 6.

Monitoring During PrEP Use

PrEP prescriptions must not exceed 90 days without interval HIV testing 1, 4:

• At 1 month: Combined HIV antibody and antigen test 1, 2
• Every 3 months (quarterly): HIV testing, STI screening (gonorrhea, chlamydia, syphilis), pregnancy testing if applicable 1, 4, 2
• At first quarterly visit, then annually: Creatinine clearance assessment 1
• More frequent renal monitoring may be needed for those with existing kidney risk factors 2

Special Populations

Pregnancy and Breastfeeding

• TDF/FTC is safe and recommended during pregnancy and breastfeeding 1, 7
• Long-acting cabotegravir has a growing safety profile in pregnancy and lactation 1

Chronic Hepatitis B

• Exercise caution when discontinuing PrEP in patients with chronic hepatitis B due to risk of hepatitis flares 2

People Who Inject Drugs

• Daily oral TDF/FTC is effective for this population 2
• Ensure access to clean injection equipment and substance use treatment 4

Key Clinical Considerations

PrEP does not prevent other sexually transmitted infections—only HIV 4. Quarterly STI screening remains essential, as approximately half of PrEP users may experience at least one incident STI 3.

Adherence is the primary determinant of efficacy: Studies show 44-75% risk reduction with good adherence 8, but poor adherence (as seen in the FEM-PrEP trial) results in no protective benefit 8.

Common mild adverse events include diarrhea, headache, nausea, and dizziness, typically time-limited and more common with daily dosing (31%) than on-demand dosing (8%) 3.