Progressive multifocal leukoencephalopathy (PML), a fatal demyelinating disease caused by JC virus (JCV) infection of oligodendrocytes, may develop in patients with immune disorders following reactivation of chronic benign infection. Mutations of JCV capsid viral protein 1 (VP1), the capsid protein involved in binding to sialic acid cell receptors, might favor PML onset. Cerebrospinal fluid sequences from 37/40 PML patients contained one of several JCV VP1 amino acid mutations, which were also present in paired plasma but not urine sequences despite the same viral genetic background. VP1-derived virus-like particles (VLPs) carrying these mutations lost hemagglutination ability, showed different ganglioside specificity, and abolished binding to different peripheral cell types compared with wild-type VLPs. However, mutants still bound brain-derived cells, and binding was not affected by sialic acid removal by neuraminidase. JCV VP1 substitutions are acquired intrapatient and might favor JCV brain invasion through abrogation of sialic acid binding with peripheral cells, while maintaining sialic acid-independent binding with brain cells.

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ObjectivesThe aim of the study was to assess whether pill burden is associated with self-reported adherence to current combination antiretroviral regimens and health status in a large sample of unselected and chronically treated HIV-infected patients. MethodsAn adherence and health status questionnaire was offered to all patients collecting their drugs between March and May 2010 at our clinic; both parameters were primarily evaluated using a visual analogue scale. Linear correlations were evaluated using Spearman's correlation coefficient. Wilcoxon's rank-sum test and the c 2 test were used to compare quantitative and qualitative variables. The generalized linear model was used in multivariable analyses. ResultsAmong 2763 subjects on treatment during the study period, 2114 (78.8% male; mean age 46.9 Ϯ 8.84 years) were tested for adherence; 1803 (85.3%) had viral loads < 50 HIV-1 RNA copies/mL.After adjusting for age, gender, HIV risk factor, current CD4 count, pill burden and dosing interval, adherence was higher in patients with undetectable HIV RNA (P < 0.0001) and directly associated with current CD4 count (P = 0.029). After adjusting for the same variables, health status was better in patients with undetectable viraemia (P = 0.004) and in men who have sex with men (MSM) and heterosexuals compared with injecting drug users and those with other risk factors (P < 0.0001 for MSM and P = 0.008 for heterosexuals); it was also directly associated with current CD4 count (P < 0.0001) and inversely associated with age (P < 0.0001) and pill burden (P = 0.019). ConclusionsIn this highly adherent population, the number of daily pills was related to self-reported health status but not to self-reported adherence, whereas the dosing interval did not influence self-reported adherence or health status. [5], patients offered a switch to a regimen using the same drugs but fewer pills [3], or patients treated with complicated antiretroviral regimens that are no longer used, such as those involving thrice-daily administrations or a large number of daily pills [6][7][8]. Furthermore, a recent metaanalysis found that once-daily regimens significantly improved adherence in treatment-naïve but not treatmentexperienced patients, and that the difference in adherence did not correspond to any overall difference in the rates of viral suppression [2].The primary aim of this study was to assess whether the number of daily pills is associated with self-reported adherence to current combination antiretroviral therapy (cART) regimens and health status in a large sample of chronically treated patients not selected on the basis of formal inclusion/exclusion criteria. The secondary objective was to investigate whether the currently used dosing schedules [once daily (qd) or twice daily (bid)] affect self-reported adherence and health status in this setting. MethodsThis was a cross-sectional study of HIV-infected patients receiving cART who were attending the out-patient clinic of the Department of Infectious Diseases, San Raffaele Scientific Ins...

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