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 over-exposure on OHC function, both experimental and control mice were exposed I wk later, while still on the drug regimen, to a 10-kHz octave-band noise (OBN) at 105-dB SPL for I h. A major outcome of the sound over-exposure episode was that the NRTI-pretreated mice showed significantly greater permanent OBN-induced 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 NRTls and intense sounds in that such pre-exposure drug treatments produced greater noise-induced decreases in DPOAE activity than did noise exposure alone. This drug/noise interaction is consistent with the known harmful effects of NRTls on cellular mitochondrial activity. (c) 2008 Elsevier B. V. All rights reserved.