US CDC updated guidelines on PEP (May 2025)

Simon Collins, HIV i-Base

On 8 May 2025, the US CDC updated the guidelines on non-occupational use of PEP.

This is the first update since 2016.

PEP is recommended ideally withiin 24 hours and not later than 72 hours.
The main new recommendation concerns choice of PEP. Preferred PEP now is with on second generation INSTI (bictegravir or dolutegravir) plus tenofovir (TAF or TDF) plus xTC.
The guidelines only clearly recommended when a potential partner is known to be living with HIV and to have a detectable or unknown viral load. However, they also allow PEP on a case by case basis when the risk would clearly be negligible or zero, including when viral load is know to be undetectable.
They still have the 2016 recommendations about when PEP should be prescribed.
The guidelines continue to have very useful sections on counselling including after sexual assault, and on transitioning from PEP to PrEP.
In Table 1, the guidelines still refer to the time needed to achieve maximum protection as needing 7 days for receptive anal sex and 21 days for receptive vaginal sex or injection drug use. Time for insertive sex is stated as unknown.
Rather than just being based on condom use, it might be more helpful if Table 2 showed a range of risks based on clinical factors including viral load which would range from zero to likely >10%. Fir example, the risk per exposure from insertive and receptive penile-vaginal sex as being 4 and 8 per 10,000 exposures (0.04 and 0.08% respectively). The risk from insertive and receptive penile-anal sex as being 11 and 138 per 10,000 exposures (0.11 and 1.38% respectively). Importantly, there is still no reference to local HIV incidence as a factor, which even if just focused in the US might be much higher or lower in different States.

comment

Although this update is the result of an evidence review that started in 2025 the approach to pharmacokinetics and zero-risk situations could have been more helpful aand up-to-date.

The guideliines include a discussion about alternative duration for PEP and two-drug PEP, neither of which are recommended.
The discussion doesn’t include the data supporting initiating PEP with a double-dose to rapidly each therapeutic drug levels within hours rather than weeks (based on event-based dosing for PrEP.
It also misses the option of using rapid PrEP, if available, to help reduce the time to protection, during the often-extended time taken to access PEP.

Given the emphasis for PEP to be started as early as possible in order to reach therapeutic drug levels quickly, the guidelines should have at least discussed the benefits from starting PEP with a double-dose, similar to event-based dosing in BHIVA/BASHH and IAS-USA PrEP guidelines.

This would guarantee either the dual NRTI or the whole PEP regimen potentially reaching therapeutic levels within hours rather than weeks.

It is also a shame that zero-risk situations are not more clearly emphasised, learning from the U-U campaign, as allowing a theoretical insignificant risk is likely to add to the stress of someone who is particularly anxious.

Reference

US CDC. Antiretroviral Postexposure Prophylaxis After Sexual, Injection Drug Use, or Other Nonoccupational Exposure to HIV — CDC Recommendations, United States, 2025. MMWR 2025 / 74(1);1–56. (8 May 2025).
https://www.cdc.gov/mmwr/volumes/74/rr/rr7401a1.htm

Links to other websites are current at date of posting but not maintained.