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.