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Si us plau utilitzeu sempre aquest identificador per citar o enllaçar aquest document: https://hdl.handle.net/2445/208683
Assessment of different post-exposure prophylaxis regimens for prevention of HIV infection in exposed individuals
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[eng] Background: Post-exposure prophylaxis (PEP) is a biomedical strategy to prevent HIV infection when initiated within 72 hours after exposure and maintained for 28 days. Although human efficacy trials are ethically and methodologically limited, animal models support early and sustained PEP use. Despite guideline recommendations, clinical data remain heterogeneous and of low quality.
Hypothesis: The adherence, tolerability, of PEP regimens vary significantly influencing the effectiveness. Integrase inhibitor-based regimens may offer improved tolerability and PK/PD profiles compared to protease inhibitors.
Materials and methods: This doctoral thesis evaluated PEP through both clinical and experimental approaches. The clinical branch examined effectiveness, adherence, tolerability, follow-up, dropout causes, and seroconversion, while the laboratory branch focused on infectivity assays, PK/PD, and immunologic profiles in human rectal explant models. The research included a retrospective study, a randomized clinical trial, a one-arm clinical trial, experimental analyses, and a network meta-analysis. Studies focused on vulnerable populations, including sexual assault survivors and men who have sex with men (MSM).
Results: In the descriptive study, 883 of 1,600 individuals received PEP following sexual assault. Low completion (29%) and follow-up rates were observed. Over half experienced adverse events (mostly gastrointestinal), and discontinuation was common—especially with protease inhibitors. One seroconversion occurred among MSM participants. In the randomized trial (n=157), elvitegravir/cobicistat showed better adherence, fewer adverse events, and lower discontinuation rates than lopinavir/ritonavir. One seroconversion was observed after repeated exposures. Experimental analyses showed higher mucosal drug concentrations for elvitegravir compared to lopinavir/ritonavir, though neither regimen prevented infection in explant models. CD8+ T-cell activation inversely correlated with infectivity. In the one-arm trial (n=399), doravirine/lamivudine/tenofovir disoproxil showed 96% adherence, 29% non-completion, 31% mild adverse events, and no seroconversions. Across the three studies, PEP non-completion was associated with younger age, adverse events (gastrointestinal or neurological), poor adherence, use of protease inhibitors (especially lopinavir/ritonavir), and loss to follow-up. The network meta-analysis (n=1,105) confirmed that EVG/c had the highest probability of treatment completion and tolerability. Maraviroc had the lowest rate of discontinuation due to adverse events, while LPV/r showed the poorest outcomes overall.
Conclusion: This thesis provides robust, interdisciplinary evidence to support the preferential use of integrase inhibitor-based PEP. By addressing key clinical, pharmacologic, and immunologic gaps, it lays the groundwork for future updates to prevention guidelines and contributes to a more person-centered, evidence-based approach to HIV prevention.
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INCIARTE PORTILLO, Alexy. Assessment of different post-exposure prophylaxis regimens for prevention of HIV infection in exposed individuals. [consulta: 15 de desembre de 2025]. [Disponible a: https://hdl.handle.net/2445/208683]