What is the recommended Post-Exposure Prophylaxis (PEP) dose?

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Last updated: October 7, 2025View editorial policy

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Recommended Post-Exposure Prophylaxis (PEP) Dosing Regimen

For HIV post-exposure prophylaxis, the recommended regimen is a 28-day course of a three-drug combination consisting of tenofovir disoproxil fumarate (TDF) plus lamivudine (3TC) or emtricitabine (FTC) as the backbone, with lopinavir/ritonavir (LPV/r) or atazanavir/ritonavir (ATV/r) as the preferred third drug. 1

Basic PEP Regimen Components

Preferred Backbone Regimen

  • TDF + 3TC (or FTC) is the recommended backbone regimen for HIV PEP in adults and adolescents 1
  • For children ≤10 years, ZDV (zidovudine) + 3TC is the preferred backbone 1

Preferred Third Drug

  • LPV/r or ATV/r are suggested as the preferred third drug for adults and adolescents 1
  • Alternative options include raltegravir (RAL), darunavir/ritonavir (DRV/r), or efavirenz (EFV) 1
  • For children ≤10 years, LPV/r is recommended as the preferred third drug 1

Timing and Duration

  • PEP should be initiated as soon as possible after exposure, ideally within 72 hours 1
  • The full 28-day course of PEP should be prescribed at the initial assessment 1
  • Treatment completion is critical for effectiveness - studies show 86-90% completion rates with newer regimens 2, 3

Alternative Regimens

If the preferred regimens are not available or not tolerated, alternative options include:

  • TDF/FTC/rilpivirine (RPV) as a single-tablet regimen, which has shown good tolerability with 86.1% treatment completion rates 2
  • Dolutegravir (DTG) with TDF-FTC has demonstrated 90% completion rates with good tolerability 3

Special Considerations

  • For pregnant healthcare workers, ZDV + 3TC (Combivir) is considered a safe regimen 1
  • For individuals with renal impairment, dose adjustments may be necessary 4
  • TAF (tenofovir alafenamide) + FTC may be considered for individuals with creatinine clearance between 30-60 ml/min or with known bone density issues 1, 4

Monitoring and Follow-up

  • Evaluate exposed persons taking PEP within 72 hours after exposure 1
  • Monitor for drug toxicity for at least 2 weeks 1
  • Perform HIV-antibody testing at baseline, 6 weeks, 3 months, and 6 months post-exposure 1
  • Advise exposed persons to use precautions to prevent secondary transmission during the follow-up period 1
  • Seek immediate medical evaluation for any acute illness occurring during follow-up 1

Common Side Effects and Management

  • Common side effects include fatigue (26%), nausea (25%), diarrhea (21%), and headache (10%) 3
  • Side effects are generally manageable with antimotility and antiemetic agents 1
  • Serious toxicity is rare when used for PEP 1

Historical Context

It's worth noting that older regimens included ZDV + 3TC (Combivir) as the basic regimen 1, but newer combinations have improved tolerability profiles and higher completion rates. The evolution toward three-drug regimens reflects the standard approach used in HIV treatment and provides better coverage against potential drug resistance 1.

Professional Medical Disclaimer

This information is intended for healthcare professionals. Any medical decision-making should rely on clinical judgment and independently verified information. The content provided herein does not replace professional discretion and should be considered supplementary to established clinical guidelines. Healthcare providers should verify all information against primary literature and current practice standards before application in patient care. Dr.Oracle assumes no liability for clinical decisions based on this content.

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