What is the recommended regimen for HIV Pre-Exposure Prophylaxis (PrEP)?

HIV Pre-Exposure Prophylaxis (PrEP) Regimen

The recommended first-line regimen for HIV PrEP is tenofovir disoproxil fumarate 300mg/emtricitabine 200mg (TDF/FTC) as a single daily oral pill for all populations at risk for HIV acquisition. 1

Primary Regimen Selection

Standard Daily Oral PrEP

• TDF 300mg/FTC 200mg once daily is the preferred regimen for most individuals at risk, with efficacy exceeding 90% when adherence is maintained 1, 2
• For men who have sex with men (MSM) specifically, initiate with a double dose (2 pills) on the first day to achieve protective drug levels more rapidly 1
• Daily dosing is mandatory for women because tenofovir concentrates at 10-fold lower levels in vaginal tissue compared to rectal tissue, with faster clearance 3

Alternative Formulations

• Tenofovir alafenamide/emtricitabine (TAF/FTC) daily is recommended specifically for MSM who have or are at risk for kidney dysfunction, osteopenia, or osteoporosis 1, 4
• TAF/FTC demonstrated non-inferior efficacy to TDF/FTC but with improved bone and renal safety profiles 4
• Injectable cabotegravir every 8 weeks is an alternative option for cisgender men and transgender women who have sex with men 1

Event-Driven PrEP (Limited Populations)

• The "2-1-1" method (2 pills 2-24 hours before sex, 1 pill 24 hours after first dose, 1 pill 48 hours after first dose) is effective for MSM and transgender women as an alternative to daily dosing 1
• This approach is NOT recommended for women due to inadequate pharmacokinetic data in vaginal tissues 1

Target Populations for PrEP

PrEP should be offered to individuals at substantial risk of HIV acquisition, including: 1

• MSM with condomless anal sex in past 6 months, multiple partners, or high risk scores on validated assessment tools
• Transgender women engaging in high-risk sexual behaviors
• HIV serodiscordant couples where the HIV-positive partner is not consistently virally suppressed
• People who inject drugs and share injection equipment
• Heterosexual men and women with high-risk sexual behaviors (e.g., inconsistent condom use with partners of unknown HIV status)

Pre-Initiation Assessment (Critical to Avoid Resistance)

Before prescribing PrEP, you must rule out acute HIV infection to prevent drug resistance development: 1, 5

• Combined HIV antibody and antigen testing (fourth-generation test) 1
• HIV RNA testing if acute infection is suspected (symptoms include fever, rash, pharyngitis, lymphadenopathy within past 2-4 weeks) 1, 5
• Serum creatinine to calculate estimated creatinine clearance 1
• Hepatitis B surface antigen (essential due to risk of hepatitis flares if PrEP discontinued) 1
• Hepatitis C antibody 1
• Hepatitis A antibody for MSM and people who inject drugs 1
• STI screening: genital and non-genital testing for gonorrhea and chlamydia by NAAT, syphilis serology 1
• Pregnancy test for individuals of childbearing potential 3

Monitoring Schedule During PrEP Use

At 1 Month

• Combined HIV antibody and antigen test 1

Every 3 Months

• HIV testing (combined antibody/antigen) to ensure patient remains HIV-negative 1
• STI screening (gonorrhea, chlamydia, syphilis) 1
• PrEP prescriptions should not exceed 90 days without interval HIV testing 3

Every 6 Months

• Creatinine assessment to monitor kidney function 1
• More frequent monitoring needed for patients with baseline kidney disease or risk factors 1

Critical Pitfalls to Avoid

Acute HIV Infection at Initiation

• Primary HIV infection while starting PrEP is the main cause of drug resistance (though rare at <0.1%) 2, 5
• Patients with acute HIV on PrEP present with lower viral load peaks and fewer symptoms, making diagnosis more difficult 5
• PrEP prolongs seroconversion stages, potentially delaying diagnosis 5
• Always use HIV RNA testing if any symptoms suggestive of acute infection are present 1, 5

Medication-Specific Concerns

• TDF can affect bone density—consider TAF/FTC for patients with osteopenia or osteoporosis 1, 4
• Monitor kidney function closely with TDF, especially in older adults or those with baseline renal impairment 1, 4
• Hepatitis B flares can occur if PrEP is discontinued in HBsAg-positive patients—ensure appropriate hepatitis B management 1

Adherence and Efficacy

• Efficacy is highly correlated with adherence—daily dosing achieves >90% protection, but inconsistent use dramatically reduces effectiveness 2
• Only 2% discontinue due to adverse effects (mainly nausea, abdominal pain, headache), which are typically mild and transient 2, 6

STI Prevention

• PrEP does not prevent other STIs—counsel patients that condoms remain important for comprehensive protection 3
• STIs are common among PrEP users, necessitating regular screening 2