Combination antiretroviral therapy improves cognitive performance and functional connectivity in treatment-naïve HIV-infected individuals

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.Electronic supplementary materialThe online version of this article (doi:10.1007/s13365-017-0553-9) contains supplementary material, which is available to authorized users.

Changes in resting-state functional brain activity are associated with waning cognitive functions in HIV-infected children

“…However, previous studies observed improved functional connectivity in HIV patients that received medications ( Ortega et al, 2015 ). Another study showed that cART improves cognitive performance and functional connectivity in ARV treated-naïve HIV-infected individuals ( Zhuang et al, 2017 ). We are expecting similar impact of cART treatment on patients included in the current study.…”

Enhancing an HIV index case testing passive referral model through a behavioural skills‐building training for healthcare providers: a pre‐/post‐assessment in Mangochi District, Malawi

“…In Malawi, in spite of a generalized HIV epidemic and a mature HIV response, approximately 250,000 HIV‐positive adults remain unaware that they are living with HIV . This makes them unable to access antiretroviral therapy (ART) which has proven benefits for the health of the individual and prevention of horizontal and vertical transmission .…”

Axonal chronic injury in treatment-naïve HIV+ adults with asymptomatic neurocognitive impairment and its relationship with clinical variables and cognitive status

“…In both studies, the neuropsychological tests were assessed by AIDS Dementia Complex (ADC) staging according to the Memorial Sloan Kettering (MSK) staging system, and an ADC score of 0 or 0.5 was considered neurocognitive asymptomatic. Zhuang Y et al investigated WM changes in ANI patients diagnosed according to the Frascati criteria [ 3 ] and found no significant WM microstructural differences between HIV-infected and healthy controls [ 18 ]. Cysique LA et al reported that the location of WM injury in ANI cases was the anterior limb of the internal capsule [ 19 ].…”

“…The primary oligodendrocyte and myelin damage leading to secondary axonal damage (outside-in) or primary axonopathy triggering oligodendrocyte injury and demyelination (inside-out) are indistinguishable [ 20 ]. WM alterations may contribute to cognitive deficits in HIV-infected patients [ 7 , 18 , 21 ]. It is worth noting that the relationship between WM abnormalities and cognitive status has not been well characterized or systematically assessed.…”