PP508 - Impact of Central Penetration Effectiveness on Antiretroviral Ototoxicity in Humans: A Review and Meta-Analysis

Abstract:
This review seeks to understand how the CNS Penetration-Effectiveness (CPE) score of antiretroviral therapies (ARTs) relates to the ototoxic effects patients experience by examining previous literature. In doing so, we aim to fill in the gaps in understanding the relationship between varying CPE scores assigned to ARTs and the ototoxic effects patients experience.

Summary:
Objective
To investigate the relationship between the central penetration effectiveness (CPE) of antiretroviral therapies (ARTs) used in prophylactic intervention and management of HIV patients and the ototoxic effects these populations experience. 

Rationale
In 2023, nearly 40 million people were living with HIV. Of those, 77% were on Antiretroviral medications for the treatment and prevention of HIV. The CDC and other health organizations around the globe have a goal of ending the HIV epidemic by 2030. Yet both preclinical and clinical models have shown the ototoxic effects of these medications on auditory tests like extended high-frequency audiometry, otoacoustic emissions, speech in noise testing, and more (DeBacker et al. 2021, Fasunla et al 2019). There is literature that shows that ARTs permeating through the blood-brain barrier can have ototoxic effects for patients. However, there is no previous literature that states whether the penetration of these ARTs through the cerebral spinal fluid (CSF) plays a role in the auditory outcomes of patients. Using the Central Penetration-Effectiveness (CPE) score, a scoring system created to measure how effective ARTs are at penetrating the blood-brain barrier (Letendre et al. 2008), we hope to better understand the relationship between penetration scores and auditory outcomes. Using the CPE score criteria to classify the effects these therapies have on the auditory system will allow physicians to incorporate these findings into the treatment recommendations for their patients. 

Designs
The search was conducted using controlled vocabulary (e.g., MeSH or Emtree) in the following databases: PubMed, Embase, and Web of Science. Inclusion criteria included all study designs that used human subjects with exposure to ARTs and had hearing or balance-related measures,  and articles were excluded if they met any of the following conditions: study designs that included non-human subjects, no mention of ART exposure, pharmacokinetic studies that do not measure a hearing-related outcome, or opinion studies about deafness and HIV/AIDS. A total of 2059 relevant articles were identified. 935 duplicates were identified and removed.  The remaining 1,124 articles underwent abstract screening where each was reviewed by two evaluators for inclusion. Screened articles will undergo full-text screening and the final cohort of included articles will undergo data extraction to identify relevant variables including auditory outcome measures, population features, and treatment factors.

Results and Conclusions
Although the full-text review is still underway, many common themes in the literature have become apparent. Roughly ⅔ of the studies are on adults compared to children, ⅔ of studies are from outside the US, and all the studies report varying auditory outcomes from many test measures including peripheral and central tests and cognitive screeners, including audiometry, auditory brain stem responses, otoacoustic emissions, latency responses, speech test, and the Montreal Cognitive Assessment. This information shows us that the result of this study could have a global impact and help physicians and researchers better understand how ARTs affect certain populations as well as what test methods offer consistent results in monitoring. Ultimately leading to future monitoring protocols and well-informed recommendations.