| Publication Abstract Display | | Type: Published Abstract | | Title: 1H MR spectroscopy reveals NRTI associated mitochondrial impairment in HIV-infected individuals. | | Authors: Schweinsburg BC, Gonzalez R, Taylor MJ, Alhassoon OM, Ellis RJ, McCutchan JA, Brown GG, Videen JS, Patterson TL, Grant I | | Year: 2001 | | Publication: Society of Neuroscience Abstracts | | Volume: 27 Issue: 2 Pages: 527.14 | | Abstract:"Nucleoside reverse transcriptase inhibitors (NRTI) suppress HIV replication, but can cause mitochondrial (MIT) toxicity often manifested as peripheral neuropathy. dd-NRTIs (d4t, ddc, and ddl) may be the most potent inhibitors of MIT replication through inhibition of polymerase gamma. However, the effects of these drugs on brain MIT function are not well-understood. We used single voxel 1H magnetic resonance spectroscopy to assess the extent of NRTI-associated MIT dysfunction in frontal lobe gray and white matter of 8 HIV+ individuals taking an antiretroviral regimen that included dd-NRTIs (HIV+/d*), 9 HIV+ individuals with a combination regimen that included zidovudine (HIV+/ZDV), 11 HIV+ individuals who were antiretroviral nave (HIV+/nave), and 19 HIV- control participants. We hypothesized that the HIV+/d* would show evidence of reduced concentrations of N-acetylaspartate (NAA: an amino acid synthesized in neural mitochondria often associated with neuronal integrity) relative to the other HIV+ and HIV- control groups. The HIV+ groups were equated on age and indicators of disease severity. HIV+/d* individuals had significantly lower NAA (p<.05) compared to the other groups in frontal lobe gray matter (11.0% decrease), and a similar trend was found in white matter (10.8% decrease). These results suggest that individuals taking drug combinations that include dd-NRTIs may be susceptible to brain MIT dysfunction that could contribute to the neurological and neuropsychological dysfunction associated with HIV infection. |
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