ABSTRACT
INTRODUCTION: Central nervous system (CNS) penetration-effectiveness (CPE) rank was proposed in 2008 as an estimate of penetration of ARV regimen into the CNS, and validated as predictor of CSF HIV-1 replication. RESULTS on predictive role of CPE on neurocognitive and clinical outcome were conflicting. MATERIALS AND METHODS: Retrospective, cross-sectional analysis of neurocognitive profile in HIV-infected cART-treated patients. All patients underwent neuropsychological (NP) assessment by standardized battery of 14 tests on 5 different domains. People were classified as having NCI if they scored >1 standard deviation (SD) below the normal mean in at least two tests, or >2 SD below in one test. Linear and logistic regression analyses were fitted using as outcome Npz8 and impaired/not impaired respectively. RESULTS: A total of 660 HIV-infected cART-treated individuals from 2009 to 2014, contributing a total of 1003 tests (mean age 49 (IQR 43-56), male 82%; median current CD4 586/mm(3); 18% HCV infected; HIV-RNA <40 cp/mL in 84%). Current ARV regimen was 2NRTIs+1NNRTI 50.3%, 2NRTI+1PI/r in 32.6%, NRTI sparing in 11.1%. Mean CPE of current regimens was 6.6 (95% CI 6.5-6.7). As per test multivariable analysis, higher CPE values were associated to poor NP tasks (Beta=-0,09; 95% CI -0,14 -0,03; p=0.002 at multivariable linear regression). The association between higher CPE and increased NCI risk was confirmed at multivariable logistic regression, with a 1.24-fold risk of NCI occurrence for each point increase of CPE of current regimen at the time of NP testing (see Table 1). In a sensitivity analysis performed only on patients at the first NP test, the association between higher CPE and poor NP tasks and enhanced NCI risk was only marginally confirmed (Beta=-0,05; [-0,12-0,02]; p=0,19; OR 1,13 [0,95-1,34]; p=0.17). Older age, longer time from HIV diagnosis, current CD4 count <350 cell/mm(3) and lower education level were all associated to an increased risk of NCI. CONCLUSIONS: In our analysis, higher CPE rank is associated to poorly performing at NP tasking. Even if selection bias could not be excluded due to retrospective cross-sectional design, these results fitted with the direct correlation between high CPE and HIV dementia recently recorded in a large observational database. We think that CPE use to guide ART in patients neurocognitively impaired should be revised.
ABSTRACT
INTRODUCTION: Chronic liver disease leads to neurocognitive impairment (NCI) and more advanced liver fibrosis is associated with greater deficits. Further, cognitive performances do not differ significantly among patients affected by diverse types of chronic liver diseases. Thus, it would be useful to have a clinical tool associated with early cognitive change applicable to the HIV-infected population with high HCV prevalence. Aim of the analysis was to assess the association between NCI and aspartate aminotransferase-platelet ratio index (APRI) or Fibrosis-4, which are non-invasive scores used to assess liver fibrosis. MATERIALS AND METHODS: Single-centre, retrospective, cross-sectional analysis of cART-treated HIV-infected patients undergoing neuropsychological assessment (NPA) by a set of 14 standardized and comprehensive tests on five different domains: concentration and speed of mental processing; mental flexibility; memory, fine motor functioning; visual-spatial and constructional abilities. NPA obtained from the same patient were included, if collected while receiving different cART. Patients were classified as having NCI, if they scored >1 SD below the normative mean in at least two tests, or below >2 SD in one test. HIV-associated neurocognitive disorders (HAND) were classified according to Frascati's criteria, controlling for confounding comorbidities. Univariable analysis and multivariable logistic regression models were carried out. RESULTS: A total of 556 HIV-infected cART-treated patients from 2006 to 2013 were included: male 78%; IVDUs 14%; CDC stage C 31%; median CD4 nadir 200/mm(3); median current CD4 501/mm(3); undetectable HIV-RNA in 368 (67%); and HCV-positivity in 150 (29%). Frequency among score levels was for FIB-4: min-1.44=404 (73%), 1.45-3.25=118 (21%), 3.26-max=28 (5%); for APRI: min-0.5=414 (75%), 0.5-1.5=112 (20%), 1.5-max=24 (4%). Median FIB-4 and APRI were 0.98 and 0.27 in HIV+/HCV- and 1.40 and 0.50 in HIV+/HCV+ individuals, respectively. HAND was found in 176 (32%): 91 ANI, 73 MND, 12 HAD. Association of variables with NCI are shown in Table 1. CONCLUSIONS: In this large population, HAND was not associated with commonly used non-invasive liver fibrosis scores. As aetiology of cognitive dysfunction in HIV mono- and HCV co-infected patients is multifactorial and partially unknown, our results support the hypothesis of a direct or indirect effect on cognitive function of the viruses, rather than the consequence of alterations residing outside the brain.
