HIV Pre-exposure prophylaxis

HIV pre-exposure prophylaxis (PrEP) is the use of antiretroviral medications by HIV-negative individuals to prevent acquisition of HIV infection. When taken as directed, PrEP reduces the risk of HIV acquisition through sex by >99%. Emergency physicians encounter PrEP in three key contexts: initiating PrEP or bridging to outpatient care after high-risk exposures, managing adverse effects of PrEP medications, and recognizing HIV seroconversion in patients on PrEP.

Note: PrEP is for pre-exposure prevention in HIV-negative individuals. For management after a specific exposure event, see HIV post-exposure prophylaxis.

Background

• ~39,000 new HIV diagnoses annually in the United States (2023)
• An estimated 2.2 million Americans could benefit from PrEP; uptake and adherence remain suboptimal — ~50% of oral PrEP users discontinue within 6–12 months
• Four FDA-approved PrEP options (as of 2025):
  • Oral TDF/FTC (Truvada or generic) — daily pill; all exposure types including injection drug use
  • Oral TAF/FTC (Descovy) — daily pill; sexual transmission only; not approved for receptive vaginal sex
  • Injectable cabotegravir (Apretude) — IM injection every 2 months; all sexual exposure types
  • Injectable lenacapavir (Yeztugo) — SC injection every 6 months; all sexual exposure types
• On-demand (2-1-1) PrEP with TDF/FTC is an off-label option for MSM only (not for other populations)

Clinical Features

Patients requesting PrEP in the ED

• Individuals presenting after a sexual encounter who are concerned about HIV risk but do not meet PEP criteria (>72 hours since exposure, or ongoing risk rather than a discrete exposure)
• Patients who have lapsed on their PrEP regimen and want to restart
• Patients identified as high-risk during STI evaluation, sexual assault workup, or other encounters

Patients on PrEP presenting with adverse effects

• TDF/FTC: Renal dysfunction (rising creatinine, Fanconi syndrome — see Tenofovir), bone pain, GI symptoms
• TAF/FTC: Weight gain, dyslipidemia, GI symptoms
• Cabotegravir: Injection site reactions (pain, nodules, induration), headache
• Lenacapavir: Injection site reactions (including persistent subcutaneous nodules lasting months), nausea, headache

Patients on PrEP with possible HIV seroconversion

• Acute retroviral syndrome symptoms: Fever, pharyngitis, lymphadenopathy, rash, myalgias, fatigue (flu-like illness 2–4 weeks after exposure)
• May present despite being on PrEP — breakthrough infections occur, usually with nonadherence to oral regimens

Differential Diagnosis

• Acute HIV exposure requiring PEP (discrete exposure <72 hours ago)
• Acute HIV seroconversion / Acute HIV
• Adverse drug reaction to PrEP medication
• STI (concurrent evaluation should occur)
• Other causes of flu-like illness (if evaluating for seroconversion)

Evaluation

Workup

Before initiating or restarting PrEP:

• HIV Ag/Ab combination (4th generation) test — required to confirm HIV-negative status
  • If starting injectable PrEP (lenacapavir or cabotegravir), also send HIV-1 RNA (viral load). For lenacapavir, initiation should not be delayed while awaiting RNA result
  • If recently on PrEP (oral in last 3 months, cabotegravir injection in last 12 months), must test with both Ag/Ab and HIV-1 RNA (PrEP medications can delay seroconversion and cause false-negative antibody tests)
• Serum creatinine (for TDF/FTC and TAF/FTC candidates)
  • TDF/FTC: Not recommended if CrCl <60 mL/min
  • TAF/FTC: Not recommended if CrCl <30 mL/min
  • Cabotegravir and lenacapavir: No renal restrictions (except not studied in CrCl <15)
• Hepatitis B serologies (HBsAg, HBsAb, HBcAb) — TDF/FTC and TAF/FTC have anti-HBV activity; stopping them in co-infected patients risks HBV flare. Cabotegravir and lenacapavir do not treat HBV
• STI screening (gonorrhea, chlamydia at relevant sites; syphilis; hepatitis C if risk factors)
• Pregnancy test in individuals of childbearing potential
• No signs or symptoms of acute HIV (fever, rash, pharyngitis, lymphadenopathy arising 2–4 weeks after a known exposure)

If evaluating for seroconversion in a patient on PrEP:

• HIV Ag/Ab combination test and HIV-1 RNA viral load
• CBC, CMP (for general assessment)

Diagnosis

• PrEP is indicated for any HIV-negative adult or adolescent ≥35 kg who would benefit from HIV prevention
• Per CDC, prescribers should offer PrEP to anyone who asks, including those who do not report specific risk factors
• If acute HIV infection is suspected, send HIV-1 RNA — the Ag/Ab test may be negative in very early infection

Management

Same-day PrEP initiation from the ED

• The ED can serve as an access point for PrEP initiation, particularly for patients with barriers to primary care
• Same-day start is possible if:
  • HIV Ag/Ab test is negative (rapid test acceptable)
  • No signs/symptoms of acute HIV
  • Creatinine and pregnancy test obtained (results can be pending for injectable regimens)
• Oral TDF/FTC (Truvada) is the simplest to initiate from the ED:
  • 300 mg TDF / 200 mg FTC — 1 tablet PO once daily
  • Prescribe a 30-day supply with outpatient follow-up for ongoing management
  • Counsel: Take daily with or without food; efficacy depends on adherence
• On-demand (2-1-1) dosing (off-label, MSM only):
  • 2 tablets of TDF/FTC taken 2–24 hours before sex
  • 1 tablet 24 hours after the first dose
  • 1 tablet 48 hours after the first dose
• Injectable options (cabotegravir, lenacapavir) are typically initiated in outpatient settings; refer if patient prefers injectable PrEP

If a patient on PrEP tests HIV-positive

• Discontinue PrEP immediately — PrEP regimens are inadequate for HIV treatment and continued use will select for drug resistance
• Transition to a complete HIV treatment regimen (consult HIV/ID)
• Resistance testing should be performed (particularly important with cabotegravir and lenacapavir given long half-lives)

Managing PrEP adverse effects in the ED

• TDF nephrotoxicity: Check creatinine, phosphorus, UA for glycosuria. If Fanconi syndrome or AKI → hold TDF, consult ID for regimen change (see Tenofovir)
• Injection site reactions (cabotegravir/lenacapavir): Usually self-limited. Lenacapavir nodules may persist ~6 months. If severe erythema, fluctuance, or necrosis → evaluate for improper intradermal injection or abscess
• Hepatitis B flare after PrEP discontinuation: Check LFTs, HBV DNA viral load. May need urgent restart of HBV-active therapy (see Tenofovir, Emtricitabine, Lamivudine)

Key drug interactions to know

• TDF/FTC: Avoid NSAIDs in patients with renal risk factors; avoid concurrent nephrotoxins
• Cabotegravir: Contraindicated with rifampin and certain anticonvulsants (strong enzyme inducers)
• Lenacapavir: CYP3A4 interactions — remember COPPER mnemonic for inducers: Carbamazepine, Oxcarbazepine, Phenobarbital, Phenytoin, Enzalutamide, Rifampin

Disposition

• Discharge with PrEP prescription and outpatient follow-up within 1 month for:
  • HIV testing (repeat at 3 months, then quarterly for oral PrEP; at each injection visit for injectables)
  • Renal function monitoring (for tenofovir-based regimens)
  • STI screening (every 3–6 months)
  • Ongoing adherence counseling
• Refer to HIV PrEP clinic or primary care for long-term management, injectable PrEP initiation, or patients with complex needs (hepatitis B co-infection, renal impairment, pregnancy)
• Admit if:
  • Suspected acute HIV seroconversion with severe systemic illness
  • Significant TDF nephrotoxicity (AKI requiring observation or intervention)
  • Severe hepatitis B flare after PrEP discontinuation

See Also

• HIV - AIDS (main)
• HIV post-exposure prophylaxis
• Immune reconstitution syndrome
• Emtricitabine/tenofovir
• Tenofovir
• Lenacapavir

External Links

• CDC Clinical Guidance for PrEP
• NYSDOH AI PrEP Guidelines
• National HIV PrEP Curriculum (University of Washington)