Dopaminergic impact of cART and anti-depressants on HIV neuropathogenesis in older adults.

The success of combination antiretroviral therapy (cART) has transformed HIV infection into a chronic condition, resulting in an increase in the number of older, cART-treated adults living with HIV. This has increased the incidence of age-related, non-AIDS comorbidities in this population. One of the most common comorbidities is depression, which is also associated with cognitive impairment and a number of neuropathologies. In older people living with HIV, treating these overlapping disorders is complex, often creating pill burden or adverse drug-drug interactions that can exacerbate these neurologic disorders. Depression, NeuroHIV and many of the neuropsychiatric therapeutics used to treat them impact the dopaminergic system, suggesting that dopaminergic dysfunction may be a common factor in the development of these disorders. Further, changes in dopamine can influence the development of inflammation and the regulation of immune function, which are also implicated in the progression of NeuroHIV and depression. Little is known about the optimal clinical management of drug-drug interactions between cART drugs and antidepressants, particularly in regard to dopamine in older people living with HIV. This review will discuss those interactions, first examining the etiology of NeuroHIV and depression in older adults, then discussing the interrelated effects of dopamine and inflammation on these disorders, and finally reviewing the activity and interactions of cART drugs and antidepressants on each of these factors. Developing better strategies to manage these comorbidities is critical to the health of the aging, HIV-infected population, as the older population may be particularly vulnerable to drug-drug interactions affecting dopamine.