Two-drug PEP and PrEP consist of the same medication, and a subsequent exposure that occurs while someone is on a current course of PEP is similar to an exposure that occurs while taking PrEP. When used for PrEP, co-formulated tenofovir-disoproxil and emtricitabine is proven to prevent HIV acquisition.^97,98  

From the ANRS Prévenir trial of daily versus on-demand PrEP, extending the treatment for 48 hours after the last exposure is now known to be highly efficacious for the prevention of HIV acquisition via sex in MSM.⁹⁹

The iPrEx PrEP trial enrolled the highest number of transgender women to date and no HIV infections were observed in transgender women whose blood levels were compatible with taking four or more doses of PrEP weekly.¹⁰⁰ However, on stratification, PrEP did not provide a benefit for transgender women compared to the overall reduction in HIV incidence in the active study arm.

Tenofovir levels decline rapidly after cessation in the vagina and neovagina,^51,101,102 so PEP should be continued for seven days after the last high-risk exposure.

There is no empirical evidence to guide clinicians managing people who inject drugs who have a repeat HIV-risk injecting drug use exposure during the PEP course. Therefore, extending the course by a further 28 days from repeat exposures is recommended in this situation.

We recommend clinicians follow this advice:

• cis-gendered MSM with further risk exposure over 48 hours before completion of the 28-day PEP course (day 1–26)
  • do not extend the PEP course.

• cis-gendered MSM with further risk exposure under 48 hours before completion of the 28-day PEP course on either two- or three-drug PEP (day 27-28)
  • take two-drug PEP for a further 48 hours, ensuring two days with no condomless anal sex before ceasing PEP 
  • assess for PrEP.

• cis-gendered women, trans and gender diverse people having receptive penile -vaginal/neovaginal/front hole sex (day 21-28)
  • continue prescribed (two- or three-drug) PEP for an additional seven days 
  • assess for PrEP.

• people who inject drugs
  • continue prescribed (two- or three-drug) PEP for an additional 28 days 
  • assess for PrEP.