What are the recommended HIV pre‑exposure prophylaxis (PrEP) dosing regimens for adults—including daily oral Truvada (tenofovir disoproxil fumarate 300 mg + emtricitabine 200 mg), on‑demand 2‑1‑1 schedule for men who have sex with men and transgender women, daily oral Descovy (tenofovir alafenamide 25 mg + emtricitabine 200 mg), and long‑acting injectable cabotegravir 600 mg—and what monitoring and contraindications apply?

HIV Pre-Exposure Prophylaxis (PrEP) Dosing Regimens

Daily oral tenofovir disoproxil fumarate/emtricitabine (TDF/FTC, Truvada) 300 mg/200 mg remains the first-line PrEP regimen for all populations at risk of HIV acquisition, with proven efficacy exceeding 90% when adherence is maintained. 1

Oral PrEP Regimens by Population

Daily TDF/FTC (Truvada) – Universal First-Line Option

For Men Who Have Sex with Men (MSM):

• Initiate with a double dose (2 tablets) on day 1, followed by 1 tablet daily thereafter to achieve maximal protection within 24 hours 1
• When discontinuing, continue dosing for 2 days after the last at-risk sexual exposure 1
• Protection is achieved within 24 hours of the loading dose for rectal exposures 1

For Cisgender Women and Others with Vaginal/Neovaginal Exposures:

• Initiate with a double dose (2 tablets) on day 1, followed by 1 tablet daily 1
• Maximum protection requires approximately 7 days of daily dosing 1
• When discontinuing, continue dosing for at least 7 days after the last sexual activity 1
• Recent pooled data from 6,296 cisgender women demonstrated HIV incidence of only 0.13 per 100 person-years with consistently high adherence (4-6 doses/week), with zero infections among those taking daily doses 2

For Pregnant or Breastfeeding Individuals:

• Daily TDF/FTC is the recommended regimen (evidence rating: AIIa) 1
• Long-acting cabotegravir has growing safety data in pregnancy and can be used safely (evidence rating: BIIa) 1

On-Demand (2-1-1) TDF/FTC Dosing – MSM Only

This event-driven regimen is recommended exclusively for cisgender men and others having planned receptive anal sex (not for vaginal exposures or injection drug use prevention) 1:

• 2 tablets taken 2-24 hours before sexual activity
• 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

Critical caveat for transgender women: When using 2-1-1 dosing with gender-affirming hormone therapy, administer TDF/FTC with food because rectal tissue concentrations of tenofovir-diphosphate may be lower early in the regimen, which food intake largely mitigates 1

Daily TAF/FTC (Descovy) – Limited Indications

Descovy is restricted to cisgender men and transgender women whose exposures do NOT include receptive vaginal sex or injection drug use alone 1, 3:

• Dosing: 1 tablet (emtricitabine 200 mg/tenofovir alafenamide 25 mg) once daily 3
• No loading dose is required (unlike TDF/FTC) 3
• Not recommended for on-demand (2-1-1) dosing 3

Specific indications for TAF/FTC over TDF/FTC:

• MSM with creatinine clearance between 30-60 mL/min 1, 3
• Individuals with known osteopenia or osteoporosis 1, 3
• Those at high risk for bone or renal complications 1

The DISCOVER trial demonstrated non-inferior efficacy of TAF/FTC compared to TDF/FTC in MSM, with improved bone and renal safety biomarkers, though clinical correlates of these differences have not been definitively demonstrated 1, 4

Long-Acting Injectable Cabotegravir – Emerging Option

Injectable cabotegravir 600 mg every 8 weeks is recommended for cisgender men and transgender women who have sex with men 1:

• A randomized trial of 4,570 MSM and transgender women was stopped early for superiority, showing cabotegravir reduced HIV acquisition by 78% compared to daily TDF/FTC (HR = 0.22,95% CI: 0.08-0.59) 1, 5
• Injection site reactions are more common than with oral PrEP, but non-injection-related adverse events are comparable 5
• Less decrease in creatinine clearance compared to TDF/FTC 5
• Can be used safely in pregnancy and breastfeeding with growing pharmacokinetic data 1

Pre-Initiation Requirements – Mandatory Testing

Before starting any PrEP regimen, the following tests are required 1, 6:

• Combined HIV antibody and antigen testing (HIV RNA if clinical suspicion of acute HIV exists) 1
• Serum creatinine and estimated creatinine clearance 1, 6
• Hepatitis B surface antigen 1
• Hepatitis C antibody (if not previously positive) 1
• Hepatitis A antibody for MSM and people who inject drugs 1
• Gonorrhea and chlamydia testing (genital and non-genital sites by NAAT) 1

Critical warning: PrEP should not be initiated until HIV RNA results confirm uninfected status when acute HIV infection is suspected, as starting PrEP in undiagnosed acute HIV can lead to resistance (though this remains rare at <0.1%) 1, 7

Monitoring During PrEP

For Oral TDF/FTC or TAF/FTC:

At 1 Month:

• Combined HIV antibody and antigen test 1

Every 3 Months (Quarterly):

• Combined HIV antibody and antigen test 1
• Estimated creatinine clearance (at first quarterly visit, then annually if stable) 1
• Gonorrhea and chlamydia testing (genital and non-genital by NAAT) 1
• Syphilis testing 1
• Pregnancy testing for individuals of childbearing potential 1

Annually:

• Hepatitis C antibody (every 3-6 months for people who inject drugs and MSM using recreational drugs during sex if liver function is abnormal) 1

Enhanced Renal Monitoring for High-Risk Patients:

Monitor creatinine clearance every 1-3 months for patients with 6:

• Baseline creatinine clearance 60-90 mL/min 6
• Concurrent antihypertensive or diabetes medications 6
• Decompensated cirrhosis, poorly controlled hypertension, proteinuria, uncontrolled diabetes, active glomerulonephritis, concurrent nephrotoxic drugs, or solid-organ transplantation 6

If creatinine clearance falls below 60 mL/min or serum phosphate drops below 2 mg/dL, increase monitoring frequency 6

For TAF/FTC (Descovy):

Due to improved renal safety profile, creatinine clearance monitoring is required at the first quarterly visit (3 months) and then annually thereafter 3, 6

Contraindications

TDF-based PrEP is contraindicated when:

• Creatinine clearance is <60 mL/min 6
• Undiagnosed or confirmed HIV infection exists 3

TAF/FTC (Descovy) should not be used for:

• Cisgender women or anyone with receptive vaginal/neovaginal exposures 1, 3
• Prevention through injection drug use alone 1
• On-demand (2-1-1) dosing schedules 3

Adherence and Efficacy Relationship

The efficacy of oral PrEP is highly adherence-dependent 7, 2:

• Daily dosing or 4-6 doses per week provides >90% protection 1, 2
• For rectal exposures, 2 or more doses per week provides an estimated 79-88% reduction in HIV acquisition 1
• Zero HIV infections occurred among women with consistently daily adherence in pooled analysis 2

Common Pitfalls to Avoid

Do not prescribe TAF/FTC (Descovy) for cisgender women – insufficient data exist for vaginal exposures, and this is explicitly not indicated 1, 3

Do not use on-demand (2-1-1) dosing for vaginal exposures or injection drug use prevention – this schedule is validated only for receptive anal sex in cisgender men 1

Do not forget the loading dose for TDF/FTC – the double dose on day 1 is critical for MSM to achieve rapid protection 1

Do not initiate PrEP without recent HIV testing (ideally within 7 days using combination antigen/antibody assay) to avoid inadvertent prescription during acute HIV infection 1, 7

Limit prescription durations to ≤90 days without interval laboratory testing to align with quarterly monitoring requirements 6