What is the most appropriate PrEP regimen for a 32-year-old MSM with decreased sexual activity and concerns about long-term effects of daily TAF-emtricitabine?

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Appropriate PrEP Regimen for MSM with Decreased Sexual Activity

SM can take tenofovir disoproxil fumarate (TDF)-emtricitabine "on demand" utilizing two tablets prior to sexual activity, then one tablet per day for the subsequent 2 days.

Rationale for On-Demand TDF-Emtricitabine

The 2020 International Antiviral Society-USA (IAS-USA) guidelines specifically recommend the 2-1-1 (on-demand) oral dosing schedule for men who have sex with men (MSM) with an evidence rating of AIa (highest quality evidence) 1. This regimen requires:

  • Two tablets of TDF-emtricitabine taken 2-24 hours before sexual activity
  • One tablet 24 hours after the first dose
  • One final tablet 24 hours after that

For SM, who has predictable sexual activity twice monthly, this regimen is particularly appropriate as it:

  1. Reduces medication exposure compared to daily dosing
  2. Addresses his concerns about long-term medication effects
  3. Maintains high efficacy for HIV prevention in MSM

Why Not TAF-Emtricitabine On-Demand?

TAF-emtricitabine is not recommended for on-demand dosing. The IAS-USA guidelines explicitly state: "There are no data supporting event-driven use of tenofovir alafenamide/emtricitabine or tenofovir alafenamide/emtricitabine in individuals other than MSM" 1. The 2-1-1 dosing has only been validated with TDF-emtricitabine, not TAF-emtricitabine.

Why Not Switch to Daily TDF-Emtricitabine?

While switching to daily TDF-emtricitabine would be an option, it doesn't address SM's concerns about long-term medication effects, as he would still be taking a daily medication. Additionally, with his predictable twice-monthly sexual activity, on-demand dosing provides adequate protection with less medication exposure.

Why Continue Daily TAF-Emtricitabine?

Continuing daily TAF-emtricitabine would not address SM's concerns about long-term effects of daily medication. While TAF has improved renal and bone safety profiles compared to TDF 2, the on-demand TDF-emtricitabine regimen would significantly reduce overall drug exposure given his infrequent sexual activity.

Efficacy and Safety Considerations

  • The on-demand TDF-emtricitabine regimen has demonstrated high efficacy in MSM. The IPERGAY study showed an 86% reduction in HIV acquisition risk with this dosing strategy 1.
  • For MSM, maximum protection with TDF-emtricitabine is achieved within 24 hours of the double dose 1.
  • On-demand dosing reduces overall drug exposure, potentially minimizing long-term side effects while maintaining protection during periods of risk.

Important Monitoring Considerations

If SM switches to on-demand TDF-emtricitabine:

  • HIV testing should still be performed every 3 months 3
  • Renal function should be monitored every 6 months (creatinine clearance) 3
  • STI screening should be conducted at least every 6 months 3

Potential Pitfalls and Caveats

  1. Adherence to timing: SM must be counseled on the importance of taking the medication at the correct times relative to sexual activity.
  2. Planning ahead: The first dose must be taken 2-24 hours before sexual activity, requiring some planning.
  3. Multiple encounters: If SM has multiple sexual encounters over consecutive days, he should take one pill daily until 2 days after the last sexual encounter 1.
  4. Renal function: TDF has greater potential for renal toxicity than TAF. SM's renal function should be assessed before switching and monitored regularly.

By switching to on-demand TDF-emtricitabine, SM can address his concerns about long-term medication effects while maintaining effective protection against HIV acquisition during his predictable twice-monthly sexual activity.

References

1
Guideline

Guideline Directed Topic Overview

Dr.Oracle Medical Advisory Board & Editors, 2025

3
Guideline

HIV Pre-Exposure Prophylaxis (PrEP) Guidelines

Praxis Medical Insights: Practical Summaries of Clinical Guidelines, 2025

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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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