Longitudinal white matter alterations in SIVmac239 infected rhesus monkeys with and without regular cART treatment

Abstract

Objective: We use the SIV-mac239 infected Chinese rhesus monkeys to longitudinally investigate white matters alterations with and without regular cART treatment, and its relationship with clinical tests. Material and methods: Diffusion tensor imaging (DTI), CD4 T cell counts, and CD4/CD8 were obtained at baseline, 10 days, 4th week, 12th week, 24th week, and 36th week post virus inoculation. postinfection (wpi). Microstructural properties were examined within 76 white matter defined by DTI-WM atlas for rhesus macaques. Corrections for multiple comparisons were performed using a false discovery rate (p < 0.05, FDR). Correlation analyses between imaging markers and clinical measures (CD4 T-cell counts, CD4/CD8 ratio) were determined using Pearson's correlations. Results: In our model, White matter alterations in SIV-infected macaques can be detected as soon as 4 wpi in several brain regions. And with time proceeding, the combined antiretroviral therapy (cART) can reverse, relieve, or even progressive effects. CD4 T-cell count is mainly associated with DTI metrics before the cART, whereas CD4/CD8 ratio was associated with white matter alteration with and without cART. Conclusion: SIV-mac239 infection can be an idol modal to explore HIV induced HIV associated brain alterations, and the first group of white matter alterations was as soon as 4 weeks post inoculation in structure next to the periventricular area. As the time progressed, cART can bring different effect to each region, including reversed, relieved, and even progressive effects. In addition, these changes are closely linked to CD4/CD8 ratio even after cART.