Infection with the human immunodeficiency virus (HIV) remains a public health concern worldwide. Young adults are the most affected by the pandemic, with 40% of new cases concerning people from the 15-24 year age group, which also is the most sexually active. There are four prevention strategies of HIV infection. One of them is post-exposure prophylaxis (PEP) by the administration of antiretroviral therapy, which can be used in post-coital situation for exposed patients. The probability of HIV transmission depends on the type of exposure, infectivity level of the source, and susceptibility of the exposed person. The risk of acquiring HIV after an exposure incident can be calculated by multiplying the risk that the source person is HIV-positive by the risk of exposure. Prophylaxis is recommended when the risk of transmission is greater than 1/1,000 and must be considered when the risk is between 1/1,000 and 1/10,000. When this risk is below 1/10,000, prophylaxis is not recommended. All cases need to be evaluated on an individual basis. Most recent guidelines recommend two nucleoside reverse transcriptase inhibitors (NRTI) associated with either an integrase inhibitor (INI) or a boosted protease inhibitor (PI/r). The treatment should be initiated as soon as possible after exposure, preferably within 24 h or, at the latest, within 72 h. The treatment duration is 28 days. HIV serology is performed at Day 0, Week 8 and Week 12 using a 4th generation blood test. Counselling on HIV prevention should be provided during the follow-up.