04. PREP & PEP

Faculty Editor: Luis Rubi, M.D.


✔ Several studies have shown that certain antiretrovirals (ARVs) are safe and effective in reducing risk of HIV transmission in adults. There are now multiple options for PrEP including TDF/FTC (Truvada), TAF/FTC (Descovy), and injectable cabotegravir (CAB;Apretude).

Preexposure Prophylaxis (PrEP) for HIV

HIV Prevention Methods

  • Condoms
  • Access to clean needles and substance use treatment
  • Standard precautions in the workplace
  • Treatment as prevention. HIV-infected persons with an undetectable viral load have significantly reduced risk of HIV transmission.
  • Male circumcision.
  • PrEP and PEP

Identify patient who may benefit from PrEP

  • Anyone who asks for PrEP should be offered it
  • Adult persons who are substantial risk for HIV infection:
    • Sexual Transmission
      • Ongoing relationship with HIV+ partner, particularly if that partner is not taking HIV treatment
      • Recent STI
      • Inconsistent or no condom use
      • High number of sex partners (≥ 2 partners within past 6 months)
      • Commercial sex work
    • Injection Drug Use (IDU)
      • Sharing equipment or been in drug treatment in past 6 months for injection drug use
  • Clinically eligible
    • Documented HIV negative
    • No signs/symptoms of acute HIV infection
    • Normal renal function; no contraindicated medications
    • Willing to start new medication

Estimated per-act probability of acquiring HIV from infected source, by exposure type

Exposure Type

Risk per 10,000 exposures to an infected source

95% CI

Needle sharing Injection Drug Use



Percutaneous Needle Stick



Receptive Anal Intercourse



Insertive Anal Course



Receptive Penile-Vaginal Intercourse



Insertive Penile-Vaginal Intercourse



Receptive Oral Sex



Insertive Oral Sex



1Risk is considered to be low relative to other exposures, but not zero.


Initial Laboratory Testing

  • HIV Testing
    • Serum HIV Ab/Ag or HIV Ab
    • FDA-approved Rapid POC blood finger stick blood testing
    • If acute HIV infection suspected, or recent high risk contact (within 14 days) use HIV-1 RNA test
    • Rapid tests using oral fluid should not be used when considering PrEP
  • Renal Testing
    • eCrCl > 60 ml/min
  • Hepatitis Serology
    • HBV serology: HBsAg, anti-HBc, anti-HBs
    • HCV Ab
  • STI Testing
    • Syphilis
    • Gonorrhea and Chlamydia “3-site testing”: pharyngeal, rectal and urine (can be self collected with instructions)
  • Pregnancy testing for people who may become pregnant
  • DEXA for patients at high risk for osteoporosis if using TDF or TAF based regimens
  • Creatinine, eCrCl, Hepatits B serology, lipid panels and LFTs testing not routinely indicated before starting or monitoring while on CAB

Providing PrEP

  • Three FDA approved medications for PrEP
    • Daily oral TDF/FTC (Truvada)
      • Approved for all adults and adolescents at high risk of HIV through sex or IDU
      • On demand strategy also an option for men and transgender women who have sex with men (off-label per FDA)
        • 2 TDF/FTC tablets 2-24 hours before sex, 1 TDF/FTC tablet 24 hours after first drug intake, then 1 TDF/FTC tablet 24 hours later
        • If subsequent sexual intercourse, continue 1 TDF/FTC tablet daily until 2 days after last sexual intercourse
        • Do not use this method in persons with HBV infection
    • Daily oral TAF/FTC (Descovy)
      • Approved for adults and adolescents at high risk of HIV through sex excluding people at risk through receptive vaginal intercourse
      • Intermittent or on demand use not recommended
      • Consider in people with renal disease
    • Injectable CAB (Apretude) every 8 weeks
      • Approved for adult and adolescents at high risk of HIV through sex
      • Two RCTs (HPTN083 and HPTN084) showed injectable CAB was superior to daily TDF/FTC in cisgender men and transgender women who have sex with men, and cisgender women
      • Does not have HBV activity and not studied in people who inject drugs
      • First two doses given one month apart and then administered every 8 weeks
      • May be started with or without oral cabotegravir lead in
  • Patient education on limits of PrEP (does not protect against other STIs) and importance of condom use
  • Time to achieving protection with daily TDF/FTC
    • 20 days in blood and cervicovaginal tissues
    • 7 days in rectal tissue
  • TAF/FTC time to achieving protection is unknown, but likely offers similar mucosal protection and has higher intracellular concentrations
  • Injectable CAB can persist at nonprotective levels (tail phase) once discontinued, but enough to pressure mutations that confer resistance to CAB or other INSTIs (see below for management)
  • Potential Adverse Effects:
    • Serious, but rare:
      • Renal insufficiency (acute renal failure, ATN, Fanconi’s syndrome)
      • Neutropenia
      • Lactic acidosis
      • Angioedema
    • Common Benign Side Effects:
      • Nausea during first few weeks “Start up syndrome”:
      • Mild worsening of renal function
      • Decreased bone density, but no increase in fractures
      • Rash (usually self-limited)
      • Elevated lipids
      • Injection site reactions (CAB)

Clinical Follow-up and Monitoring

  • For patient on TDF/FTC or TAF/FTC:
    • Every 3 months
      • HIV Ab/Ag
      • If signs and symptoms of acute HIV send HIV-1 RNA test
      • Pregnancy testing
      • Assess side effects, adherence, and risk-reduction behaviors
      • STI testing for sexually active persons with signs or symptoms of infection, and for asymptomatic individuals at high risk for recurrent bacterial STIs (e.g., prior syphilis, gonorrhea, or chlamydia)
    • Every 6 months
      • Monitor eCrCl in persons ≥50 years or have eCrCl ≤ 90 at PrEP initiation
        • Rise in Cr is not reason for discontinuation if eCrCl remains > 60 ml/min   or > 30 ml/min for TAF/FTC
      • If other risk factors for renal disease (e.g., HTN or DM) consider UA to screen for proteinuria
      • If eCrCl steadily declining, assess for alternative etiologies and consult with nephrologist may be indicated
    • Every 12 months
      • Monitor eCrCl in all patients on PrEP
      • Monitor lipid panel and weight for patients on TAF/FTC
      • Evaluate need to continue PrEP as component of HIV prevention
      • Hepatitis C testing
  • For patients on injectable CAB
    • One month after initial injection (2nd injection)
      • Repeat HIV-1 RNA test
      • Adminsiter CAB injection
    • Every 2 months (beginning with 3rd injection)
      • HIV-1 RNA and assess for signs of acute infection
      • Administer CAB injection
    • Every 4 months
      • Bacterial STI screening for cisgender men and transgender women who have sex with men (oral, rectal, urethral, blood)
    • Every 6 months
      • Bacterial STI screening for all sexually active women and men (vaginal, rectal, urine as indicated), blood
    • Every 12 months
      • Evaluate need to continue PrEP as component of HIV prevention
      • Hepatitis C testing

Discontinuing PrEP

  • Several reasons including: personal choice, lowered risk of HIV acquisition, intolerable toxicities, chronic nonadherence, or acquisition of HIV infection
  • Provide alternate methods to reduce risk of HIV acquisition
  • Document: HIV status at time of discontinuation, reason for PrEP discontinuation, recent med adherence and sexual risk behavior
  • If wanting to resume PrEP after having discontinued, then perform same initiation evaluation including HIV test
  • For patients discontinuing CAB:
    • Educate patients about “tail” and risks of declining CAB levels
    • If ongoing risk for HIV, start TDF/FTC or TAF/FTC (if appropriate) within 8 weeks from last injection
    • Continue quarterly visits for 12 months with HIV-1 RNA testing at each visit

Special Considerations

  • Patients who become pregnant or breastfeed on PrEP
    • TDF and FTC can be continued during pregnancy (Class B drugs)—however PrEP during pregnancy should be managed by an expert, given concern about tenofovir and bone health
    • Safety of TDF/FTC for infants exposed through breastfeeding not adequately studied
    • Limited clinical experience with CAB in pregnancy (category B)
  • Patients with Chronic Active Hepatitis B Infection
    • TDF/FTC and TAF/FTC are active against HBV
    • If positive for hepatitis B surface antigen (HBsAg):
      • Test for HBV DNA prior to PrEP and every 6-12 months while on PrEP
      • Referral to clinician with experience in treatment of HBV
    • TDF and TAF have high barrier to resistance however, reinforce adherence to prevent Hep B reactivation and/or TDF-resistant HBV infection
    • If PrEP discontinued, persons should continue to receive care from clinician experienced in HBV management as HBV can flare significantly
    • CAB does not have HBV activity and requires additional HBV active antivirals
  • Patients with Renal Impairment
    • TDF/FTC should not be used in people with eCrCl < 60
    • TAF/FTC can be used in people with eCrCl 30-60  
    • eCrCl < 30 should not take TDF or TAF based PrEP
    • CAB does not require dosage adjustment, but not studied in people with end-stage renal disease (eCrCl < 15) and consider increased monitoring for adverse effects
    • Other HIV prevention methods should be used in place of PrEP
  • Nonoccupational Postexposure Prophylaxis (nPEP)
    • Persons seeking nPEP should be evaluated for PrEP after confirming HIV negative status
    • After 28-day course of nPEP, PrEP can be started immediately if indicated
    • Patients on PrEP do not need nPEP unless sporadic adherence (e.g., did not take medications within 7 days of exposure)

Post-exposure Prophylaxis

Definition of Occupational Exposures to healthcare providers (HCP)  

  • Any personnel working in healthcare setting exposed to:
    • body substances (e.g., blood, tissue, and specific body fluids)
    • contaminated medical supplies and equipment
    • contaminated environmental surfaces
    • Substances that do not place HCP at risk unless fluid visibly bloody: feces, nasal secretions, saliva, sputum, sweat, tears, urine, vomitus
  • Exposures that place HCP at risk
    • Percutaneous injury (e.g. a needlestick or cut with sharp object)
    • Mucous membrane exposure
    • Non-intact skin exposure
    • Bites resulting in blood exposure to either person involved

Definition of Non-Occupational Exposure

  • Exposure to infected blood or bodily fluid through:
    • Sexual contact
    • Injection drug use 

Risk for Occupational Transmission

  • The larger the viral inoculum, the higher the risk for transmission. Hollow bore needles placed directly into artery or vein have highest risk.

Risk of Transmission for Specific Blood-borne Pathogens





Percutaneous injury




Mucous Membrane Exposure




1Transmission rate depends on presence of HBeAg from source

Initial Steps for all occupational exposures

  • Exposed wounds and skin sites should be washed with soap and water, and mucous membranes flushed with water
  • There is controversy over antiseptics. Use of chlorhexidine, caustic agents, and wound expression is not recommended
  • Irrigate eyes with clean water, saline, or sterile solution
  • Testing of needles/sharps where infectious status is unknown is not recommended
  • If possible, determine infectious status of the source patient with HBsAg, HCV RNA (if unavailable anti-HCV), and HIV Ab. This may involve acute HIV testing.

Evaluation of exposure

  • Evaluate Susceptibility of exposed person
    • Hepatitis B vaccine status
    • HBV immune status (anti-HBs), if vaccine response status unknown
    • HCV Ab and ALT
    • HIV Ab
  • Offer PEP for exposures with risk of infection transmission
    • Counsel on risks/benefits of PEP
    • If HCP agrees, should be started as soon as possible (within 24 hours for HBV, 72 hours for HIV)
    • Strongly recommend involving occupational health and/or obstetrics if HCP is currently pregnant

PEP regimens

  • HBV
    • PEP for HBV is Hepatitis B immunoglobulin (HBIG) and Hep B vaccination series
    • Administration of HBIG depends on vaccination status of HCP and source HBsAg status
    • Consult with Occupational Health regarding recommended regimen.
  • HIV
    • Check CBC, Creatinine, LFTs and if hepatitis B vaccine status of exposed person unknown, hepatitis B serologies.
      • Preferred regimen:
        • Pregnant women: (Co-forumulated emtricirabine 200mg/tenofovir 300mg) once daily+ raltegravir 400 mg PO twice daily OR,
        • Non-pregnant adults: dolutegravir 50 mg PO daily + (Co-forumulated emtricitabine 200 mg /tenofovir 300 mg) once daily
      • Other regimens are available, but recommended under guidance of HIV consultant
      • Recheck CBC, Creatinine, LFTs at 2 and 4 weeks.
      • If source person is determined to be HIV negative, PEP should be discontinued. Otherwise, continue medication for 4 weeks.
      • If PEP Is being prescribed for non-occupational exposure, consider transition from PEP -> PrEP once PEP is completed.

Follow-up testing

  • HBV
    • Test for anti-HBs 1-2 months after last dose of vaccine or vaccine booster
    • Follow up testing not needed if exposed person immune to hepatitis or received HBIG PEP
  • HCV
    • If anti-HCV-positive, then obtain HCV RNA testing
      • If positive, refer to treatment
      • If negative, repeat HCV RNA testing >3 weeks after exposure
        • If positive, refer to care for pre-existing chronic infection
        • If negative, no further testing required
    • If anti-HCV negative, then check HCV RNA testing >3 weeks after exposure
      • If positive, refer to treatment
      • If negative, no further testing required
  • HIV
  • HIV antibody testing with EIA should be performed at 6 weeks, 12 weeks, and 6 months after exposure
  • If 4th generation HIV Ag/Ab testing is available, then follow up testing can occur at 6 weeks and 4 months after exposure
  • Consider HIV testing at 12 months for dual HIV- HCV exposure.
  • Testing should be performed for any exposed person with signs or symptoms of acute retroviral syndrome regardless of timing since exposure
  • Exposed persons with HIV positive results should be referred to HIV specialist

Additional Resources

Clinical consultation is available at the Clinician Consultation Center at http://nccc.ucsf.edu or by calling 1-855-448-7737 (PrEP) or 1-888-448-4911 (PEP)

UCSF Occupational Health Exposure Line: 415 353 7842 (STIC)


Centers for Disease Control and Prevention. US Public Health Service: Preexposure prophylaxis for the prevention of HIV infection in the United States- 2021 Update: a clinical practice guideline. https://www.cdc.gov/hiv/pdf/risk/prep/cdc-hiv-prep-guidelines-2021.pdf Published 2021

Centers for Disease Control and Prevention. MMWR: Updated U.S. Public Health Service Guidelines for the Management of Occupational Exposures to HBV, HCV, and HIV and Recommendations for Postexposure Prophylaxis. 2001, June 29.

Centers for Disease Control and Prevention. US Public Health Service: Updated Guidelines or Antiretroviral Posteexposure Prophylaxis After Sexual, Injection Drug Use, or Other Nonoccupational Exposure to HIV. Published 2016

Landovitz RJ, Li S, Eron JJ Jr, Grinsztejn B, Dawood H, Liu AY, Magnus M, Hosseinipour MC, Panchia R, Cottle L, Chau G, Richardson P, Marzinke MA, Eshleman SH, Kofron R, Adeyeye A, Burns D, Rinehart AR, Margolis D, Cohen MS, McCauley M, Hendrix CW. Tail-phase safety, tolerability, and pharmacokinetics of long-acting injectable cabotegravir in HIV-uninfected adults: a secondary analysis of the HPTN 077 trial. Lancet HIV. 2020 Jul;7(7):e472-e481. doi: 10.1016/S2352-3018(20)30106-5. Epub 2020 Jun 1. PMID: 32497491; PMCID: PMC7859863.

Patel P, Borkowf CB, Brooks JT, Lasry A, Lansky A, Mermin J. Estimating per-act HIV transmission risk: a systematic review. AIDS. 2014;28(10):1509-19.

Thurman AR, Schwartz JL, Cottrell ML, et al. Safety and pharmacokinetics of a tenofovir alafenamide fumarate-emtricitabine based oral antiretroviral regimen for prevention of hiv acquisition in women: a randomized controlled trial. EClinicalMedicine. 2021;36:100893.