To review recent cohort studies that have examined the relationship between combination antiretroviral therapy (cART) regimens with superior central nervous system (CNS) penetration (neuroCART) in the prevention, treatment and subsequent survival of patients with HIV-associated neurocognitive disorders (HAND).

HAND remains prevalent including within virologically suppressed populations. The CNS-penetrating effectiveness (CPE) scoring system is an important and evolving tool to determine the therapeutic role of neuroCART in HAND patients. NeuroCART was associated with improved survival in children with HIV encephalopathy and also in adults diagnosed with HIV-associated dementia during the pre and early-cART calendar periods. In one cohort study the benefit of neuroCART was best conferred when cART regimens with high CPE scores and containing more than three drugs were used. Recent data suggest also that neuroCART may be associated with CNS toxicity and poorer neurocognitive performance.

The therapeutic importance of neuroCART in the treatment of HAND remains a vitally relevant, unanswered question. Recent cohort studies have demonstrated that neuroCART may improve survival in children and adults with HIV dementia, although adults may require several drugs to receive full therapeutic benefit. NeuroCART/cART may be neurotoxic in some populations. A randomized controlled trial to address the role of neuroCART in HAND is needed.