Behavioral and Physical Activity Interventions for HAND

Montoya, Jessica L.; Henry, Brook L.; Moore, David J.

doi:10.1007/7854_2018_79

Cited by 5 publications

(1 citation statement)

References 146 publications

(150 reference statements)

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“…These interactive effects remain significant in virally suppressed participants receiving cART, suggesting that currently effective HIV treatment alone may not sufficiently mitigate neurocognitive dysfunction associated with the combination of genetic vulnerabilities, historically severe HIVinduced immunosupression, and cardiometabolic risk factors. In addition to cART, adjunctive behavioral therapies that target modifiable lifestyle factors could be considered as a means to address this diverse combination of risk factors90 . In particular, interventions to increase physical activity and/or reduce sleep disturbances may help stabilize DA function and cardiometabolic health, reduce inflammatory and oxidative stress burden, and subsequently ameliorate persisting neurocognitive deficits in HIV-infected patients 91-95 .…”

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confidence: 99%

COMT Val158Met Polymorphism, Cardiometabolic Risk, and Nadir CD4 Synergistically Increase Risk of Neurocognitive Impairment in Men Living With HIV

Saloner

Marquine

Sundermann

et al. 2019

JAIDS Journal of Acquired Immune Deficiency Syndromes

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Objective The Val allele of the Val158Met single-nucleotide polymorphism of the catechol-omethyltransferase gene (COMT) results in faster metabolism and reduced bioavailability of dopamine (DA). Among persons living with HIV (PLWH), Val carriers display neurocognitive deficits relative to Met carriers, presumably due to exacerbation of HIV-related depletion of DA. COMT may also impact neurocognition by modulating cardiometabolic function, which is often dysregulated among PLWH. We examined the interaction of COMT, cardiometabolic risk, and nadir CD4 on NCI among HIV+ men. Methods 329 HIV+ men underwent COMT genotyping and neurocognitive and neuromedical assessments. Cohort-standardized z-scores for body mass index, systolic blood pressure, glucose, triglycerides, and high-density lipoprotein cholesterol were averaged to derive a cardiometabolic risk score (CMRS). Neurocognitive impairment Powered by Editorial Manager® and ProduXion Manager® from Aries Systems Corporation (NCI) was defined as demographically-adjusted global deficit score≥0.5. Logistic regression modelled NCI as a function of COMT, CMRS, and their interaction, covarying for estimated premorbid function, race/ethnicity, and HIV-specific characteristics. Follow-up analysis included the 3-way interaction of COMT, CMRS, and nadir CD4. Results Genotypes were 81 Met/Met, 147 Val/Met, and 101 Val/Val. COMT interacted with CMRS (p=0.02) such that higher CMRS increased risk of NCI among Val/Val (OR=2.13, p<.01), but not Val/Met (OR=0.93, p>.05) or Met/Met (OR=0.92, p>.05) carriers. Among Val/Val, nadir CD4 moderated the effect of CMRS (p<.01) such that higher CMRS increased likelihood of NCI only when nadir CD4<180. Discussion Results suggest a tripartite model by which genetically-driven low DA reserve, cardiometabolic dysfunction, and historical immunosuppression synergistically enhance risk of NCI among HIV+ men, possibly due to neuroinflammation and oxidative stress.

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confidence: 99%