Marzia Franzetti

HIV and metabolic syndrome - A comparison with the general population

Objective:To compare the prevalence of metabolic syndrome (MS) in HIV-positive patients with that from a sample of a general Italian population. Design:Cross-sectional study. Methods:A total of 1263 HIV-infected patients 18 years of age or older were recruited in 18 centers for infectious diseases in northern and central Italy. Controls were 2051 subjects aged 25 to 74 years representative of the residents of Monza, a town in Milan province, who were enrolled in the Pressioni Arteriose Monitorate E Loro Associazioni study. Results:The prevalence of MS in the HIV group was 20.8%, whereas in the control group, it was only 15.8%, with the difference being statistically significant. The age- and gender-adjusted risk of having MS in HIV-infected patients was twice as great as that in controls. Compared with controls, HIV-infected patients had a greater prevalence of the impaired fasting glucose, increased plasma triglycerides, and reduced high-density lipoprotein cholesterol components. MS prevalence was similar in treated and never-treated HIV-infected patients, and so were the various MS components. Conclusions:The risk of MS is greater in HIV-infected patients compared with the general population because of a greater prevalence of lipid and glucose abnormalities. The prevalence of MS and its components is similar in treated and untreated HIV-positive patients.

Antiretroviral therapy and the clinical evolution of human papillomavirus-associated genital lesions in HIV-positive women

The effect of antiretroviral therapy on the natural history of human papillomavirus (HPV)-associated genital lesions was evaluated in 201 human immunodeficiency virus (HIV)-infected women who were followed-up for 1-6 years. Gynecologic examinations were performed every 6-12 months. HPV sequences in cervico-vaginal cells, analyzed by polymerase chain reaction and typed by restriction fragment-length polymorphism analysis, were repeatedly detected in 126 women; 29 had transient HPV infection. Genital lesions were found in 137 patients; prevalence was comparable in women who were receiving different antiretroviral regimens. Regression of low-grade lesions was more prevalent among patients receiving highly active antiretroviral therapy than among those receiving other regimens; high-grade lesions regressed in the majority of cases, regardless of antiretroviral therapy. HPV infection persisted in nearly 80% of the cases. In conclusion, our data show that antiretroviral therapy does not prevent the development of HPV-associated lesions and does not eliminate HPV infection; therefore, early and strict gynecologic follow-up of HIV-infected women is warranted.

Is metabolic syndrome associated to HIV infection per se? Results from the HERMES study.

HERMES is a prospective study, including all treatment-naïve patients attending scheduled visits at hospitals in the CISAI group in 2007. The present cross-sectional analysis aims to assess the baseline prevalence and characteristics of Metabolic Syndrome (MS) in a population of HIV-positive treatment-naïve patients. MS was diagnosed using the National Cholesterol Education Program (NCEP) definitions. A total of 292 subjects were enrolled, median age was 37 years, 75% of them were males. The prevalence of MS was 12.3%. The most frequent trio of abnormalities that led to the diagnosis of MS was high blood pressure, triglycerides and HDL. Univariate analysis showed that MS was associated with the following variables: age, education, physical activity, advanced HIV disease (CDC stage C or HIV-RNA >100,000 copies + CD4 <100 cells/mm(3)). Higher educational levels remained protectively associated with MS in multivariate analysis. A higher risk of MS was also associated with advanced HIV disease. Actually, treatment-naïve HIV-positive patients in an advanced stage of the disease have a higher prevalence of abnormal levels of triglycerides, HDL cholesterol and blood glucose than those at a less advanced stage. These findings of the HERMES study suggest, therefore, that HIV infection per se is associated to MS.

Both Human Immunodeficiency Virus Cellular DNA Sequencing and Plasma RNA Sequencing Are Useful for Detection of Drug Resistance Mutations in Blood Samples from Antiretroviral-Drug-Naive Patients

ABSTRACT Genotypic antiretroviral testing is recommended for newly infected drug-naive subjects, and the material of choice is plasma RNA. Since drug resistance mutations (DRMs) may persist longer in cellular DNA than in plasma RNA, we investigated whether the use of peripheral blood mononuclear cell (PBMC) human immunodeficiency virus (HIV) DNA increases the sensitivity of genotypic testing in antiretroviral-drug-naive subjects. We compared the rate of primary drug resistance in plasma RNA and PBMC DNA in 288 HIV type 1-infected drug-naive persons tested at a single clinical virology center from June 2004 to October 2006. Resistance in the plasma compartment to at least one drug was detected for 64 out of 288 (22.2%) naive patients and in the PBMC compartment for 56 (19.4%) patients. Overall, DRMs were found in 80 out of 288 (27.8%) patients. PBMC DRMs were present in plasma RNA from 16 subjects with wild-type virus infections. Another nine patients had additional DRMs in PBMCs with respect to those detected in plasma RNA. On the other hand, extra plasma DRMs were detected in PBMCs for 24 and 8 subjects with wild-type and drug-resistant virus, respectively. Resistance to more than one class of antiretroviral drug was detected by plasma and PBMC analysis for 25.0% and 36.2% of the subjects, respectively. Our data support the potential utility of genotypic resistance testing of PBMC DNA in conjunction with the currently recommended plasma RNA analysis.

Pancreatic hyperamylasemia during acute gastroenteritis: incidence and clinical relevance

BackgroundMany case reports of acute pancreatitis have been reported but, up to now, pancreatic abnormalities during acute gastroenteritis have not been studied prospectively.ObjectivesTo evaluate the incidence and the clinical significance of hyperamylasemia in 507 consecutive adult patients with acute gastroenteritis.MethodsThe clinical significance of hyperamylasemia, related predisposing factors and severity of gastroenteritis were assessed.ResultsHyperamylasemia was detected in 10.2 % of patients studied. Although amylasemia was found over four times the normal values in three cases, the clinical features of acute pancreatitis were recorded in only one case (0.1%). Hyperamylasemia was more likely (17%) where a microorganism could be identified in the stools (p < 0.01). Among patients with positive stool samples, Salmonella spp. and in particular S. enteritidis, was the microorganism most frequently associated with hyperamylasemia [17/84 (20.2 %) and 10/45 (22.2%), respectively], followed by Rotavirus, Clostridium difficile and Campylobacter spp. Patients with hyperamylasemia had more severe gastroenteritis with an increased incidence of fever (80 % vs 50.6 %, O.R. 3.0; P < 0.01), dehydration (18% vs 8.5%; O.R. 2.5; P < 0.05), and a higher mean number of evacuations per day (9.2 vs 7.5; P < 0.05) than those with amylasemia in the normal range. Hyperamylasemia was significantly associated with cholelithiasis, (30.0 % vs 10.7%, O.R. 3.5; P < 0.01) and chronic gastritis or duodenal ulceration (22.0 % vs 10.2%, O.R. 2.4, P < 0.05).ConclusionsHyperamylasemia is relatively frequent, and is associated with severe gastroenteritis. However, acute pancreatitis in the setting of acute gastroenteritis, is a rare event.

Present, old and future strategies for anti-HCV treatment in patients infected by genotype-1: estimation of the drug costs in the Calabria Region in the era of the directly acting antivirals.

BackgroundIn Italy, anti-HCV drugs are provided free of charge by the National Health System. Since 2011, three drug regimens including a directly acting antiviral (DAA) are considered the gold standard for HCV treatment. However, these drugs add a significant cost (roughly €26,000) to the combination of pegylated-interferon-α/ribavirin (PEG-IFN/RBV), which before DAA represented the unique treatment. To provide the National Health System potential useful information, we estimated costs to provide anti-HCV drugs to treat a population experienced for PEG-INF/RBV.MethodsGenotype 1 HCV mono-infected or HIV/HCV co-infected individuals who were treated with PEG-IFN/RBV between 2008 and 2013 were included. The cost to treat these patients with PEG-IFN/RBV was calculated (cost 1). We also estimated costs if we had to treat these patients with a lead-in period of PEG-INF/RBV followed by PEG-IFN/RBV and a DAA in naïves (cost 2), in addition to cost 1 plus the estimated cost to re-treat with PEG-IFN/RBV and a DAA patients who had a relapse or a non response (cost 3). Moreover, all costs were normalized by SVR. Rates of foreseen response with DAA were obtained from literature data.ResultsThe overall study population consisted of 104 patients. The rate of sustained virological response (SVR) was 55%, while it was estimated that SVR would be obtained in 75% of patients with a lead-in period with PEG-IFN/RBV followed by a DAA combination, and in 78% if this treatment is used to re-treat experienced patients with a DAA. Drug costs associated with these treatments were: €1,214,283 for cost 1, €3,474,977 for cost 2 and €3,002,095 for cost 3. Costs per SVR achieved were: €22,284 for cost 1, €44,643 for cost 2 and €38,322 for cost 3.ConclusionsTreatments including DAAs achieve a SVR in more patients than PEG-IFN/RBV but they cost around three times more than PEG-IFN/RBV alone regimens. Also, cost per SVR is almost twofold greater than PEG-IFN/RBV regimens. Therefore, it is mandatory to implement use of DAA in clinical practice, but the National Health System should allocate adequate resources to provide drugs, which challenges sustainability. Cost reduction for anti-HCV drugs should be pursued.

Extensive anal condylomatosis: prognosis in relation to viral and host factors

Objective  To evaluate the clinical course of extensive anal condylomatosis in relation to treatment modalities, patient comorbidity and immune function, and associated papillomavirus (HPV) sequences.

Muscle symptoms and creatine phosphokinase elevations in patients receiving raltegravir in clinical practice: results from a multicenter study

7‐11 November 2010, Tenth International Congress on Drug Therapy in HIV Infection, Glasgow, UK

Epstein-Barr and cytomegalovirus DNA salivary shedding correlate with long-term plasma HIV RNA detection in HIV-infected men who have sex with men.

The aim of the study was to evaluate cytomegalovirus (CMV) and Epstein–Barr virus (EBV) DNA salivary shedding in HIV‐positive men who have sex with men (MSM) and to determine whether viro‐immunological parameters and long‐term (24 months) plasma HIV RNA (pHIV) detection may predict herpesviruses replication. A total of 193 HIV‐positive MSM were consecutively recruited (mean CD4+ cell count 607 cells/mm3 and mean nadir value 333 cells/mm3); pHIV was analyzed for 24 months prior to saliva sampling: patients were categorized as successfully suppressed (SS) and not suppressed (NS). The EBV viral load was categorized as high viral load (HVL), intermediate (IVL), or low (LVL), CMV DNA as positive or negative. NS patients experienced both herpesviruses detectability more frequently respect to SS patients (P = 0.034); conversely, no salivary shedding was more frequent in SS patients (P = 0.014). HVL EBV was more frequent in NS patients than in SS subjects (P = 0.038 for isolated EBV detection and P = 0.001 when CMV shedding was associated). NS subjects with HVL EBV had a median pHIV of 43,820 copies/ml, significantly higher respect to IVL and LVL patients (P = 0.027 and P = 0.0005, respectively). CMV shedding was mostly associated to EBV shedding. NS patients showed a significantly higher frequency of saliva HVL EBV detection compared to SS patients; moreover, NS patients with HVL EBV had a higher pHIV respect to those with IVL and LVL shedding. Our results suggest that a successful pHIV suppression could reduce the burden of salivary EBV replication and likely the risk of herpesviruses‐related cancers. J. Med. Virol. 88:1211–1221, 2016.

Liver stiffness is not associated with short- and long-term plasma HIV RNA replication in immunocompetent patients with HIV infection and with HIV/HCV coinfection

Background Human immunodeficiency virus (HIV) may be directly responsible for liver damage but there are contrasting data regarding the influence of detectable plasma viremia. We analyzed the influence of plasma HIV RNA (pHIV) detectability and of other clinical and viro-immunological variables on liver stiffness (LS) measurement in adult immunocompetent HIV-monoinfected patients and in patients coinfected with hepatitis C virus (HCV). Methods Logistic regression analysis was performed using the value of LS>7.1 kPa as the dependent variable. A linear regression model was applied using LS measurement after log10 transformation (lkpa) as the dependent variable and we analyzed the predicted values versus the observed lkpa values; pHIV was classified as detectable or undetectable in the 12- and 36-month study periods before LS measurement. Results We studied 251 patients (178 with HIV monoinfection), most of whom were on antiviral treatment; 36-month study time was available for 154 subjects. The mean CD4+ cell count was 634 cells/mm3 in HIV-monoinfected patients and 606 cells/mm3 in coinfected patients. No difference in LS was found between patients with detectable or undetectable pHIV in either the 12- or the 36-month study period before transient elastography. The mean LS was higher in HIV/HCV coinfected patients (P<0.0001) than in the HIV-monoinfected subjects; lkpa was positively correlated with HCV coinfection (P<0.0001) and aspartate aminotransferase levels (P<0.0001). Detectable pHIV failed to reach significance. Eight HIV-monoinfected patients had a predicted LS measurement lower than the observed one, while eight patients had the opposite result. Conclusion LS was not correlated with ongoing HIV replication during the 12- and 36-month study periods in immunocompetent HIV-monoinfected and HIV/HCV-coinfected patients.