. Author manuscript; available in PMC: 2024 Apr 26.

Published in final edited form as: Nat Rev Neurol. 2023 Oct 10;19(11):668–687. doi: 10.1038/s41582-023-00879-y

Table 3 |.

Examples of potential treatment strategies for HIV-associated NCI illustrating mechanisms described in this Review

Intervention	Proposed mechanism	Status of research	Effectiveness
Iptakalim	Reduced neuroinflammation	In vivo studies	Inhibited microglia-mediated neuroinflammation in rats⁴⁹³
Antibody to IFNAR2	Blocks downstream interferon-stimulated cascade	In vivo studies	Reduced inflammation in animals⁴⁹⁴
Intranasal IFNβ	IFNβ has antiviral effects and anti-inflammatory effects	In vivo study in model system	Neuroprotection in vivo¹⁶⁵
Interferons with or without ART	Type I interferons reduce viral replication and prevent infection of new targets	Human clinical trials (NCT02471430, NCT02767193, NCT01935089, NCT02227277)	Ongoing, aiming at reduced HIV reservoir⁴⁹⁵
Letermovir	Antiviral against cytomegalovirus, reducing inflammation	Proposed secondary end point in ongoing human clinical trial (NCT04840199)	Ongoing
Physical exercise	Improved mitochondrial biogenesis, hippocampal neurogenesis^a	In vivo studies	In mice, exercise is associated with mitochondrial biogenesis and hippocampal neurogenesis⁴⁹⁶
Mindful meditation	Improved function in brain networks supporting attention and emotion regulation^a	Human clinical trial (NCT02936401)	Not yet published
Ketogenic diet	Antioxidant increases mitochondrial biogenesis^a	Human clinical trial	Ketogenic drink improved cognition in mild cognitive impairment⁴⁹⁷

ART, antiretroviral therapy.

Non-pharmacological interventions.