@article{2998618,
    title = "Chronic distress and the vulnerable host: A new target for HIV treatment and prevention?",
    author = "Contoreggi, C. and Chrousos, G.P. and Di Mascio, M.",
    journal = "Neurobehavioral HIV Medicine",
    year = "2016",
    volume = "7",
    pages = "53-75",
    publisher = "Dove Medical Press Ltd",
    doi = "10.2147/nbhiv.s86309",
    keywords = "3 (6 dimethylamino 4 methyl 3 pyridinyl) 7 dipropylamino 2,5 dimethylpyrazolo[1,5 a]pyrimidine;  antalarmin;  carbamazepine;  corticotropin releasing factor;  lamotrigine;  lithium;  mifepristone;  mood stabilizer;  neuropeptide;  valproic acid, behavior therapy;  chronic disease;  chronic stress;  disease exacerbation;  disease predisposition;  distress syndrome;  drug effect;  drug efficacy;  epigenetics;  gastritis;  high risk population;  homeostasis;  human;  Human immunodeficiency virus infection;  hypothalamus hypophysis adrenal system;  immunomodulation;  major depression;  mania;  mental disease;  morbidity;  mortality;  nervous system inflammation;  Review;  rheumatoid arthritis;  substance abuse;  virus replication;  vulnerable population",
    abstract = "Pathologic stress (distress) disturbs immune, cardiovascular, metabolic, and behavioral homeostasis. Individuals living with HIV and those at risk are vulnerable to stress disorders. Corticotropin-releasing hormone (CRH) is critical in neuroendocrine immune regulation. CRH, a neuropeptide, is distributed in the central and peripheral nervous systems and acts principally on CRH receptor type 1 (CRHR1). CRH in the brain modulates neuropsychiatric disorders. CRH and stress modulation of immunity is two-pronged; there is a direct action on hypothalamic- pituitary-adrenal secretion of glucocorticoids and through immune organ sympathetic innervation. CRH is a central and systemic proinflammatory cytokine. Glucocorticoids and their receptors have gene regulatory actions on viral replication and cause central and systemic immune suppression. CRH and stress activation contributes to central nervous system (CNS) viral entry important in HIV-associated neurocognitive disorders and HIV-associated dementia. CNS CRH overproduction short-circuits reward, executive, and emotional control, leading to addiction, cognitive impairment, and psychiatric comorbidity. CRHR1 is an important therapeutic target for medication development. CRHR1 antagonist clinical trials have focused on psychiatric disorders with little attention paid to neuroendocrine immune disorders. Studies of those with HIV and those at risk show that concurrent stress-related disorders contribute to higher morbidity and mortality; stress-related conditions, addiction, immune dysfunction, and comorbid psychiatric illness all increase HIV transmission. Neuropsychiatric disease, chronic inflammation, and substance abuse are endemic, and chronic distress is a pathologic factor. It is being understood that stress and CRH are fundamental to neuroendocrine immunity; therapeutic interventions with existing and novel agents hold promise for restoring homeostasis, reducing morbidity and mortality for those with HIV and possibly reducing future disease transmission. © 2016 Contoreggi et al."
}