What is the Pre-Exposure Prophylaxis (PrEP) with the lowest side effects?

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Last updated: March 25, 2025View editorial policy

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From the Guidelines

Tenofovir alafenamide/emtricitabine (TAF/FTC) is the recommended Pre-Exposure Prophylaxis (PrEP) with the lowest side effects, particularly for men who have sex with men (MSM) with or at risk for kidney dysfunction, osteopenia, or osteoporosis, as it causes less kidney stress and less bone mineral density loss compared to tenofovir disoproxil fumarate/emtricitabine (TDF/FTC) 1. The key benefits of TAF/FTC include:

  • Lower concentrations of tenofovir in the bloodstream, reducing the risk of kidney damage and bone mineral density loss
  • High levels of tenofovir in the tissues where HIV exposure typically occurs, maintaining effective prevention
  • A similar side effect profile to TDF/FTC, with mild and typically temporary side effects such as nausea, headache, and stomach discomfort
  • Once-daily dosing, making it a convenient and manageable option for individuals at risk of HIV infection It's essential to note that while TAF/FTC is recommended for certain populations, TDF/FTC is still an effective and widely used PrEP option, and the choice between the two should be made in consultation with a healthcare provider, taking into account individual risk factors and medical history 1. Regular monitoring, including HIV testing every 3 months and kidney function tests, is necessary for all individuals on PrEP.

From the Research

Pre-Exposure Prophylaxis (PrEP) Options

The available evidence suggests that there are several PrEP options with varying side effect profiles.

  • Tenofovir/emtricitabine (TDF/FTC) is a commonly used PrEP regimen, which has been shown to have a good safety profile 2, 3.
  • The main adverse effects observed with TDF/FTC are gastrointestinal related, including mild to moderate nausea, vomiting, and diarrhea 2.
  • Long-acting cabotegravir is a newer PrEP option that has been shown to have a manageable safety profile and is more effective than TDF/FTC in preventing HIV infection 4.
  • Compared to TDF/FTC, long-acting cabotegravir is associated with a lower risk of HIV infection and less decreased creatinine clearance, but more tolerated injection sites adverse events 4.

Side Effect Comparison

A meta-analysis of 13 randomized trials of PrEP found no significant difference in the risk of grade 3/4 clinical adverse events or serious adverse events between TDF/FTC and control 3.

  • Long-acting cabotegravir has been shown to have a lower risk of decreased creatinine clearance compared to TDF/FTC 4.
  • However, long-acting cabotegravir is associated with more tolerated injection sites adverse events compared to TDF/FTC 4.

PrEP Regimens with Lower Side Effects

Based on the available evidence, long-acting cabotegravir may be a PrEP option with lower side effects compared to TDF/FTC, particularly in terms of decreased creatinine clearance 4.

  • However, the choice of PrEP regimen should be individualized based on patient preferences, medical history, and other factors 5, 6.

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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