Abstract
Our study aimed to investigate the short-term effect of combination antiretroviral therapy (cART) on cognitive performance and functional and structural connectivity and their relationship to plasma levels of antiretroviral (ARV) drugs. Seventeen ARV treatment-naïve HIV-infected individuals (baseline mean CD4 cell count, 479 ± 48 cells/mm3) were age matched with 17 HIV-uninfected individuals. All subjects underwent a detailed neurocognitive and functional assessment and magnetic resonance imaging. HIV-infected subjects were scanned before starting cART and 12 weeks after initiation of treatment. Uninfected subjects were assessed once at baseline. Functional connectivity (FC) was assessed within the default mode network while structural connectivity was assessed by voxel-wise analysis using tract-based spatial statistics (TBSS) and probabilistic tractography within the DMN. Tenofovir and emtricitabine blood concentration were measured at week 12 of cART. Prior to cART, HIV-infected individuals had significantly lower cognitive performance than control subjects as measured by the total Z-score from the neuropsychological tests assessing six cognitive domains (p = 0.020). After 12 weeks of cART treatment, there remained only a weak cognitive difference between HIV-infected and HIV-uninfected subjects (p = 0.057). Mean FC was lower in HIV-infected individuals compared with those uninfected (p = 0.008), but FC differences became non-significant after treatment (p = 0.197). There were no differences in DTI metrics between HIV-infected and HIV-uninfected individuals using the TBSS approach and limited evidence of decreased structural connectivity within the DMN in HIV-infected individuals. Tenofovir and emtricitabine plasma concentrations did not correlate with either cognitive performance or imaging metrics. Conclusions: Twelve weeks of cART improves cognitive performance and functional connectivity in ARV treatment-naïve HIV-infected individuals with relatively preserved immune function. Longer periods of observation are necessary to assess whether this effect is maintained.
Highlights
HIV infection is associated with injury of the central nervous system (CNS) (Navia et al 1986)
To study the early time course progression of CNS injury in HIV infection, we focused on the default mode network (DMN) as the major region to investigate because it has been widely studied and reported to be affected by HIV infection (Becker et al 2013; Herting et al 2015; Ortega et al 2015; Thomas et al 2013)
Neuroimaging has been used as a noninvasive tool to assess CNS injury in HIV-infected individuals
Summary
HIV infection is associated with injury of the central nervous system (CNS) (Navia et al 1986). The clinical manifestations of CNS injury vary from a mild decrease in cognitive performance without associated functional deficits to dementia (Antinori et al 2007). Most of the recent literature on HIV-associated cognitive impairment that has included neuroimaging is derived from patient with long established HIV infection and on stable combination antiretroviral treatment (cART) (Hua et al 2013). One plausible explanation is that irreversible CNS damage occurs very early in HIV infection which, when limited, causes subtle cognitive changes measurable to some degree with extensive neuropsychological tests. In this case, effective cART would prevent progression of CNS injury but not reverse previous damage (Tozzi et al 2005). We report our initial findings, assessing whether cognitive, functional, and structural brain connectivity were altered prior to the initiation of cART and whether there were measurable changes after 12 weeks of cART treatment
Sign-in/Register to view highlights & summary Sign-in/Register to access full text options 
Free) 
Talk to us
Join us for a 30 min session where you can share your feedback and ask us any queries you have
Schedule a call
