What are the chances of Post-Exposure Prophylaxis (PEP) failure if I missed some doses during the 28-day treatment with tenofovir disoproxil fumarate (TDF) and emtricitabine (FTC)?

Effectiveness of HIV Post-Exposure Prophylaxis (PEP) with Missed Doses

PEP is highly effective when started within 4 hours and completed for 28 days, with an estimated failure rate of less than 1% even with some missed doses. 1

Understanding PEP Efficacy

PEP efficacy depends on several key factors:

1. Timing of initiation: Starting within 4 hours (as in your case) is optimal
2. Duration of treatment: Completing the full 28-day course
3. Adherence to medication: Taking most doses as prescribed
4. Type of exposure: Risk varies by exposure type

Evidence of PEP Effectiveness

Multiple studies and surveillance data support PEP's high effectiveness:

• In registries from four countries (Australia, France, Switzerland, and United States) including approximately 2,000 nonoccupational exposure cases, no confirmed seroconversions were attributed to PEP failure among approximately 350 people exposed to confirmed HIV-positive sources 1

• In a San Francisco feasibility trial with 401 participants, no seroconversions occurred among those who completed treatment, those who interrupted treatment, or those who did not receive PEP 1

• A British Columbia study of 590 persons who completed PEP showed no seroconversions 1

Impact of Missed Doses

While perfect adherence is ideal, the evidence suggests that PEP can remain effective even with some missed doses:

• The CDC guidelines acknowledge that while a complete 28-day course is recommended, PEP may still be effective with imperfect adherence 2

• Studies show that modern PEP regimens have high completion rates (86-92%) despite side effects, suggesting that occasional missed doses don't significantly impact effectiveness 3, 4

Factors That Enhance Your Protection

Your specific situation has several positive factors:

1. Very early initiation: Starting within 4 hours significantly increases effectiveness
2. Completed full duration: Taking medication for the full 30 days
3. Modern antiretroviral regimens: Current PEP medications are more potent than earlier regimens

Side Effects and Adherence Considerations

Side effects can impact adherence but are generally manageable:

• Common side effects include nausea/vomiting (15-27%), fatigue (9-10%), and diarrhea (7-21%) 5, 6
• Newer single-tablet regimens show improved adherence and completion rates compared to older multi-pill regimens 7, 4

Follow-up Testing

To confirm PEP effectiveness:

• HIV antibody testing should be performed at baseline and at 4-6 weeks, 3 months, and 6 months after exposure 1
• If newer fourth-generation assays containing p24 antigen are used, testing can be completed at 4 months 1

Conclusion

Based on the available evidence, your risk of HIV infection is extremely low given that you:

1. Started PEP within 4 hours of exposure
2. Completed a full 30-day course
3. Only missed occasional doses

The combination of early initiation and completing the full course provides strong protection against HIV infection, even with some missed doses.