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Combination antiretroviral therapy improves cognitive performance and functional connectivity in treatment-naive 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.

SUBMITTER: Zhuang Y

PROVIDER: S-EPMC5655604 | biostudies-literature | 2017 Oct

REPOSITORIES: biostudies-literature

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

Zhuang Yuchuan Y Qiu Xing X Wang Lu L Ma Qing Q Mapstone Mark M Luque Amneris A Weber Miriam M Tivarus Madalina M Miller Eric E Arduino Roberto C RC Zhong Jianhui J Schifitto Giovanni G

Journal of neurovirology 20170808 5

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/mm<sup>3</sup>) were age matched with 17 HIV-uninfected individuals. All subjects underwent a detailed neurocognitive and functional assessment and magnetic reson ...[more]

PMID: 28791662

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Project description:ImportanceDespite the introduction of combination antiretroviral therapy (cART), HIV-associated neurocognitive disorders continue to be a problem for treated HIV-positive individuals. The cause of this impairment remains unclear.ObjectiveTo determine if detectable brain changes occur during a 2-year period in HIV-positive individuals who were aviremic and treated with cART.Design, setting, and participantsIn this longitudinal case-control study, participants underwent neuroimaging and neuropsychological assessment approximately 2 years apart. Data were collected from October 26, 2011, to March 1, 2016. Data from 92 HIV-positive individuals were acquired at Washington University in St Louis from ongoing studies conducted in the infectious disease clinic and AIDS Clinical Trial Unit. A total of 55 HIV-negative control participants were recruited from the St Louis community and a research participant registry. A total of 48 HIV-positive individuals who were aviremic and treated with cART and 31 demographically similar HIV-negative controls met the study requirements and were included in the analyses.Main outcomes and measuresBrain volumes were extracted with tensor-based and voxel-based morphometry and cortical modeling. Raw scores from neuropsychological tests quantified cognitive performance. Multivariable mixed-effects models assessed the effect of HIV serostatus on brain volumes and cognitive performance, and determined if HIV serostatus affected how these measures changed over time. With HIV-positive participants, linear regression models tested whether brain volumes and cognitive performance were associated with measures of infection severity and duration of infection.ResultsThe 2 groups were demographically similar (HIV-positive group: 23 women and 25 men; mean [SD] age, 47.7 [13.2] years; mean [SD] educational level, 13.3 [3.4] years; and HIV-negative group, 16 women and 15 men; mean [SD] age, 51.2 [12.9] years; mean [SD] educational level, 14.5 [2.1] years). The HIV-positive participants had poorer neuropsychological test scores compared with controls on the Trail Making Test Part A (5.9 seconds; 95% CI, 1.5-10.3; P = .01), Trail Making Test Part B (27.3 seconds; 95% CI, 15.0-39.6; P < .001), Digit Symbol Substitution Task (-12.5 marks; 95% CI, -18.9 to -6.0; P < .001), Letter-Number Sequencing (-2.5 marks; 95% CI, -3.7 to -1.3; P < .001), Letter Fluency (-6.6 words; 95% CI, -11.5 to -1.6; P = .01), and Hopkins Verbal Learning Test-Revised immediate recall (-2.4 words; 95% CI, -4.4 to -0.4; P = .05), after adjusting for age, sex, and educational level. Only changes in Trail Making Test Part A significantly differed between the groups. Cortical thickness and subcortical volumes were smaller in HIV-positive individuals compared with controls. However, changes in brain volume over time were similar between the groups.Conclusions and relevanceThese findings are consistent with the idea that cognitive and structural brain changes may occur early after seroconversion, and argue that maintaining aviremia with cART can prevent or minimize progressive brain injury.