Psychosocial Influences on HIV-1 Disease Progression: Neural, Endocrine, and Virologic Mechanisms

Department of Medicine, Division of Hematology-Oncology, UCLA School of Medicine, the Norman Cousins Center, Jonsson Comprehensive Cancer Center, UCLA AIDS Institute, California 90095-1678, USA.
Psychosomatic Medicine (Impact Factor: 3.47). 07/2008; 70(5):562-8. DOI: 10.1097/PSY.0b013e3181773bbd
Source: PubMed


This review surveys empirical research pertinent to the hypothesis that activity of the hypothalamus-pituitary-adrenal (HPA) axis and/or the sympathetic nervous system (SNS) might mediate biobehavioral influences on HIV-1 pathogenesis and disease progression. Data are considered based on causal effects of neuroeffector molecules on HIV-1 replication, prospective relationships between neural/endocrine parameters and HIV-relevant biological or clinical markers, and correlational data consistent with in vivo neural/endocrine mediation in human or animal studies. Results show that HPA and SNS effector molecules can enhance HIV-1 replication in cellular models via effects on viral infectivity, viral gene expression, and the innate immune response to infection. Animal models and human clinical studies both provide evidence consistent with SNS regulation of viral replication, but data on HPA mediation are less clear. Regulation of leukocyte biology by neuroeffector molecules provides a plausible biological mechanism by which psychosocial factors might influence HIV-1 pathogenesis, even in the era of effective antiretroviral therapy. As such, neural and endocrine parameters might provide useful biomarkers for gauging the promise of behavioral interventions and suggest novel adjunctive strategies for controlling HIV-1 disease progression.

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    • "There is growing evidence about the biological mechanisms that mediate the relation between general psychosocial factors and HIV-related outcomes, including contributions of the sympathetic nervous system and the hypothalamic-pituitary-adrenal axis (Cole, 2008). Also, in the general stress literature there is strong support for behavioral factors that may influence these relations, including treatment nonadherence, substance abuse, and sexual risk behaviors (Gore-Felton & Koopman, 2008). "
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    • "If the HPA axis were sending the proper anti-inflammatory cortisol signal, why would stressed people's leukocytes not downregulate NF-κB transcription of inflammatory genes? The answer appears to involve a reduction in the GR's sensitivity to cortisol – rendering the leukocyte transcriptome deaf to the brain's request to down-regulate pro-inflammatory genes (Cole et al., 2007;Miller et al., 2008). Both chronic loneliness and threat of social loss appear to disconnect this key physiologic feedback system, and may thereby increase the risk of inflammation-related disease (Seeman, 1996). "
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    • "For example, elevated body mass index (BMI) and waist-to-hip ratio (WHR) are health risks among the general HIV− population, but body wasting and associated low BMI and WHR are important health risks for HIV+ samples. Also, elevated cortisol is sometimes associated with poor HIV outcomes (Antoni et al. 2000, 2005; Cruess et al. 2000; Ironson et al. 2002; Leserman 2003) but findings are inconsistent and mechanisms of cortisol dysregulation remain complex (Cole 2008; Sapolsky et al. 2007). The significant associations found here between the bi-directional composite and HIV variables (CD4 cell counts and medication adherence) are promising, future studies must confirm that a bi-directional biomarker composite is predictive of meaningful clinical outcomes and psychological symptoms. "
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