View source for HIV Pre-exposure prophylaxis

HIV pre-exposure prophylaxis (PrEP) is the use of antiretroviral medications by HIV-negative individuals to prevent acquisition of [[HIV - AIDS (main)|HIV]] infection. When taken as directed, PrEP reduces the risk of HIV acquisition through sex by >99%.<ref name="CDC2025">CDC. Clinical Guidance for PrEP. HIV Nexus. Updated 2025.</ref> 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)<ref name="MMWR2025">CDC. Clinical Recommendation for the Use of Injectable Lenacapavir as HIV Preexposure Prophylaxis — United States, 2025. ''MMWR''. 2025;74(35).</ref>
*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<ref name="MMWR2025"/>
*Four FDA-approved PrEP options (as of 2025):<ref name="CDC2025"/>
**'''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|lenacapavir]]''' (Yeztugo) — SC injection every 6 months; all sexual exposure types<ref name="MMWR2025"/>
*'''On-demand (2-1-1) PrEP''' with TDF/FTC is an off-label option for MSM only (not for other populations)<ref name="NYSDOH">NYSDOH AI. PrEP to Prevent HIV and Promote Sexual Health. Clinical Guidelines Program. 2025.</ref>

==Clinical Features==
===Patients requesting PrEP in the ED===
*Individuals presenting after a sexual encounter who are concerned about HIV risk but do '''not''' meet [[HIV post-exposure prophylaxis|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==
*[[HIV post-exposure prophylaxis|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:'''<ref name="CDC2025"/>
*'''HIV Ag/Ab combination (4th generation) test''' — required to confirm HIV-negative status
**If starting injectable PrEP ([[Lenacapavir|lenacapavir]] or cabotegravir), also send '''HIV-1 RNA''' (viral load). For lenacapavir, initiation should not be delayed while awaiting RNA result<ref name="MMWR2025"/>
**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)<ref name="CDC2025"/>
*'''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<ref name="CDC2025"/>
*Per CDC, prescribers should '''offer PrEP to anyone who asks''', including those who do not report specific risk factors<ref name="CDC2025"/>
*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:<ref name="CDC2025"/>
**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):<ref name="NYSDOH"/>
**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<ref name="CDC2025"/>
*Transition to a complete HIV treatment regimen (consult [[HIV - AIDS (main)|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: '''C'''arbamazepine, '''O'''xcarbazepine, '''P'''henobarbital, '''P'''henytoin, '''E'''nzalutamide, '''R'''ifampin<ref name="NYSDOH"/>

==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==
*[https://www.cdc.gov/hivnexus/hcp/prep/index.html CDC Clinical Guidance for PrEP]
*[https://www.hivguidelines.org/guideline/hiv-prep/ NYSDOH AI PrEP Guidelines]
*[https://www.hivprep.uw.edu/ National HIV PrEP Curriculum (University of Washington)]

==References==
{{reflist|2}}