In the ongoing UK PIVOT study, detailed neuropsychological testing is being assessed prospectively in subjects on PI monotherapy vs. standard therapy, the results of which

will be of great interest to this field. Given the above theoretical concerns regarding the CNS activity of PI monotherapy, and for the majority of HIV-positive subjects Ganetespib mouse it may be possible to select other ARV regimens, we suggest this approach is currently avoided in neurologically symptomatic subjects. In patients with ongoing or worsening NC impairment despite ART, we recommend the following best practice management (GPP): Reassessment for confounding conditions. Assessment of CSF HIV RNA, CSF HIV genotropism and genotyping of CSF HIV RNA. In subjects with detectable CSF HIV RNA, modifications to ART should be based on plasma and CSF genotypic and genotropism results. Several published randomized

controlled studies, assessing both intensification of ART with a new ARV agent [131] and with adjunctive therapies [132-135] have been published. Unfortunately, NVP-BKM120 none of these studies describe improvements in cognition subsequent to the study interventions. Without evidence-based interventions, the Writing Group outlines below a best practice approach based on the current literature. As HIV-associated NC disorders are a diagnosis of exclusion, re-evaluation of subjects with ongoing NC impairment despite ART for confounding conditions, with expert input from other clinical specialties such as psychiatry, neurology and neuropsychology, is recommended and, where possible, input from an HIV neurology service. Assessment of CSF HIV RNA, CSF HIV genotropism and genotypic analysis of CSF RNA may be useful tools in the management of subjects with ongoing NC for the following reasons. First, data from cohorts of untreated HIV-positive subjects would suggest

CSF HIV RNA to be greater in subjects with HIV-associated dementia and cognitive decline [136, 137] and therefore suppression of CSF HIV RNA may be beneficial for cognitive function. Secondly, in subjects with ongoing NC impairment, higher degrees of genetic diversity between HIV viral strains in the CSF and plasma compartment may exist [138], even in subjects with undetectable plasma HIV RNA [139]. Therefore, Edoxaban assessment for CSF HIV resistance may be worthwhile to tailor ART. We recommend patients with HIVAN start ART immediately irrespective of CD4 cell count (1C). We recommend patients with end-stage kidney disease who are suitable candidates for renal transplantation start ART irrespective of CD4 cell count (1C). Proportion of patients with HIVAN started on ART within 2 weeks of diagnosis of CKD. The use of ART has been associated with a decline in the incidence of HIVAN in HIV cohort studies [140], with renal histological improvement in case reports [141, 142], and with delayed progression to end-stage kidney disease in case series [143, 144].