Suboptimal adherence to therapy may occur more frequently in subjects with NC impairment, hence adequate support services to optimize adherence are essential. We recommend patients with HIV-associated NC disorders start standard combination ART regimens (1C). Proportion of patients with HIV-associated NC disorders on ART containing two NRTIs and

one of an NNRTI, a PI/r or an INI. Although during the earlier MG132 years of ART, clear benefits on cerebral function of individual ARV drugs such as ZDV were reported [11] and the benefits of combination therapy overall are well described [8], data are sparse regarding any differences in these benefits between individual agents or combinations. Within Proteasome inhibitor cohort studies, the use of the NRTI class within ARV regimens has been associated with a reduced risk of severe HIV-associated dementia [12] compared with the use of other regimens; however, the confounders of a cohort study limit interpretation of these

data. Recently, attempts have been made to establish a relationship between cognitive function and CNS ARV drug delivery based on an ARV scoring system known as the clinical penetration effectiveness (CPE) score [13]. The CPE score aims to rationally score the cerebral effects of individual ARV agents. However, the system is predominantly designed around pharmacokinetic modelling rather than pharmacodynamic endpoints such as data describing changes in NC function. Studies that have assessed the correlation between the CPE scores of ARV regimens with NC function report conflicting findings Tolmetin with some cohorts reporting a positive association [14, 15], and others describing a negative association [16]. Given the potential flaws outlined in the

design of the CPE score, a lack of prospective clinical data and discrepancies in findings within cohort studies, the CPE score should not influence therapeutic decisions in subjects with NC impairment commencing ART. One small prospective study has assessed the cerebral effects of three different ARV regimens in neurologically asymptomatic subjects reporting greater improvement in NC function in subjects commencing a quadruple nucleoside regimen compared with an EFV- or ATV/r-containing regimen [17]. However, subjects were asymptomatic from a neurological point of view, limiting the relevance of these findings to neurologically symptomatic subjects.