Methamphetamine stimulates interferon inducible genes in HIV infected brain

Objective: To study the synergism of HIV and methamphetamine. Design and methods: We undertook a microarray study using RNA from the frontal cortex of 15 individuals with HIV infection to initially identify genes that are differentially regulated by HIV encephalitis (HIVE). From the analysis of the microarray data, we identified candidate genes to be validated by quantitative real time PCR (qRT-PCR) and to assess if these genes were differentially modulated in individuals with HIVE and documented methamphetamine use. Results: Analysis of microarray data revealed that genes involved in several categories were dysregulated in HIVE. We then chose 15 candidate genes for validation by qRT-PCR and analyzed the tissue concentration of these genes across three groups: those with HIV infection and no brain pathology, those with HIVE, and those with both HIVE and a history of methamphetamine use. We noted that there was upregulation of interferon inducible genes in the HIVE with methamphetamine using group, which together as a gene group was highly statistically significant (p = 0.0064). Conclusion: These findings indicate that dysregulation of interferon inducible genes may underlie the pathogenic mechanism resulting in greater neurodegenerative and neurocognitive burden that occurs in methamphetamine using HIV infected individuals.