HIV Cerebrospinal Fluid Escape and Neurocognitive Pathology in the Era of Combined Antiretroviral Therapy: What Lies Beneath the Tip of the Iceberg in Sub-Saharan Africa?

Neurocognitive impairment remains an important HIV-associated comorbidity despite combination antiretroviral therapy (ART). Since the advent of ART, the spectrum of HIV-associated neurocognitive disorder (HAND) has shifted from the most severe form to milder forms. Independent replication of HIV in the central nervous system despite ART, so-called cerebrospinal fluid (CSF) escape is now recognised in the context of individuals with a reconstituted immune system. This review describes the global prevalence and clinical spectrum of CSF escape, it role in the pathogenesis of HAND and current advances in the diagnosis and management. It highlights gaps in knowledge in sub-Saharan Africa where the HIV burden is greatest and discusses the implications for this region in the context of the global HIV treatment scale up.