Simulating the development and progression of Chronic Kidney Disease and osteoporosis in people living with HIV

The "chronicization" of HIV infection brings about a growing necessity to attentively evaluate current and potential complications when prescribing the individual therapeutic regimen. Starting from this need, we developed two HIV-comorbidity simulators that, basing on the evidence available in medical literature and starting from the current clinical and demographic features of the individual patient, project and compare the risks of developing and worsening of nephropathy and osteopathy associated with possible ARV regimens. These simulators are embedded in a desktop, user-friendly software thought to be used by the treating physician during prescription discussion with his/her patients, in order to highlight expected clinical outcomes and healthcare resource consumption that may differ according to the therapeutic strategy selected. In this article we present the sources and methods used in developing the mathematical models, alongside a set of examples and the results of cohort-level validation runs

Antiretroviral therapy management and rationalisation of available resources

The treatment of HIV disease has led to a new division of management costs by shifting most of the necessary resources from inpatient treatment to outpatient management. Among the initiatives aimed at rationalising the resources available, we compared efficacy, tolerability and pharmacoeconomic impact of different regimes of antiretroviral therapy (ART). The survey covered the first 50 patients, clinically stable and with good viro-immunological response, who switched in June 2012 from an ART based on the triple combination of tenofovir (TDF), emtricitabine (FTC) and a protease inhibitor boosted with ritonavir (PI/r) or a non-nucleoside reverse transcriptase inhibitor (NNRTI), to a treatment based on abacavir (ABC), lamivudine (3TC) and a PI/r or NNRTI. Of the 50 patients who operated the switch, 39 replaced a PI with nevirapine (NVP), for which the largest group of patients was treated with ABC + 3TC + NVP. On 31 May 2015, all patients completed the observation period of 96 weeks, with a mean observation period of 132 weeks and clinical-laboratory checks every four months. Laboratory analysis revealed an optimal maintenance of viral suppression and absolute and relative number of CD4 + lymphocytes and improving trend of creatinine, proteinuria, serum phosphate and bone alkaline phosphatase. There was a variable effect on lipids, with a drop in triglycerides associated with a modest increase in total cholesterol. Much of the HIV-positive population reporting to our hospitals (>50%) comprises individuals who have for years been in stable viraemic suppression, making a satisfactory immune recovery while in good overall clinical condition. This type of patient was the target of the present survey. At the end of 96 weeks of observation the new regimes were well tolerated and did not lead to viro-immunological or clinical deterioration. Pharmacoeconomic analysis showed better containment of the overall costs. No patient needed to be hospitalised during the observation period

Parietal intrahemispheric source connectivity of resting-state electroencephalographic alpha rhythms is abnormal in Naïve HIV patients

Previous evidence showed abnormal parietal sources of resting-state electroencephalographic (EEG) delta (< 4 Hz) and alpha (8-12 Hz) rhythms in treatment-Naive HIV (Naive HIV) subjects, as cortical neural synchronization markers in quiet wakefulness. Here, we tested the hypothesis that these local abnormalities may be related to functional cortical dysconnectivity as an oscillatory brain network disorder.The present EEG database regarded 128 Naive HIV and 60 Healthy subjects. The eLORETA freeware estimated lagged linear EEG source connectivity (LLC). The area under receiver operating characteristic (AUROC) curve indexed the accuracy in the classification between Healthy and HIV individuals.Parietal intrahemispheric LLC solutions in alpha sources were abnormally lower in the Naive HIV than in the control group. Furthermore, those abnormalities were greater in the Naive HIV subgroup with executive and visuospatial deficits than the Naive HIV subgroup with normal cognition. AUROC curves of those LLC solutions exhibited moderate/good accuracies (0.75-0.88) in the discrimination between the Naive HIV individuals with executive and visuospatial deficits vs. Naive HIV individuals with normal cognition and control individuals.In quiet wakefulness, Naive HIV subjects showed clinically relevant abnormalities in parietal alpha source connectivity. HIV may alter a parietal "hub" oscillating at the alpha frequency in quiet wakefulness as a brain network disorder

Cortical sources of resting state electroencephalographic rhythms probe brain function in naïve HIV individuals

Objective Here we evaluated the hypothesis that resting state electroencephalographic (EEG) cortical sources correlated with cognitive functions and discriminated asymptomatic treatment-naïve HIV subjects (no AIDS). Methods EEG, clinical, and neuropsychological data were collected in 103 treatment-naïve HIV subjects (88 males; mean age 39.8 years ± 1.1 standard error of the mean, SE). An age-matched group of 70 cognitively normal and HIV-negative (Healthy; 56 males; 39.0 years ± 2.0 SE) subjects, selected from a local university archive, was used for control purposes. LORETA freeware was used for EEG source estimation in fronto-central, temporal, and parieto-occipital regions of interest. Results Widespread sources of delta (<4 Hz) and alpha (8â\u80\u9312 Hz) rhythms were abnormal in the treatment-naïve HIV group. Fronto-central delta source activity showed a slight but significant (p < 0.05, corrected) negative correlation with verbal and semantic test scores. So did parieto-occipital delta/alpha source ratio with memory and composite cognitive scores. These sources allowed a moderate classification accuracy between HIV and control individuals (area under the ROC curves of 70â\u80\u9375%). Conclusions Regional EEG abnormalities in quiet wakefulness characterized treatment-naïve HIV subjects at the individual level. Significance This EEG approach may contribute to the management of treatment-naïve HIV subjects at risk of cognitive deficits

-No evidence of hematopoietic stem cell mobilization in patients submitted to hepatectomy or in patients with acute on chronic liver failure

BACKGROUND: Liver regeneration is a heterogeneous phenomenon involving the proliferation of different cell lineages in response to injury. Under a strong positive selection pressure bone marrow derived stem cells may be involved in this process, by making a contribution to both parenchymal restoration and endothelial cell replacement. We investigate bone marrow stem cell migration to the liver in patients undergoing hepatectomy or with acute on chronic liver failure. METHODS: We enrolled 6 patients submitted to hepatectomy, 6 patients to cholecystectomy and 8 patients with acute decompensation of liver cirrhosis. Mobilization of CD34+ cells was evaluated by cytofluorimetry on peripheral blood samples at different time points; baseline, 1, 3, 7, 15 and 30 days after surgery and at admission, 1, 7 and discharge among patients with acute on chronic liver failure. 10 healthy subjects undergoing blood donation were also enrolled to evaluated the basal value of CD34+ cells. RESULTS: White blood cell counts remained in the normal range (4.1-9.8 x 10(9)/L) in all groups throughout the follow-up. In all patients of Groups 1, 2 and 3, circulating CD34+ failed to show statistically significant differences both as the absolute number and as the percentage at any time point compared to healthy controls. CONCLUSIONS: Bone marrow derived cell mobilization can not be detected after hepatectomy or during an acute decompensation on a cirrhotic liver. Under these circumstances liver regeneration can probably call upon mature hepatocytes and endogenous progenitor cells. The involvement of extrahepatic progenitors if any, is a rare and limited phenomenon