Prioritization of adverse events related to integrase inhibitors and NNRTIs: a disproportionality analysis using data from the FAERS database.

BACKGROUND AND OBJECTIVES: Integrase strand transfer inhibitors (INSTIs) and NNRTIs are widely used in the treatment of HIV, but the real-world adverse events (AEs) profiles of these drugs remain inadequately characterized. We prioritized AEs reported with INSTIs and NNRTIs using data from the FDA Adverse Event Reporting System (FAERS).

METHODS: Using FAERS data (from FDA approval to June 2024) for 10 drugs (cabotegravir, dolutegravir, raltegravir, elvitegravir, bictegravir, nevirapine, efavirenz, rilpivirine, doravirine and etravirine), we assessed AE clinical priority using a multi-criteria score. The score evaluated four criteria: clinical relevance, reporting proportion, case fatality rate and signal stability. We calculated reporting odds ratios (RORs) with 95% CIs; signals required the lower limit of 95% CIs of the ROR, ROR025 > 1 after Bonferroni correction across [N] tested AEs per drug. Events related to medication errors or HIV-related conditions were excluded. A case-by-case assessment was conducted to evaluate the confounding factors from co-medications and indications.

RESULTS: We found 4487/6362 (70.5%) were low priority (0-2 points) and 1849/6362 (29.1%) were moderate (3-5 points), 2, 8, 6 and 15 marginally high-priority (≥4.5 points) adverse pregnancy outcomes were identified with dolutegravir, raltegravir, nevirapine, efavirenz, respectively; 26 AEs were high clinical priorities (>5 points). After case-by-case assessment, five noteworthy AEs remained. These included efavirenz-related haemolytic anaemia, etravirine-related hepatic failure, dolutegravir-related foetal death, raltegravir-related drug reaction with eosinophilia and systemic symptoms, and raltegravir-related hepatic failure.

CONCLUSIONS: This study provides a systematic framework for evaluating post-marketing AEs of INSTIs and NNRTIs using a semi-quantitative scoring system. Our findings identified five high-priority AEs that require clinical validation and further investigation.