Suppression of a SARS-CoV-2 outbreak in the Italian municipality of Vo'.

On 21 February 2020, a resident of the municipality of Vo', a small town near Padua (Italy), died of pneumonia due to severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection1. This was the first coronavirus disease 19 (COVID-19)-related death detected in Italy since the detection of SARS-CoV-2 in the Chinese city of Wuhan, Hubei province2. In response, the regional authorities imposed the lockdown of the whole municipality for 14 days3. Here we collected information on the demography, clinical presentation, hospitalization, contact network and the presence of SARS-CoV-2 infection in nasopharyngeal swabs for 85.9% and 71.5% of the population of Vo' at two consecutive time points. From the first survey, which was conducted around the time the town lockdown started, we found a prevalence of infection of 2.6% (95% confidence interval (CI): 2.1-3.3%). From the second survey, which was conducted at the end of the lockdown, we found a prevalence of 1.2% (95% CI: 0.8-1.8%). Notably, 42.5% (95% CI: 31.5-54.6%) of the confirmed SARS-CoV-2 infections detected across the two surveys were asymptomatic (that is, did not have symptoms at the time of swab testing and did not develop symptoms afterwards). The mean serial interval was 7.2 days (95% CI: 5.9-9.6). We found no statistically significant difference in the viral load of symptomatic versus asymptomatic infections (P = 0.62 and 0.74 for E and RdRp genes, respectively, exact Wilcoxon-Mann-Whitney test). This study sheds light on the frequency of asymptomatic SARS-CoV-2 infection, their infectivity (as measured by the viral load) and provides insights into its transmission dynamics and the efficacy of the implemented control measures.

Soluble CD163 and soluble CD14 plasma levels but not cellular HIV-DNA decrease during successful interferon-free anti-HCV therapy in HIV-1-HCV co-infected patients on effective combined anti-HIV treatment.

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.

Time course of cellular HIV-DNA and low-level HIV viremia in HIV-HCV co-infected patients whose HCV infection had been successfully treated with directly acting antivirals.

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.

Virological efficacy of abacavir: systematic review and meta-analysis.

OBJECTIVES: The efficacy of abacavir/lamivudine has been reported to be inferior to tenofovir/emtricitabine. Several randomized clinical trials (RCTs) investigated the effectiveness and safety of abacavir/lamivudine and tenofovir/emtricitabine combined antiretroviral treatment (cART) and we have reviewed the available evidence. DESIGN: Systematic review and meta-analysis of RCTs using standard Cochrane Collaboration methodologies. METHODS: We calculated risk ratios (RRs) with 95% CIs. The primary outcome was the rate of patients with viral load (VL) below the pre-defined cut-off at 48 weeks and/or at 96 weeks. Where available, results were analysed according to VL screening levels (<100,000 or >100,000 copies/mL) with conventional meta-analytical pooling by subgroups and meta-regression. RESULTS: Meta-analytical pooling of RCTs with a direct comparison of abacavir/lamivudine and tenofovir/emtricitabine according to baseline VL at 48 weeks (six trials, 4118 patients) showed that the proportions of subjects with VL <50 copies/mL were similar in the overall comparison (RR 0.98; 95% CI 0.94-1.03), in the low baseline VL strata (RR 1.01; 95% CI 0.99-1.03) and in the high baseline VL strata (RR 0.96; 95% CI 0.90-1.03). Meta-regression analysis at 48 weeks confirms the results of subgroup analysis. Similar virological results were found at 96 weeks (four trials, 2003 patients). Differences in the occurrence of adverse events requiring discontinuation of treatment favoured tenofovir recipients (RR 1.26; 95% CI 0.99-1.61), but this difference, mostly related to suspected abacavir hypersensitivity reaction, was not statistically significant. CONCLUSIONS: Our cumulative, cross-sectional data suggest a similar virological efficacy of abacavir/lamivudine and tenofovir/emtricitabine regardless of the baseline VL.

Abacavir-based triple nucleoside regimens for maintenance therapy in patients with HIV.

BACKGROUND: Regimen simplification can be defined as a change in established effective therapy to reduce pill burden and dosing frequency, to enhance tolerability, or to decrease specific food and fluid requirements. Many patients on suppressive antiretroviral therapy may be considered candidates for a simplification strategy and, among them, those who have achieved virologic suppression. Several clinical trials have evaluated the efficacy of triple nucleoside combination as a simplification therapy in patients who achieved virologic suppression OBJECTIVES: The aim of this review is to combine randomised, controlled trials to examine whether in patients with undetectable viraemia on a Protease inhibitor (PI) based regimen simplification treatment with abacavir (ABC)-based triple-nucleoside combinations has similar rates of efficacy and tolerability compared with a PI regimen or simplification with a NNRTIs (efavirenz-EFV- or nevirapine-NVP) containing regimen. Studies were included if they had at least two of the three interventions, including one 3NRTI arm. SEARCH METHODS: Electronic databases and conference proceedings were searched (1996-2012) with relevant search terms without limits to language. SELECTION CRITERIA: Randomised controlled trials (RCTs) only are included in this review. Patients population is represented by HIV-infected adult patients treated with a PI-containing regimen (PI or boosted PI),  with undetectable viral load. Patients on a PI-containing regimen had three possibilities: continue the PI regimen or switch to a simplification maintenance regimen, including switch to a NNRTI (EFV or NVP) containing regimen, or switch to a triple-NRTI regimen (ABC-zidovudine-lamivudine) DATA COLLECTION AND ANALYSIS: The primary outcomes were: proportion of patients discontinuing or switching antiretroviral therapy due to virologic failure or to adverse events; death (all cause) and AIDS defining illness; occurrence of myocardial infarction and cardiovascular disease. Secondary outcomes  were: proportion of patients maintaining an undetectable viral load (e.g. HIV-RNA <50 or <400 copies/mm(3)); change in mean CD4+ cell count; occurrence of lipodystrophy. We applied Cochrane Collaboration tools to assess each individual study for risk for bias. MAIN RESULTS: We included eight RCT, for a total of 1,610 patients. All the studies included HIV-1 infected patients virologically suppressed after a successful treatment with PI containing ART. Articles included in the analysis were published between 2001 and 2010, and could be classified as low risk of bias trials in most of the domains considered. Overall, there was no significant difference between the participants on triple nucleoside combination and controls, either PI-based or NNRTI based in terms of overall failures, death and AIDS related events, and rates of patients with viral load below the detectability cut-off. For the outcomes discontinuation for adverse events and virologic failures, the RRs were not significant , albeit  being not far from the alpha level of 0.05, thus suggesting a weak evidence of lower incidence of side effects  and an higher incidence of virologic failure in the 3NRTI group compared to controls . Change in lipids and in CD4 cells from baselines were reported in 7 studies, but inconsistency in reporting these data did not allow quantitative analysis. However, all agreed that simplification with ABC had a favourable and significant impact on lipid metabolism compared to control group. An increase in CD4 cells count from baseline was evident in all analysed studies, without significant differences between ABC and controls in individual studies. AUTHORS' CONCLUSIONS: The strategy of switching to triple nucleoside regimens shows weak evidence of lower incidence of side effects and a higher incidence of virologic failure in the 3NRTI group compared to controls. Simplification with 3NRTI holds the advantages of preserving other classes of antiretroviral drugs, to lower blood lipids, and to be cost effective and simple to administer.Thus, simplification with triple nucleoside regimens AZT + 3TC + ABC should be still considered for individuals who are unable to tolerate or have contraindications to NNRTI or PI based regimens. Additional data are needed on longer-term efficacy of triple NRTI regimens, particularly on the development of antiretroviral resistance. Though studies in the current review were conducted between 2001 and 2010, the large majority of patients from studies analysed received old PI regimens (e.g., indinavir, ritonavir, nelfinavir, saquinavir) not longer recommended by International Guidelines. Since current guidelines recommend new "lipid -friendly" PI, future studies should compare regimens containing these news PIs to triple NRTI regimens. More realistically, however, there are opportunities to examine these issues in existing cohorts.

Rome Consensus Conference - statement; human papilloma virus diseases in males.

BACKGROUND: Human Papillomavirus (HPV) is a very resistant, ubiquitous virus that can survive in the environment without a host. The decision to analyse HPV-related diseases in males was due to the broad dissemination of the virus, and, above all, by the need to stress the importance of primary and secondary prevention measures (currently available for women exclusively). The objective of the Consensus Conference was to make evidence-based recommendations that were designed to facilitate the adoption of a standard approach in clinical practice in Italy. METHODS: The Sponsoring Panel put a series of questions to the members of the Scientific Committee who prepared a summary of the currently available information, relevant for each question, after the review and grading of the existing scientific literature. The summaries were presented to a Jury, also called multidisciplinary Consensus Panel, who drafted a series of recommendations. RESULTS: The prevalence of HPV in males ranges between 1.3-72.9%;. The prevalence curve in males is much higher than that in females and does not tend to decline with age. Women appear to have a higher probability of acquiring HPV genotypes associated with a high oncogenic risk, whereas in males the probability of acquiring low- or high-risk genotypes is similar. The HPV-related diseases that affect males are anogenital warts and cancers of the penis, anus and oropharynx. The quadrivalent vaccine against HPV has proved to be effective in preventing external genital lesions in males aged 16-26 years in 90.4%; (95%; CI: 69.2-98.1) of cases. It has also proved to be effective in preventing precancerous anal lesions in 77.5%; (95%; CI: 39.6-93.3) of cases in a per-protocol analysis and in 91.7%; (95%; CI: 44.6-99.8) of cases in a post-hoc analysis. Early ecological studies demonstrate reduction of genital warts in vaccinated females and some herd immunity in males when vaccine coverage is high, although males who have sex with males gained no benefit at all. Males with an immunodeficiency disease are at greater risk of developing disease. Infertility seems to be caused by HPV in some cases. Studies demonstrate vaccination to both genders can be more efficacious and social equity matters are to be taken into consideration. CONCLUSIONS: The Jury made Recommendations based on the scientific evidence presented by the Scientific Committee. Accordingly, for prevention purposes and social fairness and equality, as both sexes are affected by the disease, the vaccination of 12-year-old males against HPV should be recommended in order to guaranty protection to everyone. Aspects related to healthcare policy and economic sustainability, are to be discussed by respective public system representatives. More campaigns to raise awareness through all institutional channels are needed, not only regarding anogenital warts, but for HPV-related diseases in general in males in accordance to new scientific evidences.

Comparable Post-Vaccination Decay of Neutralizing Antibody Response to Wild-Type and Delta SARS-CoV-2 Variant in Healthcare Workers Recovered from Mild or Asymptomatic Infection.

We described the long-term decay of neutralizing antibody (NtAb) to the wild-type and Delta SARS-CoV-2 variant after three antigen stimulations (mild or asymptomatic natural infection followed by two doses of the BNT162b2 mRNA vaccine after a median of 296 days) in immunocompetent healthcare workers (HCWs). Live virus microneutralization against the B.1 and Delta SARS-CoV-2 variants was performed in VERO E6 cell cultures. The median NtAb titers for B.1 and Delta were comparable and highly correlated at both 20 and 200 days after the second vaccine dose in the 23 HCWs enrolled (median age, 46 years). A small group of naturally infected unvaccinated HCWs had comparable NtAb titers for the two strains after a median follow-up of 522 days from infection diagnosis. The NtAb response to the Delta VoC appears to follow the same long-term dynamics as the wild-type response regardless of the vaccinal boost; data collected after three antigen stimulations (natural infection followed by two doses of the BNT162b2 mRNA vaccine) may be helpful for tailoring the continuous monitoring of vaccine protection against SARS-CoV-2 variants over time.

Latent Tuberculosis Infection in Haematopoietic Stem Cell Transplant Recipients: A Retrospective Italian Cohort Study in Tor Vergata University Hospital, Rome.

The results of tuberculosis (TB) screening and reactivation in a cohort of 323 adult patients undergoing haematopoietic stem cell transplantation (HSCT) from 2015 to 2019 at the University Hospital of Tor Vergata, Rome, Italy, were reported. A total of 260 patients, 59 (18.3%) autologous and 264 (81.7%) allogeneic transplants, underwent Interferon Release (IFN)-γ (IGRA) test screening: 228 (87.7%) were negative, 11 (4.2%) indeterminate and 21 (8.1%) positive. Most of the IGRA-positive patients were of Italian origin (95.2%) and significantly older than the IGRA-negative (p < 0.001); 22 (8.5%) patients underwent a second IGRA during the first year after transplantation, and 1 tested positive for IGRA. Significantly lower monocyte (p = 0.044) and lymphocyte counts (p = 0.009) were detected in IGRA negative and IGRA indeterminate patients, respectively. All latent TB patients underwent isoniazid prophylaxis, and none of them progressed to active TB over a median follow-up period of 63.4 months. A significant decline in TB screening practices was shown from 2015 to 2019, and approximately 19% of patients were not screened. In conclusion, 8.1% of our HSCT population had LTBI, all received INH treatment, and no reactivation of TB was observed during the follow-up period. In addition, 19% escaped screening and 8% of these came from countries with a medium TB burden, therefore at higher risk of possible development of TB.

Hepatitis B-Related Hepatic Flare During Immune Reconstitution Syndrome After Antiretroviral Treatment Initiation in an HBV Surface Antigen-Positive Patient With HIV: Viroimmunological and Histological Characterization.

HIV and hepatitis B virus (HBV) coinfection is relatively common. Initiation of antiretroviral therapy (ART) in people with HIV (PWH) causes a progressive restoration of cell-mediated immune functions. In the presence of overt or occult coinfections, immune restoration might lead to immune reconstitution inflammatory syndrome (IRIS). Here, we describe the clinical, immunological, virological, and histological characterization of a case of HBV-related IRIS hepatitis in a PWH after ART initiation. A liver biopsy was performed during HBV-related IRIS hepatic flare, and liver samples were analyzed through immunohistochemistry and molecular techniques, with the assessment of intrahepatic HBV-DNA, covalently closed circular DNA, and HBV pregenomic RNA through a droplet digital polymerase chain reaction system. Immune activation and senescence were also longitudinally assessed. In this clinical case, the hepatic flare occurred 6 weeks after ART initiation with a therapeutic regimen including tenofovir alafenamide (TAF) and emtricitabine (FTC). The episode was self-limiting, characterized by hyperactivation of peripheral blood CD4+ and CD8+ T-lymphocytes, and resolved without ART discontinuation, leading to the achievement of HBsAg seroconversion (HBsAg-/HBsAb+) and HBV-DNA plasma undetectability. Notably, hyperactivation of the immune system plays a pivotal role in promoting the control of HBV replication, thus triggering the achievement of HBsAg seroconversion during treatment with TAF/FTC.

KSHV DNA viremia correlates with low CD4+ cell count in Italian males at the time of diagnosis of HIV infection.

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.

Anal and oral human papillomavirus (HPV) infection in HIV-infected subjects in northern Italy: a longitudinal cohort study among men who have sex with men.

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.

Legal scenarios in the coronavirus time: Medico legal implications in the aspects of governance.

Along with rising levels of the infection around the world, the state of emergency prompted by the COVID-19 pandemic has also been having a heavy legal impact. The situation is posing important criminal challenges, as well as an ocean of social and public health issues around the world. It has not only directly affected constitutionally-guaranteed rights and individual freedoms, but also brought to the fore certain types of criminal offence that had previously been of little practical importance, such as the crime of 'maliciously or unintentionally causing an epidemic'. Different countries and states have introduced policies to manage the emergency at different times and in different ways. The measures adopted have been the object of much criticism, also raising questions of constitutional legitimacy in countries like Italy. The present contribution begins with a brief outline of the different international scenarios. Then we examine some of the medicolegal aspects of criminal offences previously envisaged and newly introduced since the arrival of the pandemic. We suggest the need for a sort of 'code of public health laws for the time of coronavirus', that could also be applied to other public health emergencies, pandemic or otherwise. The idea is to give operators in the sector and the general population the opportunity to identify clear and simple rules to follow in the current complex global situation. We need a new, appropriate interpretation of the 'boundaries' of our individual rights in relation to the need to safeguard the wider community and its more vulnerable members.

Marked decrease in acquired resistance to antiretrovirals in latest years in Italy.

OBJECTIVES: The aim of this study was to evaluate acquired drug resistance in Italy in the 2009-2018 period. METHODS: We analysed 3094 patients from the Italian ARCA database who had failed antiretroviral treatment and who had received a genotypic test after 6 months of treatment. Drug resistance mutations were identified using International AIDS Society (IAS)-USA tables and the Stanford HIVdb algorithm. The global burden of acquired resistance was calculated among all subjects with antiretroviral failure. Time trends and correlates of resistance were analysed using standard statistical tests. RESULTS: Patients of non-European origin and non-B subtypes increased significantly from 11.5% (103/896) to 19.2% (33/172) and from 13.1% (141/1079) to 23.8% (53/223), respectively, over time. Overall, 14.5% (448/3094), 12.1% (374/3094) and 37.8% (1169/3094) of patients failed first, second and later lines, respectively. According to both IAS and HIVdb, in the study period resistance to any class, nucleoside reverse inhibitor, non-nucleoside reverse inhibitor, and protease inhibitors (PIs) declined significantly. Integrase strand transfer inhibitor (INSTI) resistance declined significantly from 31% (36/116) to 20.8% (41/197) according to HIVdb but not to IAS. Divergent data were highlighted regarding the proportion of non-European patients carrying any, PI and INSTI resistance using IAS tables compared with the Stanford HIVdb algorithm, as the former failed to detect a decrease in resistance while the latter indicates a reduction of 1.6-, 5- and 1.8-fold resistance for such drug classes. In the multivariate analysis, the risk of resistance increased in patients with a larger number of treatment lines and higher viraemia and decreased in those starting therapy in the last biennium of the study. DISCUSSION: A marked reduction in drug resistance was observed over 10 years, compatible with higher genetic barrier and potency of new antiretrovirals. Nonetheless, concerns remain for subjects with non-B subtypes when using mutation lists instead of interpretation systems because of the extensive polymorphism of the protease region.

Deep neck abscess due to Acinetobacter baumannii infection.

Acinetobacter baumannii strains are isolated in up to 1% of nosocomial infections mostly from intensive care units immunocompromised patients and are associated with high mortality rates. A baumannii infections include pneumonia, urinary tract infection, endocarditis, skin and soft-tissue infections, surgical-site infection, meningitis, osteomyelitis, and septicemia. We report an extremely rare case of deep neck abscess due to multidrug-resistant A baumannii infection. The isolate strain was analyzed by a repetitive sequence-based polymerase chain reaction typing method: the isolate profile was compared with other strains obtained from isolates recovered in the hospital in that period. Our patient underwent 2 neck explorations and antibiotic treatment (tigecycline 50 mg, twice per day). Five weeks after admission, the patient was discharged in good general conditions. Considering the other obtained strains, 4 different profiles were identified, one as prominent (profile A, 18 isolates), the index case (B), and 2 others (C, D) as divergent.

COVID-19: The wrong target for healthcare liability claims.

Regrettably, after a first moment of appreciation and praise of the citizens for healthcare personnel facing COVID 19 pandemia, numerous episodes of actions taken against them on the issue of their legal liability followed. Impelling is to start an argumentation on this problem that aims to establish a shared conduct in dealing with them. The authors propose a basis for discussion on which to begin a constructive debate.

Unboosted fosamprenavir is associated with low drug exposure in HIV-infected patients with mild-moderate liver impairment resulting from HCV-related cirrhosis.

OBJECTIVES: The aim of this study was to compare amprenavir pharmacokinetics in HIV/hepatitis C virus (HCV)-co-infected cirrhotic patients receiving non-boosted fosamprenavir 700 mg twice daily with HCV/HIV-co-infected non-cirrhotic subjects and HIV-mono-infected subjects receiving fosamprenavir/ritonavir 700/100 mg twice daily. Liver stiffness at baseline and alanine aminotransferase levels at baseline and during follow-up were measured in order to find a correlation between drug levels and liver fibrosis or hepatotoxicity. METHODS: Amprenavir plasma concentration was determined by HPLC. Liver stiffness was measured by transient elastometry. Liver function tests were determined every 1-3 months during follow-up. RESULTS: Nineteen HIV-infected patients were included. Eight had chronic HCV hepatitis (group NC), five had HCV-related liver cirrhosis (group C) and six were HIV-mono-infected (group M). In group C patients, amprenavir C(trough), AUC(0-12) and half-life were 86%/83%, 64%/55% and 58%/59% lower when compared with controls and co-infected subjects without cirrhosis, respectively; conversely, drug clearance in cirrhotics was 181%/124% higher. In 3/5 cirrhotic patients (60%) and in 2/14 non-cirrhotic patients (14%), C(trough) was below the minimum target concentration of 400 ng/mL; nonetheless, in all these patients, HIV viral load was undetectable. No correlation was found between amprenavir pharmacokinetics and liver stiffness or hepatotoxicity at follow-up. CONCLUSIONS: On the basis of these data, it seems reasonable to boost fosamprenavir with ritonavir even in cirrhotic patients; amprenavir pharmacokinetics could not be predicted by liver stiffness and seem not to predict hepatotoxicity at follow-up.

Dolutegravir based antiretroviral therapy compared to other combined antiretroviral regimens for the treatment of HIV-infected naive patients: A systematic review and meta-analysis.

BACKGROUND: Numerous randomized clinical trials (RCTs) were conducted to evaluate dolutegravir based triple antiretroviral therapy (ART) compared to other triple antiretroviral regimens in naïve patients, and a summary of the available evidence is required to shed more light on safety and effectiveness issues. METHODS: Systematic review and meta-analysis of RCTs comparing dolutegravir-containing ART to non-dolutegravir containing ART in HIV-infected naive patients. Primary outcomes: % of patients with viral load<50 copies/mL at 48 weeks, stratified according to baseline viral load levels (< or >100.000 copies/mL); overall rate of discontinuation and/or switching for any cause (virologic failure, clinical failure, adverse events). Measure of treatment effect: Risk Difference (RD) with 95% confidence intervals (CIs). The GRADE system was used to assess the certainty of the body of evidence. RESULTS: We included 7 RCTs (13 reports, 6407patients) comparing dolutegravir containing to non-dolutegravir containing ART, both in combination with 2 NRTIs. Controls were raltegravir or bictegravir (3 RCTs), boosted atazanavir or darunavir (2 RCTs) or efavirenz (2 RCTs). Rates of patients with VL <50 copies/ml were higher in dolutegravir recipients compared to controls at 48 weeks (RD, 0.05; 95% CIs, 0.03/0.08, p = 0.0002) and 96 weeks (RD, 0.06; 95% CIs, 0.03/0.10, p<0.0001); the average benefit of using dolutegravir was particularly evident at 48 weeks in the subgroup of patients with high baseline viral load (RD, 0.10; 95% CIs, 0.05/0.15; p< 0.0001; GRADE assessment: "high certainty of evidence"). Overall rate of discontinuation were lower in dolutegravir compared to controls (RD,-0.03, 95% CIs -0.05/-0.01; p = 0.007). No significant differences were observed in rates of discontinuation due to adverse events (RD, -0.02; 95% CIs, -0.05/0.00), virologic failure (RD, -0.01; 95% CIs, -0.02/0.01), and most common adverse events (GRADE assessment: from "very-low" to "moderate certainty of evidence"). CONCLUSION: Starting treatment in naive patients with dolutegravir containing ART has an increased likelihood of achieving viral suppression in the comparison with non-dolutegravir containing ART. The average benefit is particularly evident in those with high baseline viral load.

Development and validation of a simple and robust HPLC method with UV detection for quantification of the hepatitis C virus inhibitor daclatasvir in human plasma.

Daclatasvir is an inhibitor of hepatitis C virus NS5A protein that is used for the therapy of chronic hepatitis. So far, published methods for analysis of daclatasvir in plasma are exclusively based on mass spectrometry, which is not always available in standard clinical laboratories. Thus, we wished to develop and validate a simple, but still reliable and sensitive high-performance liquid chromatography (HPLC) assay with UV detection for the quantification of daclatasvir, feasible for a wide-spread clinical routine use. The method consisted of solid-phase extraction of daclatasvir using Waters Oasis HLB 1cc cartridges, reversed-phase liquid chromatography with a Waters XTerra RP18 (150mm×4.6mm, 3.5µm) column and a mobile phase of ammonium acetate buffer (pH 5.0, 10mM) and acetonitrile (56:44, v/v), and UV detection at 318nm. This assay proved to be sensitive (lower limit of quantification of 0.05µg/mL), linear (correlation coefficients ≥0.997), specific (no interference with various potentially co-administrated drugs), reproducible (both intra-day and inter-day coefficients of variation ≤8.9%), and accurate (deviations ranged from -2.2 to 8.0% and from -6.5 to 9.2% for intra-day and inter-day assays, respectively). The method was applied to therapeutic monitoring of patients undergoing daclatasvir therapy for hepatitis C and showed to be reliable and robust. Thus, this method provides a simple, sensitive, precise, and reproducible assay for dosing daclatasvir that can be readily adaptable to routine use by clinical laboratories with standard equipment. In addition, the stability of daclatasvir in plasma was evaluated under various conditions, including after the heating procedure required for inactivation of infectious viruses and in different light exposure conditions. These studies evidenced photo-instability of the compound under sunlight exposure over time. Thus, blood sampling and the whole handling procedure have to be performed quickly and with minimal light exposure.