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Recombination is the main contributor to RNA virus evolution, and SARS-CoV-2 during the pandemic produced several recombinants. The most recent SARS-CoV-2 recombinant is the lineage labeled XBB, also known as Gryphon, which arose from BJ.1 and BM. 1.1.1. Here we performed a genome-based survey aimed to compare the new recombinant with its parental lineages that never became dominant. Genetic analyses indicated that the recombinant XBB and its first descendant XBB.1 show an evolutionary condition typical of an evolutionary blind background with no further epidemiologically relevant descendant. Genetic variability and expansion capabilities are slightly higher than parental lineages. Bayesian Skyline Plot indicates that XBB reached its plateau around October 6, 2022 and after an initial rapid growth the viral population size did not further expand, and around November 10, 2022 its levels of genetic variability decreased. Simultaneously with the reduction of the XBB population size, an increase of the genetic variability of its first sub-lineage XBB.1 occurred, that in turn reached the plateau around November 9, 2022 showing a kind of vicariance with its direct progenitors. Structure analysis indicates that the affinity for ACE2 surface in XBB/XBB.1 RBDs is weaker than for BA.2 RBD. In conclusion, nowadays XBB and XBB.1 do not show evidence about a particular danger or high expansion capability. Genome-based monitoring must continue uninterrupted in order to individuate if further mutations can make XBB more dangerous or generate new subvariants with different expansion capability.

OBJECTIVES Two-drug antiretroviral regimens based on lamivudine (3TC) plus either a protease inhibitor (PI) or dolutegravir (DTG) are becoming increasingly popular in switch strategies. Our goal was to derive a predictive score for virological failure (VF). METHODS We retrospectively analysed data for a cohort of 587 virologically suppressed (HIV RNA

Over the last months, pandemic SARS‐CoV‐2 caused a significant challenge for clinicians. Unfortunately, no approved and validated treatments are available. Intravenous tocilizumab, an antirheumatic drug, seems to be promising in counteracting cytokine storm caused by SARS‐CoV‐2 infection with associated clinical improvements. We report herein a case series of patients with COVID‐19 pneumonia who were treated with tocilizumab administrated, for the first time, subcutaneously with good clinical and radiological outcomes. This article is protected by copyright. All rights reserved.

Objectives The aim of the study was to investigate the relationship between metabolic comorbidities, cardiovascular risk factors or common carotid intima-media thickness (cIMT) and cognitive performance in HIV-infected patients. Methods Asymptomatic HIV-infected subjects were consecutively enrolled during routine out-patient visits at two clinical centres. All patients underwent an extensive neuropsychological battery and assessment of metabolic comorbidities and cardiovascular risk factors. Moreover, cIMT was assessed by ultrasonography. Cognitive performance was evaluated by calculating a global cognitive impairment (GCI) score obtained by summing scores assigned to each test (0 if normal and 1 if pathological). Results A total of 245 patients (median age 46 years; 84.1% with HIV RNA < 50 copies/mL; median CD4 count 527 cells/μL) were enrolled in the study. Cardiovascular risk factors were highly prevalent in our population: the most frequent were dyslipidaemia (61.2%), cigarette smoking (54.3%) and hypertension (15.1%). cIMT was abnormal (≥ 0.9mm) in 31.8% of patients. Overall, the median GCI score was 2 [interquartile range (IQR) 1–4]; it was higher in patients with diabetes (P = 0.004), hypertension (P = 0.030) or cIMT ≥ 0.9 mm (P

Studies on the pharmacokinetic interaction between atazanavir and lopinavir with ritonavir (lopinavir/ritonavir) report contradictory results. We aimed to establish the in vivo interaction between these two protease inhibitors as well as the variables influencing drug exposure.Pharmacokinetic parameters were investigated in HIV-infected patients treated with atazanavir 300 mg with ritonavir 100 mg q24h (group A) or lopinavir/ritonavir 400/100 mg q12h (group B) or atazanavir 300 mg q24h with lopinavir/ritonavir 400/100 mg q12h (group C). Patients receiving other concomitant protease inhibitors or non-nucleoside reverse transcriptase inhibitors were excluded.In group A (n=10), mean +/- standard deviation atazanavir C(min) was 390 +/- 460 ng/mL, C(max) 3051 +/- 1996 ng/mL and AUC(24) 29 913 +/- 17 686 ng/mL/h. In group B (n=9), lopinavir C(min) was 7562 +/- 4292 ng/mL, C(max) 12 944 +/- 4838 ng/mL and AUC(0-12) 122 313 +/- 38 225 ng/mL/h. In group C (n=7), atazanavir C(min) was 876 +/- 460 ng/mL (P=0.039 vs. group A), C(max) 3421 +/- 3399 ng/mL and AUC(0-24) 65 055 +/- 49 843 ng/mL/h (two-sided P0.05 for each comparison with group A), lopinavir C(min) was 7471 +/- 3745 ng/mL, C(max) 10 143 +/- 5217 ng/mL and AUC(0-12) 104 501 +/- 43 565 ng/mL/h (P0.05 for each comparison with group B). When analysing all the groups, including controls from routine clinical practice, higher body mass index was associated with lower atazanavir C(min) and with lower lopinavir C(max). Atazanavir C(min) showed a correlation with total bilirubin levels.Combination with lopinavir/ritonavir provides higher atazanavir C(min) than combination with ritonavir alone, possibly because of an effect of the additional ritonavir dose. Low BMI may be associated with higher drug exposure.

In this study, the effects of the quinoline antimalarials, chloroquine and mefloquine, were tested on: (1) HIV-1 replication; (2) virus response to existing antiretrovirals; (3) functional activity of drug efflux pumps; and (4) intracellular accumulation of antiretrovirals. Antiretroviral activity was evaluated using cells acutely infected with drug-sensitive/resistant HIV-1 isolates or retroviral vectors, chronically infected cell lines, and syncytium assays. Drug interactions were assessed isobolographically. Activity of efflux pumps was tested using specific fluorochromes. Antitretroviral concentrations were quantitated by HPLC. Results indicated that: (1) the antimalarials (mefloquine 4 chloroquine) inhibited the replication of drug-sensitive and drug-resistant HIV-1 at therapeutically achievable concentrations and specifically impaired the formation of fusion-competent viral glycoproteins; (2) anti-HIV-1 effects were additive to those of zidovudine and nevirapine, and synergistic to those of lopinavir; (3) the antimalarials (mefloquine 4 chloroquine) inhibited the P-glycoprotein, multidrug-resistance-associated proteins, and breast-cancer resistance-associated protein; (4) Chloroquine, but not mefloquine, increased lopinavir concentrations in peripheral blood mononuclear cells (PBMCs) by approximately 5 (five)-fold. Thus quinoline antimalarials inhibited HIV-1 replication by a novel mechanism, resulting in additive or synergistic effects in combination with known antiretrovirals. These drugs may also have an impact on the cellular pharmacokinetics of antiretrovirals. Drug Dev. Res. 67:806-817, 2006. � c 2007 Wiley-Liss, Inc.

BACKGROUND: There are conflicting opinions regarding the effect of positive direct antiglobulin test (DAT) on hemoglobin (Hb) levels in human immunodeficiency virus–infected (HIV+) patients. STUDY DESIGN AND METHODS: A total of 166 samples from HIV+ outpatients were studied. The DAT was performed with the tube test and column agglutination technology (CAT). RESULTS: The DAT was positive in 18.67 percent with the tube method and 33.73 percent with the CAT. Patients with DAT-positive results showed lower Hb levels than DAT-negative patients, 12.3 g per dL versus 14.3 g per dL (p = 0.0002). The univariate logistic regression enabled us to study the phenomenon better and fit the probability of having a DAT-positive result on the basis of the Hb levels. The relationship between the CAT and the tube test when washing the red blood cells (RBC) at 4°C was stronger than when washing these at room temperature (φ = 0.8156; p = 0.000). The Hb levels were significantly lower in the positive DATs of Stage C (acquired immune deficiency syndrome [AIDS]) and Stage B (symptomatic non-AIDS patients), which showed decreasing Hb values for increasing agglutination strengths (p = 0.000). Anemia was related with the DAT results (odds ratio [OR], 8.005; p = 0.000) but not to the AIDS condition (OR, 1.741; p = 0.221). DISCUSSION: Our study indicates that the DAT-positive results may be specifically related to lower Hb levels in HIV+ patients. The immunologic RBC clearance could be part of the anemic multifactorial condition in HIV+ patients.

– Objective: To investigate the problems in seeking dental care faced by HIV-positive individuals in Italy. Methods: A multicenter observational study was performed by distributing an anonymous self-administered questionnaire to patients of six public healthcare facilities specialized in the treatment of individuals with HIV infection. The questions concerned personal data potentially correlated with discrimination, the patient–dentist relationship before and after HIV diagnosis, and the reasons for seeking dental care in public facilities. We also evaluated the patients’ discomfort in the patient–dentist relationship after HIV diagnosis, performing univariate and multivariate analyses. Results: Of the 1500 questionnaires distributed; 883 were filled-out completely. A total of 630 persons received dental care after HIV diagnosis: 209 (33.2%) did not tell the dentist that they were seropositive. Of those who did, 56 were refused care. For patients treated by a private dentist, having been treated by the same dentist before diagnosis was a risk factor for great discomfort in the patient–dentist relationship (P

Objectives: The aim of the study was to statistically model the relative increased risk of cardiovascular disease (CVD) per year older in Data collection on Adverse events of anti-HIV Drugs (D:A:D) and to compare this with the relative increased risk of CVD per year older in general population risk equations. Methods: We analysed three endpoints: myocardial infarction (MI), coronary heart disease (CHD: MI or invasive coronary procedure) and CVD (CHD or stroke). We fitted a number of parametric age effects, adjusting for known risk factors and antiretroviral therapy (ART) use. The best-fitting age effect was determined using the Akaike information criterion. We compared the ageing effect from D:A:D with that from the general population risk equations: the Framingham Heart Study, CUORE and ASSIGN risk scores. Results: A total of 24323 men were included in analyses. Crude MI, CHD and CVD event rates per 1000 person-years increased from 2.29, 3.11 and 3.65 in those aged 40-45 years to 6.53, 11.91 and 15.89 in those aged 60-65 years, respectively. The best-fitting models included inverse age for MI and age + age(2) for CHD and CVD. In D:A:D there was a slowly accelerating increased risk of CHD and CVD per year older, which appeared to be only modest yet was consistently raised compared with the risk in the general population. The relative risk of MI with age was not different between D:A:D and the general population. Conclusions: We found only limited evidence of accelerating increased risk of CVD with age in D:A:D compared with the general population. The absolute risk of CVD associated with HIV infection remains uncertain.

We evaluated phenotype and apoptotic status of normal CD4+CD69+ and CD8+CD69+ peripheral blood T-lymphocytes after short-term challenge with escalating concentrations of phytohemagglutinin (PHA). The frequency of CD69-coexpressing CD4+ and CD8+ T-cells and CD69 staining intensity increased following T-cell mitogenic stimulation; these changes were proportional to PHA concentration in culture medium. A considerable fraction of lymphocytes underwent blast transformation, displaying increased forward and side scatter signals. Interestingly enough, PHA-responsive T-cells exhibited a predominantly CD25negCD38negTCRαβpos phenotype; APO-1/Fas antigen (CD95) could be detected on a minority of activated CD69+ T-cells. A considerable proportion of CD69+ lymphocytes expressed intracellular perforin; in addition, an average 16 ± 6% CD69+ T-lymphocytes were apoptotic after 4 h of stimulation, as evaluated by 7-amino-actinomycin-D staining and by annexin-V binding. CD69+ activated lymphocytes comprise phenotypically heterogeneous cell subpopulations potentially devoted to diverse immunological functions, i.e., proliferation, apoptosis, or cell cytotoxicity; moreover, our findings indicate that CD69 expression is proportional to the intensity of the activating stimulus and that the capacity to upregulate CD69 antigen following short-term mitogenic challenge may be restricted to unactivated CD38negCD25negTCRαβpos T-lymphocytes. Cytometry (Comm. Clin. Cytometry) 38:95–101, 1999. © 1999 Wiley-Liss, Inc.

Three-color flow cytometric analysis of CD16+ natural killer (NK) cells was assessed in HIV seropositive patients and healthy heterosexual controls. A selective depletion of lymphocytes with the CD16+ NK phenotype was found among the HIV+ infected patients. When the CD16 lymphocyte subset was further evaluated by three-color flow cytometry, cells bearing both the CD8 and CD56 antigens were significantly decreased. Analysis of activation antigens revealed a large proportion of CD16+ NK cells from HIV+ patients expressed HLA-DR, but this did not correlate with CD25 (IL-2 receptor) expression. The overall loss of the CD8 and CD56 antigens among the NK population with an increase in activation status may be due to differential loss of the NK cell subsets or, alternatively, to the loss of immunoregulatory cytokines, which have been shown to be important in maintaining NK activity. Whether these changes in the NK compartment may influence the outcome of individuals with HIV disease still remains an open question but is an important issue when performing phenotypic analysis of HIV+ subjects. © 1995 Wiley-Liss, Inc.

OBJECTIVE: To evaluate the risk factors associated with the emergence of fluconazole resistant Candida spp. in HIV-infected patients with oral candidiasis. METHODS: Candida spp. were isolated from oral swabs and tested in vitro for resistance to fluconazole. The factors potentially correlated with vazole-resistent Candida spp. infections were investigated. RESULTS: Fifty-one out of 118 patients (43%) with oral candidiasis had fluconazole resistant Candida spp. The following factors were significantly associated with the development of fluconazole resistance: (1) more than five episodes of oral candidiasis in the previous year (P < 0.001); (2) fluconazole therapy in the previous 6 months (P < 0.001); (3) C3 category of HIV infection (P< 0.001); and (4) low number of TCD4+ cells (

Introduction : This descriptive, non-interventional study on HIV-1-infected patients treated with DRV/r in the usual clinical setting, with a single-arm prospective observational design, collected data on utilization of darunavir/ritonavir (DRV/r) under the conditions described in marketing authorization in usual clinical practice in Italy to evaluate efficacy and safety of DRV/r-based antiretroviral (ARV) treatment. This analysis focussed on the safety profile of DRV/r in HIV-1 infected patients. Materials and Methods : Data were analyzed from four cohorts of HIV-1-infected patients treated with DRV/r in the real-world setting, including an ARV-naive-DRV/r-naive cohort (Cohort 1), an ARV-experienced-DRV/r-naive cohort (Cohort 2) and two ARV-DRV/r-experienced cohorts (Cohorts 3 and 4), one of which (Cohort 3) was from the DRV/r Early Access Program. The objective of this analysis was to examine the safety data obtained in these four cohorts in patients enrolled from June 2009 to November 2011 and observed until December 2012 or DRV/r discontinuation. Results : Safety data from 875 patients were analyzed. DRV/r-based treatment was well tolerated, with 36.2% of patients reporting ≥1 adverse event (AE) and very few discontinuations due to study drug-related AEs (3.0% overall). The most frequent AEs were diarrhoea (2.7%), reduced bone density (2.6%) and hypercholesterolaemia (2.1%) (Table 1). Regarding metabolic parameters, levels of liver enzymes alanine aminotransferase (ALT) and aspartate aminotransferase (AST) remained stable from baseline to the last study visit (LSV) in DRV-experienced patients and decreased in DRV-naive patients. Blood glucose concentrations remained stable in all cohorts. Serum triglyceride and cholesterol concentrations remained stable in DRV-experienced patients but increased in naive patients, yet were still within normal range. Conclusions : In HIV-1-infected patients treated with DRV/r in these settings, the tolerability profile was favourable and similar to (or better than) that reported in controlled clinical trials. These data confirm DRV/r to be a safe treatment choice in DRV/r-experienced and naive patients. (Published: 2 November 2014) Citation : Abstracts of the HIV Drug Therapy Glasgow Congress 2014 Antinori A et al. Journal of the International AIDS Society 2014, 17(Suppl 3) :19573 http://www.jiasociety.org/index.php/jias/article/view/19573 | http://dx.doi.org/10.7448/IAS.17.4.19573

Immunological studies on 29 children with congenital cytomegalovirus (CMV) infection were performed. Two groups of patients were considered according to the presence or absence of clinical symptoms. Asymptomatic patients had increased numbers of natural killer (NK) cells (CD 16+), activated NK cells (CD16+/ HLA-DR), and activated suppressor/cytotoxic cells (CD8+/HLA-DR+/TAC). In addition, cells from this group of patients showed increased NK activity against fibroblasts infected with CMV and a significant proliferative response to CMV antigens. In contrast, cells from symptomatic patients had reduced NK activity against fibroblasts infected with CMV and a defective proliferative response to CMV antigens. In both groups, the number of total T, T-helper, and T-suppressor/cytotoxic cells was normal, as was the ratio of helper/suppressor. The reported differences in the immunological parameters between the asymptomatic and symptomatic patients suggest that cell-mediated immunity may play an important role in determining the outcome of the infection.

Ultrasound was used for a serial evaluation of gallbladder modifications in 61 patients with acute viral hepatitis during both the acute phase of the illness and recovery. Most of the patients studied within 7 days from the onset of symptoms and/or jaundice showed sonographic abnormalities of the gallbladder (increased wall thickness, reduced volume, abnormal bile content). A normal ultrasound pattern of the gallbladder was progressively restored during the clinical recovery in most of the patients. A statistical correlation was found between the gallbladder wall thickness and the alanine transferase index.