With NIH support, the Ubongo Sikivu cohort of both people living with HIV (PLWH) and uninfected controls was established in Tanzania and has had regular assessments of their peripheral hearing ability over 10+ years with detailed central auditory and neurocognitive assessments added over the last 5 years. This cohort is uniquely positioned to address the issues posed by PAR-20-127 “Advancing HIV/AIDS Research within the Mission of the NIDCD.” Data from the cohort has already answered important questions about the ototoxicity of anti-retrovirals, the effects of HIV infection and treatment on both peripheral and central hearing parameters, and the relationship of central auditory test (CAT) results to neurocognitive performance. By following this cohort longitudinally questions about how CATs could be used to predict or track neurocognitive performance and how age and long-term anti-retroviral treatment affect the auditory system can be answered. To date, the most significant result has been demonstrating that CAT results correlate with cognitive performance. This suggests CAT results might be useful for forecasting or tracking cognitive decline over time. The next important steps are determining whether worsening CAT performance precedes the later development of cognitive deficits in PLWH and which central auditory tests and other variables can predict neurocognitive deficits accurately. Neurocognitive screening tests are often sensitive to education, literacy, and culture. Full neurocognitive test batteries can be difficult to employ, particularly in the developing world where clinician time is limited, few trained personnel are available, and normative data often do not exist. Using CATs would be a major advance for following HIV+ patients because the CATs can be short (a gap detection test takes 5 minutes), easy to explain (the hearing-in-noise test and triple digit task involve identifying words or numbers in background noise), or effortless for the subject (the FFR test requires no subject input at all). This project’s goal is tracking the trajectory of peripheral auditory, central auditory, and neurocognitive performance over time by continuing to follow this cohort. With these longitudinal data machine learning and other statistical techniques will be applied to assess which factors forecast the subsequent development of cognitive deficits and which factors or combination of factors identify those with existing neurocognitive deficits. An international team with experience in central auditory testing and neurocognitive testing in PLWH has been assembled. Dr. Nina Kraus and her Northwestern team are internationally recognized experts in the auditory FFR. The Dar es Salaam team has extensive experience in otolaryngology and performing peripheral auditory, central auditory, and neurocognitive tests. Drs. Roth and Boivin are experts in assessing neurocognitive function. Dr. Gui has diverse biostatistical experience. Dr. Niemczak is an expert in peripheral and central auditory processing. This team and longitudinal cohort offer the unique ability to assess the use of CATs in evaluating cognition as well as the effects of aging and medications on both central and peripheral auditory function in PLWH.

Project Narrative This study will study a unique cohort including both people living with HIV and uninfected controls in Tanzania to determine whether central auditory tests could predict the subsequent development of cognitive programs or screen for cognitive problems in those with HIV. This could alter clinical practice if these easy-to-perform central auditory tests could be used clinically to screen for or track central nervous system effects in people living with HIV This study will also evaluate the long-term auditory effects of HIV infection and treatment.