Immune System

HIV post-exposure prophylaxis: occupational and non-occupational

Clinical Overview and When to Suspect HIV Exposure Requiring PEP

— Occupational PEP (oPEP): healthcare/laboratory workers exposed via needlestick, sharps, mucous membrane, or non-intact skin contact with blood/body fluids

— Non-occupational PEP (nPEP): sexual assault, consensual condomless sex with known/suspected HIV+ partner, injection drug use sharing, bite/splash exposures outside healthcare

— Initiate as soon as possible, ideally within 2 hours

— Maximum effective window: 72 hours from exposure; beyond 72 h PEP is generally not offered

— Hollow-bore needle from known HIV+ source with detectable viral load → high risk

— Receptive anal intercourse with HIV+ partner not on suppressive ART → highest per-act sexual risk (~138/10,000)

— Sexual assault → offer PEP empirically regardless of assailant serostatus (usually unknown)

— Shared injection equipment within 72 h

— Intact skin contact, kissing, human bites without blood exchange, exposure to urine/feces/sweat/tears/saliva (unless visibly bloody)

— Source known HIV-negative, or source on ART with documented sustained viral suppression (U=U) — clinical judgment still applies

Board pearl: The 72-hour clock starts at the moment of exposure, not at presentation — a patient presenting at hour 70 still gets PEP started in the ED before source testing returns. Never delay the first dose waiting for labs. Step 3 stems frequently bury the exposure time in the HPI; calculate it explicitly. PEP is prevention, not treatment — if the patient is already HIV+ at baseline, the regimen becomes inadequate ART and may select resistance.

Definition: HIV post-exposure prophylaxis (PEP) is a 28-day antiretroviral regimen initiated after a discrete potential exposure to HIV to prevent seroconversion

Two regulatory categories with overlapping pharmacology but different logistics:

Time window is the single highest-yield concept:

When to suspect a PEP-eligible event:

Exposures that generally do not warrant PEP:

Presentation Patterns and Key History

— What fluid: blood, semen, vaginal/rectal secretions, CSF, synovial, pleural, peritoneal, pericardial, amniotic = infectious; saliva/urine/tears/sweat = not infectious unless visibly bloody

— Where on body: percutaneous > mucous membrane > non-intact skin >> intact skin (not an exposure)

— When: exact hour of exposure → hours elapsed

— Who is the source: known HIV status? On ART? Most recent viral load? Hepatitis B/C status?

— Weapon/mechanism: hollow-bore vs solid suture needle, depth, visible blood on device, gloves worn

— Type of act (receptive anal > insertive anal > receptive vaginal > insertive vaginal > oral)

— Condom use and integrity, ejaculation, presence of genital ulcers/STIs (amplifies risk)

— Number of episodes, recency of last exposure

— In assault: forensic exam coordination, plan for STI prophylaxis, emergency contraception

— Prior HIV testing date and result

— Hepatitis B vaccination status and surface antibody

— Pregnancy status, contraception, breastfeeding

— Renal function history, current medications (drug–drug interactions)

— Symptoms suggestive of acute retroviral syndrome from a prior unrecognized exposure (fever, pharyngitis, lymphadenopathy, mononucleosis-like illness)

Step 3 management: Do not delay the first PEP dose to complete a perfect history — give dose one, then finish the interview. The classic stem: "healthcare worker stuck with hollow-bore needle 90 minutes ago, source is hospitalized patient with AIDS and VL 250,000." Answer: start tenofovir/emtricitabine + dolutegravir (or raltegravir) now, then obtain baseline labs and source testing.

Patients rarely present with symptoms — they present with an event and anxiety. Your history must rapidly establish PEP eligibility and risk magnitude

Exposure characterization (the "5 W's"):

Sexual exposure specifics:

Injection drug use: shared needle vs cooker/cotton, time since use, source person

Baseline patient assessment:

Physical Exam Findings and Wound/Site Assessment

— Percutaneous wound: wash with soap and water; do not squeeze, do not apply bleach or caustic agents (no proven benefit, increases tissue damage)

— Mucous membrane: copious water or saline irrigation for at least several minutes

— Eye: irrigate with saline or eyewash station; remove contact lenses after irrigation

— Document depth (superficial scratch vs deep puncture), bleeding, contamination

— For sexual assault: defer detailed genital exam to SANE (Sexual Assault Nurse Examiner) when available to preserve forensic evidence

— Lymphadenopathy (cervical, axillary, inguinal) — could indicate undiagnosed chronic HIV

— Oral thrush, hairy leukoplakia, generalized adenopathy → suggests baseline HIV, alters management

— Genital ulcers (HSV, syphilis chancre) → STI co-screening priority and amplifies HIV transmission risk

— Track marks, abscesses → IDU history corroboration

— Jaundice, hepatomegaly → hepatitis screening urgency

Key distinction: Findings of chronic HIV (oral candidiasis, generalized lymphadenopathy, wasting) on the patient receiving PEP suggest pre-existing infection — the appropriate response is to still start PEP empirically while running 4th-generation Ag/Ab testing, because a positive baseline test converts the regimen into early ART (which is beneficial) and prevents resistance from monotherapy. Never withhold the first dose for exam findings alone.

Physical exam in PEP encounters is focused, not comprehensive — it documents the exposure and screens for confounders

Immediate post-exposure site care (do before exam if not done):

Exposure site exam:

General exam findings to seek:

Vitals: generally normal; fever in a patient with recent prior exposure raises concern for acute HIV (seroconversion illness 2–4 weeks post-infection)

Pregnancy-relevant exam in reproductive-age patients: uterine size if late presentation, breast exam if breastfeeding

Diagnostic Workup — Baseline Labs at PEP Initiation

— 4th-generation HIV Ag/Ab immunoassay (HIV-1/2 antibody + p24 antigen) — establishes baseline status; if positive, halt PEP plan and transition to full ART workup

— HIV-1 RNA viral load if acute retroviral syndrome suspected or recent (<4 week) prior exposure

— Hepatitis B: HBsAg, anti-HBs, anti-HBc (determines need for HBIG and/or vaccination, and informs tenofovir choice)

— Hepatitis C: anti-HCV antibody (reflex to HCV RNA if positive)

— Syphilis: RPR or treponemal screen

— Gonorrhea/chlamydia NAAT (3-site: pharyngeal, rectal, urogenital based on exposure)

— Pregnancy test (β-hCG) in all persons capable of pregnancy

— CBC, CMP (creatinine for eGFR — guides tenofovir choice; ALT/AST for hepatotoxicity baseline)

— Urinalysis (proteinuria baseline before TDF)

— Rapid 4th-gen Ag/Ab assay — ideal turnaround <1 hour

— HIV viral load if known positive (informs transmission risk and resistance considerations)

— HBsAg, anti-HCV

— If source tests negative on 4th-gen Ag/Ab and is not in an active high-risk window, PEP can be discontinued — major time/cost savings

CCS pearl: Order set for needlestick — "HIV Ag/Ab, HCV Ab, HBsAg, anti-HBs, CMP, CBC, UA, β-hCG, RPR" on both exposed and source (source with consent). Simultaneously order "tenofovir-emtricitabine 1 tab PO now" and "dolutegravir 50 mg PO now." Sequence matters less than concurrency on Step 3 CCS — clock advances either way.

Critical principle: Order labs but do not wait for results before giving the first PEP dose

Exposed person baseline panel:

Source person testing (with consent where required):

For sexual assault: add emergency contraception assessment, forensic kit per protocol, and STI empiric treatment (ceftriaxone + doxycycline + metronidazole)

Diagnostic Workup — Follow-Up Testing Schedule

— Baseline (day 0)

— 6 weeks post-exposure

— 12 weeks (3 months) post-exposure

— 6 months is no longer routinely required with 4th-gen assays unless HCV co-exposure occurred (HCV can delay HIV seroconversion) — in that case test at 6 and 12 months

— Any febrile/mono-like illness during PEP or in the surveillance window → HIV RNA viral load (not just Ag/Ab) to catch acute infection

— Symptoms of acute HIV: fever, pharyngitis, rash, myalgia, lymphadenopathy, mucocutaneous ulcers

— 2-week check: creatinine, AST/ALT, adherence assessment, side-effect review

— 4-week (end of PEP): repeat CMP, urinalysis, and counsel on continued surveillance

— HBV-susceptible exposed persons: complete vaccine series; check anti-HBs at 1–2 months after series

— HCV-exposed: HCV RNA at 3–6 weeks (early viremia detection allows curative DAA therapy), HCV Ab at 6 months

Board pearl: A 4th-gen HIV Ag/Ab negative at 12 weeks effectively rules out seroconversion in the setting of completed PEP — patient can be reassured. The exception: simultaneous HCV exposure, which prolongs the HIV window to 6 months. Memorize the "6w / 12w (/6mo if HCV)" cadence — it's a recurring Step 3 distractor.

PEP is not complete at day 28; serologic surveillance confirms prevention success

Standard follow-up HIV testing schedule (CDC) using 4th-generation Ag/Ab assay:

If older 3rd-generation (antibody-only) assays are used, extend testing to 6 months

Interim symptomatic testing:

On-treatment monitoring labs (during the 28-day course):

Hepatitis follow-up:

STI follow-up after sexual exposure: repeat GC/CT NAAT and syphilis at 4–6 weeks and 3 months

Risk Stratification and Decision Logic for Offering PEP

— <72 hours → eligible

— ≥72 hours → not recommended (efficacy approaches zero; consider PrEP enrollment instead)

— Known HIV+ with detectable viremia → strongest indication

— Known HIV+ on ART with sustained undetectable viral load (≥6 months) → transmission risk effectively zero (U=U); PEP generally not required but offer if patient anxious or source confirmation incomplete

— Unknown status, high-prevalence population/behavior (MSM, IDU, commercial sex work, from endemic region) → offer PEP

— Unknown status, low-prevalence → individualized; often start and reassess after source testing

— Known HIV-negative source → PEP not indicated

— Blood transfusion: 9,250/10,000

— Needle-sharing IDU: 63/10,000

— Percutaneous needlestick: 23/10,000

— Receptive anal sex: 138/10,000

— Insertive anal sex: 11/10,000

— Receptive vaginal: 8/10,000; insertive vaginal: 4/10,000

— Oral sex: <1/10,000 (PEP usually not offered unless ejaculation + oral lesions)

Step 3 management: When the source is untraceable (discarded needle in community, anonymous assailant), default to offering PEP — the population-prevalence assumption favors treatment when exposure type carries meaningful risk. Document shared decision-making. Conversely, a needlestick from a known virally suppressed patient with documented recent undetectable VL is a defensible no-PEP decision, though many institutions still offer a starter pack.

PEP recommendation rests on three axes: exposure type, source HIV status, and time elapsed

Time axis (absolute):

Source HIV status:

Exposure-type risk (per-act, source known HIV+):

Sexual assault: offer PEP regardless of assailant status when any genital/anal penetration occurred within 72 h

Pharmacotherapy — First-Line PEP Regimen

— Tenofovir disoproxil fumarate (TDF) 300 mg + emtricitabine (FTC) 200 mg once daily (co-formulated as Truvada)

— PLUS dolutegravir (DTG) 50 mg once daily — preferred integrase strand transfer inhibitor (INSTI)

— Alternative INSTI: raltegravir 400 mg BID or bictegravir (as part of Biktarvy single-tablet regimen with TAF/FTC)

— INSTIs have rapid viral suppression, high barrier to resistance, excellent tolerability

— TDF/FTC has decades of safety data and dual HBV activity (covers a co-exposure)

— TAF/FTC (Descovy) instead of TDF/FTC if eGFR 30–60 or osteoporosis concern — less nephrotoxic, less bone loss

— Darunavir/ritonavir as PI option if INSTI contraindicated

— Avoid: nevirapine (hepatotoxicity, SJS), abacavir without HLA-B*5701 testing, efavirenz first-line (CNS side effects, teratogenicity concerns historical)

— TDF: nausea, headache, renal tubulopathy, bone density loss

— FTC: generally well tolerated; hyperpigmentation

— DTG: insomnia, headache, weight gain; rare hypersensitivity

— All: GI upset early; usually self-limited

— DTG + polyvalent cations (Ca, Mg, Fe, Al antacids): separate by 2 h before or 6 h after

— Rifampin reduces DTG levels → double DTG to 50 mg BID

Board pearl: First-line PEP = TDF/FTC + DTG (or raltegravir). The single most testable substitution: switch DTG to raltegravir 400 mg BID in pregnancy if conception is imminent or first trimester — though current evidence largely exonerates DTG of neural tube defect risk, raltegravir remains a safe alternative.

Current preferred regimen (CDC 2016 oPEP; 2025 nPEP guidance — 3-drug standard for ALL exposures):

Duration: 28 days, continuous; counsel that interruption reduces efficacy

Why this regimen:

Alternative/second-line agents:

Side effects to counsel:

Drug interactions:

Pharmacotherapy — Adherence, First Dose, and Starter Packs

— Administer in the encounter — do not send the patient to an outside pharmacy without dosing

— Most EDs and occupational health clinics stock 5–7 day starter packs; bridge prescription written for the remaining 21–23 days

— Single daily fixed-dose combinations improve adherence (e.g., Biktarvy = TAF/FTC/BIC one pill daily)

— Text reminders, follow-up call at 72 h and 1 week

— Anti-emetic prophylaxis (ondansetron) PRN for early GI side effects

— Counsel: "missing a dose is not failure — take next dose as soon as remembered; do not double up if near next dose"

— Occupational PEP: covered by workers' compensation / employer health

— Non-occupational PEP: many manufacturers offer patient assistance programs; Ready, Set, PrEP federal program; Medicaid coverage varies

— Sexual assault: covered under Violence Against Women Act funds and state crime victim compensation

— Patients with ongoing risk behavior should be assessed at the end of PEP for PrEP (TDF/FTC or TAF/FTC daily, or long-acting cabotegravir injection q2 months)

— Seamless transition: confirm HIV-negative at end of PEP, then continue same NRTI backbone as PrEP without interruption

— If source has known drug-resistant HIV, consult HIV specialist immediately for tailored regimen

— Empiric PEP with INSTI + 2 NRTIs covers most resistance patterns until source genotype available

Step 3 management: A patient on PEP who reports recurrent exposures during the 28-day course should be transitioned directly to PrEP at PEP completion without a drug-free interval. This is a high-yield ambulatory transition point — Step 3 loves transitions of care.

First dose logistics:

Adherence strategies — completion rates historically only 50–60%:

Cost and access:

Transitioning PEP to PrEP:

Resistance considerations:

Special Populations — Renal Impairment and Elderly

— eGFR ≥60 mL/min: standard TDF/FTC + DTG once daily

— eGFR 30–59 mL/min: preferred switch to TAF/FTC + DTG (TAF has minimal renal/bone toxicity); or extend TDF dosing interval (TDF 300 mg q48h + FTC 200 mg q72h) — cumbersome, avoid if possible

— eGFR 15–29 mL/min: avoid TDF; use TAF/FTC (or zidovudine/lamivudine with dose adjustment) + DTG

— eGFR <15 or dialysis: specialist consultation; zidovudine + lamivudine (renally adjusted) + DTG

— Child-Pugh A/B: standard dosing for TDF/FTC/DTG

— Child-Pugh C: avoid DTG (limited data); consider raltegravir; specialist input

— Monitor ALT/AST at baseline, 2 weeks, and 4 weeks

— TDF and TAF both treat HBV — abrupt PEP cessation in chronic HBV can cause hepatitis flare

— Screen all PEP recipients for HBV; if HBsAg+, plan transition to long-term HBV therapy at PEP end, not discontinuation

— Polypharmacy review: avoid TDF with other nephrotoxins (NSAIDs, aminoglycosides)

— Bone density: prefer TAF in osteoporosis

— DTG and metformin: DTG increases metformin levels — limit metformin to 1000 mg/day or monitor

Key distinction: TDF (disoproxil fumarate) = older, more renal/bone toxicity, generic, cheap. TAF (alafenamide) = newer prodrug, lower plasma tenofovir, safer kidneys/bones, more expensive, weight gain risk. On Step 3, switch TDF→TAF when eGFR <60, osteoporosis, or concurrent nephrotoxins.

Renal dosing is the dominant consideration because tenofovir is renally cleared and nephrotoxic

eGFR-based regimen selection:

DTG and raltegravir: no renal dose adjustment needed — major advantage

Hepatic impairment:

Hepatitis B co-infection considerations:

Elderly (≥65) considerations:

Special Populations — Pregnancy, Pediatrics, and Breastfeeding

— PEP is not contraindicated in pregnancy; benefits clearly outweigh risks

— Preferred regimen: TDF/FTC + dolutegravir OR TDF/FTC + raltegravir 400 mg BID

— Earlier concern about DTG and neural tube defects (Tsepamo study) has been largely resolved; current WHO/DHHS guidance permits DTG throughout pregnancy including first trimester, with shared decision-making

— Avoid: efavirenz historically (now considered safe but not first-line PEP), didanosine + stavudine (mitochondrial toxicity), cobicistat-boosted regimens (subtherapeutic in 2nd/3rd trimester)

— Add prenatal vitamins with folate; reassure about safety

— In US/high-resource settings, HIV+ mothers are counseled to formula feed

— For PEP recipients (presumed HIV-negative) who are breastfeeding: TDF/FTC + DTG/RAL compatible; minimal infant exposure

— Counsel on continued breastfeeding safety

— Weight-based dosing; consult pediatric ID

— Age ≥12 and ≥35 kg: adult regimens

— Younger: zidovudine + lamivudine + raltegravir (granules/chewables) commonly used

— In suspected child sexual abuse: PEP plus mandated reporting to child protective services

— Confidentiality laws vary by state — most allow minors to consent to STI/HIV testing and treatment without parental notification

— Discuss long-term PrEP options if ongoing risk

Board pearl: Pregnancy + needlestick exposure: start PEP immediately; do not delay for OB consultation. The transmission risk to the fetus from untreated maternal seroconversion (vertical transmission ~25% without ART, ~1% with ART) vastly exceeds any plausible ART teratogenicity risk. Step 3 management: TDF/FTC + raltegravir or dolutegravir, OB co-management, and 4th-gen testing at 6 and 12 weeks.

Pregnancy:

Breastfeeding:

Pediatrics (occupational and non-occupational, including child sexual abuse):

Adolescents:

Complications and Adverse Outcomes

— Renal: TDF tubulopathy (Fanconi syndrome — glycosuria, phosphaturia, proteinuria), acute kidney injury; monitor Cr and UA

— Bone: decreased BMD with TDF (less clinically relevant in 28-day course but significant if recurrent PEP)

— GI: nausea (most common cause of non-completion), diarrhea — usually first 1–2 weeks; treat with ondansetron, loperamide

— Hepatic: transaminitis (especially with HBV co-infection or alcohol use)

— Neuropsychiatric: DTG insomnia, vivid dreams, headache, rare depression/suicidality (FDA labeling)

— Weight gain: INSTIs (especially DTG, BIC) associated with weight gain; less concerning in 28-day course

— Hypersensitivity: rare with current regimens; abacavir-related HSR mandates HLA-B*5701 testing (so avoid empirically)

— Occurs in <1% when started promptly; causes include delayed initiation, poor adherence, source resistance, very high inoculum

— Manifests as acute retroviral syndrome 2–6 weeks post-exposure or positive surveillance test

— Management: full HIV genotype, transition to suppressive ART, partner notification, linkage to care

— Hepatitis B flare on TDF cessation in chronic HBV (see chunk 9)

— Untreated HCV co-infection progresses; arrange DAA therapy if HCV RNA+

— Anxiety, depression, PTSD (especially sexual assault); refer to mental health

— Disclosure stress, partner-relationship strain

Key distinction: PEP failure (seroconversion on appropriate regimen) vs baseline HIV (positive baseline test misread as failure) — always have a baseline 4th-gen Ag/Ab. If baseline was negative and 6-week test is positive, that is true seroconversion → resistance testing, transition to ART, contact tracing. Board pearl: Always send a baseline test — it protects the patient and the clinician medicolegally.

Drug-related complications during the 28-day course:

Treatment failure / seroconversion despite PEP:

Co-infection complications:

Psychosocial:

When to Escalate — Specialist Consult and Inpatient Considerations

— Source with known multidrug-resistant HIV — need genotype-guided regimen

— Baseline exposed-person HIV test positive — convert PEP to full ART workup with genotype, CD4 count, viral load, OI screen

— Pregnancy with complex exposure (some institutions)

— Pediatric exposure

— Severe renal/hepatic impairment complicating regimen choice

— Drug interactions with critical medications (anticonvulsants, TB therapy, transplant immunosuppression)

— Repeated PEP courses — consider PrEP transition, behavioral counseling

— Occupational health / employee health for healthcare worker exposures (mandatory reporting, workers' comp documentation)

— Forensic / SANE team for sexual assault

— Social work / victim advocacy for assault, IDU, homelessness

— Hepatology for chronic HBV/HCV co-management

— Psychiatry for acute distress, suicidal ideation

— Severe drug reactions (SJS/TEN — rare with current regimens)

— Acute kidney injury requiring monitoring

— Sexual assault with significant trauma requiring surgical repair

— Suicidal ideation

— Healthcare exposure: file OSHA-compliant exposure report

— HIV seroconversion: report to local/state health department (reportable disease)

— Sexual assault: report per jurisdiction (mandated in pediatrics, elder, vulnerable adults)

CCS pearl: For a healthcare worker needlestick CCS case, the move sequence is: (1) start TDF/FTC + DTG, (2) order baseline labs on worker and source, (3) consult occupational health/employee health, (4) schedule 2-week follow-up, (5) counsel on safe sex/no blood donation during PEP. Failing to consult occupational health or document the OSHA report is a common point loss.

Most PEP encounters are managed entirely in the ED, urgent care, or occupational health — inpatient admission is rare

Indications for immediate HIV specialist (ID) consultation:

Other consultations:

Inpatient admission considerations (uncommon but include):

Reporting and surveillance:

Key Differentials — Other Prevention Strategies (Same Category)

— Daily TDF/FTC or TAF/FTC, or long-acting injectable cabotegravir q2 months

— For persons with ongoing HIV exposure risk (MSM with multiple partners, serodiscordant couples, IDU, commercial sex workers)

— Initiated before any specific exposure event; ongoing

— Requires negative HIV test before start and quarterly thereafter

— TDF/FTC 2 tabs 2–24 h before sex, 1 tab 24 h later, 1 tab 48 h after first dose

— Only validated for cisgender MSM

— Not for women, transgender persons, or anal-receptive partners with high frequency exposures

— 200 mg doxycycline within 72 h of condomless sex

— Reduces syphilis, chlamydia, gonorrhea incidence

— Does not prevent HIV — co-administer with HIV PEP/PrEP if HIV exposure occurred

— HIV+ partner on suppressive ART with undetectable VL → essentially zero transmission to seronegative partner

— Reduces need for PEP in serodiscordant couples

— Condoms, syringe service programs, opioid agonist therapy

Key distinction: PEP = reactive, 28 days, after a discrete event. PrEP = proactive, ongoing, for chronic risk. The classic stem confuses these: an MSM patient with weekly condomless sex who presents asking about "the morning-after HIV pill" — he is a PrEP candidate, not just a PEP candidate. Step 3 management: offer PEP if within 72 h of last act AND transition to PrEP at completion.

Distinguish PEP from related HIV prevention modalities — Step 3 will mix them in stems

Pre-exposure prophylaxis (PrEP):

On-demand (event-driven, "2-1-1") PrEP:

Doxycycline post-exposure prophylaxis (doxy-PEP) for bacterial STIs:

HIV vaccine: none currently approved

Treatment as Prevention (TasP / U=U):

Barrier methods, harm reduction:

Key Differentials — Other-Category Considerations

— Fever, pharyngitis, mononucleosis-like rash, lymphadenopathy 2–4 weeks after exposure

— 4th-gen Ag/Ab may be positive (p24 antigen detected even before antibody seroconversion)

— HIV RNA viral load very high (often >100,000 copies/mL)

— Mistake to avoid: giving PEP (3-drug) instead of full ART for established infection — risks resistance from inadequate regimen

— Correct action: full HIV workup, genotype, transition to standard ART (often the same INSTI-based regimen continued and intensified per specialist)

— Hepatitis B exposure without prior immunity → HBIG + HBV vaccine series (within 24 h optimally, up to 7 days)

— Hepatitis C exposure → no prophylaxis available; monitor and treat with DAAs if seroconversion (high cure rate)

— Tetanus-prone wound → Tdap booster ± TIG per immunization status

— Rabies exposure (animal bite) → rabies PEP (HRIG + vaccine series)

— Suspected STI exposure without HIV risk → still consider empiric GC/CT treatment, syphilis screen

— Emergency contraception need → levonorgestrel, ulipristal, or copper IUD (most effective)

— Discarded community needle, source unknown, exposure >72 h ago → no PEP; baseline HIV/HBV/HCV testing and tetanus update only

— Solid suture needle, minimal blood, source HIV-negative → no PEP

Board pearl: Always co-manage HBV at the same encounter as HIV PEP. A non-immune healthcare worker stuck by an HBsAg+ source gets HBIG 0.06 mL/kg IM + HBV vaccine series in addition to HIV PEP. Forgetting HBV is a classic Step 3 trap.

When PEP is requested, rule out scenarios that mimic but require different management

Acute retroviral syndrome (already infected):

Other window-period infections requiring different prophylaxis:

Sexual exposure mimics:

Needle scenarios that are not PEP-indicated:

Secondary Prevention and Long-Term Plan

— Confirm 28-day completion, review adverse effects

— Repeat HIV Ag/Ab, CMP, urinalysis

— Risk reassessment: was this a one-time event or part of a pattern?

— Seamlessly continue TDF/FTC or transition to TAF/FTC daily; or cabotegravir LA injection

— Quarterly HIV testing, renal function, STI panel

— Counsel on adherence (≥4 doses/week effective for receptive anal; daily for vaginal)

— Update HBV vaccination if needed

— HPV vaccine if age-eligible (through 45)

— Annual or more frequent GC/CT/syphilis screening

— Consider doxy-PEP 200 mg within 72 h of condomless sex for MSM/transgender women

— Screen with NIDA Quick Screen; refer to OUD treatment (buprenorphine, methadone) for IDU

— Syringe service program referral

— Motivational interviewing on condom use, partner reduction

— Partner services / contact notification for confirmed STIs

— Mental health referral; PTSD screening

— Victim compensation, advocacy, legal support

— Repeat pregnancy test at 2 weeks; emergency contraception confirmed effective

— Engineering control review (safer needles, sharps containers)

— Annual exposure prevention training

— Document for workers' compensation

Step 3 management: The "right answer" at the 4-week PEP visit for an MSM with recurring condomless encounters is transition to PrEP and add doxy-PEP, not "counsel on condom use only." Step 3 rewards combining biomedical and behavioral prevention.

PEP completion is a prevention milestone, not an endpoint — leverage the encounter for sustained risk reduction

At end-of-PEP visit (week 4):

PrEP transition for ongoing risk:

STI prevention package:

Substance use:

Behavioral interventions:

Sexual assault follow-up:

Healthcare worker post-exposure:

Follow-Up, Monitoring Parameters, and Counseling

— Day 0: initiation, baseline labs, counseling, first dose, starter pack

— Day 3–7: phone or in-person check — adherence, side effects, source results review

— Week 2: in-person — CMP, ALT, adherence

— Week 4: end of PEP — repeat HIV Ag/Ab, CMP, UA; PrEP/risk reassessment

— Week 6: HIV Ag/Ab

— Week 12: HIV Ag/Ab (final test if no HCV co-exposure)

— Month 6: HIV Ag/Ab if HCV-exposed or 3rd-gen assay used

— Creatinine/eGFR at baseline, week 2, week 4

— ALT/AST at baseline, week 4 (more often if HBV/HCV+)

— Urinalysis for proteinuria (TDF tubulopathy)

— Pregnancy test at baseline and as clinically indicated

— STI panels at baseline and 4–6 weeks for sexual exposures

— Abstain from blood/tissue/sperm donation until cleared at 3 months

— Use condoms for all sexual activity during PEP and until final negative test

— Avoid breastfeeding if possible if exposure was high-risk (individualized)

— Avoid pregnancy planning until cleared (or proceed with serodiscordant conception planning if applicable)

— Take medication consistently, with or without food (DTG: avoid with antacids/multivitamins within 2 h)

— Screen PHQ-2 / PHQ-9 at week 2 and week 4

— Sexual assault: connect with advocacy / trauma-informed care

— Written instructions on dose timing, side effects, when to call

— 24-hour contact line for occupational exposures (PEPline 1-888-448-4911 in US)

CCS pearl: Order "follow-up appointment in 2 weeks" and "follow-up appointment in 4 weeks" explicitly in the CCS interface; missing scheduled follow-up is a common point deduction. Counsel "use condoms" and "no blood donation" — both score.

Visit schedule:

Monitoring parameters:

During the 28-day course, counsel patients to:

Mental health:

Patient education materials:

Ethical, Legal, and Patient Safety Considerations

— Most US states permit HIV testing of a source patient after a healthcare worker exposure without explicit consent, but laws vary — many require notification or opt-out, some require consent

— If source refuses or is unable to consent, test discarded blood specimens already drawn for other reasons (legally permissible in most jurisdictions)

— Never delay PEP while resolving source consent

— HIV status is protected health information; disclosure limited to need-to-know clinicians and per state-specific HIV confidentiality laws

— Partner notification: clinician-mediated or anonymous partner services through health department; not mandatory in all states but encouraged

— HIV seroconversion is a reportable disease in all US states

— Child sexual abuse: mandated report to child protective services regardless of patient wishes

— Elder/vulnerable adult abuse: mandated report

— Sexual assault of competent adult: patient autonomy — report only with consent in most states (unless weapon-related or other mandatory criteria)

— Document risk discussion, off-label use considerations (PEP indication is FDA-approved for many regimens but specific combinations may be guideline-based)

— Capacity assessment if intoxicated, traumatized, or cognitively impaired

— OSHA Bloodborne Pathogens Standard mandates exposure control plan, sharps safety devices, free PEP, post-exposure evaluation

— No retaliation for reporting exposures; report should not affect employment

— ED-to-PCP handoff: ensure follow-up appointment booked before discharge, medications dispensed (not just prescribed), contact information for questions — incomplete handoff is the leading cause of PEP non-completion

Step 3 management: A patient sexually assaulted presents to ED, requests no police involvement. Action: treat per protocol (PEP, EC, STI prophylaxis, SANE exam offered), document, respect autonomy regarding police — but in pediatric or vulnerable adult cases, mandatory report overrides patient/guardian preference. Know the distinction.

Source patient testing consent:

Confidentiality:

Mandatory reporting:

Informed consent for PEP:

Healthcare worker safety:

Transition-of-care risks:

High-Yield Associations and Rapid-Fire Clinical Facts

Board pearl: The number-one Step 3 trap is choosing a 2-drug regimen — all modern PEP is 3 drugs. The number-two trap is delaying the first dose for source testing — never delay.

Time window: 72 hours absolute maximum; <2 hours ideal

Duration: 28 days continuous

First-line: TDF/FTC + dolutegravir (or raltegravir), all once daily except RAL (BID)

Renal cutoff for TDF→TAF switch: eGFR <60

Hepatitis B co-exposure protocol: if non-immune, HBIG + HBV vaccine within 24 hours; TDF/FTC also covers HBV

Hepatitis C co-exposure: no PEP available; monitor RNA at 3–6 weeks, treat with DAAs if seroconverts

Per-act transmission risks (HIV+ source): receptive anal 138/10,000 (highest sexual); needlestick 23/10,000; receptive vaginal 8/10,000

U=U: undetectable = untransmittable; HIV+ partner on ART with sustained VL <200 has effectively zero transmission

Follow-up HIV testing schedule: baseline, 6 weeks, 12 weeks (6 months if HCV co-exposure)

Resistance: if source on failing ART, consult ID for tailored regimen

PrEP transition: at end of PEP for ongoing risk — no drug-free gap

Pregnancy: PEP is safe; TDF/FTC + DTG or RAL preferred

Pediatrics: weight-based; involve pediatric ID

OSHA reporting: mandatory for occupational exposures

PEPline: 1-888-448-4911 (free 24/7 clinician hotline)

Drug to avoid: nevirapine (hepatotoxicity, SJS); efavirenz not first-line

DTG–metformin interaction: DTG raises metformin levels

DTG–antacid interaction: separate by 2 h before/6 h after

Doxy-PEP: 200 mg within 72 h of condomless sex — reduces bacterial STIs only

Emergency contraception if applicable (sexual assault, contraceptive failure)

No blood donation for at least 3 months / until cleared

Acute retroviral syndrome window: 2–4 weeks; can present during PEP follow-up

4th-gen assay preferred for surveillance; shortens window to 12 weeks

Confidentiality: state-specific HIV laws apply to disclosure

Workers' comp covers oPEP; Ryan White / state programs assist nPEP

Board Question Stem Patterns

— "A medical student is stuck with a hollow-bore needle while drawing blood from a known HIV+ patient with viral load 200,000. The exposure occurred 90 minutes ago." → Start TDF/FTC + DTG immediately, baseline labs, occupational health consult, 28-day course

— "Patient presents 80 hours after condomless receptive anal sex with HIV+ partner of unknown ART status." → PEP not indicated (>72 h); offer PrEP initiation after baseline HIV testing

— "Healthcare worker exposed to blood from patient with HIV on ART, viral load <20 for 2 years." → Counsel that transmission risk is negligible (U=U); PEP generally not required, document shared decision-making

— "20-year-old woman sexually assaulted 4 hours ago, assailant unknown HIV status." → PEP (TDF/FTC + DTG) + emergency contraception (ulipristal or levonorgestrel) + GC/CT/syphilis empiric treatment (ceftriaxone + doxycycline + metronidazole) + HBV vaccine if non-immune + SANE exam + counseling

— "26-year-old G2P1 at 14 weeks pregnant has needlestick from HIV+ source." → Start PEP immediately with TDF/FTC + DTG or RAL; do not delay for OB consult; pregnancy is not a contraindication

— "55-year-old with CKD stage 3, eGFR 45, exposed to HIV." → TAF/FTC + DTG (not TDF)

— "Healthcare worker, unvaccinated for HBV, stuck by HBsAg+ source." → HBIG + HBV vaccine series + HIV PEP all together

— "MSM completing PEP after 4th exposure this year." → Transition to PrEP + STI screening + behavioral counseling + consider doxy-PEP

— "Patient starting PEP has positive 4th-gen HIV test on baseline draw." → Do not continue PEP as PEP; transition to full ART evaluation (genotype, CD4, viral load) and treatment

Key distinction: Step 3 stems differ from Step 2 by emphasizing what to order next and follow-up cadence — memorize the 6-week / 12-week testing schedule and the end-of-PEP PrEP transition.

Stem 1 — The hollow-bore needlestick:

Stem 2 — The delayed presenter:

Stem 3 — The virally suppressed source:

Stem 4 — The sexual assault:

Stem 5 — The pregnant exposed person:

Stem 6 — The renal patient:

Stem 7 — The HBV co-exposure:

Stem 8 — The recurring exposer:

Stem 9 — The positive baseline test:

One-Line Recap

HIV post-exposure prophylaxis is a 28-day, 3-drug antiretroviral regimen — preferably tenofovir/emtricitabine plus dolutegravir — initiated within 72 hours (ideally <2 hours) of a discrete blood or sexual exposure, with baseline and serial 4th-generation HIV testing at 6 and 12 weeks, and seamless transition to PrEP if exposure risk continues.

Board pearl: If you remember only three things from this topic — (1) 72 hours, (2) 28 days, (3) three drugs (TDF/FTC + INSTI) — you will answer the majority of Step 3 PEP questions correctly. The remaining points come from knowing the 6/12-week follow-up schedule, recognizing the PrEP transition opportunity, and never delaying the first dose for labs or consults.

The 72-hour rule and the 28-day course are the two non-negotiable numbers — every PEP question hinges on whether the time window is met and whether the patient completes the full duration

TDF/FTC + dolutegravir (or raltegravir) is the universal default; substitute TAF/FTC when eGFR <60, and never use 2-drug regimens or nevirapine

Always co-manage hepatitis B (HBIG + vaccine if non-immune source HBsAg+) and always screen for hepatitis C, syphilis, GC/CT, and pregnancy at the same encounter; for sexual assault add emergency contraception and SANE coordination

Follow-up testing cadence: baseline → 6 weeks → 12 weeks (extend to 6 months only if HCV co-exposure or older 3rd-generation assay); the end-of-PEP visit at week 4 is the moment to transition to PrEP for any patient with ongoing risk, closing the prevention loop without a drug-free interval