In terms of survival prediction, neurocART was not very important to the models in comparison with these covariates. We did not directly examine NCI-associated mortality, although an important rationale for this study was the possible improvement in survival attributable to the beneficial effect of neurocART on mild, and possibly undiagnosed and
unmeasured, NCI [1]. Although previous studies Selumetinib have demonstrated a sizeable frequency of mild NCI in certain populations [8,9], we do not have comprehensive data on the incidence of mild NCI-associated mortality in APHOD. To our knowledge, there is no strong existing evidence of survival attributable to the beneficial effects of neurocART on mild NCI. A recent paper by Smurzynski et al. [25] showed an adjusted association between increases in CPE score and neuropsychological test scores when accounting for an interaction with the number of ARVs per regimen. While Patel et al. did not find a significant association between CNS penetration and the incidence of HIV encephalopathy,
they did observe a significant survival benefit associated with CNS penetration in HIV encephalopathy cases [1]. In contrast, while Garvey et al. did not observe a significant adjusted association between CPE score and CNS opportunistic diseases, they noted that the lowest and highest CPE scores were associated with increased mortality [21], but suggested that this was a consequence of clinical status affecting prescribing practice. Overall, our findings do not demonstrate the posited association between neurocART-reduced NCI and Ferrostatin-1 purchase improved survival in APHOD. Our findings, which describe prospective data for the period 1999–2009, can be contrasted with those of a recent study by Lanoy et al. [20], where
all-cause mortality 4��8C in neuroAIDS diagnoses was associated with CPE score for each of the periods 1992–1995 and 1996–1998 but not for 1999–2004. In that study, the authors attributed the lack of an associated effect in the period 1999–2004 to improved control of plasma viral load (which was not adjusted for in initial models) by cART regimens in general. In the same study, a secondary analysis for the period 1997–2004 showed no change in survival associated with CPE score after including plasma HIV RNA as a covariate. While our results reflect a lack of a differentiable survival effect of neurocART use in the later cART period for all HIV-positive patients, they also suggest that plasma viral load adds little extra descriptive power after the inclusion of CD4 cell count as a covariate in multivariate models when examining neurocART survival outcomes. Similarly, while Patel et al. were unable to adjust for viral load in their primary analysis, sensitivity analyses suggested that measured CNS effects were not confounded by the omission of this covariate [1]. In this regard, temporal changes in the measured CPE effect as observed by Lanoy et al.