What is the preferred regimen, first-line or alternative, for post-exposure prophylaxis (PEP) following a needle stick injury?

First-Line vs. Alternative Regimens for Post-Exposure Prophylaxis After Needle Stick Injury

The first-line regimen for post-exposure prophylaxis (PEP) following a needle stick injury is bictegravir/emtricitabine/tenofovir alafenamide or dolutegravir plus tenofovir (either alafenamide or disoproxil fumarate) plus emtricitabine or lamivudine. 1

Risk Assessment and Timing

• PEP should be initiated as soon as possible after exposure, ideally within 24 hours but no later than 72 hours 1
• The initial dose should not be delayed pending laboratory test results 1
• A rapid HIV test should be performed on the exposed individual before starting PEP 1
• Risk assessment should consider the severity of exposure and likelihood of HIV transmission 1

First-Line PEP Regimen

• The Centers for Disease Control and Prevention recommends a first-line regimen of:
  • Bictegravir/emtricitabine/tenofovir alafenamide OR
  • Dolutegravir plus (tenofovir alafenamide or tenofovir disoproxil fumarate) plus (emtricitabine or lamivudine) 1
• This regimen is recommended for adults and adolescents based on efficacy, tolerability, and resistance profiles 1

Alternative PEP Regimens

• Alternative backbone options include tenofovir disoproxil fumarate (TDF) plus lamivudine (3TC) or emtricitabine (FTC) 1
• Alternative third drugs include:
  • Lopinavir/ritonavir (LPV/r)
  • Atazanavir/ritonavir (ATV/r) 1
• Older regimens included zidovudine (ZDV) plus lamivudine (3TC) as the basic regimen, which was the historical standard but is no longer first-line due to side effect profile 2

Evolution of PEP Recommendations

• Earlier guidelines (1998-2001) recommended a basic 4-week regimen of two drugs (zidovudine and lamivudine) for most HIV exposures 2
• These guidelines also included an expanded regimen with the addition of a protease inhibitor (indinavir or nelfinavir) for higher-risk exposures 2
• Current recommendations have evolved to include newer antiretroviral agents with better tolerability profiles 1

Duration and Follow-up

• The recommended PEP course is 28 days, regardless of exposure severity 1
• A full 28-day prescription should be provided following initial risk assessment 1
• Follow-up HIV antibody testing at 4-6 weeks and 3 months post-exposure is recommended 1
• Enhanced adherence counseling is recommended for all individuals on PEP 1

Considerations for Regimen Selection

• Tolerability is crucial for adherence - newer regimens have fewer side effects than older ones 2
• The most common adverse effects with older regimens included nausea or vomiting (27%), diarrhea (21%), and headache (15%) 2
• Source patient's antiretroviral treatment history and potential resistance patterns should be considered when selecting a regimen 1
• Special situations requiring expert consultation include:
  • Delayed exposure report (beyond 24-36 hours)
  • Unknown source (e.g., needle in sharps container)
  • Pregnancy in the exposed person
  • Known or suspected resistance of source virus to antiretroviral agents 1

Efficacy and Evidence

• A retrospective case-control study found that healthcare workers who used zidovudine after occupational exposure were 81% less likely to become HIV-infected than those who did not 2
• The efficacy of combination PEP is likely higher than monotherapy, though direct comparative data are limited 2
• Animal studies support the use of PEP for a duration of 28 days 2

Common Pitfalls and Caveats

• Do not delay PEP initiation while waiting for source person's HIV test results 1
• Do not test needles or sharp instruments directly for HIV 1
• PEP is unlikely to be effective when initiated more than 72 hours after exposure 1
• Long-acting injectable cabotegravir is not recommended for PEP due to lack of data on safety, tolerability, and efficacy in this setting 3

In conclusion, the first-line regimen is preferred over alternative regimens due to better tolerability, improved adherence, and potentially greater efficacy against resistant strains. The choice between first-line and alternative regimens should prioritize medications that are most likely to be effective and tolerable to ensure completion of the full 28-day course.