A Rationale and Approach to the Development of Specific Treatments for HIV Associated Neurocognitive Impairment

Abstract

Neurocognitive impairment (NCI) associated with HIV infection of the brain impacts a large proportion of people with HIV (PWH) regardless of antiretroviral therapy (ART). While the number of PWH and severe NCI has dropped considerably with the introduction of ART, the sole use of ART is not sufficient to prevent or arrest NCI in many PWH. As the HIV field continues to investigate cure strategies, adjunctive therapies are greatly needed. HIV imaging, cerebrospinal fluid, and pathological studies point to the presence of continual inflammation, and the presence of HIV RNA, DNA, and proteins in the brain despite ART. Clinical trials exploring potential adjunctive therapeutics for the treatment of HIV NCI over the last few decades have had limited success. Ideally, future research and development of novel compounds need to address both the HIV replication and neuroinflammation associated with HIV infection in the brain. Brain mononuclear phagocytes (MPs) are the primary instigators of inflammation and HIV protein expression; therefore, adjunctive treatments that act on MPs, such as immunomodulating agents, look promising. In this review, we will highlight recent developments of innovative therapies and discuss future approaches for HIV NCI treatment.

Protein cargo of Nef-containing exosomal extracellular vesicles may predict HIV-associated Neurocognitive Impairment status

“…Despite successful suppression of HIV viral loads by anti-retroviral therapy (ART) to undetectable levels, many aviremic HIV-infected individuals still develop neurocognitive deficits [1][2][3][4][5][6]. The exact mechanism(s) of HIV-associated neurocognitive disorder (HAND) in aviremic patients is still unclear.…”

Recent Advances in HIV-Associated Neurocognitive Disorders

“…HIV-related neurocognitive disorders (HAND) can be classified into asymptomatic neurocognitive impairment (ANI), mild neurocognitive disorder (MND), and HIV-associated dementia (HAD) [1]. The prevalence of HAND ranges from 15% to 50% [2].…”

“…As the disease progresses, patients may experience long-term memory decline, decreased ability to recognize objects, poor expression and comprehension of language. In the later stages, symptoms such as slow hand movement, unstable gait, difficulty walking, impaired coordination, and urinary and fecal incontinence may occur[1] [17]. These nonspecific clinical manifestations are often reported by patients during the diagnostic and treatment process.…”