Abstract
Older HIV-infected adults have a higher risk of neurocognitive impairment, but the underlying mechanisms are poorly understood. Here, we investigated the associations between levels of HIV DNA in peripheral blood, soluble markers of inflammation and cellular trafficking in blood and cerebrospinal fluid (CSF) and neurocognitive functioning among 18 younger (22–40 years) and 26 older (50–71 years) HIV-infected subjects, who were administered a comprehensive neurocognitive battery. Older HIV-infected individuals presented higher levels of inflammation in CSF and blood compared to younger individuals, but no difference was observed in HIV DNA levels. Among older participants, higher HIV DNA levels were significantly associated with more severe neurocognitive impairment (p = 0.005), particularly in the Executive Functions domain (p = 0.004). No association was observed between HIV DNA and neurocognition among younger individuals. Despite significantly increased inflammation observed in the older group, none of the inflammatory markers were associated with neurocognitive impairment among older HIV+ individuals (p > 0.05). Our study supports the involvement of peripheral HIV DNA reservoir in the pathogenesis of neurocognitive disorder during suppressive ART. Correlates of neurocognitive impairment might differ between younger and older adults, suggesting that future treatment and prevention strategies for HIV-associated neurocognitive disorders likely need to be tailored based on age.
Highlights
A notable shift in the demographics of the HIV epidemics has been observed over the last decade, with individuals over 50 years of age expected to comprise more than 75% of the HIV-infected population in the United States by 20201
At the time of sample collection, 31 (70.5%) subjects were on a protease inhibitor (PI)-based antiretroviral treatment (ART) and 13 (29.5%) subjects were on a combination regimen consisting of a nucleoside reverse transcriptase inhibitor (NRTI) with either a non-nucleoside reverse transcriptase inhibitor (NNRTI) or an integrase strand transfer inhibitor (INSTI)
As part of our primary analysis, we evaluated whether HIV DNA levels in peripheral blood and other inflammatory or clinical markers were associated with worse neurocognitive impairment (NCI) in each age group
Summary
A notable shift in the demographics of the HIV epidemics has been observed over the last decade, with individuals over 50 years of age expected to comprise more than 75% of the HIV-infected population in the United States by 20201. In subjects on suppressive ART, factors associated with NCI are mostly related to low CD4 nadir, demographics and comorbidities, like co-infections, cardiovascular disease and increased age[5,18,19,20]. In the setting of virologic suppression, greater HIV DNA contributes to persistent immune activation in tissues, including the brain[23] Such persistent immune activation in turn contributes to neurodegeneration and cognitive impairment[24]. These effects are likely to be cumulative and to differ based on the duration of HIV disease and age, as a consequence of multiple factors like immune senescence and altered blood-brain barrier permeability[25]. The primary goal of this study goal was to evaluate HIV proviral burden in circulating peripheral blood mononuclear cells as a potential correlate of neurocognitive impairment in relation to age
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