HIV Cerebrospinal Fluid Escape: Interventions for the Management, Current Evidence and Future Perspectives

Neurocognitive impairment is an important cause of HIV-associated morbidity. The advent of antiretroviral therapy (ART) has shifted the spectrum of HIV-associated cognitive impairment from HIV-associated dementia to milder forms of cognitive impairment. Independent replication of HIV within the central nervous system in those on effective ART with peripheral suppression is a recognised phenomenon known as cerebrospinal fluid (CSF) HIV RNA escape. CSF HIV RNA escape is independently associated with neurocognitive impairment but has also been detected in asymptomatic persons with HIV. The current consensus for management of CSF HIV RNA escape is based on expert opinion rather than empirical evidence. The current evidence suggests having a low threshold to investigate for CSF HIV RNA escape and optimising ART based on resistance profiles. The use of central nervous system (CNS) penetration effectiveness scores is no longer recommended. The evidence for statins, SSRIs, minocycline, lithium and valproate is limited to small-scale studies. There are potential new developments in the form of nanoparticles, Janus Kinase inhibitors and latency reversal agents.