What are the safety, efficacy, and considerations for using emtricitabine (Emtricitabine) and tenofovir alafenamide (Tenofovir Alafenamide) (FTC/TAF) for Pre-Exposure Prophylaxis (PrEP)?

FTC/TAF for HIV Pre-Exposure Prophylaxis: Safety, Efficacy, and Clinical Considerations

Emtricitabine/tenofovir alafenamide (FTC/TAF) is highly effective for HIV prevention with non-inferior efficacy to FTC/TDF, demonstrating superior bone and renal safety profiles, making it the preferred alternative for patients with renal impairment, osteoporosis, or age >50 years. 1, 2

Efficacy for HIV Prevention

FTC/TAF demonstrates robust HIV prevention efficacy comparable to the established FTC/TDF regimen:

• In the landmark DISCOVER trial with 5,387 participants (cisgender men who have sex with men and transgender women), FTC/TAF showed non-inferiority to FTC/TDF with an HIV incidence rate ratio of 0.47 (95% CI 0.19-1.15) at the primary analysis 3
• At 96 weeks of follow-up, HIV incidence was 0.16 infections per 100 person-years with FTC/TAF versus 0.30 per 100 person-years with FTC/TDF (IRR 0.54,95% CI 0.23-1.26) 4
• Efficacy exceeds 90% when adherence is maintained with detectable drug levels 1
• Approximately 78-82% of participants reported taking medication more than 95% of the time across all study visits 4

Safety Profile and Advantages Over FTC/TDF

FTC/TAF demonstrates superior safety in bone and renal parameters compared to FTC/TDF:

Renal Safety

• FTC/TAF showed superiority over FTC/TDF in prespecified renal biomarker safety endpoints 3
• This advantage was maintained through 96 weeks of follow-up 4
• TAF can be used in patients with creatinine clearance 30-60 mL/min, whereas TDF requires ≥60 mL/min 2
• No dosage adjustment required for mild, moderate, or severe renal impairment 5

Bone Mineral Density

• FTC/TAF demonstrated superiority in all prespecified bone mineral density endpoints compared to FTC/TDF 3
• This makes FTC/TAF the preferred option for patients with osteopenia, osteoporosis, or age >50 years 1, 2

Tolerability

• Both regimens were well tolerated with low discontinuation rates: 1% (36/2,694) for FTC/TAF versus 2% (49/2,693) for FTC/TDF 3
• No unexpected adverse events were reported 3

Weight Considerations

• Median weight gain was higher with FTC/TAF (1.7 kg) compared to FTC/TDF (0.5 kg) at 96 weeks (p<0.0001) 4
• This should be discussed with patients but does not typically warrant discontinuation 4

Patient Selection and Indications

FTC/TAF is specifically indicated for the following patient populations:

Primary Indications for FTC/TAF Over FTC/TDF

• Creatinine clearance 30-60 mL/min (FTC/TDF contraindicated below 60 mL/min) 2
• Osteopenia or osteoporosis 1, 2
• Age >50 years with renal risk factors 1, 2
• Patients taking hypertension or diabetes medications with renal concerns 1

General PrEP Eligibility (applies to both FTC/TAF and FTC/TDF)

• Men who have sex with men with condomless anal intercourse in past 6 months, multiple partners, HIV-positive partner(s), recent STI diagnosis, or stimulant use 1
• Transgender women engaging in condomless anal intercourse or with multiple partners 1
• Heterosexual individuals with HIV-positive sexual partner not consistently virally suppressed 1, 2
• Populations with HIV incidence ≥2% per year 1, 2

Critical Contraindications

FTC/TAF must not be prescribed in the following circumstances:

• Positive or unknown HIV status (absolute contraindication) 2
• Creatinine clearance <30 mL/min 2
• Decompensated hepatic impairment (Child-Pugh B or C) 5
• Patients not receiving chronic hemodialysis with ESRD (estimated CrCl <15 mL/min) 5

Pre-Initiation Testing Requirements

Before prescribing FTC/TAF for PrEP, the following tests are mandatory:

• Combined HIV antibody and antigen testing (mandatory to confirm HIV-negative status) 1, 2
• HIV RNA testing if acute HIV infection is suspected 6
• Serum creatinine and estimated glomerular filtration rate 1, 2
• Hepatitis B surface antigen (HBsAg) 1, 2
• Hepatitis C antibody 1
• Three-site STI screening (genital and nongenital gonorrhea and chlamydia by NAAT) 1, 7
• Syphilis testing 1
• Pregnancy testing for individuals of childbearing potential 1, 7, 2

Monitoring Schedule During PrEP Use

Ongoing monitoring is essential for safe FTC/TAF use:

Every 3 Months

• Combined HIV antibody/antigen testing (prescriptions should not exceed 90 days without HIV testing) 1, 2
• Three-site STI screening 1, 2
• Syphilis testing 1
• Pregnancy testing for individuals of childbearing potential 1, 2
• Assessment of adherence and risk behaviors 2

Every 6-12 Months

• Serum creatinine and estimated glomerular filtration rate 1, 2
• More frequent renal monitoring required for patients >50 years, taking hypertension/diabetes medications, or baseline eGFR <90 mL/min 1, 2
• Hepatitis C serologic testing (at least annually, more frequently with elevated transaminases or in people who inject drugs) 6

Initial Follow-Up

• Visit at 1 month after initiation recommended for HIV testing, adverse effect assessment, and adherence support 1

Dosing and Administration

Standard dosing for FTC/TAF PrEP:

• Emtricitabine 200 mg/tenofovir alafenamide 25 mg once daily 1, 2
• Can be taken with or without food 5
• A 7-day lead-in period is recommended before adequate tissue levels are achieved for protection 6, 1
• After discontinuation, continue for 1 week after last sexual exposure 6

Special Population Considerations

Pregnancy and Breastfeeding

• FTC/TAF is safe during pregnancy with no documented adverse fetal effects 1
• TAF and tenofovir are present in human milk, but no adverse effects on breastfed children have been reported 5
• Continue FTC/TAF during pregnancy and breastfeeding as the preferred regimen 1

Hepatitis B Co-infection

• For HBsAg-positive individuals, discontinuation of FTC/TAF can lead to acute hepatitis B flares or hepatic decompensation, particularly with cirrhosis 6
• Consider indefinite continuation or transition to hepatitis B treatment if PrEP is stopped 1
• Monitor closely with ALT/AST testing after discontinuation 1

Cisgender Women

• Critical limitation: FTC/TAF is NOT currently recommended as first-line PrEP for cisgender women 7, 2
• Tenofovir concentrates at 10-fold lower levels in vaginal tissue compared to rectal tissue, with faster clearance 7
• For women at risk through vaginal exposure, FTC/TDF remains the only approved and effective option 7, 2
• Daily dosing is especially critical for women to maintain adequate drug levels in vaginal tissue 7

Adolescents

• Adolescents are classified in the same category as adults for PrEP prescribing 1
• Enhanced adherence counseling is recommended for all adolescents initiating PrEP 1

Pharmacokinetic Considerations

Understanding drug levels is important for adherence monitoring:

• Plasma TAF has a terminal elimination half-life of 0.6 hours, TFV 31.6 hours, and FTC 6.9 hours 8
• Intracellular TFV-diphosphate and FTC-triphosphate (the active metabolites) remain stable over 24 hours at approximately 1,000-1,500 and 2,000-3,000 fmol/punch respectively 8
• Intracellular levels vary widely among individuals but remain stable within each individual, making them useful for adherence monitoring 8
• Plasma concentrations do not directly affect intracellular concentrations of active metabolites 8

Cost and Access Considerations

• FTC/TAF is approximately 30 times more expensive per 30-tablet supply than FTC/TDF 9
• In a Scottish sexual health service evaluation, only 0.4% (7/1,744) of PrEP patients were initiated on FTC/TAF, with the majority (6/7) for renal reasons and one for bone mineral density concerns 9
• All patients in this evaluation met appropriate eligibility criteria, demonstrating judicious use 9
• Financial forecasting should account for selective use based on specific clinical indications 9

Common Pitfalls to Avoid

Critical errors to prevent in FTC/TAF PrEP prescribing:

• Never prescribe FTC/TAF to cisgender women as first-line PrEP - insufficient evidence for vaginal protection; use FTC/TDF instead 7, 2
• Never prescribe without confirming HIV-negative status - risk of developing resistance if HIV-positive 2
• Never exceed 90-day prescriptions without interval HIV testing - mandatory safety requirement 1, 2
• Never discontinue abruptly in HBsAg-positive patients - risk of severe hepatitis flares 6, 1
• Never assume immediate protection - require 7-day lead-in period for adequate tissue levels 6, 1
• Never prescribe for ESRD patients not on chronic hemodialysis - safety not established 5

Transition from PEP to PrEP

For patients completing post-exposure prophylaxis with ongoing risk:

• Immediate transition from nPEP to PrEP is beneficial for persons with anticipated repeat or ongoing HIV exposures 6
• Perform HIV testing at completion of nPEP regimen before transitioning to PrEP 6
• This seamless transition is recommended to maintain continuous protection 6