OBJECTIVES:Abnormal hearing tests have been noted in human immunodeficiency virus (HIV)–infected patients in several studies, but the nature of the hearing deficit has not been clearly defined. The authors performed a cross-sectional study of both HIV+ and HIV− individuals in Tanzania by using an audiological test battery. The authors hypothesized that HIV+ adults would have a higher prevalence of abnormal central and peripheral hearing test results compared with HIV− controls. In addition, they anticipated that the prevalence of abnormal hearing assessments would increase with antiretroviral therapy (ART) use and treatment for tuberculosis (TB). DESIGN:Pure-tone thresholds, distortion product otoacoustic emissions (DPOAEs), tympanometry, and a gap-detection test were performed using a laptop-based hearing testing system on 751 subjects (100 HIV− in the United States, plus 651 in Dar es Salaam, Tanzania, including 449 HIV+ 130 ART− and 319 ART+, and 202 HIV−, subjects. No U.S. subjects had a history of TB treatment. In Tanzania, 204 of the HIV+ and 23 of the HIV− subjects had a history of TB treatment. Subjects completed a video and audio questionnaire about their hearing, as well as a health history questionnaire. RESULTS:HIV+ subjects had reduced DPOAE levels compared with HIV− subjects, but their hearing thresholds, tympanometry results, and gap-detection thresholds were similar. Within the HIV+ group, those on ART reported significantly greater difficulties understanding speech in noise, and were significantly more likely to report that they had difficulty understanding speech than the ART− group. The ART+ group had a significantly higher mean gap-detection threshold compared with the ART− group. No effects of TB treatment were seen. CONCLUSIONS:The fact that the ART+/ART− groups did not differ in measures of peripheral hearing ability (DPOAEs, thresholds), or middle ear measures (tympanometry), but that the ART+ group had significantly more trouble understanding speech and had higher gap-detection thresholds indicates a central processing deficit. These data suggest that(1) hearing deficits in HIV+ individuals could be a CNS side effect of HIV infection, (2) certain ART regimens might produce CNS side effects that manifest themselves as hearing difficulties, and/or (3) some ART regimens may treat CNS HIV inadequately, perhaps due to insufficient CNS drug levels, which is reflected as a central hearing deficit. Monitoring of central hearing parameters could be used to track central effects of either HIV or ART.