title: Untangling the Gordian knot of HIV, stress, and cognitive impairment.
abstract: As individuals live longer with HIV, this "graying of the HIV epidemic" has introduced a new set of challenges including a growing number of age and inflammation-related diseases such as cardiovascular disease, type II diabetes, cancer, and dementia. The biological underpinnings of these complex and co-morbid diseases are not fully understood and become very difficult to disentangle in the context of HIV and aging. In the current review we examine the contributions and interactions of HIV, stress, and cognitive impairment and query the extent to which inflammation is the linchpin in these dynamic interactions. Given the inter-relatedness of stress, inflammatory mechanisms, HIV, and cognitive impairment, future work will either need to address multiple dimensions simultaneously or embrace the philosophy that breaking the aberrant cycle at any one point will subsequently remedy the other related systems and processes. Such a single-point intervention may be effective in early disease states, but after perpetuation of an aberrant cycle, adaptations in an attempt to internally resolve the issue will likely lead to the need for multifaceted interventions. Acknowledging that HIV, inflammation, and stress may interact with one another and collectively impact cognitive ability is an important step in fully understanding an individual's complete clinical picture and moving towards personalized medicine.
authors.affiliation: Emory University Medical Scientist Training Program, USA; Emory University Department of Cell Biology, USA.
authors.forename: Arielle N
authors.initials: AN
authors.lastname: Valdez
authors.affiliation: Univeristy of Illinois at Chicago, Department of Psychiatry, USA.
authors.forename: Leah H
authors.initials: LH
authors.lastname: Rubin
authors.affiliation: Emory University Department of Physiology, USA; Emory University Department of Psychiatry & Behavioral Sciences, USA.
authors.forename: Gretchen N
authors.initials: GN
authors.lastname: Neigh
keywords: ACTH, Adrenocorticotropic hormone; AIDS, Acquired immune deficiency syndrome; ANI, Asymptomatic neurocognitive impairment; ART, Antiretroviral therapy; CBSM, Cognitive behavioral stress management; CD4; CNS, Central Nervous System; CRP, C-reactive protein; Cognition; GALT, Gut-associated lymphoid tissue; GR, Glucocorticoid receptor; HAD, HIV-associated dementia; HANA, HIV-associated, Non-AIDS; HAND, HIV-associated neurocognitive disorders; HIV; HPA, Hypothalamic–Pituitary Adrenal; HRV, Heart rate variability; IL-12, Interleukin-12; IL-18, Interleukin-18; IL-1β, Interleukin-1β; IL-2, Interleukin-2; IL-6, Interleukin-6; INSTIs, Integrase strand transfer inhibitors; Inflammation; LPS, Lipopolysaccharide; LTP, Long-term potentiation; MND, Mild neurocognitive disorder; NNRTIs, Non-nucleoside reverse transcriptase inhibitors; NRTIs, Nucleoside reverse transcriptase inhibitors; PFC, Prefrontal cortex; PIs, Protease inhibitors; PLWH, People living with HIV; PTSD, Posttraumatic stress disorder; ROS, Reactive oxygen species; Stress; TNFα, Tumor necrosis factor alpha; Vpr, Viral protein r; WIHS, Women's Interagency HIV Study; hsCRP, High-sensitivity C-reactive protein