Antiretroviral therapy reduces neurodegeneration in HIV infection

Abstract

Objective To determine the effect of virally-suppressive antiretroviral therapy on cortical neurodegeneration and associated neurocognitive impairment. Design Retrospective, postmortem observational study. Methods Clinical neuropsychological and postmortem neuropathology data were analyzed in 90 human immunodeficiency virus-infected volunteers from the general community who had never undergone antiretroviral therapy (n=7, “naïve”) or who had undergone antiretroviral therapy and whose plasma viral load was detectable (n = 64 “unsuppressed”) or undetectable (n = 19, “suppressed”) at the last clinical visit prior to death. Subjects were predominately male (74/90, 82%) with a mean age of 44.7 years (SD 9.8). Cortical neurodegeneration was quantified by measuring microtubule-associated protein (MAP2) and synaptophysin (SYP) density in midfrontal cortex tissue sections. Results The suppressed group had higher SYP density than the naïve group (p = 0.007) and higher MAP2 density than the unsuppressed group (p = 0.04). The suppressed group had lower odds of human immunodeficiency virus-associated neurocognitive disorders than naïve (OR 0.07, p = 0.03). Higher SYP was associated with lower likelihood of human immunodeficiency virus-associated neurocognitive disorders in univariable (OR 0.8, p=0.03) and multivariable models after controlling for antiretroviral treatment and brain human immunodeficiency virus p24 protein levels (OR 0.72, p=0.01). Conclusions We conclude that virally suppressive antiretroviral treatment protects against cortical neurodegeneration. Further, we find evidence supporting the causal chain from treatment-mediated peripheral and central nervous system viral load suppression to reduced neurodegeneration and improved neurocognitive outcomes.

Lifetime methamphetamine dependence is associated with cerebral microgliosis in HIV-1-infected adults

“…4a–c), and that for MAP2 revealed immunoreactive neuronal soma and dendrites (Fig. 4d–f) (Bryant et al 2015). The SYP density correlated directly with the MAP2 density ( n =52, r s =0.78, p <0.0001, Spearman’s rank correlation coefficient).…”

Proton Chemical Shift Imaging Study of the Combined Antiretroviral Therapy Impact on Neurometabolic Parameters in Chronic HIV Infection

“…This finding could support a relatively new concept of neurodegeneration in treated HIVϩ subjects, with some indications that HAND is a (potentially reversible) metabolic encephalopathy rather than pure subcortical dementia. 1 In addition, a recent study by Hidalgo et al 22 systematically addressed the question of the relationship between HIV infection and some personal habits, such as nicotine smoking, abuse or use of alcohol and some recreational drugs (cannabis, marijuana), and psychostimulants. All of these substances are claimed to have a certain, most often synergistic, effect on the neurodegenerative process and neurocognitive impairment in HIV-infected individuals, though through different mechanisms and pathways.…”

“…C ombined antiretroviral therapy (cART) has substantially altered the clinical course and epidemiology of HIV infection during the past decade. 1 cART has been revolutionary in the control of peripheral viral replication and has reduced the high prevalence of HIV-associated neurocognitive disorders (HAND). HAND includes a variety of neurologic disorders ranging from asymptomatic neurocognitive impairment (ANI) and mild neu-rocognitive disorders to HIV-associated dementia.…”

The effects of HIV and aging on subcortical shape alterations: A 3D morphometric study

“…This pattern of insidious neural insult is seen in disorder such as Parkinson's disease [Braak et al, 2004], Alzheimer's disease [Hynd et al, 2004;Ballatore, Lee & Trojanowski, 2007], and other forms of progressive neurodegenerative disorders. Similarly, there is reason to believe that HIV associated neurologic damage unfolds well before overt cognitive manifestations emerge [Masliah et al, 1995;Zhang et al, 2003;Jones et al, 2007;Thames et al, 2011;Fields et al, 2014;Bryant et al, 2015]. Therefore, an analytic method with greater spatial resolution may provide the sensitivity needed to capture neural changes that occur due to deleterious interaction effects of advancing age and HIV infection Shape analysis, a method of Bayesian surface based analysis, is one such methodology that may be more sensitive to regional (e.g., specific nuclei) changes not detectable by standard volumetric methods [Patenaude et al, 2011].…”