Therapeutic Considerations in HIV-Associated Neurocognitive Disorders (HAND)

HIV-associated neurocognitive disorders (HAND) persist globally despite the effectiveness of suppressive combination antiretroviral therapy (cART) in dramatically reducing the prevalence of HIV-associated dementia, the severest sub-type of HAND. Nonetheless, less severe HAND can be disabling for employment and other activities of daily living, and it remains a large health burden. Success in preventing and treating HAND requires maximizing viral suppression in the central nervous system and other body compartments, modulating the potentially toxic and metabolic effects of early blood–brain barrier injury and virus persistence even in the absence of replication, and enhancing the potential for nervous system recovery. Recent pilot study successes in improving cART regimens for CNS efficacy (improving penetrance, targeting the HIV chemokine co-receptor CCR5 and delivery (nanoformulations) suggest that more complete and sustained suppression of HIV replication is achievable, and this may indeed even further reduce the prevalence of symptomatic HAND. Targeting associated pathogenic pathways with currently available FDA-approved drugs used for other disorders can also serve as adjunctive treatments to cART by adding broad suppression of neuroinflammation and oxidative stress, modulating neurotransmitter metabolism, and perhaps supporting neuroregeneration. Interest in neurotrophic factors is rapidly growing, with limited study thus far. Adjunctive cognitive behavioral therapy and aerobic exercise combined with each of these may further improve outcomes.