Psychological risk factors for HIV pathogenesis: Mediation by the autonomic nervous system

Background: Epidemiologic studies have identified psychological risk factors for specific physical diseases, but the biological mechanisms mediating these relationships remain poorly defined. Methods: Social inhibition and autonomic nervous system (ANS) activity were assessed on multiple occasions in 54 gay men with asymptomatic human immunodeficiency virus (HIV) infection. Following baseline ANS assessment, plasma HIV-1 viral load and CD4+ T cell levels were monitored for 12-18 months to assess relationships between ANS activity and HIV pathogenesis. Results: We confirmed the previously reported relationship between socially inhibited temperament and vulnerability to viral pathology. Plasma viral load set-point was elevated eight-fold in socially inhibited individuals, and these individuals showed poorer virologic and immunologic response to initiation of highly active antiretroviral therapy (HAART). Effects were independent of duration of infection, HAART regimen, demographic characteristics, and health-relevant behavior. Neurophysiologic assessments documented elevated ANS activity in socially inhibited individuals, and mediational analyses showed that such differences could account for 64%-92% of the covariance between social inhibition and virologic parameters. Conclusions: These data provide the first clinical evidence that differential neural activity mediates relationships between psychological risk factors and infectious disease pathogenesis. Such findings also suggest novel targets for adjunctive therapy in long-term control of HIV-1 disease.