This subproject is one of many research subprojects utilizing the resources provided by a Center grant funded by NIH/NCRR. The subproject and investigator (PI) may have received primary funding from another NIH source, and thus could be represented in other CRISP entries. The institution listed is for the Center, which is not necessarily the institution for the investigator. The neurological complications of HIV infection remain poorly understood. In clinical studies, in vivo magnetic resonance spectroscopy (MRS) demonstrates brain injury caused by HIV infection even when the MRI is normal. Our goal was to better understand the dynamics of cerebral injury by performing a longitudinal in vivo MRS study of the SIV/macaque model of neuroAIDS. We serially imaged 8 SIVmac251-infected rhesus macaques to terminal AIDS or the endpoint of 2 years. During the acute period of infection, we observed stereotypical brain MRS changes, dominated by elevation of the Cho/Cr ratio. Subsequently, brain metabolic patterns diverged. Strikingly, we found an elevation of basal ganglia Cho/Cr four weeks post-inoculation in the 2 animals destined to develop encephalitis (p = 0.022). Thus, this metabolite ratio may be an early marker of animals destined to progress to SIVE. Additionally, we found a significant positive correlation between a change in frontal lobe Cho/Cr and plasma viral load (P 0.001, R = 0.80), and a negative correlation between NAA/Cr in the basal ganglia and the plasma viral load (P 0.02, R = -0.73). Our findings that markers for cerebral inflammation and neuronal injury correlate with viral levels in the periphery supports the use of drugs capable of controlling the propagation and trafficking of virus into the CNS, and may help explain the reduction in incidence of HIV-associated dementia in the era of HAART despite the inability of most of those drugs to effectively enter the
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