What is the recommended regimen and dosing for Tenofovir disoproxil fumarate (TDF) + Lamivudine (3TC) for Post-Exposure Prophylaxis (PEP)?

Tenofovir Disoproxil Fumarate (TDF) + Lamivudine (3TC) Regimen for HIV Post-Exposure Prophylaxis (PEP)

For HIV post-exposure prophylaxis, TDF + 3TC is recommended as the preferred backbone regimen for adults and adolescents at a dosage of TDF 300mg once daily and 3TC 150mg twice daily for a full 28-day course. 1

Recommended PEP Regimen Components

Basic Two-Drug Backbone

• TDF + 3TC is the preferred backbone regimen for HIV PEP in adults and adolescents (Strong recommendation) 1
  • TDF: 300mg once daily
  • 3TC: 150mg twice daily

Third Drug (Required for Complete PEP Regimen)

The basic two-drug backbone should be combined with a third drug:

• Preferred third drugs: Lopinavir/ritonavir (LPV/r) or Atazanavir/ritonavir (ATV/r) 1
• Alternative third drugs: Raltegravir (RAL), Darunavir/ritonavir (DRV/r), or Efavirenz (EFV) 1

Duration and Timing

• PEP should be initiated as soon as possible after exposure, ideally within 24 hours but no later than 72 hours 2
• A full 28-day course must be completed for maximum effectiveness 1
• The complete 28-day prescription should be provided at initial assessment rather than partial "starter packs" 1

Pediatric Considerations

For children ≤10 years:

• Zidovudine (ZDV) + 3TC is the preferred backbone 1
• TDF + 3TC can be considered as an alternative regimen 1
• Lopinavir/ritonavir is the preferred third drug 1

Adherence and Follow-up

• Enhanced adherence counseling is recommended for all individuals initiating PEP 1
• Follow-up testing should occur at baseline, 6 weeks, 3 months, and 6 months post-exposure 1
• Initial follow-up should occur within 72 hours of starting PEP with monitoring for drug toxicity for at least 2 weeks 1

Efficacy and Tolerability Considerations

While TDF + 3TC remains the WHO-recommended backbone, newer studies show that regimens containing integrase inhibitors may offer better tolerability:

• A study of dolutegravir with TDF-FTC showed 90% completion rates with good tolerability 3
• Bictegravir/FTC/TAF demonstrated 90.4% completion rates with fewer side effects than historical PEP regimens 4

Common Side Effects

• Gastrointestinal symptoms (nausea, vomiting, diarrhea)
• Fatigue
• Headache
• Laboratory abnormalities may include elevated liver enzymes and decreased renal function 5

Important Caveats

1. Complete the full course: Partial prophylaxis may not provide adequate protection
2. Start as soon as possible: Efficacy decreases with delayed initiation
3. Monitor for side effects: Particularly renal function with TDF-containing regimens
4. Drug resistance considerations: If the source patient is known to be on antiretroviral therapy, consider potential resistance patterns when selecting the regimen
5. Transition to PrEP: For those with ongoing HIV risk, consider transition to pre-exposure prophylaxis (PrEP) after completing PEP 2

The TDF + 3TC backbone represents a cost-effective option with established efficacy when used as part of a complete three-drug regimen for PEP. While newer regimens may offer improved tolerability and convenience, the WHO continues to recommend TDF + 3TC as the preferred backbone for adults and adolescents requiring PEP.