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ObjectivesOur aim was to investigate the durability of different initial regimens in patients starting ART with CD4+ counts 5 log10 copies/mL.MethodsThis was a retrospective study of HIV-infected patients prospectively followed in the ICONA cohort. Those who started ART with boosted protease inhibitors (bPIs), NNRTIs or integrase strand transfer inhibitors (InSTIs), with CD4+ 5 log10 copies/mL, were included. The primary endpoint was treatment failure (TF), a composite endpoint defined as virological failure (VF, first of two consecutive HIV-RNA >50 copies/mL after 6 months of treatment), discontinuation of class of the anchor drug or death. Independent associations were investigated by Poisson regression analysis in a model including age, gender, mode of HIV transmission, CDC stage, HCV and HBV co-infection, pre-treatment HIV-RNA, CD4+ count and CD4+/CD8+ ratio, ongoing opportunistic disease, fibrosis FIB-4 index, estimated glomerular filtration rate, haemoglobin, platelets, neutrophils, calendar year of ART initiation, anchor drug class (treatment group) and nucleos(t)ide backbone.ResultsA total of 1195 patients fulfilled the inclusion criteria: 696 started ART with a bPI, 315 with an InSTI and 184 with an NNRTI. During 2759 person-years of follow up, 642 patients experienced TF. Starting ART with bPIs [adjusted incidence rate ratio (aIRR) (95% CI) 1.62 (1.29–2.03) versus starting with NNRTIs; P ConclusionsIn patients starting ART with 5 log10 HIV-RNA copies/mL, the durability of regimens based on InSTIs was longer than that of NNRTI- and bPI-based regimens.

ObjectiveGiven the aging of people living with HIV (PLWH) and the high prevalence of HIV-associated neurocognitive disorders, we aimed at describing the clinical, instrumental, and CSF features of PLWH diagnosed with Alzheimer dementia (AD).MethodsThe databases of 3 large Italian outpatient clinics taking care of more than 9,000 PLWH were searched for the diagnosis of AD. After obtaining patients' or their next of kin's consent for publication, anonymous data were collected in an excel spreadsheet and described. Routinely collected CSF biomarkers and radiologic imaging results were recorded whether available.ResultsFour patients were included in this case series who were diagnosed with AD aged between 60 and 74 years. All participants were on highly active antiretroviral therapy and showed nondetectable serum HIV RNA. Memory impairment was the most prominent cognitive feature. The diagnosis was obtained considering the exclusion of other potential causes, MRI and fluorodeoxyglucose-PET features, and, in (in 2/4), CSF AD biomarkers levels. In 1 patient, longitudinal CSF tau/p-tau increased, and beta-amyloid1–42 decreased over time despite antiretroviral therapy containing nucleotide reverse transcriptase inhibitors.ConclusionsIn older PLWH cognitive symptoms may represent the onset of AD: a multidisciplinary team may be needed for reaching a likely in vivo diagnosis.

Background Infectious diseases are more common and severe in patients with HIV, which show different response to vaccines and a diminished protection. It is therefore very important to assess knowledge and attitudes towards vaccination in people with HIV, since precise vaccination coverage and vaccine hesitancy are not well established in this subgroup of patients. Methods A sample of 119 patients with HIV completed a cross-sectional survey. Patients were recruited during their routine medical examination at the infectious diseases clinic in Turin. The survey explored these main areas: demographics and history of HIV infection, vaccination history, attitudes towards vaccination, confidence in the public health system, contagion risk and disease seriousness perception. In this preliminary phase descriptive analysis were conducted. Results Preliminary data show that mean age of the participants was 49.51 years, 80% were males. The median of HIV infection duration was 10 years, while the median of the lymphocyte count was 762.50 cells/mm3. The disease with the highest vaccination coverage was tetanus (88.7%), considered a serious or very serious disease by 85.6% of the participants, despite low or very low contagion risk perception (84.1%). The disease with the lowest vaccination coverage was Herpes Zoster (7.3%), despite high or very high seriousness perception (70%). Furthermore, 99.1% of the participants showed high or very high confidence toward public health system professionals, and the majority of them (59.5%) stated that vaccines are more useful for the community than for the single person. Conclusions Vaccination coverage is still not fully satisfactory regarding diseases considered infrequent or mild. Considering the high level of confidence toward the public health system that has emerged, it is necessary to implement informative and operative strategies about vaccination for European HIV patients, which are particularly at risk regarding infectious diseases. Key messages Vaccination coverage and risk perception in HIV patients is not satisfactory for many diseases and an effort to implement informative strategies in Europe is needed. The role of vaccination in preventing infectious diseases in HIV patients should be recognized and strengthened by relying on the high level of confidence toward European public health systems.

The aim of this study was to evaluate the factors that can influence an incomplete viral response (IVR) after acute and early HIV infection (AEHI).This was a retrospective, observational study including patients with AEHI (Fiebig stages I-V) diagnosed between January 2008 and December 2014 at 20 Italian centres. IVR was defined by: (1) viral blip (51-1000 HIV-1 RNA copies/mL after achievement of 50 HIV-1 RNA copies/mL); (2) virologic failure [ 1000 copies/mL after achievement of 200 copies/mL, or ≥ 200 copies/mL after 24 weeks on an antiretroviral therapy (ART)]; (3) suboptimal viral response ( 50 copies/mL after 48 weeks on ART or two consecutive HIV-1 RNA levels with ascending trend during ART). Cox regression analysis was used to calculate the hazard ratios (HRs) and 95% confidence intervals (95% CIs) for IVR.In all, 263 patients were studied, 227 (86%) males, with a median [interquartile range (IQR)] age of 38 (30-46) years. During a median follow-up of 13.0 (5.7-31.1) months, 38 (14.4%) had IVR. The presence of central nervous system (CNS) symptoms was linked to a higher risk of IVR (HR = 4.70, 95% CI: 1.56-14.17), while a higher CD4/CD8 cell count ratio (HR = 0.13, 95% CI: 0.03-0.51 for each point increase) and first-line ART with three-drug regimens recommended by current guidelines (HR = 0.40, 95% CI: 0.18-0.91 compared with other regimens including four or five drugs, older drugs or non-standard backbones) were protective against IVR.Patients with lower CD4/CD8 ratio and CNS symptoms could be at a higher risk of IVR after AEHI. The use of recommended ART may be relevant for improving short-term viral efficacy in this group of patients.

The aim of this retrospective, multicentre, observational study was to assess the durability, safety, immune recovery and effectiveness on viral suppression of antiretroviral therapy (ART) in a maraviroc (MVC)-based cohort. We collected clinical, demographical, immunological and virological parameters of adult HIV patients who were infected by CCR5-tropic virus and started an ART regimen containing MVC from 2005 to 2012. We created a longitudinal mixed model to assess the change over time of data. We enrolled 126 drug-experienced patients; the median duration of MVC treatment was 25 months. The probability of stopping ART at one year was 13.3%, and at three years was 27.3%. Statistically significant changes were observed for CD4+ cell count increase ( p 3 at baseline while nine of them reached this threshold at nine months (7.6%), 17 (13%) after nine months and six (5%) remained below 200 cells/mm3 at the end of the study. Overall, 114 patients (90.5%) achieved an HIV-RNA ≤ 50 cp/ml. A majority of patients maintained CD4 cell counts of ≥ 200 cells/mm3 and achieved an undetectable HIV viral load within three months. MVC-containing regimens are safe and appear to be a feasible therapeutic option for ART.

The relationship between hepatic tolerance and hepatitis C virus (HCV) co-infection has not been extensively studied in clinical practice. We assessed the efficacy and safety of raltegravir-based therapy in an Italian cohort of HIV/HCV co-infected patients. One hundred and forty patients with HIV/HCV co-infection initiating raltegravir from SCOLTA project (Surveillance Cohort Long-Term Toxicity Antiretrovirals) were examined. Of them, 43 were women, with mean age of 45.4. ±. 6.4. years; 65 (46%) had undetectable HIV-RNA. < 50. copies/mL and 75 (54%) HIV-RNA. ≥. 50. copies/mL. According to CDC classification, 49 (35%) were in stage C. Based on Fib4 score at the time of starting raltegravir, patients were classified in class I in 41 cases, class II in 68 and in class III in 31 cases. Globally, the Fib4 score slightly decreased during 24. months follow-up, from 2.2 to a value of 1.8. Hepatic adverse events of any grade were observed in 67 patients, of which only 2 cases (3%) had severe liver toxicity (grade 3-4). Only one patient had to discontinue the therapy because of adverse events. According to univariate analysis, being in CDC stage C represented a risk for the development of liver toxicity, with a hazard ratio (HR) of 2.27 (95% CI 1.06-4.84, P= 0.033). None of the other variables considered (age, sex, years since detection of HIV and HCV-RNA detectable, years of previous HIV therapy, concomitant therapy with PI or NRTI, CD4+ cell count, Fib4, and transaminases level at baseline) resulted statistically correlated to the outcome. In conclusion, raltegravir-based regimens can be safely used in HCV infected patients; in this study, the hepatic toxicity has been found to be more frequent in patients with an advanced HIV disease (CDC stage C), independently of HIV-RNA suppression at raltegravir initiation.

Background Geriatric Patients Living with HIV/AIDS (GEPPO) is a new prospective observational multicentre cohort consisting of all the HIV-positive geriatric patients being treated at 10 clinics in Italy, and HIV-negative controls attending a single geriatric clinic. The aim of this analysis of the GEPPO cohort was to compare prevalence and risk factors of individual non-communicable diseases (NCD), multi-morbidity (MM) and polypharmacy (PP) amongst HIV positive and HIV negative controls at enrolment into the GEPPO cohort. Methods This cross-sectional study was conducted between June 2015 and May 2016. The duration of HIV infection was subdivided into three intervals: 20 years. The NCD diagnoses were based on guidelines defined criteria, including cardiovascular disease, hypertension, type 2 diabetes, chronic kidney disease, dyslipidaemia, chronic obstructive pulmonary disease. MM was classified as the presence of two or more co-morbidities. The medications prescribed for the treatment of comorbidities were collected in both HIV positive and HIV negative group from patient files and were categorized using the Anatomical Therapeutic Chemical (ATC) classification. PP was defined as the presence of five or more drug components other than anti-retroviral agents. Results The study involved a total of 1573 patient: 1258 HIV positive and 315 HIV negative). The prevalence of individual comorbidities was similar in the two groups with the exception of dyslipidaemia, which was more frequent in the HIV-positive patients (p

BACKGROUND Adults aging with HIV are at greater risk for several comorbidities. The CD4 cell count and CD4/CD8 ratio often fail to normalize in elderly patients despite prolonged antiretroviral therapy; this has been associated with concomitant diseases and poor prognosis. METHODS A cross-sectional analysis in antiretroviral-treated HIV-positive patients aged 65 years and older. The aim of the study was to describe the predictors of normalized T-cell subsets ("nT", CD4/CD8 ratio ≥1 and CD4 ≥500 cells/μL) in a cohort of geriatric HIV-positive patients and its association with HIV-associated non-AIDS conditions (HANA). RESULTS One thousand ninety-two patients were included: nT was observed in 340 patients (31.1%). Multivariate binary logistic analysis showed that plasma HIV RNA

After the introduction of highly active antiretroviral treatment, the course of HIV infection turned into a chronic disease and most of HIV-positive patients will soon be over 50 years old. This paper reviews the multiple aspects that physicians have to face while taking care of HIV-positive ageing patients including the definitions of frailty and the prevalence and risk factors of concomitant diseases. From a therapeutic point of view pharmacokinetic changes and antiretroviral-specific toxicities associated with ageing are discussed; finally therapeutic approaches to frailty are reviewed both in HIV-positive and negative patients. We conclude by suggesting that the combined use of drugs with the least toxicity potential and the promotion of healthy behaviours (including appropriate nutrition and exercise) might be the best practice for ageing HIV-positive subjects.

Objectives Evaluate gender differences with regard to baseline characteristics and outcome of therapy in cohorts of the SCOLTA (surveillance cohort long-term toxicity of antiretrovirals) project. Methods The SCOLTA project is an active pharmacovigilance system for new antiretroviral drugs. Since 2002, patients were enrolled in nine cohorts (lopinavir, tenofovir, atazanavir, fosamprenavir, enfuvirtide, tipranavir, darunavir, raltegravir and maraviroc). Results Two thousand one hundred and fifty-four patients were included in 5 PI cohorts; 607 (28.2%) were female. Women were younger and less frequently HCV-coinfected than men. At study entry, they were less frequently in CDC stage C, but CD4+ cells/mm 3 and detectable HIV-RNA were not different by gender. Women had triglycerides alterations less frequently than men, but showed a higher proportion of low HDL-cholesterol. Women were protected from incident grade 2-4 triglycerides increase (odds ratio = 0.39, 95% confidence interval 0.18–0.88; P = 0.02). Mean CD4+ cell count increased in both men and women; despite a non-significantly lower initial CD4+ level, women had a better immunological recovery. Women discontinued PI treatment for adverse events and their own will more frequently. Conclusions In these cohorts, gender distribution mirrored the Italian HIV population. Women were younger than men when they started their first ARV therapy and when they entered our cohorts. On the same treatment, they had a better immune response, though no significant difference emerged on virologic control and treatment durability. As compared to men, women appeared at lower risk of hypertriglyceridaemia. They stopped PI-based treatment of their own will more frequently than men, suggesting the need for a focused effort on adherence.

The possible role of histamine locally applied into the nucleus accumbens on exploratory behaviours measured in 'conflictive' and 'non-conflictive' environments was studied in adult male rats. It was assumed that in conflictive environments the brain mechanisms involved in processing incentive environmental clues (novelty) were interacting with mechanisms involved in the processing of fearful or 'anxiogenic' environmental clues. As a model of conflictive environment, the elevated asymmetric-plus maze (APM) was used. As a model of a non-conflictive environment, a modified holebroad enriched with an object (OVM) was used. The exploration score in any of the arms of the APM was considered an approximate index of exploratory motivation. The permanency score (non-exploratory behaviours) was considered an inverse approximate index of emotionality. Other variables such as the frequency of entries into any arm, the latency time and central activity were also measured. In the OVM, the general motor activity and head-dipping, vertical rearing and focalized exploration were measured. Results show that histamine in the APM had a dual effect. On the one hand, an increase of exploration was observed in those arms considered more 'anxiogenic'. On the other hand, a decrease in exploration occurred in one of the arms considered less 'anxiogenic'. No changes of permanency was observed in the 'anxiogenic' arms, and a decrease of permanency took place in the arms considered less 'anxiogenic'. In the OVM, histamine did not change the overall motor activity, but head-dipping was inhibited by the imidazolamine treatment. Histamine effects on exploration parameters were counteracted by pre-treatment with H1- and H2-histamine antagonists. Nevertheless, some behaviours were not blocked by the histamine receptor antagonists. The present results give support to the role of the nucleus accumbens in the exploratory motivation mechanisms and suggest that histamine might be an endogenous regulator.

As the risk of tenofovir-associated renal toxicity has been found to be proportional to the drug plasma concentration, our aim was to measure the determinants of tenofovir plasma exposure in HIV-positive patients with normal renal function. A cross-sectional analysis was conducted in HIV-positive patients chronically receiving tenofovir-containing highly active antiretroviral therapies (HAARTs). Patients on tenofovir-containing antiretroviral regimens, presenting 22 to 26 h after drug intake, having estimated glomerular filtration rates above 60 ml/min, reporting high adherence to antiretroviral medications (above 95% of the doses), and signing a written informed consent were included. Plasma tenofovir concentrations were measured through a validated high-performance liquid chromatography–mass spectrometry (HPLC/LC-MS) method. The tenofovir trough concentrations in 195 patients (median, 50 ng/ml, and interquartile range, 35 to 77 ng/ml) were significantly associated with the estimated glomerular filtration rate, body mass index, and third-drug class (protease-containing versus protease-sparing regimens) (with the highest exposure in unboosted-atazanavir recipients). The results of multivariate analysis showed that the third-drug class and the weight/creatinine ratio were independent predictors of tenofovir trough concentrations. This cross-sectional study shows that tenofovir trough concentrations are predicted by the weight/creatinine ratio and by the coadministered antiretrovirals, with protease inhibitors (whether boosted or unboosted) being associated with the highest plasma exposure. These data, previously available in healthy subjects or for some drugs only, could be useful for designing strategies to manage tenofovir-associated toxicity, since this toxicity has been reported to be dose dependent.

Purpose of the study : Promising research suggest that maraviroc (MVC) has favourable clinical outcome in HIV-infected patients (pts). Aim of the study is to assess: durability, safety profile and immunovirological recovery in a large MVC-based cohort. Methods : All HIV pts treated with antiretroviral therapy (ART) containing MVC for at least 6 months (all viruses CCR-5 tropic analyzed by genotypic and phenotypic test) were recruited in an observational multicenter study. Eight Infectious Diseases Centers in Liguria and Piedmont (Italy) collected at baseline and every 3 months demographics, clinical and immunovirological data on a web-based system (by MedinfoDist, University of Genoa). We used SPSS for Pearson Chi square test and for generalized estimating equation (GEE); in this model for longitudinal data and frequency analysis we considered altered: TCD4+ ≤350/mmc, HIVRNA >50 cp/ml, total cholesterol >200 mg/dl, triglycerides >160 mg/dl, transaminase >40 mg/dl, creatinine >1.3 mg/dl and we divided data in 5 time periods: baseline, 1-6, 9-12, 15-24 and 24-45 months. Summary of results : We enrolled 55 pts: 36 (65%) males, median age 49.6 years (yrs) (range [r] 18.2-76.6, IQR 44.5-53.3), 11 (20%) HCVRNA-positive, 4 (7%) HBsAg-positive, 1 both infection. Twenty-four (44%) pts were classified as CDC C stage, median nadir TCD4+ was 219/mmc (r 11-529, IQR 125-317), median duration of ART was 15.3 yrs (r 1.3-27.3, IQR 12-16.8), median duration of treatment with MVC was 23 months (r 6-47, IQR 14-36). At baseline 42 (76%) pts had HIVRNA >50 cp/ml, 11 (20%) HIVRNA ≤50 cp/ml, 2 (4%) pts no data; on treatment at the last examination 53 pts (96%) had HIVRNA ≤50 cp/ml, 2 pts still had HIVRNA >50 cp/ml (CCR5 tropic) and median TCD4+ count was 469/mmc (r 73-1802, IQR 302-592). One pt died and only 2 pts shifted to X4. Chi square test at 9-12 months showed p=0.0001 and the 80% of pts had TCD4+ >350/mmc; at the same observation time 83.3% of pts had HIVRNA ≤50 cp/ml (p=0.0001). About cholesterol, triglycerides, transaminase and creatinine no significative differences were found and the median value showed no changes. Conclusions : In our study a majority of pts treated with ART containing MVC achieved a count of TCD4 >350/mmc and HIVRNA undetectable within 9-12 months. This regimen is a safe, feasible option and in pts with a poor immunological stage, MVC offered a remarkable TCD4+ count gain with limited X4 strains onset. (Published: 11 November 2012) Citation: Abstracts of the Eleventh International Congress on Drug Therapy in HIV Infection Dentone C et al. Journal of the International AIDS Society 2012, 15 (Suppl 4):18265 http://www.jiasociety.org/index.php/jias/article/view/18265 | http://dx.doi.org/10.7448/IAS.15.6.18265

Purpose: 15-30% of HAART-treated HIV-1-positive patients (pts) lack CD4+ increase despite full HIV viremia suppression. The increased risk for INR to progress till AIDS led us to investigate maraviroc (MVC) as a tool to intensify HAART in terms of immunological recovery. Methods: Randomised, multicentre, proof-of-concept study enrolling 100 pts divided into 2 arms (1:1), A:HAART+MVC, B:HAART. Inclusion criteria were: CD4 count ≥200 cells/µL and/or a recovery of CD4 cells

Summary The aim of the study was to evaluate the cardiovascular risk factors associated with subclinical carotid atherosclerosis in antiretroviral therapy-naïve HIV-infected patients. The HERMES (HIV Exposure and Risk of Metabolic Syndrome) study enrolled therapy-naïve patients attending hospitals in the Italian coordination group for the study of allergies and HIV infection (CISAI [Coordinamento Italiano per lo Studio Allergia e Infezione da HIV]) in 2007. It was designed to identify metabolic syndrome (MS) and cardiovascular risk factors. The present analysis is a nested cross-sectional study with a subset of patients examined by carotid ultrasonography. Consecutive antiretroviral therapy-naïve HIV patients attending the facilities involved in the CISAI were included. Their 10-year probability of cardiovascular events was calculated using the Framingham Risk Score (FRS) and three other cardiovascular algorithms (the Global Framingham Risk Score – GFRS, ‘Progetto Cuore’ and ‘SCORE’). Vascular age was estimated using a new model derived from GFRS and was compared with chronological age. The diagnosis of MS was based on the National Cholesterol Education Programme and International Diabetes Federation (IDF) definitions. Subclinical atherosclerosis was determined as ultrasound carotid intima-media thickness >0.9 mm. Out of 140 patients enrolled in the HERMES study by the four centres participating in the nested study, a total of 72 (51.4%) subjects, with no overt cardiovascular disease, were examined using carotid ultrasonography. The median age was 40 years, 79.2% men. The vascular age was 7.6 years higher than the chronological age. The factors associated with subclinical atherosclerosis were age (P < 0.0001), vascular age (P = 0.0002), body mass index (P = 0.003), waist circumference (P = 0.0002), MS (IDF definition, P = 0.004) and all the cardiovascular (CV) models (FRS, P = 0.01, GFRS, P = 0.002, Progetto Cuore, P = 0.018, SCORE, P = 0.03). Independent of other significant factors, waist circumference was significantly associated with pathological results (P = 0.007). The GFRS (area under the receiver-operating characteristic curves, 0.78; P < 0.001) had slightly better predictive accuracy than the other three CV models (FRS, areas under the curve [AUC] = 0.71, P = 0.003; Progetto Cuore, AUC = 0.74, P = 0.0005; SCORE, AUC = 0.77, P < 0.0001); 55% of patients at intermediate risk (6–20%) had subclinical carotid lesions. Subclinical carotid lesions had a highly significant direct association with all the CV risk predictors. The GFRS and vascular age were highly predictive. We recommend a carotid ultrasonographic examination at least among HIV patients with GFRS >6% or with an elevated waist circumference.

In this study we evaluated the efficacy of boosted and unboosted ATV in different regimens in a cohort of HIV-1 infected patients.

Bone marrow transplantation (BMT) represents a potentially curative treatment of thalassemia. For patients without an HLA-identical sibling donor, recourse to an unrelated donor is a practicable option but the candidates and their families are faced with a difficult decision. They can either choose to continue the supportive therapy, with no chance of definitive cure, or they accept the mortality risk of BMT in the hope of obtaining a definitive resolution of the disease. We investigated the communication strategies and the post transplantation quality of life (QoL) in 19 adult thalassemia patients surviving after an unrelated donor BMT. The patients were given two questionnaires: a questionnaire to evaluate pre-transplantation communication factors and the EORTC QLQ-C30 questionnaire to assess global QoL. All patients were satisfied with the communication modalities employed by the physicians. The global post transplantation QoL in our patient cohort was found to be good. The approach used in this study may offer a contribution to understanding the decision-making process leading to the choice of a treatment with a high mortality risk for a chronic, non-malignant disease. Finally, some ethical issues of this therapeutic approach are briefly addressed.

The progression of HIV-1 infection towards its more advanced stages is accompanied by changes in iron metabolism and increased body iron stores.Given the ability of HIV to alter iron metabolism, we studied the principal (transferrin system) and alternative (citrate system) iron pathways in a group of 65 HIV-infected patients (symptomatic stage B1-B3) and in a group of 36 healthy seronegative individuals. We determined serum citrate levels, haptoglobin (Hp) haplotypes, expression of transferrin receptor (CD71) on cell lines infected with HIV-1 as well as iron markers including blood iron, transferrin and ferritin.Our data showed decreased serum citrate levels in the HIV-infected patients compared to controls (92.9 +/- 22.4 microM/l vs 126.2 +/- 29.2 microM/L; p0.01). In particular, the serum citrate levels negatively correlated with HIV-1 RNA copy number (mean: 2.53 +/- 1.88 x 10(5)/ml, r(s) = 0.70, p0.01) and positively correlated with CD4+ T-lymphocyte count (mean: 241 +/- 168/ml, r(s) = 0.64, p0.05). Accordingly, blood iron, transferrin and red cell concentrations were lower in HIV-infected patients compared to the controls, whereas serum ferritin levels were higher in HIV-infected patients. Moreover, the Hp haplotype distribution showed significant differences only in the group of HIV-infected patients (p = 0.02; chi2 test).Our results show that iron metabolism is altered in patients with HIV-1 infection. The alternative pathway (citrate system) is particularly affected, since when citrate levels are low, both aconitase activity and HIV-1 replication need iron.

Human herpesvirus 8 (HHV-8) is involved in the pathogenesis of Kaposi's sarcoma, of B-cells lymphomas, and of Castelman's disease. However, the role of this virus is not yet well known. To investigate the relationship between HHV-8 infection and diseases correlated with human immunodeficiency virus (HIV), we studied a cohort of 67 HIV-seropositive subjects, some of them coinfected with HHV-8. An indirect immunofluorescence test was employed to detect the antibodies against this virus. Positive cases were 31 (46.3%); among the 67 patients, 14 were weakly positive, or + (20.9%); 11 were significantly positive, or ++ (16.4%); and 6 were strongly positive, or (8.9%). These last six patients were the most affected by opportunistic infections, and all were affected by neoplastic pathologies. Moreover, the HHV-8 positive subjects showed hematologic and martial alterations more severe than those in the negative subjects. HHV-8 seroprevalence in HIV-seropositive patients of our cohort was higher (46.3%) than in normal population (0-10%). The presence of disseminated Kaposi's sarcoma and other neoplasms associated with high HIV-RNA levels in HHV-8-positive patients, and particularly in those with strong positivity, corroborates the hypothesis that the virus is correlated with the progression of HIV infection and with its related diseases, especially those that are neoplastic. Last, the severe alterations of iron metabolism found in the patients coinfected with HHV-8 and the negative effect of this virus on the lymphocytic populations can contribute to the unfavorable evolution of HIV infection and also might facilitate tumor development.

The possible role of histamine locally applied into the nucleus accumbens on exploratory behaviours measured in 'conflictive' and 'non-conflictive' environments was studied in adult male rats. It was assumed that in conflictive environments the brain mechanisms involved in processing incentive environmental clues (novelty) were interacting with mechanisms involved in the processing of fearful or 'anxiogenic' environmental clues. As a model of conflictive environment, the elevated asymmetric-plus maze (APM) was used. As a model of a non-conflictive environment, a modified holebroad enriched with an object (OVM) was used. The exploration score in any of the arms of the APM was considered an approximate index of exploratory motivation. The permanency score (non-exploratory behaviours) was considered an inverse approximate index of emotionality. Other variables such as the frequency of entries into any arm, the latency time and central activity were also measured. In the OVM, the general motor activity and head-dipping, vertical rearing and focalized exploration were measured. Results show that histamine in the APM had a dual effect. On the one hand, an increase of exploration was observed in those arms considered more 'anxiogenic'. On the other hand, a decrease in exploration occurred in one of the arms considered less 'anxiogenic'. No changes of permanency was observed in the 'anxiogenic' arms, and a decrease of permanency took place in the arms considered less 'anxiogenic'. In the OVM, histamine did not change the overall motor activity, but head-dipping was inhibited by the imidazolamine treatment. Histamine effects on exploration parameters were counteracted by pre-treatment with H1- and H2-histamine antagonists. Nevertheless, some behaviours were not blocked by the histamine receptor antagonists. The present results give support to the role of the nucleus accumbens in the exploratory motivation mechanisms and suggest that histamine might be an endogenous regulator.

Background HIV infection is a complex medical problem that requires careful monitoring of adherence to treatment, efficacy, development of resistances and toxicities. The estimated life expectancy of patients is increasing, this makes it necessary to find efficient ways to optimise switching therapy away from HAART in order to reduce costs and increase its efficacy. At Amedeo di Savoia Hospital of Turin, the regional centre in Piedmont for HIV infection diagnosis and treatment, hospital pharmacists work in a multidisciplinary team with infectiologists, nurses, psychologists and dieticians. The team follows every aspect of the clinical pathway, leading to an improvement in the clinical management of HIV patients. Purpose To monitor HAART for all patients on therapy To identify patients with a switch of therapy To create a multidisciplinary database including adherence, economic and clinical data before and after the switch To monitor the distribution of available resources in relation with virological outcome and adherence response of patients To achieve a rational use of resources Materials and Methods Collecting data from Oliamm Software and File F using a specific software application, we analysed cost and adherence by the pharmacy refill method (days supplies between refill dates/duration of dispensed therapy x 100) for each switch of treatment between March 2010 and March 2012. From clinical reports we also evaluated the reasons for switching (toxicity, simplification, treatment failure) and the success of variation in term of virological outcome. Results Switching of antiretroviral treatments occured in 250 patients (male 177, female 73, median age 48 years), out of about 1,835 HIV-positive people in treatment, considering overall 310 switches (about 8% at the patient’s request). In 151 cases the switch led to a financial saving and in 159 cases to an increase in cost, leading overall to an excess of cost of 4396,6€ each month (an additional €17,59 for each patient for each month). The reasons for the variation were: treatment failure in 30%, simplification of the treatment in 20%, toxicity in 44% and other causes in 6%. Focus on simplification evidenced: 13% decrease in pill burden, 17% on STR, 55% on LDR, 10% on QD therapy. We also analysed the causes of toxicities. From our study we observed an increased number of patients with suppressed viral load (from 60% to 77%) as evidence of efficacy. 67 out of 125 patients (54%) with pre-switch viral load non-suppressed, had a suppression after switch. 172 patients out of 185 patients (93%) with pre switch viral load suppressed, conserved suppression after switch, but 13 patients (7%) had viral rebound. The change of the treatment didn’t impact on adherence in 50.32% cases and produced an improvement in adherence in 39.03% of switched patients. Only in 10.65% did a decrease of adherence improve. We have also analysed the cost distribution, observing a better use of resources to obtain a viral load under 20 cp/ml and a financial saving for treatment of patients already suppressed pre-switch. Conclusions In our study an analysis of switching treatment has demonstrated a correct distribution of budget and an improvement in adherence. It has also demonstrated the importance of working in team for better management of the therapeutic path. No conflict of interest.

Two herbaria, dating at the end of XIII century and now in Firenze and Vienna, offer an interesting documentation about the history of medicine and pharmacy in Italian Southern Italy during Federico II's age. Their inluminures allow to paint a faithful picture of the medioeval attitude towards illness and pain.

Methods ADONE is a prospective, multicenter study in patients chronically treated with FTC+TDF+EFV or 3TC+TDF+EFV, showing a stable viremia

On the basis of the known action of several hormones on the development and functions of the mammary glands, it is concluded that, in addition to an excessive estrogen action or a deficiency of progestins, as is commonly believed, several other hormonal dysfunctions may favor the appearance and development of breast dysplasia and hyperplasia. Therefore, the areas to be studied are, 1st of all, the ovaries, and, in case of negative findings, the pituitary gland, the adrenal glands, and the thyroid. Furthermore, in case of significant changes in the level of 1 or more hormones, before treating the gland to which such change is usually attributed, the physician should take into account the possibility of other alterations involving the transport or transformation and elimination of hormones (such as diseases capable of altering serum proteins or liver and kidney diseases that effect the catabolism of hormones). Breast dysplasia is predisposed subjects may be favored by alterations involving any of the hormones acting on the breast, but also by other causes, and this should be considered before resorting to hormone treatment, which, in some cases, could be useless or even harmful.

To identify the mechanism(s) of the altered glucoregulatory response to a glucose load in subjects with impaired glucose tolerance, we selectively quantitated the components of net splanchnic glucose balance, i.e., splanchnic glucose uptake and hepatic glucose output, as well as peripheral glucose uptake, by combining [3-3H]glucose infusion with hepatic vein catheterization. After intravenous glucose infusion (6 mg X kg-1 X min-1 for 90 min), blood glucose rose to 172 +/- 7 mg/dl in controls and 232 +/- 13 mg/dl in subjects with impaired glucose tolerance (P less than 0.01). The response of plasma insulin did not differ significantly between the two groups (29 +/- 4 vs. 40 +/- 10 microU/ml at 90 min in control and in glucose intolerant subjects, respectively; P = NS). In both groups, glucose infusion caused the net splanchnic glucose balance to switch from the net output of the basal state to a net glucose uptake. However, this effect was more marked in subjects with impaired glucose tolerance than in control subjects (at 90 min: 2.83 +/- 0.53 vs. 1.60 +/- 0.18 mg X kg-1 X min-1, respectively: P less than 0.05). The different pattern of splanchnic glucose balance was entirely accounted for by a greater rise in splanchnic glucose uptake in the group of glucose intolerants , as the suppression of endogenous glucose output by the glucose load was practically complete in both groups. In contrast, glucose uptake by peripheral tissues increased considerably less in subjects with impaired glucose tolerance than in controls (2.2-2.6 vs 3.6-4.1 mg X kg-1 X min-1, respectively, between 60 and 90 min; P less than 0.01-0.001). Furthermore, a net splanchnic lactate uptake was present in the basal state, which was inhibited by the glucose load and switched to a comparable net lactate output in both groups. These results indicate that the mechanism responsible for the altered glucoregulation in subjects with impaired glucose tolerance resides entirely in the peripheral tissues whose ability to dispose of a glucose load is drastically reduced. On the other hand, no defect is detectable in any of the explored mechanisms regulating splanchnic glucose metabolism during the disposal of an exogenous glucose load.