Developments in Neuroprotection for HIV-Associated Neurocognitive Disorders (HAND)

Area of Science:

• Neuroscience
• Infectious Diseases
• Pharmacology

Background:

• HIV-associated neurocognitive disorders (HAND) persist despite advances in combination antiretroviral therapy (cART).
• Milder forms of HAND remain a significant challenge, impacting quality of life for people living with HIV.
• Current cART effectively reduces HIV replication but does not fully eliminate the risk of HAND.

Purpose of the Study:

• To review current strategies for reducing the risk of HAND.
• To explore the potential of novel cART regimens and adjunctive therapies for neuroprotection.
• To accelerate the testing of neuroprotective interventions for HAND prevention and treatment.

Main Methods:

• Review of recent advancements in cART development focusing on central nervous system (CNS) efficacy.
• Evaluation of pilot studies on modified cART regimens, including improved penetrance and nanoformulations.
• Assessment of existing drugs for neuroinflammatory, neuropsychiatric, and metabolic disorders as potential adjuncts.
• Consideration of non-pharmacological interventions such as cognitive brain therapy and aerobic exercise.

Main Results:

• Modified cART regimens demonstrate potential for enhanced CNS efficacy and improved neuroprotection.
• Adjunctive therapies targeting neuroinflammation, oxidative stress, and metabolism show promise.
• FDA-approved drugs, cognitive therapy, and aerobic exercise are identified as plausible adjunctive strategies.
• Combining improved cART with these adjuncts offers a multifaceted approach to managing HAND.

Conclusions:

• Optimizing cART for CNS penetration and efficacy is crucial for HAND prevention.
• Adjunctive neuroprotective therapies, including repurposed drugs and lifestyle interventions, can complement cART.
• A combined strategy of enhanced cART and adjunctive therapies holds significant potential for preventing and treating HAND.
• Further research and accelerated clinical testing are needed to validate these promising strategies.