Literature review

Noise-induced hearing loss in mice treated with antiretroviral drugs (Betkas et al., 2008)

  • Betkas et al describe the effects of regular dosing with a common antiretroviral drug combination on outer hair cell (OHC) function using measures of 2f1-f2 distortion product otoacoustic emissions (DPOAEs) and auditory brainstem responses (ABRs)
  • 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 to noise 1 wk later
  • A major outcome of the sound over-exposure episode was that the NRTI-pretreated mice showed significantly greater permanent noise-induced reductions in DPOAE levels at 2 wk postexposure than were observed for the untreated control animals (which is similar to this case of human patient 1 vs. 2)
  • These findings support the notion that a synergistic relationship exists between certain NRTIs and intense sounds in that such preexposure 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 NRTIs on cellular mitochondrial activity

 

Marra et al. (1997) explored the relationship between hearing loss and HIV patients undergoing antiretroviral therapy

  • Hearing loss was common, seen in 29 subjects (29%).
  • It was significantly associated with age and history of ear infection and tended to be more common in subjects prescribed antiretroviral agents.
  • An interaction existed between age and antiretroviral therapy; the association between hearing loss and antiretroviral therapy was significant for subjects aged 35 years or older, but not for subjects younger than 35 years (as seen in this presentation, with patient 3)

Note: a more recent, larger study has not supported the association of hearing loss and HIV treatment:

REFERENCES

Barr SD, Smiley JR, Bushman FD (February 2008). “The interferon response inhibits HIV particle production by induction of TRIM22″. PLoS Pathog. 4 (2).

Betkas, D., Martin, G.K., Stanger, B.B., & Lonsbury-Martin, B. (2008). Noise-induced hearing loss in mice treated with antiretroviral drugs. Department of Otorhinolaryngology, Head and Neck Surgery, Karadeniz Technical University Medical School, Trabzon, Turkey. Hear Res. 2008 May;239(1-2):69-78.

Dybul M, Fauci AS, Bartlett JG, Kaplan JE, Pau AK; Panel on Clinical Practices for Treatment of HIV (September 2002). “Guidelines for using antiretroviral agents among HIV-infected adults and adolescents”. Ann. Intern. Med. 137 (5 Pt 2): 381–433.

Gordon M, Bihari B, Goosby E (1998). “A placebo-controlled trial of the immune modulator, lentinan, in HIV-positive patients: a phase I/II trial”. Journal of Medicine 29 (5-6): 305–30.

Marra, C.M., Wechkin, H.A., Longstreth, W.T., Rees, T.S., Syapin, C., & Gates, G.A. (1997). Hearing loss and antiretroviral therapy in patients infected with HIV-1. Department of Neurology, University of Washington, Seattle, USA. Arch Neurol. 1997 Apr;54(4):407-10.

Odani S, Tominaga K, Kondou S (June 1999). “The inhibitory properties and primary structure of a novel serine proteinase inhibitor from the fruiting body of the basidiomycete, Lentinus edodes”. European Journal of Biochemistry 262 (3): 915–23.

Panacos Pharmaceuticals. “Clinical Trial: Phase 2 Safety and Efficacy Study of Bevirimat Functional Monotherapy in HIV Treatment-Experienced Patients for 2 Weeks*”. ClinicalTrials.gov.

Suzuki H, Okubo A, Yamazaki S, Suzuki K, Mitsuya H, Toda S (April 1989). “Inhibition of the infectivity and cytopathic effect of human immunodeficiency virus by water-soluble lignin in an extract of the culture medium of Lentinus edodes mycelia (LEM)”. Biochemical and Biophysical Research Communications 160 (1): 367–73.

Tochikura TS, Nakashima H, Yamamoto N (1989). “Antiviral agents with activity against human retroviruses”. Journal of Acquired Immune Deficiency Syndromes 2 (5): 441–7.