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Abstract Background A study including 166 subjects was performed to investigate the frequency and persistence over a 6-month interval of concurrent oral and anal Human Papillomavirus (HPV) infections in Human Immunodeficiency Virus (HIV)-infected men who have sex with men (MSM). Methods Patients with no previously documented HPV-related anogenital lesion/disease were recruited to participate in a longitudinal study. Polymerase chain reaction (PCR) was performed to detect HPV from oral and anal swabs and to detect Human Herpes Virus 8 (HHV-8) DNA in saliva on 2 separate specimen series, one collected at baseline and the other collected 6 months later. A multivariate logistic analysis was performed using anal HPV infection as the dependent variable versus a set of covariates: age, HIV plasma viral load, CD4+ count, hepatitis B virus (HBV) serology, hepatitis C virus (HCV) serology, syphilis serology and HHV-8 viral shedding. A stepwise elimination of covariates with a p-value > 0.1 was performed. Results The overall prevalence of HPV did not vary significantly between the baseline and the follow-up, either in the oral (20.1 and 21.3%, respectively) or the anal specimens (88.6 and 86.3%). The prevalence of high-risk (HR) genotypes among the HPV-positive specimens was similar in the oral and anal infections (mean values 24.3% and 20.9%). Among 68 patients with either a HR, low-risk (LR) or undetermined genotype at baseline, 75% had persistent HPV and the persistence rates were 71.4% in HR infections and 76.7% in LR infections. There was a lack of genotype concordance between oral and anal HPV samples. The prevalence of HR HPV in anus appeared to be higher in the younger patients, peaking (> 25%) in the 43-50 years age group. A decrease of the high level of anal prevalence of all genotypes of HPV in the patients > 50 years was evident. HHV-8 oral shedding was positively related to HPV anal infection (p = 0.0046). A significant correlation was found between the persistence of HHV-8 shedding and HIV viral load by logistic bivariate analysis (Odds Ratio of HHV-8 persistence for 1-log increase of HIV viral load = 1.725 ± 0.397, p = 0.018). Conclusions A high prevalence of HPV infection was found in our cohort of HIV-infected MSM, with a negative correlation between anal HPV infection and CD4 cell count.

The environmental impact of the main landfill of the city of Zagreb (Croatia), which contains about 5 million tons of waste, on the adjacent groundwater was studied. The waste is disposed of directly onto the highly permeable alluvial sediments, only few kilometres upstream of a large protected groundwater zone. Systematic monitoring was performed in the framework of a major project aimed to assess strategies for remediation of the landfill. Results obtained in 6 sampling campaigns during 1995--96 were used to determine the redox zones in the leachate plume and to describe horizontal and vertical distributions ofselected contaminants. A relatively narrow non-continuous iron-reducing zone was found along the edge of the landfill in the prevailing directions of the groundwater flow. Even after a distance of 1200 m the redox conditions in the aquifer still remained anaerobic (nitrate-reducing), while a permanently aerobic zone was present only upstream from the landfill. The horizontal distribution of the contaminants was highly dependant on the hydrological regime, but the preferential direction of spreading was toward the protected groundwater zone. Moreover, it was shown that this aquifer section is polluted not only in the surface layer but across its whole vertical profile (as deep as 60 m). (c) 1998 IAWQ. Published by Elsevier Science Ltd. [ABSTRACT FROM AUTHOR]

Introduction: The Centre of Pressure (COP) is the single point summarising all forces transferred to the hoof during the stance phase of a stride. COP path (COPp) is the trajectory that COP follows from footstrike to lift-off. Aim of the present study was to characterize the COP and COPp in horses affected by osteoarthritis and chronic lameness., Materials and Methods: Seventeen adult horses with a diagnosis of osteoarthritis and single limb chronic lameness were recruited. The COP was recorded using a wireless pressure measuring system (TekScan®) with sensors taped to the hooves (either fore- or hind limb, depending on lameness location). The COPp coordinates were further processed. Procrustes analysis was performed to assess the variability of single strides COPp and average COPp among strides, gaits, and limbs by calculating Procrustes distances (D-values). A linear mixed-effects model was run to analyse D-values differences for lame and sound limbs. Additionally, average COPp D-values and COPp hoofprint shape indices were compared for lame and sound limbs with the Signed Rank Test., Results: At walk and trot the single-stride COPp D-values were significantly lower in lame than in sound limbs (marginal effects p<0.001). Analysis of the average COPp D-values confirmed that each hoof COPp is highly consistent with itself over subsequent trials but is different from the contralateral. COPp and hoofprint shape indices did not differ between sound and lame limbs. Footstrike and lift-off within the hoofprint showed that most horses had lateral footstrike and lift-off, independently of the lameness location., Conclusion: Our findings are in line with previous observations that COPp are highly repetitive and characteristic for each horse and limb. There seems to be a further decrease in COPp variability in the presence of a painful limb pathology., Competing Interests: The authors have declared that no competing interests exist., (Copyright: © 2023 Buser et al. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.)

Background: Few studies focused on longitudinal modifications over time of high-risk HPV (HR-HPV) at anal and oral sites in HIV+ men who have sex with men (MSM)., Methods: We described patterns and longitudinal changes of HR-HPV detection and the prevalence of HR-HPV covered by the nonavalent HPV vaccine (vax-HPV) at oral and anal sites in 165 HIV+ MSM followed in an Italian hospital. The samples were collected at baseline and after 24 months (follow-up). The presence of HPV was investigated with Inno-LiPA HPV Genotyping Extra II., Results: Median age was 44 years (IQR 36-53), median CD4+ cell count at nadir was 312 cells/mm 3 (IQR 187-450). A total of 120 subjects (72.7%) were receiving successful antiretroviral therapy (ART). At baseline and follow-up, the frequency of HR-HPV was significantly higher in the anal site (65.4% vs 9.4 and 62.4% vs 6.8%, respectively). Only 2.9% of subjects were persistently HR-HPV negative at both sites. All oral HR-HPV were single at baseline vs 54.6% at baseline at the anal site (p = 0.005), and all oral HR-HPV were single at follow-up vs 54.4% at anal site at follow-up (p = 0.002). The lowest rate of concordance between the oral and anal results was found for HR-HPV detection; almost all HR-HPV positive results at both anal and oral sites had different HR-HPV.The most frequent HR-HPV in anal swabs at baseline and follow-up were HPV-16 and HPV-52.At follow-up at anal site, 37.5% of patients had different HR-HPV genotypes respect to baseline, 28.8% of subjects with 1 HR-HPV at baseline had an increased number of HR-HPV, and patients on ART showed a lower frequency of confirmed anal HR-HPV detection than untreated patients (p = 0.03) over time. Additionally,54.6 and 50.5% of patients had only HR-vax-HPV at anal site at baseline and follow-up, respectively; 15.2% had only HR-vax-HPV at baseline and follow-up., Conclusions: We believe that it is important testing multiple sites over time in HIV-positive MSM. ART seems to protect men from anal HR-HPV confirmed detection. Vaccination programmes could reduce the number of HR-HPV genotypes at anal site and the risk of the first HR-HPV acquisition at the oral site.

Background and Aims: We investigated the conditioning roles of viral tropism and other variables on plasma HIV RNA levels after 6 months of combination antiretroviral therapy (cART) in an HIV-infected Italian naïve population using regression tree, random forest regression, and path analysis (PA). Patients in this multicenter observational study were treated with all antiviral drugs that are currently recommended as first-line therapies., Methods: Adult patients with chronic HIV infection were enrolled at the beginning of first-line cART (T0). The main variables were age, gender, tropism, "lcd4&#95;0" and "lcd4&#95;6" (log10 CD4+counts at T0 and after 6 months of cART, respectively), and "lrna0" (log10 HIV RNA at T0). Regression tree and random forest analyses were applied. The predictive effect on lrna6 (log10-transformed plasma HIV RNA after 6 months of cART) was also investigated via PA (x4->lcd4&#95;0->lrna0->lrna6) with a treatment selection step included as a dependent (mediator) variable for each third drug and, as predictive covariates, age, female, x4&#95;10, x4&#95;5, lcd4&#95;0, and lrna0. Tropism was assessed in plasma using the Geno2pheno algorithm with 2 false positive rate (FPR) cut-offs: 5% (x4&#95;5) and 10% (x4&#95;10)., Results: The study included 571 subjects (21% x4&#95;10 and 10.7% x4&#95;5). The only important predictor of lrna6 was lrna0, and a positive indirect effect of bearing X4 virus in plasma was suggested. A significant direct positive effect of protease inhibitors on lrna6 was found (p = 0.022), and a significant negative effect of integrase strand transfer inhibitor (INSTI) was also detected (p = 0.003 for FPR ≤ 5% and p = 0.01 for FPR < 10%). PA predicted mean residual viremias of 40 copies/mL without INSTI and 3 copies/mL with INSTI., Conclusions: PA indicated a possible indirect role of HIV tropism on lrna6 with both FPR < 10% and ≤ 5%. Patients treated with INSTI had a predicted residual viremia of 3 copies/mL., Competing Interests: The authors have declared that no competing interests exist.

Background: This longitudinal study described Cytomegalovirus (CMV) DNA, Epstein-Barr (EBV) DNA and human herpesvirus 8 (HHV-8) DNA asymptomatic salivary shedding in HIV-positive men who have sex with men (MSM). We aimed to 1-analyze frequency and persistence of herpesvirus shedding, 2-correlate herpesvirus positivity and HIV viroimmunological parameters and 3-assess the association between HIV-RNA suppression and herpesvirus replication., Methods: Herpesvirus DNA was tested with an in-house real-time PCR in 2 salivary samples obtained at T0 and T1 (24 months after T0). HIV-RNA was evaluated in the 24 months prior to T0 and in the 24 months prior to T1; MSM were classified as successfully suppressed patients (SSPs), viremic patients (VPs) and partially suppressed patients (PSPs). EBV DNA load was classified as low viral load (EBV-LVL, value ≤10,000 copies/ml) and as high viral load (EBV-HVL,> 10,000 copies/ml). Mann-Whitney U test tested the difference of the median between groups of patients. Chi-squared test and Fisher's exact test compared categorical variables according to the frequencies. Kruskal-Wallis test compared continuous data distributions between levels of categorical variables., Results: Ninety-two patients (median CD4+ count 575 cells/mm3, median nadir 330 CD4+ cells/mm3) were included: 40 SSPs,33 VPs and 19 PSPs. The more frequently single virus detected was EBV, both at T0 and at T1 (in 67.5 and 70% of SSPs, in 84.8 and 81.8% of VPs and in 68.4 and 73.7% of SPSs) and the most frequently multiple positivity detected was EBV + HHV-8. At T1, the percentage of CMV positivity was higher in VPs than in SSPs (36.4% vs 5%, p < 0.001), the combined shedding of HHV-8, CMV and EBV was present only in VPs (15.1%, p = 0.01 respect to SSPs) and no VPs confirmed the absence of shedding found at T0 (vs 17.5% of SSPs, p = 0.01). EBV-HVL was more frequent in VPs than in SSPs: 78.6% at T0 (p = 0.03) and 88.9% at T1 (p = 0.01)., Conclusions: The relationship between uncontrolled plasma HIV viremia and CMV, EBV, and HHV-8 shedding is multifaceted, as demonstrated by the focused association with EBV DNA load and not with its frequency and by the persistent combined detection of two oncogenic viruses as EBV and HHV-8 regardless of HIV virological control.

Soluble CD163, soluble CD14 and cellular HIV-1-DNA levels reflect two different aspects of HIV infection: immune activation and the reservoir of infected cells. The aim of this study was to describe their relationships in a cohort of HIV-HCV co-infected patients successfully treated for both HCV and HIV infections. Fifty-five patients were recruited and studied prior to the start of direct-acting antivirals (DAAs) (T0), at week 12 of DAA treatment (T1) and 24 weeks after T0 (T2). The subjects were classified as having undetectable plasma HIV viraemia (UV) or low-level viraemia (LLV) in the 18 months before T2. Plasma levels of sCD163 and of sCD14 were comparable in patients with UV and in subjects with LVL at T0, T1 and T2. The HIV DNA level was positively correlated with LLV but not with sCD163 and sCD14 levels; these two markers of inflammation were positively correlated (p = 0.017). Soluble CD163 and sCD14 decreased over time from T0 to T2 (p = 0.000 and p = 0.034, respectively). In conclusion, the significant decrease in sCD163 and sCD14 levels in patients cured of HCV infection, regardless of the presence of LLV, suggests a main role for HCV in immune activation in HIV-HCV co-infected patients.

This longitudinal study described cellular HIV-DNA changes and their correlation with HIV low-level plasma viremia (LLV) in HIV-HCV co-infected patients on successful antiretroviral and anti-HCV therapy by treatment with direct-acting antivirals (DAA). Thirty-nine patients were examined prior to the start of DAA (T0), after week 12 (T1) and 24 weeks (T2) of anti-HCV therapy. Cellular PBMC HIV-DNA was analysed as an absolute value and as the percentage of increase or decrease from T0 to T2. Patients were classified as having undetectable plasma HIV viraemia (UV) or LLV in the year before the start of anti-HCV treatment and within the T0-T2 study period. Thirty-five patients (89.7%) of the 39 subjects enrolled had the same plasma HIV viraemia control in the year before HCV treatment and in the T0-T2 interval. The HIV-DNA value at T0 and at T2 was higher in patients with LLV than in subjects with UV (p = 0.015 and p = 0.014, respectively). A similar proportion of patients with LLV and UV experienced an increase or decrease of HIV-DNA from T0 to T2. The percentage increase in HIV-DNA value (262.8%) from T0 to T2 was higher compared to the decrease (43.5%) in patients with UV (p = 0.012), and it was higher compared to the percentage increase in HIV-DNA value reported in subjects with LLV (262.8 versus 49%, p = 0.026). HIV-HCV co-infected patients experienced a multifaceted perturbation of cellular HIV-DNA levels within a 24-week period during anti-HCV treatment; the extent of the phenomenon was greater in subjects with UV. Fast HCV-RNA clearance seemed to have a greater influence on the cellular reservoir than on plasma HIV-RNA.

Objectives: To characterize the prevalence of transmitted drug resistance mutations (TDRMs) by plasma analysis of 750 patients at the time of HIV diagnosis from January 1, 2013 to November 16, 2016 in the Veneto region (Italy), where all drugs included in the recommended first line therapies were prescribed, included integrase strand transfer inhibitors (InNSTI)., Methods: TDRMs were defined according to the Stanford HIV database algorithm., Results: Subtype B was the most prevalent HIV clade (67.3%). A total of 92 patients (12.3%) were expected to be resistant to one drug at least, most with a single class mutation (60/68-88.2% in subtype B infected subjectsand 23/24-95.8% in non-B subjects) and affecting mainly NNRTIs. No significant differences were observed between the prevalence rates of TDRMs involving one or more drugs, except for the presence of E138A quite only in patients with B subtype and other NNRTI in subjects with non-B infection. The diagnosis of primary/recent infection was made in 73 patients (9.7%): they had almost only TDRMs involving a single class. Resistance to InSTI was studied in 484 subjects (53 with primary-recent infection), one patient had 143C in 2016, a total of thirteen 157Q mutations were detected (only one in primary/recent infection)., Conclusions: Only one major InSTI-TDRM was identified but monitoring of TDRMs should continue in the light of continuing presence of NNRTI-related mutation amongst newly diagnosed subjects, sometime impacting also to modern NNRTI drugs recommended in first-line therapy., (Copyright © 2017 International Society for Chemotherapy of Infection and Cancer. Published by Elsevier Ltd. All rights reserved.)

Whole-genome sequencing of Staphylococcus xylosus strain JW2311 from bovine mastitis milk identified the novel 49.3-kb macrolide-lincosamide-streptogramin B (MLS B ) resistance plasmid pJW2311. It contained the macrolide resistance gene mph (C), the macrolide-streptogramin B resistance gene msr (A), and the new MLS B resistance gene erm (48) and could be transformed into Staphylococcus aureus by electroporation. Functionality of erm (48) was demonstrated by cloning and expression in S. aureus ., (Copyright © 2017 American Society for Microbiology.)

Objectives: We described Klebsiella pneumoniae producing carbapenemase (CPKP) spread from 01/01/2015 to 13/09/16 in a tertiary level hospital., Methods: The first positive surveillance rectal swab (SRS) or clinical sample (CS) collected in the medical department (MD), surgical department (SD) and intensive care department (ICD) were included in the study. A validated in-house Real-Time PCR method was used to detect carbapenemases; multilocus sequence typing (MLST) was used for further characterization of the strains., Results: 21535 patients were included: 213 CPKP strains from surveillance rectal swab (SRS) and 98 from clinical samples (CS) were collected. The percentage of CPKP detected in SRS with respect to CS increased in the medical MD from 2015 to 2016 (p=0.01) and in ICD from 2012 to 2015 (p=0.0001), while it decreased in SD from 2014 to 2016 (p=0.003); 68.5% of the positive SRS had a previous negative SRS; CPKP was more frequently identified in CS than in SRS in MD. Twelve strains harboured more than one carbapenemase gene. Many other species harbouring a carbapenemase gene were collected., Conclusions: MDs need more inclusive surveillance criteria. The late detection of positive SRS underlined the risk of colonization during hospitalization., (Copyright © 2017 The Author(s). Published by Elsevier Ltd.. All rights reserved.)

Objectives: To evaluate the role of pre-treatment co-receptor tropism of plasma HIV on the achievement of viral suppression (plasma HIV RNA 1.69 log 10 copies/mL) at the sixth month of combination antiretroviral therapy (cART) in a cohort of naive patients using, for the first time in this context, a path analysis (PA) approach., Patients and Methods: Adult patients with chronic infection by subtype B HIV-1 were consecutively enrolled from the start of first-line cART (T0). Genotypic analysis of viral tropism was performed on plasma and interpreted using the bioinformatic tool Geno2pheno, with a false positive rate of 10%. A Bayesian network starting from the viro-immunological data at T0 and at the sixth month of treatment (T1) was set up and this model was evaluated using a PA approach., Results: A total of 262 patients (22.1% bearing an X4 virus) were included; 178 subjects (67.9%) achieved viral suppression. A significant positive indirect effect of bearing X4 virus in plasma at T0 on log 10 HIV RNA at T1 was detected (P = 0.009), the magnitude of this effect was, however, over 10-fold lower than the direct effect of log 10 HIV RNA at T0 on log 10 HIV RNA at T1 (P = 0.000). Moreover, a significant positive indirect effect of bearing an X4 virus on log 10 HIV RNA at T0 (P = 0.003) was apparent., Conclusions: PA overcame the limitations implicit in common multiple regression analysis and showed the possible role of pre-treatment viral tropism at the recommended threshold on the outcome of plasma viraemia in naive patients after 6 months of therapy., (© The Author 2016. Published by Oxford University Press on behalf of the British Society for Antimicrobial Chemotherapy. All rights reserved. For Permissions, please e-mail: journals.permissions@oup.com.)

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 log 10 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/mm 3 in HIV-monoinfected patients and 606 cells/mm 3 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., Competing Interests: Conflict of Interest: None

Objectives: Effective treatment with direct-acting antiviral drugs against hepatitis C virus (HCV) is a medical need in cirrhotic HIV-HCV co-infected patients., Methods: This study investigated the plasma levels of daclatasvir (DCV) and ribavirin (RBV) in HIV-HCV co-infected subjects treated with DCV, sofosbuvir, and RBV. Drug concentrations were quantified using validated high-performance liquid chromatography methods with ultraviolet detection. The HCV non-structural protein 5A and non-structural protein 5B coding regions were analyzed by population-based sequencing., Results: DCV was dosed at week 4 and at week 8 of treatment, and RBV at week 8. One patient had the lowest DCV level, corresponding to 32.7% of the overall median value of the other patients at week 4 and about 40% at week 8. The Y93H variant was detected in this subject at weeks 8, 16, and 20 of treatment, but not before treatment or at day 2, and the patient experienced virological failure. Another subject with the Y93H variant at baseline and appropriate DCV levels had HCV RNA <12 IU/ml at week 12 and undetectable at week 16., Conclusions: Sub-optimal DCV drug levels allow the selection of resistance-associated variants and fail to contribute to antiviral activity. No definite reason for the low DCV level was found. Quantifying the drug is suggested in difficult-to-treat patients., (Copyright © 2016 The Author(s). Published by Elsevier Ltd.. All rights reserved.)

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/mm(3) and mean nadir value 333 cells/mm(3) ); 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., (© 2015 Wiley Periodicals, Inc.)

Objective: The study aimed to describe the prevalence of HSV DNA, VZV DNA, Enterovirus RNA, Parechovirus RNA, CMV DNA, EBV DNA, adenovirus DNA, HHV-6 DNA, HHV-7 DNA, HHV-8 DNA and Parvovirus B19DNA in children aged less 14 years with a suspected viral infection of the central nervous system in a clinical practice setting., Methods: Between January 2012 and May 2015, cerebrospinal fluids from 304 children were tested with an in-house real-time PCR method., Results: A positive PCR was detected in 64 subjects (21%): the mean number of tests performed in patients who showed a viral infection was 7.5, significantly higher (p = 0.001) with respect to that reported in negative samples (6.4). Enterovirus is the leading virus detected: 12 out of the 37 positive children reported were newborns (85.7% of all the newborns with a positive result). The second most frequently identified virus was HHV-7 (5 positive PCR out of 105 samples tested, 4.8%, if we excluded a child with a concomitant S. pneumoniae isolated), a prevalence significantly higher with respect to VZV (p = 0.02) and to CMV (p = 0.04). HHV-6 was the third most commonly identified aetiology (4.2%). All children were immunocompetent., Significance: Only a minority of children had a specific viral aetiology identified: the rate of HHV-7 positivity suggests a routine testing of these viruses within the diagnostic algorithm in immunocompetent paediatric patients. This approach could help to define the clinical role of this herpesvirus., (Copyright © 2016 European Paediatric Neurology Society. Published by Elsevier Ltd. All rights reserved.)

Objectives: Very few data exist on viral meningitis and encephalitis in elderly patients (>65 years old)., Methods: This study investigated the detection of herpes simplex virus (HSV), varicella zoster virus (VZV), human herpes virus 6 (HHV-6), HHV-7, HHV-8, cytomegalovirus (CMV), Epstein-Barr virus (EBV), enterovirus (EV), human adenovirus (HAdV), human parechoviruses (HPeVs), and tick-borne encephalitis virus (TBEV) through real-time PCR (RT-PCR) in patients >65 years old who had cerebrospinal fluid (CSF) tested for a suspected central nervous system infection., Results: A total of 2868 RT-PCRs were performed on 502 CSF samples. Overall, 65 positive RT-PCRs were found: 23 for HSV (35.4% of positives), 15 for EV (23.1% of positives), 14 for EBV (21.5% of positives), 12 for VZV (18.5% of positives), and one for CMV (1.5% of positives). A positive RT-PCR in CSF was detected in 24 (17.4%) patients aged ≥ 80 years and in 35 (9.6%) patients aged 65-79 years (p=0.02). VZV was more frequently detected in the oldest subjects (5.9% vs. 1.6%, p=0.03)., Conclusions: HSV was the most common viral aetiology identified in the study, with VZV infection being recognized more frequently in those patients aged ≥ 80 years., (Copyright © 2016 The Authors. Published by Elsevier Ltd.. All rights reserved.)

Introduction: Aim of the study was to evaluate the relevance of baseline (BL) plasma tropism of HIV on the achievement of a viral suppression within six months of antiviral therapy (ARV) in naïve patients by a structural-equation-modelling., Materials and Methods: Two-hundred and twenty-seven patients were enrolled; viral tropism on plasma was determined at baseline (BL) by sequencing and interpretation by genotopheno algorithm. Booster atazanavir or lopinavir , or efavirenz or nevirapine were used, in combination with either abacavir/lamivudine or tenofovir-emtricitabine., Results: X4-tropism correlate negatively with CD4 cell count at BL and follow-up (FU), and CD4 correlate negatively with BL-plasma viremia (PLV). BL-PLV correlate positively with FU-PLV. We have developed the hypothesis that the variables BL-CD4 and BL-PLV represent a mediators chain among X4-tropism and outcome of plasma viraemia at six months. This model, after structural-equation-modelling (SEM, Stata13), is shown in Figure 1. The indirect effect of X4-tropism on Fup-PLV is significant (p<0.01) but about 10 fold lower than the direct effect by BL-PLV. X4-tropism also has a direct negative effect on BL-CD4 (p<0.001) and an indirect positive effect on BL-PLV (p<0.001), irrespective of the drug regimen. Path model explaining direct and mediated effects of "tro (tropism)," "gender," "age," "cd0 (BL-CD4)" and "lrna0 (BL-PLV)" on the final outcome ("lrna1-Fup-PLV)," where "tro," "gender," and "age" are exogenous, cd0 and lrna0 are endogenous (mediators). Numbers on the arrows indicate direct effects. Circles indicate residuals related to endogenous/dependent variables; numbers near to circles are the corresponding variances., Conclusions: This model shows the relevance of BL-tropism on the outcome of plasma viraemia in naïve patients after six months of therapy, irrespective of drug regimen used.

The present study was designed to prospectively monitor transmitted drug resistance mutations (TDRMs) in the Veneto Region, Italy. Genotypic resistance testing was conducted on the plasma of 1882 patients consecutively enrolled at the time of diagnosis of human immunodeficiency virus (HIV) infection from 2004 to 2012. TDRMs were defined according to the Stanford HIV database algorithm. In total, 214 (16.1%) B subtype-infected and 58 (10.5%) non-B subtype-infected individuals were identified as having a primary or recent HIV-1 infection. In subtype B-infected subjects in 2004-2006, the prevalence of TDRMs was 20.0% in chronic infections and 25.5% in recent infections; in 2007-2009 the rates were 11.5% and 5.3%, respectively; and in 2010-2012 they were 11.3% and 15.2%, respectively. In non-B subtype-infected subjects in 2004-2006, the prevalence of TDRMs was 18.0% in chronic infections and 16.5% in recent infections; in 2007-2009 the rates were 5.7% and 0%, respectively; and in 2010-2012 they were 6.2% and 8.7%, respectively. Protease inhibitor resistance and combined resistance to two or three classes of drugs declined during the three study periods. The observed decrease in TDRMs and a simplification of the resistance patterns may reflect a change over time in the characteristics of the infecting subjects who are often unaware of their infection and transmit a wild-type strain., (Copyright © 2013 International Society for Chemotherapy of Infection and Cancer. Published by Elsevier Ltd. All rights reserved.)

Background: To determine if tropism for CXCR4 or CCR5 correlates with cellular HIV DNA load, residual viraemia and CD4 count in 219 successfully treated naive subjects with HIV infection enrolled in five infectious diseases units in Northeastern Italy., Methods: A subset of subjects, achieving plasma HIV RNA level <50 copies/ml after initiation of first-line therapy and maintaining it until follow-up time points, was retrospectively selected from a prospective cohort. Blood samples were collected before the beginning of therapy (T0), at the first follow-up time (T1) and, when available, at a second (T2) follow-up time., Results: HIV DNA, CD4 count and plasma viraemia were available from all 219 patients at T0 and T1, and in 86 subjects at T2, while tropism determinations were available from 109 subjects at T0, 219 at T1, and from 86 subjects at T2. Achieving residual viraemia <2.5 copies/ml at T1 correlated with having the same condition at T2 (p = 0.0007). X4 tropism at T1 was negatively correlated with the possibility of achieving viraemia<2.5 copies/ml at T2 (p = 0.0076). T1-T2 tropism stability was significant (p <0.0001). T0 tropism correlated with T1 and T2 tropism (p < 0.001); therefore the stability of the tropism over the two follow-up periods was significant (p = 0.0003). An effective viremic suppression (viraemia<2.5 copies/ml) correlated with R5 coreceptor affinity (p= 0.047)., Conclusions: The tropism of archived virus was stable during an effective treatment, with 15-18% of subjects switching over time, despite a viraemia<50 copies/ml. R5 tropism and its stability were related to achieving and maintaining viraemia<2.5 copies/ml.

Cellular human immunodeficiency virus type 1 (HIV-1) DNA may be considered a marker of disease progression with significant predictive power, but published data on its correlation with plasma HIV RNA levels and CD4 counts in acute and chronic patients are not conclusive. We evaluated a cohort of 180 patients naïve for antiretroviral therapy before the beginning of treatment and after a virological response in order to define the indicators correlated with HIV DNA load decrease until undetectability. The following variables were evaluated as continuous variables: age, CD4 cell count and log(10) HIV DNA level at baseline and follow-up, and baseline log(10) HIV RNA level. Primary HIV infection at the start of therapy, an HIV RNA level at follow-up of <2.5 copies/ml, origin, gender, and transmission risk were evaluated as binary variables. The decline of HIV DNA values during effective therapy was directly related to baseline HIV DNA and HIV RNA values, to an increase in the number of CD4 cells, and to the achievement of an HIV RNA load of <2.5 copies/ml. An undetectable cellular HIV DNA load was achieved by 21.6% of patients at the follow-up time point and correlated significantly with lower baseline cellular HIV DNA values and with being in the primary stage of infection when therapy started. In conclusion, early treatment facilitated the achievement of undetectable levels of plasma viremia and cellular HIV DNA and a better recovery of CD4 lymphocytes. HIV DNA levels before and during highly active antiretroviral therapy may be used as a new tool for monitoring treatment efficacy.

Background: A study including 166 subjects was performed to investigate the frequency and persistence over a 6-month interval of concurrent oral and anal Human Papillomavirus (HPV) infections in Human Immunodeficiency Virus (HIV)-infected men who have sex with men (MSM)., Methods: Patients with no previously documented HPV-related anogenital lesion/disease were recruited to participate in a longitudinal study. Polymerase chain reaction (PCR) was performed to detect HPV from oral and anal swabs and to detect Human Herpes Virus 8 (HHV-8) DNA in saliva on 2 separate specimen series, one collected at baseline and the other collected 6 months later. A multivariate logistic analysis was performed using anal HPV infection as the dependent variable versus a set of covariates: age, HIV plasma viral load, CD4+ count, hepatitis B virus (HBV) serology, hepatitis C virus (HCV) serology, syphilis serology and HHV-8 viral shedding. A stepwise elimination of covariates with a p-value > 0.1 was performed., Results: The overall prevalence of HPV did not vary significantly between the baseline and the follow-up, either in the oral (20.1 and 21.3%, respectively) or the anal specimens (88.6 and 86.3%). The prevalence of high-risk (HR) genotypes among the HPV-positive specimens was similar in the oral and anal infections (mean values 24.3% and 20.9%). Among 68 patients with either a HR, low-risk (LR) or undetermined genotype at baseline, 75% had persistent HPV and the persistence rates were 71.4% in HR infections and 76.7% in LR infections. There was a lack of genotype concordance between oral and anal HPV samples. The prevalence of HR HPV in anus appeared to be higher in the younger patients, peaking (> 25%) in the 43-50 years age group. A decrease of the high level of anal prevalence of all genotypes of HPV in the patients > 50 years was evident. HHV-8 oral shedding was positively related to HPV anal infection (p = 0.0046). A significant correlation was found between the persistence of HHV-8 shedding and HIV viral load by logistic bivariate analysis (Odds Ratio of HHV-8 persistence for 1-log increase of HIV viral load = 1.725 ± 0.397, p = 0.018)., Conclusions: A high prevalence of HPV infection was found in our cohort of HIV-infected MSM, with a negative correlation between anal HPV infection and CD4 cell count.

To evaluate the relevance and the virological and immunological markers of Kaposi sarcoma herpesvirus 8 (KSHV) viremia in Italian male patients at the time of diagnosis of infection with HIV-1, 481 men infected with HIV were recruited consecutively. The presence of KSHV DNA was evaluated in peripheral blood mononuclear cells (PBMCs) and in plasma and correlated with demographic and viro-immunological parameters. Seventy-four patients had KSHV DNA detected in PBMCs. By univariate analysis, the presence of KSHV DNA was associated significantly with unprotected homosexual relationships (P=0.003) and it was significantly higher in patients with CD4+ cell <350 (P=0.025). By multivariate analysis, homosexual relationships were associated independently with KSHV DNA in PBMCs (OR: 3.25; 95% CI: 1.1-9.7; P=0.035). Among the 74 patients with KSHV DNA detected in PBMCs, plasma samples from 60 were analyzed and 33 were positive for KSHV DNA. The CD4+ cell counts and percentages were significantly lower in patients with KSHV DNA in both PBMCs and plasma as compared to patients with only KSHV DNA in PBMCs (P=0.006 and P=0.019, respectively). Among the patients with KSHV DNA detected in PBMCs, all 13 patients with CD4+ cells count <200 had detectable levels of KSHV in their plasma. By multivariate analysis adjusted for the epidemiologic and virological parameters, low CD4+ cell count was the only independent variable associated with the presence of KSHV DNA in plasma (OR, 0.001; 95% CI: <0.001-0.001; P=0.03). In HIV-positive antiretroviral therapy-naïve males, KSHV active replication as detected by KSHV DNA in plasma was associated significantly with low CD4+ cell count., (Copyright © 2011 Wiley-Liss, Inc.)