Accelerated aging in people living with HIV: The neuroimmune feedback model

People living with HIV (PLWH) experience earlier onset of aging-related comorbidities compared to their counterparts without HIV. This paper lays out a theoretical model to explain why PLWH experience accelerated aging. Briefly, the model is structured as follows. PLWH experience disproportionately heavy burdens of psychosocial stress across the life course. This psychosocial stress increases risks for depressive symptoms and problematic substance use. Depressive symptoms and problematic substance use interfere with long-term adherence to antiretroviral therapy (ART). Lower ART adherence, in turn, exacerbates the elevated systemic inflammation stemming from HIV infection. This inflammation increases risks for aging-related comorbidities. Systemic inflammation also reduces connectivity in the brain's central executive network (CEN), a large-scale brain network that is critical for coping with stressful circumstances. This reduced capacity for coping with stress leads to further increases in depressive symptoms and problematic substance use. Together, these changes form a neuroimmune feedback loop that amplifies the impact of psychosocial stress on aging-related comorbidities. In this paper, I review the existing evidence relevant to this model and highlight directions for future research.