How is pre‑exposure prophylaxis (PrEP) for HIV evaluated and initiated, including eligibility criteria, baseline testing (fourth‑generation antigen/antibody test, estimated glomerular filtration rate, hepatitis B and C status, pregnancy status, CBC, lipid panel), medication options (Truvada (emtricitabine/tenofovir disoproxil fumarate), Descovy (emtricitabine/tenofovir alafenamide), Apretude (cabotegravir) and on‑demand 2‑1‑1 schedule), dosing regimens, and follow‑up monitoring?

Pre-Exposure Prophylaxis (PrEP) for HIV Prevention: Evaluation and Implementation

Offer PrEP to all sexually active individuals, anyone requesting it, and those using nonprescription drugs or substances, without requiring specific risk criteria or screening tools. 1

Eligibility and Patient Selection

Universal Offer Approach

• Adopt a serostatus-neutral approach where all individuals testing HIV-negative are informed about and navigated to PrEP services if desired, eliminating stigma-based barriers. 1
• PrEP should be discussed with all sexual partners of individuals with HIV, those who share injection drug equipment with persons of unknown HIV status, and anyone requesting PrEP regardless of perceived risk level. 1
• For monogamous partners of persons with HIV who are virally suppressed (<200 copies/mL) on ART, deferring PrEP is reasonable, but providing it upon request is also appropriate due to possible undisclosed exposures. 1

Pre-Initiation Testing Requirements

Mandatory Baseline Laboratory Work

Before prescribing PrEP, obtain the following tests: 2, 3, 4

• HIV testing: Combined fourth-generation HIV antibody/antigen test (laboratory-based, not rapid only) 1, 2
• HIV RNA test if available, particularly for high-risk individuals or those with recent exposures within the past month 1, 3
• Renal function: Serum creatinine with calculated estimated glomerular filtration rate (eGFR) or creatinine clearance 2, 5, 4
• Hepatitis B surface antigen (HBsAg) 2, 3
• Hepatitis C antibody (IgG) 2, 3
• STI screening: Nucleic acid amplification testing (NAAT) for gonorrhea and chlamydia at all exposure sites (genital, rectal, pharyngeal), plus syphilis serology 2, 3
• Pregnancy test for individuals of childbearing potential 2, 3

Critical Pre-Initiation Caveat

TDF-based PrEP is contraindicated when creatinine clearance is <60 mL/min/1.73 m². 5, 4

Medication Options and Dosing Regimens

First-Line: Daily Oral TDF/FTC (Truvada)

Standard dosing for all populations: Tenofovir disoproxil fumarate 300 mg/emtricitabine 200 mg once daily. 1, 2, 3

Population-Specific Initiation Strategies

For cisgender men who have sex with men (MSM): 2, 3

• Loading dose: 2 tablets (600 mg/400 mg) on day 1, then 1 tablet daily thereafter
• This achieves maximal protection within 24 hours of the double dose
• When stopping PrEP, continue daily dosing for 2 days after the last at-risk exposure

For cisgender women, transgender women, and persons with vaginal/neovaginal/"front-hole" exposures: 2, 3

• No loading dose—start with standard single-tablet dose (300 mg/200 mg) once daily
• Requires approximately 7 days of daily dosing to achieve full protective effect
• When stopping PrEP, continue daily dosing for 7 days after the last at-risk exposure
• Daily dosing is mandatory—on-demand dosing is NOT recommended for vaginal exposures due to 10-fold lower tenofovir concentrations in vaginal tissue compared to rectal tissue

For persons who inject drugs (PWID): 3

• Use the same standard daily dosing regimen (300 mg/200 mg once daily)

Alternative Dosing: On-Demand "2-1-1" Schedule

Only for cisgender MSM with planned receptive anal sex: 1, 2, 3

• 2 tablets taken together 2-24 hours before sexual activity
• 1 tablet 24 hours after the first dose
• 1 tablet 48 hours after the first dose
• This regimen is NOT validated for women or other populations

Second-Line: Daily Oral TAF/FTC (Descovy)

Tenofovir alafenamide 25 mg/emtricitabine 200 mg once daily should be considered ONLY for: 2, 3

• MSM with creatinine clearance 30-60 mL/min
• MSM with osteopenia, osteoporosis, or high risk for bone complications
• TAF/FTC lacks efficacy data for receptive vaginal sex and should NOT be used as first-line for cisgender women 3

Third-Line: Long-Acting Injectable Cabotegravir (Apretude)

Injectable cabotegravir every 8 weeks is recommended where available and approved. 1, 2

Rapid PrEP Initiation

Same-Day Start Protocol

• If HIV test results from within the past 7 days are negative, initiate PrEP immediately while awaiting further diagnostics and safety assessments. 1
• If no recent HIV test is available, conduct testing and initiate PrEP once results are negative, assuming reliable remote communication for follow-up. 1
• Asymptomatic individuals who are HIV-seronegative by rapid assay can start daily oral TDF/FTC without awaiting baseline creatinine, HBsAg, STI, or fourth-generation HIV assay results. 1

Post-Exposure Prophylaxis (PEP) to PrEP Transition

• For individuals completing a 28-day course of 3-drug PEP who remain at ongoing risk, transition seamlessly from PEP to PrEP after a negative fourth-generation HIV test at PEP completion. 1
• If substantial HIV exposure occurred within 72 hours, initiate 3-drug PEP first, then transition to PrEP. 1

Follow-Up Monitoring Schedule

HIV Testing

• At 1 month after initiation, then every 3 months thereafter. 2, 3, 4
• Use combined HIV antibody/antigen testing at each visit. 2, 3
• For long-acting cabotegravir PrEP, use rapid HIV antibody test plus laboratory-based antigen/antibody test—routine RNA testing is NOT recommended. 1
• If RNA testing is unavailable, repeat antigen/antibody testing 1 month after starting or resuming tenofovir-based oral PrEP. 1

Renal Function Monitoring

For TDF/FTC (Truvada): 5

• Baseline serum creatinine and eGFR
• At 1 month after initiation
• Every 3 months during the first year
• Every 6 months thereafter if renal function remains stable

For patients at higher renal risk (baseline CrCl 60-90 mL/min, diabetes, hypertension, age >50, concurrent nephrotoxic drugs, proteinuria, cirrhosis, transplant): 5

• Monitor every 1-3 months

For TAF/FTC (Descovy): 5

• Creatinine clearance at first quarterly visit (3 months), then annually thereafter

STI Screening

• Every 3 months: NAAT for gonorrhea and chlamydia at all exposure sites, plus syphilis serology. 2, 3

Pregnancy Testing

• Every 3 months for individuals of childbearing potential. 2, 3

Prescription Duration Limits

• PrEP prescriptions should not exceed 90 days without interval HIV testing. 2, 5

Special Populations

Pregnancy and Breastfeeding

• TDF/FTC is safe during pregnancy and breastfeeding with no documented adverse fetal effects—continue PrEP throughout. 2, 3
• Long-acting cabotegravir has a growing safety profile in pregnancy and breastfeeding. 2

Chronic Hepatitis B (HBsAg-Positive)

• Consider indefinite continuation of TDF/FTC or transition to hepatitis B treatment if stopping PrEP, as discontinuation can cause severe hepatitis flares or hepatic decompensation. 3

Adolescents

• Adolescents weighing ≥35 kg are classified in the same category as adults for PrEP prescribing, with TDF/FTC as the preferred regimen. 3, 4

Critical Safety Considerations

Preventing Drug Resistance

• PrEP must never be prescribed without confirming HIV-negative status, as inadvertent use in HIV-positive persons can lead to drug-resistant virus (typically M184V/I mutation). 1, 6
• Resistance when PrEP is used correctly is rare (<0.1%) and usually occurs when initiated during undiagnosed acute HIV infection with false-negative antibody/antigen testing. 6

Condom Use

• Condoms are recommended for all penetrative sexual acts to prevent STIs, as PrEP does not protect against gonorrhea, chlamydia, syphilis, or other infections. 1, 3

Adherence Counseling

• Adherence is critical to PrEP efficacy—efficacy exceeds 90% with consistent daily use but is highly correlated with degree of adherence. 7, 6
• Assess adherence at every quarterly visit. 3

Bacterial STI Prevention (DoxyPEP)

• Doxycycline 200 mg within 72 hours after condomless sex is recommended for cisgender MSM and transgender women, regardless of HIV status. 1
• Dosing no more frequently than daily. 1
• Pharmacokinetic modeling suggests efficacy for vaginal exposures—recommend on a case-by-case basis for cisgender women at risk. 1
• Prescribe 30 doses (60 tablets/capsules) at a time. 1