HIV and neurocognitive dysfunction

Abstract

The spectrum of HIV-associated neurocognitive disorder (HAND) has been dramatically altered in the setting of widely available effective antiretroviral therapy (ART). Once culminating in dementia in many individuals infected with HIV, HAND now typically manifests as more subtle, though still morbid, forms of cognitive impairment in persons surviving long-term with treated HIV infection. Despite the substantial improvement in severity of this disorder, the fact that neurologic injury persists despite ART remains a challenge to the community of patients, providers and investigators aiming to optimize quality of life for those living with HIV. Cognitive dysfunction in treated HIV may reflect early irreversible CNS injury accrued before ART is typically initiated, ongoing low-level CNS infection and progressive injury in the setting of ART, or comborbidities including effects of treatment which may confound the beneficial reduction in viral replication and immune activation effected by ART.

Fig. 1

Paired HIV RNA levels in the blood (red) and cerebrospinal fluid (blue) compartments with respect to estimated days post HIV infection at initial sampling in antiretroviral naïve subjects with acute and primary HIV infection. Circles denote values measured in acute HIV subjects in Thailand with predominantly subtype CRF01_AE virus (adapted from [37], with permission); triangles denote values obtained in subjects from the USA, Sweden, Italy, and Australia with predominantly subtype B virus (updated from [•], with permission). Note the approximately 15 percent of CSF samples with HIV RNA concentrations at or below the standard level of detection (50 copies/ml), often in the presence of high plasma HIV RNA, within the first 6 months after infection