Noise-induced hearing loss in mice treated with antiretroviral drugs

Abstract

The results reported here for CBA/CaJ mice describe the effects of regular dosing with a common antiretroviral drug combination on outer hair cell (OHC) function using measures of 2f 1 -f 2 distortion product otoacoustic emissions (DPOAEs) and auditory brainstem responses (ABRs). Specifically, experimental mice were treated daily over a 3-mo period with the nucleoside reverse transcriptase inhibitors (NRTIs), zidovudine (ZDV) and lamivudine (3TC), dissolved in their drinking water, while their control counterparts received untreated water. DPOAE levels and ABR detection thresholds prior to and after 12 wk of NRTI treatment did not differ between experimental and control groups. To assess whether NRTI treatment potentiates the adverse effects of noise overexposure on OHC function, both experimental and control mice were exposed 1 wk later, while still on the drug regimen, to a 10-kHz octave-band noise (OBN) at 105 dB SPL for 1 h. A major outcome of the sound overexposure episode was that the NRTI-pretreated mice showed significantly greater permanent OBNinduced reductions in DPOAE levels at 2 wk postexposure than were observed for the untreated control animals. These findings support the notion that a synergistic relationship exists between certain NRTIs and intense sounds in that such preexposure drug treatments produced greater noiseinduced decreases in DPOAE activity than did noise exposure alone. This drug/noise interaction is consistent with the known harmful effects of NRTIs on cellular mitochondrial activity.

Hearing profile of gold miners with and without tuberculosis

“…The effect of HIV and antiretroviral therapy, which has reported ototoxicity in some cases,20 was not accounted for in this study since information on the HIV status of employees was unavailable. According to current estimates, however, as many as 85–90% of the TB cohort may have been affected with HIV 3 5.…”

“…According to current estimates, however, as many as 85–90% of the TB cohort may have been affected with HIV 3 5. The role of immune suppression, opportunistic infections, the neurotropic nature of HIV, tumours, antiretroviral medication, ototoxic medications, etc, on the hearing status of the miners must therefore also be considered 5 20 38. TB status consequently represents a larger group of complex risk factors predisposing affected individuals to progressive hearing loss 39…”

“…Noise-induced threshold shifts also depend on the interaction between intrinsic and environmental factors 18. Environmental factors or concurrent and contributing factors may include ototoxic drugs (eg, streptomycin), infection or illness (eg, HIV/AIDS and TB) and age 18 20. Cochlear ototoxicity proceeds stepwise in the damaging of the cochlear structures, affecting the outer hair cells first followed by the inner hair cells 21.…”

“…HIV may also cause hearing changes, possibly due to its neurotropic nature with direct involvement of the eighth cranial nerve. Between 21% and 49% of HIV-infected patients have been reported to develop a sensorineural hearing loss, which predominantly involves the higher frequencies 20. Furthermore, the same genes that are responsible for age-related hearing loss are also responsible for NIHL,18 22 23 and the effects of age add linearly to the effects of occupational noise exposure 23…”

Audiological monitoring for ototoxic tuberculosis, human immunodeficiency virus and cancer therapies in a developing world setting

“…noise) due to effects on outer hair cell mitochondria. 28 This may have implications for HIVpositive patients receiving HAART, in terms of noise exposure and noise-induced hearing loss.…”