Non-occupational post-exposure prophylaxis (nPEP) is a public health instrument in HIV prevention. Treatment efficacy depends on round the clock availability, adequate prescription, drug efficacy and treatment adherence. Efforts should be made to achieve the most adequate treatment prescription and highest treatment retention for patients exposed to HIV. This thesis investigated treatment prescription, determinants of treatment completion and a strategy to improve treatment completion in a mixed population from a tertiary HIV reference. We showed that adherence to nPEP guidelines is 98.8% in emergency physicians prescribing nPEP round the clock in the emergency department. A low treatment adherence of 60% was identified by this study and strategies to improve it were searched. A second study identified independent determinants of adherence such as men who have sex with men (MSM) sexual orientation (OR, 1.40; 95%CI,1.04–1.90), being a native Belgian (OR, 1.50; 95%CI, 1.18–1.90), older age (OR, 1.02; 95%CI, 1.01–1.04), being a sexual assault survivor (OR, 0.59; 95%CI, 0.38–0.91), having had a previous nPEP treatment (OR, 1.44; 95%CI, 1.02–2.02), consultation during daytime (OR, 1.35; 95%CI, 1.07–1.70) and coverage from a health insurance (OR, 2.11; 95%CI, 1.58–2.89). A third study evaluated how a single tablet regimen of emtricitabine/tenofovir disoproxil fumarate plus cobicistat-boosted elvitegravir (OR 1.62; 95%CI, 1.08-2.42; p=0.019), as well as psychological support (OR: 3.13, 95%CI: 2.00–4.17, p<0.001), increase treatment completion rates in nPEP in sexual assault victims when compared to older regimens or absence of psychological support. We conclude that a system relying on emergency physicians to prescribe PEP is accurate, that determinants of low completion rates should be addressed during consultation and follow-up, that psychological support should be offered to all sexual assault victims and that a modern single tablet regimen should be preferred for nPEP initiation at the emergency ward. ; Doctorat ...