2-1-1 PrEP

On-demand HIV pre-exposure prophylaxis (PrEP; also known as “nondaily PrEP,” “event-driven PrEP,” or “2-1-1 PrEP”) is being requested more frequently by patients, so here is a quick update:

  • The 2018 IAS-USA Panel states: “… ‘2-1-1’ dosing may be considered as an alternative to daily PrEP for MSM with infrequent sexual exposures (evidence rating AIa). This regimen is not recommended in other risk groups or in patients with active HBV infection because of the risk of hepatitis flare and hepatic decompensation (evidence rating BIIa).” The San Francisco Department of Public Health, the NYS DOH, and CDPH also endorse 2-1-1 dosing strategy as an alternative to daily PrEP.
  • 2-1-1 PrEP reduced HIV risk by 97% in the IPERGAY trial which included MSM and transgender women who have sex with men (TGWM), who were HBsAg negative and had a CrCl > 60 mL/min. It was also studied in an open label trial with no infections documented while patients were taking 2-1-1 PrEP (two infections occurred after stopping PrEP).
  • 2-1-1 PrEP was studied in a small sample size of TGWM and data show reductions in tenofovir and FTC levels when used with feminizing hormones in TGWM. Therefore, 2-1-1 PrEP can be used in TGWM with caution.
  • The dosing instruction is: take a loading dose of 2 TDF/FTC tabs 2-24hrs before sex, followed by 3rd tab 24hrs and 4th tab 48hrs after the loading dose
  • It is associated with the same short-term adverse events as daily PrEP including GI symptoms and rare renal dysfunction.
  • It requires planning (to remember the loading dose 2-24hrs before sex) and some level of organization (to remember single doses at 24 and 48hrs)
  • Contraindications are positive HBsAg or creatinine clearance >60 mL/min
  • It requires the same labs as daily PrEP at baseline and every 3 months
  • Prescriptions can be written for Truvada, #30, 2 refills, “take as directed” using ICD-10 code Z20.6
  • We have no data on using Descovy on-demand but would recommend a clinical consultation with Dr. Parya Saberi, Dr. Hyman Scott, and/or the National PrEPline


Please see attached publication by Drs. Saberi and Scott on 2-1-1 PrEP which includes this handy figure to explain dosing instructions to patients (downloadable handout available here):