Disclosed is the use of a nucleotide reverse transcriptase inhibitor, a nucleotide reverse transcriptase inhibitor, and an integrase inhibitor prior to an exposure to a potential human immunodeficiency virus (HIV) infection, to protect the subject from the HIV infection. In some embodiments, a prophylactically effective amount of emtricitabine (FTC), a prophylactically effective amount of tenofovir or a tenofovir prodrug, such as tenofovir alafenamide (TAF) or tenofovir disoproxil fumarate (TDF), a prophylactically effective amount of the integrase inhibitor elvitegravir (EVG), and optionally cobicistat (COBI) are used to inhibit or prevent an HIV infection, wherein these agents are administered only prior to the exposure. In specific non-limiting examples, only one dose of the anti-retroviral viral agents is administered to a subject prior to the exposure.
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