This technology includes combinations of currently approved antiretrovirals (ARVs) which could allow for simpler dosing regimens that improve adherence to HIV prevention strategies. Event-Driven PrEP (ED-PrEP) with 2 oral doses of tenofovir disoproxil fumarate (TDF)/emtricitabine (FTC) taken 2-24 hours before sex, a 3rd dose 24 hours after sex, and a 4th dose 48 hours after sex (2+1+1) is considered as a PrEP option by the World Health Organization for men who have sex with men (MSM). Recommended post-exposure prophylaxis (PEP) regimens require 28 days of daily oral dosing. Simpler ED-PrEP and PEP dosing strategies with ARV combinations allowing for one or two doses that effectively reduce risk of infection could provide alternatives conducive to improved adherence. Rapid penetration of elvitegravir and darunavir in rectal tissues could prevent initial rounds of virus replication in mucosal tissues exposed to HIV and persistence of tenofovir diphosphate and emtricitabine triphosphate in rectal tissues may prevent dissemination of virus from sites of virus exposure.