Clinical drug investigation · 2026
Formulation-Specific Safety Issues of HIV Pre-exposure Prophylaxis Drugs: A Disproportionality Analysis of the FAERS Database.
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Rozza Davide, Poluzzi Elisabetta, Antonazzo Ippazio Cosimo, Boccia Angela, Paccini Marco, Gallucci Fortuna, Ponticelli Domenico, Geraci Giulio, Agüero Fernando, Mazzaglia Giampiero, Mantovani Lorenzo Giovanni, Raschi Emanuel, Ferrara Pietro
Аннотация
BACKGROUND AND OBJECTIVE: As human immunodeficiency virus (HIV) pre-exposure prophylaxis (PrEP) use expands, real-world post-marketing safety evidence remains limited, particularly regarding potential formulation-specific adverse-event patterns across oral and long-acting agents. We aimed to characterise the post-marketing safety profiles of FDA-approved PrEP drugs using the FDA Adverse Event Reporting System (FAERS).
METHODS: We conducted a disproportionality analysis using the FDA Adverse Event Reporting System (FAERS) data from 2012 to 2024. Individual Case Safety Reports (ICSRs) listing emtricitabine/tenofovir disoproxil fumarate (FTC/TDF), emtricitabine/tenofovir alafenamide (FTC/TAF) or cabotegravir (CAB) as suspected PrEP drugs were included. Two comparator groups were used: all non-PrEP ICSRs and ICSRs involving non-PrEP HIV drugs. Disproportionality was evaluated at the MedDRA high-level term (HLT) level using reporting odds ratios and 95% confidence intervals (CIs), identifying signals of disproportionate reporting (SDRs) with a lower bound of the 95%CIs > 1. Sensitivity analyses explored sex, reporter type, and indication.
RESULTS: We identified 3201 PrEP-related ICSRs (FTC/TDF: 2688; FTC/TAF: 463; CAB: 50), predominantly involving young adult males. FTC/TDF exhibited a broad pattern of SDRs-including renal/metabolic abnormalities, muscular signals, mucosal disorders and some previously under-characterised signals-many of which attenuated when using HIV-treated comparators. FTC/TAF showed a narrower, highly consistent pattern dominated by hepatobiliary and metabolic monitoring procedures, renal function evaluations and neurosensory disturbances. CAB showed specific, reproducible signals for injection-site, dermatologic and procedure-related events.
CONCLUSIONS: PrEP agents display distinct, formulation-specific and reproducible safety patterns in FAERS. Comparator choice substantially influences the detection and interpretation of SDRs and can help distinguish reproducible formulation-related reporting patterns from findings that may be driven by the clinical and reporting context. These insights highlight priority areas for future research.
METHODS: We conducted a disproportionality analysis using the FDA Adverse Event Reporting System (FAERS) data from 2012 to 2024. Individual Case Safety Reports (ICSRs) listing emtricitabine/tenofovir disoproxil fumarate (FTC/TDF), emtricitabine/tenofovir alafenamide (FTC/TAF) or cabotegravir (CAB) as suspected PrEP drugs were included. Two comparator groups were used: all non-PrEP ICSRs and ICSRs involving non-PrEP HIV drugs. Disproportionality was evaluated at the MedDRA high-level term (HLT) level using reporting odds ratios and 95% confidence intervals (CIs), identifying signals of disproportionate reporting (SDRs) with a lower bound of the 95%CIs > 1. Sensitivity analyses explored sex, reporter type, and indication.
RESULTS: We identified 3201 PrEP-related ICSRs (FTC/TDF: 2688; FTC/TAF: 463; CAB: 50), predominantly involving young adult males. FTC/TDF exhibited a broad pattern of SDRs-including renal/metabolic abnormalities, muscular signals, mucosal disorders and some previously under-characterised signals-many of which attenuated when using HIV-treated comparators. FTC/TAF showed a narrower, highly consistent pattern dominated by hepatobiliary and metabolic monitoring procedures, renal function evaluations and neurosensory disturbances. CAB showed specific, reproducible signals for injection-site, dermatologic and procedure-related events.
CONCLUSIONS: PrEP agents display distinct, formulation-specific and reproducible safety patterns in FAERS. Comparator choice substantially influences the detection and interpretation of SDRs and can help distinguish reproducible formulation-related reporting patterns from findings that may be driven by the clinical and reporting context. These insights highlight priority areas for future research.