The role of early life programming in vulnerability and resilience in relation to HIV

Abstract

The pathogenesis of human immunodeficiency virus (HIV)-1 infection has a variable progression rate. Although some individuals progress rapidly to autoimmune deficiency syndrome (AIDS), others may remain asymptomatic for years. Among the many factors responsible for the progression of the disease, the impact of the psychosocial environment of the patient has been receiving increased attention. Psychological stress, depression and lack of social support have all been described as contributing to a poor prognosis. Physiological mechanisms mediating these effects include alteration of the immune and neuroendocrine responses. As such, a shift to an anti-inflammatory cytokine response, increased activity of the hypothalamic-pituitary-adrenal (HPA) axis and the autonomic nervous system (ANS) are suggested to underlie the psychological processes contributing to the progression of the disease. Preclinical and clinical data indicate that preexisting physiological and psychological vulnerabilities prior to the infection may predict the disease progression rates in some individuals. The emerging field of perinatal programming of health and disease implicates the role of the early life environment in the development of physiological and behavioural systems. In particular, exposure to physiological or psychological stress during early development has been demonstrated to result in altered immune, endocrine and behavioural functioning, associated with increased stress responsivity and psychopathology in later life. These increases in stress and stress-related behaviours, in turn, play a role in modulating immune function and thus the potential to alter the rate of HIV disease progression. This chapter aims to extend the current understanding of the individual variability in vulnerability and resilience to the virus, by integrating the framework of perinatal programming in the setting of HIV infection. In addition to the possible phenotypic differences, identification of biomarkers of early life stress in infected individuals may improve current therapeutic strategies, with a specific focus on increased psychosocial support that these patients may require.