What is the best regimen for post-exposure prophylaxis (PEP) following a needle stick injury?

Best Regimen for Post-Exposure Prophylaxis (PEP) Following a Needle Stick Injury

The current recommended PEP regimen following a needle stick injury 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

Initial Assessment and Timing

• PEP should be initiated as soon as possible after exposure, ideally within 72 hours, as effectiveness decreases significantly after this window 2, 1
• The full 28-day course of PEP should be prescribed at the initial assessment 1
• Immediate care to the exposure site should include washing wounds and skin with soap and water 2

Risk Assessment

• Determine risk associated with exposure by evaluating:
  • Type of fluid (e.g., blood, visibly bloody fluid, other potentially infectious fluid) 2
  • Type of exposure (percutaneous injury, mucous membrane exposure) 2
• Evaluate the source person for HBsAg, anti-HCV, and HIV antibody when possible 2
• For unknown sources, assess risk of exposure to HIV infection 2

Recommended PEP Regimens

Preferred Regimen:

• Three-drug regimen: TDF + 3TC/FTC + LPV/r or ATV/r 1
  • This provides maximal suppression of viral replication to prevent infection 2

Alternative Regimens:

• Two-drug regimen: Consider for concerns about adherence and toxicity 2
  • Combination of two reverse transcriptase inhibitors 2

Newer Options with Improved Tolerability:

• Single-tablet regimen: Bictegravir/emtricitabine/tenofovir alafenamide (BIC/FTC/TAF) has shown excellent tolerability with 90.4% completion rates and minimal side effects 3
• TDF/FTC/rilpivirine: French guidelines recommend this single-tablet regimen with good tolerability (86.1% completion rate) 4

Special Considerations

Pregnant Healthcare Workers:

• Zidovudine (ZDV) + lamivudine (3TC) is considered a safe regimen 1

Renal Impairment:

• For individuals with creatinine clearance between 30-60 ml/min or with known bone density issues, consider tenofovir alafenamide (TAF) + FTC 1

Source Patient with Known Antiretroviral Resistance:

• When possible, consider the source person's history of antiretroviral medication use and recent viral load measurement when selecting PEP medications 2
• In cases of multi-drug resistant virus, alternative agents like maraviroc may be considered in consultation with HIV specialists 5

Monitoring and Follow-up

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

Side Effects Management

• Common side effects include nausea, vomiting, fatigue, and diarrhea 3
• Side effects are generally manageable with antimotility and antiemetic agents 1
• Serious toxicity is rare when used for PEP 1

Common Pitfalls and Caveats

• Delayed initiation beyond 72 hours significantly reduces effectiveness 2
• Poor knowledge of PEP guidelines among healthcare workers may increase the risk of seroconversion 6
• Low adherence due to side effects can compromise effectiveness - selecting regimens with better tolerability profiles may improve completion rates 3, 4
• Failure to complete the full 28-day course reduces effectiveness 1
• Not considering the source patient's treatment history and potential drug resistance 2

Remember that initiating PEP should not be delayed pending HIV test results or additional source person risk factor assessment, as the sooner PEP is administered after exposure, the more likely it is to interrupt transmission 2.