As the SARS-CoV-2 pandemic continues to rage worldwide, the emergence of numerous variants of concern (VOC) represents a challenge for the vaccinal protective efficacy and the reliability of ...commercially available high-throughput immunoassays. Our study demonstrates the administration of two doses of the BNT162b2 vaccine that elicited a robust SARS-CoV-2-specific immune response which was assessed up to 3 months after full vaccination in a cohort of 37 health care workers (HCWs). SARS-CoV-2-specific antibody response, evaluated by four commercially available chemiluminescence immunoassays (CLIA), was qualitatively consistent with the results provided by the gold-standard in vitro neutralization assay (NTA). However, we could not observe a correlation between the quantity of the antibody detected by CLIA assays and their neutralizing activity tested by NTA. Almost all subjects developed a SARS-CoV-2-specific T-cell response. Moreover, vaccinated HCWs developed a similar protective neutralizing antibodies response against the EU (B.1), Alpha (B.1.1.7), Gamma (P.1), and Eta (B.1.525) SARS-CoV-2 variants, while Beta (B.1.351) and Delta (B.1.617.2) strains displayed a consistent partial immune evasion. These results underline the importance of a solid vaccine-elicited immune response and a robust antibody titre. We believe that these relevant results should be taken into consideration in the definition of future vaccinal strategies.
The validity of lung ultrasound (LUS) in the diagnosis of interstitial or focal lung pathologies is well documented, we assessed its accuracy in the diagnosis of pulmonary tuberculosis (PTB).
...Sonographic signs suggestive of PTB and their diagnostic accuracy were evaluated in patients admitted with clinical suspicion of PTB. Consolidations, subpleural nodules, pleural thickenings or irregularities and pleural effusion were assessed. LUS signs significantly associated with PTB in the univariate analysis (p < .05) were entered in a multivariate logistic regression model.
PTB was confirmed in 51 out of 102 patients. Multiple consolidations (OR 3.54, 95%CI 1.43–8.78), apical consolidations (OR 9.65, 95%CI 3.02–30.78), superior quadrant consolidations (OR 4.01, 95%CI 1.76–9.14), and subpleural nodules (OR 5.29, 95%CI 2.27–12.33) were significantly associated with PTB diagnosis. Apical consolidation (OR 9.67, 95%CI 2.81–33.25, p 0.003) and subpleural nodules (OR 5.30, 95%CI 2.08–13.52, p 0.005) retained a significant association in a multivariate model, with an overall accuracy of 0.799.
Our data suggest a possible role of LUS in the diagnosis of PTB, a high burden pathological condition for which the delay in diagnosis still represents a critical point in the control of the disease.
•Lung ultrasound is a transportable, low cost, bedside diagnostic tool.•Lung ultrasound has potential but unstudied role in pulmonary tuberculosis diagnosis.•Apical consolidations and subpleural nodules are correlated with tuberculosis diagnosis.•Apical consolidations and subpleural nodules show good diagnostic accuracy for tuberculosis.
Intestinal mucosal immune system is an early target for human immunodeficiency virus type 1 (HIV-1) infection, resulting in CD4(+) T-cell depletion, deterioration of gut lining, and fecal microbiota ...composition. We evaluated the effects of a prebiotic oligosaccharide mixture in highly active antiretroviral therapy (HAART)-naive HIV-1-infected adults. In a pilot double-blind, randomized, placebo-controlled study, 57 HAART-naive HIV-1-infected patients received a unique oligosaccharide mixture (15 or 30 g short chain galactooligosaccharides/long chain fructooligosaccharides/pectin hydrolysate-derived acidic oligosaccharides (scGOS/lcFOS/pAOS) daily) or a placebo for 12 weeks. Microbiota composition improved significantly with increased bifidobacteria, decreased Clostridium coccoides/Eubacterium rectale cluster, and decreased pathogenic Clostridium lituseburense/Clostridium histolyticum group levels upon prebiotic supplementation. In addition, a reduction of soluble CD14 (sCD14), activated CD4(+)/CD25(+) T cells, and significantly increased natural killer (NK) cell activity when compared with control group were seen in the treatment group. The results of this pilot trial highly significantly show that dietary supplementation with a prebiotic oligosaccharide mixture results in improvement of the gut microbiota composition, reduction of sCD14, CD4(+) T-cell activation (CD25), and improved NK cell activity in HAART-naive HIV-infected individuals.
Aim
This study aimed to investigate the role of resistance‐associated substitutions (RASs) to direct‐acting‐antivirals (DAAs) in HCV genotype 3 (GT3).
Methods
Within the Italian VIRONET‐C network, a ...total of 539 GT3‐infected patients (417 DAA‐naïve and 135 DAA‐failures, of them, 13 at both baseline and failure) were analysed. Sanger sequencing of NS3/NS5A/NS5B was performed following home‐made protocols.
Results
The majority of patients were male (79.4%), 91.4% were injection drug users, 49.3% were cirrhotic and 13.9% were HIV co‐infected. Phylogenetic analysis classified sequences as GT3a‐b‐g‐h (98%‐0.4%‐0.2%‐1.2%) respectively.
Overall, 135 patients failed a DAA regimen: sofosbuvir (SOF)/daclatasvir (DCV) or velpatasvir (VEL)±ribavirin (RBV) (N = 91/15) and glecaprevir (G)/pibrentasvir (P) (N = 9). Moreover, 14.8% of patients were treated with suboptimal regimens for GT3: 3D ± RBV (Paritaprevir/r + Ombitasvir+Dasabuvir, N = 15), SOF + Simeprevir (SIM) (N = 1) or SOF/Ledipasvir (LDV) ± RBV (N = 4).
RAS prevalence was 15.8% in DAA‐naïve patients. At failure, 81.5% patients showed at least one RAS: 11/25 (44.0%) in NS3, 109/135 (80.7%) in NS5A, 7/111 (6.3%) in NS5B SOF‐failures. In NS5A‐failures, Y93H RAS was the most prevalent (68.5% vs 5.1% DAA‐naïve, P < .001) followed by A30K (12.7% vs 2.8% in DAA‐naïve, P < .001). Analysing baseline samples, a higher prevalence of NS5A‐RASs was observed before treatment in DAA‐failures (5/13, 38.5%) vs DAA‐naïves (61/393, 15.5%, P = .04). Regarding 228 DAA‐naïve patients with an available outcome, 93.9% achieved a SVR. Interestingly, patients with baseline Y93H and/or A30K had SVR rate of 72.2% vs 95.7% for patients without NS5A‐RASs (P = .002).
Conclusions
In this real‐life GT3 cohort, the majority of failures harboured resistant variants carrying NS5A‐RASs, the most frequent being Y93H. The presence of natural NS5A‐RASs before treatment was associated with failure. Further analyses are needed to confirm this observation, particularly for the new current regimens.
HCV infection has been hypothesized as a contributor of poor CD4+ recovery in patients living with HIV (PLWHIV). Aim of this study was to evaluate CD4+, CD8+ cells and CD4/CD8 ratio trends before and ...after HCV treatment with direct acting agents (DAA) in PLWHIV. HIV/HCV patients enrolled in ICONA and HepaICONA cohorts with HIV‐RNA≤50 copies/ml who achieved a sustained viral response after DAA treatment were studied. A linear regression model was used to investigate CD4+, CD8+ and CD4/CD8 changes 12 months before and after DAA treatment. A total of 939 HIV/HCV patients were included, 225 (24.0%) female, median age: 53 years (IQR 50–56). At DAA initiation, CD4+ T cell count was <350 cells/mm3 in 164 patients (17.5%), and 246 patients (26.2%) had liver stiffness>12.5 kPa. Trends of CD4+ and CD4/CD8 ratio were similar before and after DAA in all study populations (CD4+ change +17.6 cells/mm3 (95%CI −33.5; 69.4, p = 0.494); CD4/CD8 change 0.013 (95%CI −0.061; 0.036, p = 0.611). However, patients treated with ribavirin (RBV)‐free DAA showed a significant decrease in CD8+ cells (−204.3 cells/mm3, 95%CI −375.0;‐33.4, p = 0.019), while patients treated with RBV experienced CD8+ cell increase (+141.2 cells/mm3, 95%CI 40.3; 242.1, p = 0.006). In conclusion, HCV eradication following DAA treatment does not seem to have an impact on CD4+ T cell recovery in PLWHIV. However, a fast decline of CD8+T cells has been observed in patients treated without RBV, suggesting a favourable effect of HCV clearance on the general state of immune activation.
Abstract
Objectives
To investigate the long-term safety and efficacy of a treatment switch to dual ART with atazanavir/ritonavir + lamivudine versus continuing a standard regimen with ...atazanavir/ritonavir + 2NRTI in virologically suppressed patients.
Methods
ATLAS-M is a 96 week open-label, randomized, non-inferiority (margin −12%) trial enrolling HIV-infected adults on atazanavir/ritonavir + 2NRTI, with stable HIV-RNA <50 copies/mL and CD4 counts >200 cells/mm3. At baseline, patients were randomized 1:1 to switch to atazanavir/ritonavir + lamivudine or to continue the previous regimen. Here, we report the 96 week efficacy and safety data. The study was registered with ClinicalTrials.gov, number NCT01599364.
Results
Overall, 266 subjects were enrolled (133 in each arm). At 96 weeks, in the ITT population, patients free of treatment failure totalled 103 (77.4%) with atazanavir/ritonavir + lamivudine and 87 (65.4%) with triple therapy (difference +12.0%, 95% CI +1.2/+22.8, P = 0.030), demonstrating the superiority of dual therapy. Two (1.5%) and 9 (6.8%) virological failures occurred in the dual-therapy arm and the triple-therapy arm, respectively, without development of resistance to any study drug. Clinical adverse events occurred at similar rates in both arms. A higher frequency of grade 3–4 hyperbilirubinemia (66.9% versus 50.4%, P = 0.006) and hypertriglyceridaemia (6.8% versus 1.5%, P = 0.031) occurred with dual therapy, although this never led to treatment discontinuation. A significant improvement in renal function and lumbar spine bone mineral density occurred in the dual-therapy arm. The evolution of CD4, HIV-DNA levels and neurocognitive performance was similar in both arms.
Conclusions
In this randomized study, a treatment switch to atazanavir/ritonavir + lamivudine was superior over the continuation of atazanavir/ritonavir + 2NRTI in virologically suppressed patients, with a sustained benefit in terms of improved renal function and bone mineral density.
The Italian roe deer is classified as "vulnerable" in the International Union for Conservation of Nature Red List of Threatened Species, as the few specimens of this endemism may have a high risk of ...extinction. Conservation efforts for the Italian roe deer cannot prescind from the study of the feeding habits of the taxon. Therefore, in the present study, the spring diet composition of the Italian roe deer from two protected areas was estimated by using the micro-histological technique of faecal analysis. Univariate measures of alpha and beta diversity were computed to assess spatial differences in diet composition between the sites. A total of 79 different species of plants were identified, with few species (mainly woody plants) comprising over a quarter of the diet. The most consumed species were Rubia peregrina, Quercus suber and Osyris alba in Site 1, and Q. cerris, Carpinus betulus and Crataegus monogyna in Site 2. Alpha diversity analysis showed that diet composition was quite rich and diverse in both sites, with nearly all the shared species eaten to an equal extent. Moreover, the values of alpha diversity indices were not significantly different between the sites. The degree of dietary overlap ranged from "low" to "high", as most of the identified plants were unshared, whereas the consumption of some shared plants differed between the sites. In conclusion, our results showed that that this subspecies of Capreolus is capable of exhibiting both a generalist and an opportunistic behaviour in relation of food resource availability.
Abstract
Objectives
To evaluate the incidence and risk factors for liver enzyme elevations (LEE) in patients initiating first-line ART in the ICONA prospective observational cohort, between June 2009 ...and December 2017.
Patients and methods
In total, 6575 ART-naive patients were selected, initiating two NRTIs with the third drug being a boosted PI (n=2436; 37.0%), an NNRTI (n=2384; 36.3%) or an integrase strand transfer inhibitor (INSTI) (n=1755; 26.7%). HBV surface antigen and HCV RNA were detected in 3.9% and 5.8% of the study population. Inverse probability weighted Cox regression analysis was used to calculate the HRs, according to first-line regimen, for LEE, defined as ALT or AST increases of ≥2.5× upper limit of normal (ULN) for patients with normal baseline values or ≥2.5× baseline for patients with higher baseline values.
Results
One hundred and eighty-three LEE occurred over 20722 patient-years of follow-up. After adjusting for the main confounders, the risk of LEE halved with INSTIs compared with NNRTIs (HR 0.46, 95% CI 0.25–0.86), with a significant reduction in the raltegravir group (HR 0.11, 95% CI 0.02–0.84 using the NNRTI class as reference). HRs for LEE were significantly higher in subjects with HBV or HCV coinfection, in patients with poorly controlled HIV infection and in those who acquired HIV through homosexual transmission.
Conclusions
In our study, INSTI use almost halved the risk of LEE compared with other regimens. This finding could be particularly important for choosing ART in patients with risk factors for liver toxicity such as HCV and HBV coinfections.
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