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Objectives We aimed to investigate and compare the efficacy and safety of two dolutegravir-based two-drug regimens: dolutegravir + lamivudine versus dolutegravir + rilpivirine. Methods We analysed a cohort of people living with HIV (PLWHIV) switching to dolutegravir + lamivudine or dolutegravir + rilpivirine. We excluded from the analysis PLWHIV with no available pre-switch genotypic test or with a known resistance mutation to one of the study drugs. We evaluated incidence of virological failure (VF) and treatment discontinuation (TD), as well as changes in immunological and metabolic parameters. Results We enrolled 592 PLWHIV: 306 in the lamivudine group and 286 in the rilpivirine group. We observed nine VFs in the lamivudine group [1.4 VF per 100 patient-years of follow-up (PYFU)] and four VFs in the rilpivirine group (0.6 VF per 100 PYFU). Subsequent genotypic analysis showed no acquired resistance-associated mutations in those experiencing VF. Estimated probability of maintaining virological suppression at 144 and 240 weeks were 96.6% and 92.7%, respectively, in the lamivudine group and 98.7% and 98.7%, respectively, in the rilpivirine group (log-rank P = 0.172). The estimated probability of maintaining study regimen at Week 240 was 82.3% in the lamivudine group and 85.9% in the rilpivirine group (log-rank P = 0.018). We observed a significant improvement in CD4+ cell count at Week 240 in the lamivudine group (P = 0.012); in the rilpivirine group we registered a significant increase in CD4/CD8 ratio (P = 0.014). Conclusions Both analysed strategies are effective and safe as switch strategies in clinical practice, with a low incidence of VF and a favourable immunological recovery, even in the long term.

To determine whether the duration of respiratory distress symptoms in severe COVID-19 pneumonia affects the need for invasive mechanical ventilation and clinical outcomes.An observational multicentre cohort study of patients hospitalised in five COVID-19-designated ICUs of the University Hospitals of Emilia-Romagna Region. Patients included were adults with pneumonia due to SARS-CoV-2 with PaO₂/FiO₂ ratio300 mmHg, respiratory distress symptoms, and need for mechanical ventilation (invasive or non-invasive). Exclusion criteria were an uncertain time of respiratory distress, end-of-life decision, and mechanical respiratory support before hospital admission.We analysed 171 patients stratified into tertiles according to respiratory distress duration (distress time, DT) before application of mechanical ventilation support. The rate of patients requiring invasive mechanical ventilation was significantly different (p 0.001) among the tertiles: 17/57 patients in the shortest duration, 29/57 in the intermediate duration, and 40/57 in the longest duration. The respiratory distress time significantly increased the risk of invasive ventilation in the univariate analysis (OR 5.5 [CI 2.48-12.35], p = 0.003). Multivariable regression analysis confirmed this association (OR 10.7 [CI 2.89-39.41], p 0.001). Clinical outcomes (mortality and hospital stay) did not show significant differences between DT tertiles.Albeit preliminary and retrospective, our data raised the hypothesis that the duration of respiratory distress symptoms may play a role in COVID-19 patients' need for invasive mechanical ventilation. Furthermore, our observations suggested that specific strategies may be directed towards identifying and managing early symptoms of respiratory distress, regardless of the levels of hypoxemia and the severity of the dyspnoea itself.

Background The aim of this study was to investigate the impact of anti-HBc (HBcAb) positivity on the progression of liver fibrosis (Fibrosis-4 score >3.25) in the Italian cohort of HIV-infected individuals naïve to antiretroviral treatment (ICONA). Methods All patients with FIB-4 Results Patients who were HBcAb+/HCV-/HBs antigen (HBsAg)- and HCV+/HBcAb+/HBsAg- or HBsAg+/HBcAb+/HCV- had CD4+ cell counts below the nadir and significantly higher prevalence of AIDS diagnosis at baseline than the other groups (P < .0001). A Cox regression model adjusted for age, HIV transmission mode, country of birth, and alcohol consumption showed a higher relative risk (HR) of progression to FIB-4 >3.25 in HCV+/HBcAb+/HBsAg- patients (HR, 7.2; 95% CI, 3 8–13.64). Conclusions HBcAb+ contributes to liver damage in HIV+/HCV+/HBcAb+/HBsAg- subjects. A careful monitoring for signs of previous HBV infection is needed in this kind of patients.

Introduction: Since the beginning of the HIV epidemic in resource-rich countries, Pneumocystis jirovecii pneumonia (PjP) is one of the most frequent opportunistic AIDS-defining infections. The Collaboration of Observational HIV Epidemiological Research Europe (COHERE) has shown that primary Pneumocystis jirovecii Pneumonia (PjP) prophylaxis can be safely withdrawn in patients with CD4 counts of 100 to 200 cells/µL if plasma HIV-RNA is suppressed on combination antiretroviral therapy. Whether this holds true for secondary prophylaxis is not known, and this has proved difficult to determine due to the much lower population at risk. Methods: We estimated the incidence of secondary PjP by including patient data collected from 1998 to 2015 from the COHERE cohort collaboration according to time-updated CD4 counts, HIV-RNA and use of PjP prophylaxis in persons >16 years of age. We fitted a Poisson generalized additive model in which the smoothed effect of CD4 was modelled by a restricted cubic spline, and HIV-RNA was stratified as low (10,000copies/mL). Results: There were 373 recurrences of PjP during 74,295 person-years (py) in 10,476 patients. The PjP incidence in the different plasma HIV-RNA strata differed significantly and was lowest in the low stratum. For patients off prophylaxis with CD4 counts between 100 and 200 cells/µL and HIV-RNA below 400 copies/mL, the incidence of recurrent PjP was 3.9 (95% CI: 2.0 to 5.8) per 1000 py, not significantly different from patients on prophylaxis in the same stratum (1.9, 95% CI: 0.1 to 3.7). Conclusions: HIV viraemia importantly affects the risk of recurrent PjP. In virologically suppressed patients on ART with CD4 counts of 100 to 200/µL, the incidence of PjP off prophylaxis is below 10/1000 py. Secondary PjP prophylaxis may be safely withheld in such patients. While European guidelines recommend discontinuing secondary PjP prophylaxis only if CD4 counts rise above 200 cells/mL, the latest US Guidelines consider secondary prophylaxis discontinuation even in patients with a CD4 count above 100 cells/µL and suppressed viral load. Our results strengthen and support this US recommendation. © 2021 The Authors. Journal of the International AIDS Society published by John Wiley & Sons Ltd on behalf of the International AIDS Society.

Objectives: Although outcomes of antiretroviral therapy (ART) have been evaluated in randomized controlled trials, experiences from subpopulations defined by age, CD4 count or viral load (VL) in heterogeneous real-world settings are limited. Methods: The study design was an international multicohort collaboration. Logistic regression was used to compare virological and immunological outcomes at 12±3months after starting ART with an integrase strand transfer inhibitor (INSTI), contemporary nonnucleoside reverse transcriptase inhibitor (NNRTI) or boosted protease inhibitor (PI/b) with two nucleos(t)ides after 1 January 2012. The composite treatment outcome (cTO) defined success as VL'200 HIV-1 RNA copies/mL with no regimen change and no AIDS/death events. Immunological success was defined as a CD4count '750cells/μL or a 33% increase where the baseline CD4 count was ≥500 cells/μL. Poisson regression compared clinical failures (AIDS/death≥14days after starting ART). Interactions between ART class and age, CD4 count, and VL were determined for each endpoint. Results: Of 5198 ART-naïve persons in the International Cohort Consortium of Infectious Diseases (RESPOND), 45.4% started INSTIs, 26.0% PI/b and 28.7% NNRTIs; 880 (17.4%) were aged ' 50years, 2539 (49.4%) had CD4 counts '350 cells/μL and 1891 (36.8%) had VL'100000 copies/mL. Differences in virological and immunological success and clinical failure among ART classes were similar across age groups (≤ 40, 40–50 and '50 years), CD4 count categories (≤ 350 vs. '350 cells/μL) and VL categories at ART initiation (≤ 100000 vs. '100000copies/mL), with all investigated interactions being nonsignificant (P'0.05). Conclusions: Differences among ART classes in virological, immunological and clinical outcomes in ART-naïve participants were consistent irrespective of age, immune suppression or VL at ART initiation. While confounding by indication cannot be excluded, this provides reassuring evidence that such subpopulations will equally benefit from contemporary ART.

HIV+ patients present an increased risk of vaccine-preventable invasive bacterial diseases (IBDs), infections characterized by high lethality and frequency of serious complications. Considering that these patients frequently have to face a complex clinical-care pathway, it has been necessary to design a clear vaccination protocol in order to prevent IBDs and to guarantee adequate patient adherence. In 2013 the Local Health Unit Company of Modena's Public Health Department and the University Hospital of Modena developed a shared vaccination protocol to prevent the most common causes of IBDs: Neisseria meningitidis, Streptococcus pneumoniae and Haemophilus influenzae type B. The protocol applies to HIV+ patients receiving antiretroviral therapy who have a CD4 + cell count > 200 cells / µL. It provides the following vaccination schedule: administration of PCV13 + MenACWY vaccines; after 15 days administration of MenB + Hib vaccines; after 45 days administration of the MenB vaccine; after at least 60 days, administration of PPSV23 + MenACWY vaccines. The first vaccination counselling is proactively carried out by the Public Health Department healthcare workers and takes place at the Infectious Diseases Division in order to improve patient acceptance and adherence to the protocol. From October 2013 to January 2020, 503 HIV+ patients (378 males and 125 females) were vaccinated. Among these patients, 338 (67.2%) completed the vaccination schedule; 110 (21.9%) interrupted the schedule, 34 (6.7%) have a vaccination schedule currently underway and 21 (4.2%) never started the planned vaccination protocol. Overall, the percentage of patients who have completed the vaccination schedule or have scheduled appointments is 73.9%. The data analysis shows a high adherence to the protocol thanks to the collaboration between public health and infectious disease specialists, which improves the compliance of patients with a complex clinical-care pathway. Key messages HIV patients present an increased risk of IBDs and require a tailor-made vaccination protocol. Collaboration between specialists improves the compliance of patients with a complex clinical-care pathway.

Las masas ovaricas, tanto si son organicas (tumores benignos o malignos) como funcionales, se diagnostican a cualquier edad durante la infancia o la adolescencia, casi siempre por dolor abdominal o por la palpacion de una masa abdominal. La ecografia pelvica suprapubica con la vejiga llena es el examen de referencia para la exploracion de los ovarios, completada con la resonancia magnetica abdominopelvica, que permite cartografiar la masa. La determinacion de los marcadores tumorales es esencial para el diagnostico de los tumores ovaricos y debe realizarse antes de la cirugia de exeresis. La cirugia es esencial en el tratamiento de la mayoria de las masas ovaricas. Es importante poder anticipar la naturaleza probablemente benigna o seguramente maligna de la masa para proponer el tratamiento adecuado. En caso de masa ovarica tumoral que no presente ningun signo clinico, radiologico o biologico sospechoso de malignidad, el acto adecuado es una tumorectomia con conservacion del parenquima ovarico, con el objetivo de preservar la fertilidad. A la inversa, debe realizarse una ooforectomia o una anexectomia en caso de un tumor maligno para no comprometer el pronostico de la paciente. La quimioterapia completa el tratamiento en caso de ciertos tumores malignos.

Introduction Plusieurs cas de syndrome nephrotique secondaire a une nephropathie a lesions glomerulaires minimes (LGM) ont ete rapportes apres vaccination, notamment contre la grippe. Quelques cas commencent a etre rapportes avec les vaccins a ARNm anti SARS-CoV-2. Description Nous rapportons un cas de syndrome nephrotique survenant apres une premiere dose vaccinale anti SARS-CoV-2 (ChAdOx1 nCoV-19, Astra-Zeneca®). Methodes Un homme de 44 ans, sans antecedents medicaux, a ete hospitalise pour un tableau d’anasarque d’installation brutale survenant 3 semaines apres une premiere dose vaccinale. Le bilan biologique montrait un syndrome nephrotique (albumine 12,5 g/l, proteinurie 9,1 g/g) et une insuffisance renale aigue definie par une creatininemie a 187 μmol/l. Le titre d’anticorps anti-proteine Spike etait de 67 U/ml. La serologie anti-nucleocapside etait negative. Resultats La ponction biopsie renale montrait des lesions de hyalinose segmentaire et focale (HSF) avec trois « tip lesions » ( Fig. 1 ). L’evolution clinique et biologique (creatinine 73 μmol/l, albumine 34 g/l, proteinurie 27 mg/mmol) ont ete rapidement favorables sous corticotherapie 1 mg/kg/j. Conclusion La survenue d’un syndrome nephrotique dans les jours qui suivent la vaccination anti-COVID 19 souleve la question de l’imputabilite du vaccin et du mecanisme physiopathologique sous-jacent. La stimulation de l’immunite cellulaire T et une reponse cytokinique mediee par la vaccination pourraient contribuer a la survenue de lesions de LGM/HSF post-vaccination. Les resultats des etudes de pharmacovigilance restent necessaires pour determiner s’il existe un lien causal entre la survenue d’un syndrome nephrotique et la vaccination.

Introduction La COVID-19 peut etre associee a une hyalinose segmentaire et focale (HSF) collapsante nommee COVAN de mauvais pronostic. Description Nous rapportons quatre cas de patients ayant presente une aggravation de leur insuffisance renale chronique (IRC) dans les suites d’une infection COVID-19. Methodes Entre novembre 2020 et avril 2021, quatre patients d’origine Africaine âges de 47 a 74 ans, suivis dans notre service, ont ete hospitalises pour une aggravation de leur IRC. Leur nephropathie sous-jacente etait une nephroangiosclerose (n = 2), un diabete (n = 1), une HSF collapsante (n = 1) prouvee par ponction biopsie renale (PBR). Lors du suivi, leur clairance etait en moyenne de 47 mL/min/1,73 m2 avec une proteinurie negative ou Resultats Les patients ont ete hospitalises pour une aggravation majeure de leur IRC. A l’admission, la clairance moyenne etait de 18 mL/min/1,73 m2 associee a une proteinurie de rang nephrotique. Une infection COVID-19 a ete retrouvee dans les deux mois precedents chez deux des quatre patients. Tous avaient une serologie COVID-19 positive, ainsi que les alleles a risque du gene ApoL1 (homozygote G1/G1 ou heterozygote G1/G2). Deux patients ont eu une PBR retrouvant une HSF collapsante. La PBR n’a pas ete realisee chez les autres en raison d’une hypotrophie renale. Durant le suivi, deux patients sont restes stables, un a necessite le recours a l’hemodialyse et le dernier a ete traite par corticoides 0,5 mg/kg/j, permettant une diminution de la proteinurie et une amelioration partielle de la fonction renale. La particularite de notre serie est l’existence d’une IRC sous-jacente regulierement suivie. Il reste a determiner si la presence d’une IRC constitue un facteur favorisant la survenue d’une COVAN ( Tableau 1 ). Conclusion L’aggravation rapide d’une IRC et d’une proteinurie doit maintenant faire rechercher une anteriorite d’infection par la COVID-19. La COVAN est probablement sous-estimee chez ces patients pour lesquels la PBR n’est la plupart du temps pas effectuee.

Introduction L’infection VIH est connue pour donner de nombreuses atteintes renales directement liees au virus ou d’origine iatrogene. Cependant, l’amelioration de la prise en charge a permis une diminution de ces atteintes renales. Le syndrome de restauration immunitaire (IRIS) reste une complication classique mais rare du VIH. Description Une patiente de 39 ans suivie pour un VIH depuis 2005, en rupture therapeutique depuis 2018 presente un syndrome febrile depuis decembre 2019. Elle est traitee par plusieurs antibiotiques sans succes et une tritherapie est reintroduite mi-mars alors que les CD4 sont a 202/μL et la charge virale > 7 log. Elle est hospitalisee debut avril et il est diagnostique une infection disseminee a Mycobacterium avium pour laquelle est debutee une antibiotherapie adaptee. La patiente reste febrile et presente mi-avril une insuffisance renale aigue (creatinine a 107 μmol/L vs 47 μmol/L) avec hematurie microscopique, sans proteinurie, associee a des troubles ioniques evoquant une tubulopathie proximale. Methodes La biopsie renale (BR) retrouve une nephrite interstitielle aigue avec nette predominance de lymphocytes CD4+ (ratio CD4/CD8 > 10). Le diagnostic d’IRIS est retenu et une corticotherapie est debutee permettant l’apyrexie et une recuperation complete de la fonction renale en quelques jours. Resultats Les atteintes renales au cours du VIH sont variees. Plusieurs hypotheses pouvaient etre evoquees chez notre patiente. Une tubulopathie aux antiretroviraux, un syndrome d’infiltration lymphocytaire diffus ou une atteinte interstitielle liee a la mycobacterie. Un IRIS etait egalement possible compte tenu de la reintroduction recente du traitement antiretroviral mais ce syndrome est habituellement decrit lorsque les CD4 sont Fig. 1 ). Conclusion L’atteinte renale de l’IRIS bien que rare reste encore possible de nos jours. Les diagnostics differentiels peuvent etre nombreux et seule la BR permet le diagnostic de certitude.

Background Outcome of Mitral Valve Prolapse (MVP) was controversial for long time. Many studies reported great differences in the incidence of cardiovascular events due, above all, to heterogeneous and small studied populations. Most of theme were also published to late '80 of the last century till early '00. Purpose To make a contemporary survey on the incidence of cardiovascular events in a selected population of patients affected by primary MVP referred to a tertiary cardiovascular center for the medical and surgical care of valvular heart disease. Methods We reviewed our MVP database; patients with at least 2 cardiologic evaluations inclusive of echocardiographic examination and at least 6 months follow up were enrolled. A total of 250 patients (126 F) were selected. Their mean age was 52.1 years (ranging from 13 to 88 yo). The average follow-up time was 100 months (8,33 yrs). Results At the first medical and echocardiographic examination 8 patients (3,2%) had no mitral regurgitation (MR), 104 (41.6%) have a trace/mild MR, 93 (37,2%) a moderate MR and 46 (18,4%) a severe MR. They were widely asymptomatic (NYHA I 205-82%, NYHA II 44-17.60%, NYHA III 1- 0.40%). Most of theme presented a bileaflet (140-55.8%) or a posterior MVP (94 - 37.6%); an isolated anterior MVP was rare (16 - 6,4%). Flail leaflet was present in 8 (3,2%) and 25 (10%) had a chordal rupture. Respectively 165 (65,6%) and 115 (46,1%) patients had thick and redundant leaflets. Mean antero-posterior mitral annulus diameter was 37 mm. During the follow up 7 patients died of non-cardiac cause and 5 (2%) of suspected cardiac cause (2 because of acute coronary syndrome and 3 died suddenly). MR progresses in 43 (17,2%) patients and finally we observed 81 (32,4%) moderate/severe and severe MR. 12 new chordal rupture occurred during the follow up in most cases concerning mitral chordae linked to posterior mitral leaflet (10 cases-83,3%). The worsening of MR provoked an evolution of the clinical condition of 48 patients (19.2%) which developed Dyspnea On Excertion (DOE) with 42 new NYHA II and 6 new NYHA III. At the end of the follow up the amount of patients symptomatic for DOE was 93 (37.2% vs 18% at the initial evaluation). A total of 45 patients (18%) underwent mitral valve surgery. 40 needed in-hospital treatment in most cases due to the development of atrial fibrillation (19 -7.6%) or heart failure ( 8- 3,2%). Endocarditis occurred in 4 patients (1.6%) and cerebrovascular accidents/cardioembolic event in 6 (2.4%). The overall cardiovascular event rate was 4,33/100 patients-year, significantly higher than reported in community based studies. Conclusions The prognosis of a MVP population referred to a tertiary cardiovascular center is not benign. The most frequent complications are progression of MR and MV surgery. Sudden death is also more frequent than in general population. More studies are needed to identify what patients with MVP are at risk for it.

We surveyed European medical schools regarding teaching of prudent antibiotic prescribing in the undergraduate curriculum. We performed a cross-sectional survey in 13 European countries (Belgium, Croatia, Denmark, France, Germany, Italy, Netherlands, Norway, Serbia, Slovenia, Spain, Switzerland, United Kingdom) in 2013. Proportional sampling was used, resulting in the selection of two to four medical schools per country. A standardized questionnaire based on literature review and validated by a panel of experts was sent to lecturers in infectious diseases, medical microbiology and clinical pharmacology. In-depth interviews were conducted with four lecturers. Thirty-five of 37 medical schools were included in the study. Prudent antibiotic use principles were taught in all but one medical school, but only four of 13 countries had a national programme. Interactive teaching formats were used less frequently than passive formats. The teaching was mandatory for 53% of the courses and started before clinical training in 71%. We observed wide variations in exposure of students to important principles of prudent antibiotic use among countries and within the same country. Some major principles were poorly covered (e.g. reassessment and duration of antibiotic therapy, communication skills). Whereas 77% of the respondents fully agreed that the teaching of these principles should be prioritized, lack of time, mainly due to rigid curriculum policies, was the main reported barrier to implementation. Given the study design, these are probably optimistic results. Teaching of prudent antibiotic prescribing principles should be improved. National and European programmes for development of specific learning outcomes or competencies are urgently needed. Clinical Microbiology and Infection © 2014 European Society of Clinical Microbiology and Infectious Diseases. Published by Elsevier Ltd. All rights reserved

OBJECTIVES Frailty is a predictor of adverse health outcomes and can be measured across the life course, including among people living with HIV. The purpose of this study was to examine two commonly used measures of frailty - the frailty index (FI) and frailty phenotype - to assess common characteristics and to describe associations with multimorbidity, falls, and disability in people aging with HIV. METHODS This was a cross-sectional observational study including 482 consecutive HIV-infected patients (mean age 53.9 ± SD 6.9 years; 75% male) attending the multidisciplinary metabolic clinic at the University of Modena, Italy. Frailty was measured with the frailty phenotype and a 37-item FI. RESULTS The mean FI score was 0.28±0.1 and frailty phenotype categories were: 3.1% frail, 51.9% pre-frail, and 45% robust. The duration of antiretroviral therapy was significantly different across levels of frailty as measured by both frailty tools (P < 0.01), but the nadir CD4 count was only significant for the FI (P = 0.01); current CD4 count was not significantly different across frailty levels using either tool. Both frailty measures were associated with multimorbidity; the FI was associated with Instrumental Activities of Daily Living impairment and falls history, whereas the frailty phenotype was not. CONCLUSIONS The frailty phenotype and the FI demonstrated similar characteristics in patients at a tertiary-level HIV clinic. The FI had a stronger association with age, nadir CD4 count, comorbidities, falls, and disability. Integrating frailty assessments in clinical practice will be crucial for the development of interventions in age-related conditions, including disability and falls, in older persons living with HIV.

Background: CD4 cell recovery following first-line combination ART (cART) is poorer in HIV-2+ than in HIV-1+ patients. Only large comparisons may allow adjustments for demographic and pretreatment plasma viral load (pVL). Methods: ART-naive HIV+ adults from two European multicohort collaborations, COHERE (HIV-1 alone) and ACHIeV2e (HIV-2 alone), were included, if they started first-line cART (without NNRTIs or fusion inhibitors) between 1997 and 2011. Patients without at least one CD4 cell count before start of cART, without a pretreatment pVL and with missing a priori-defined covariables were excluded. Evolution of CD4 cell count was studied using adjusted linear mixed models. Results: We included 185 HIV-2+ and 30321 HIV-1+ patients with median age of 46 years (IQR 36-52) and 37 years (IQR 31-44), respectively. Median observed pretreatment CD4 cell counts/mm3 were 203 (95% CI 100-290) in HIV-2+ patients and 223 (95% CI 100-353) in HIV-1+ patients. Mean observed CD4 cell count changes from start of cART to 12months were +105 (95% CI 77-134) in HIV-2+ patients and +202 (95% CI 199-205) in HIV-1+ patients, an observed difference of 97 cells/mm3 in 1 year. In adjusted analysis, the mean CD4 cell increase was overall 25 CD4 cells/mm3/year lower (95% CI 5-44; P=0.0127) in HIV-2+ patients compared with HIV-1+ patients. Conclusions: A poorer CD4 cell increase during first-line cART was observed in HIV-2+patients, even after adjusting for pretreatment pVL and other potential confounders. Our results underline the need to identify more potent therapeutic regimens or strategies against HIV-2.

Background. Numerous studies have shown that baseline drug resistance patterns may influence the outcome of antiretroviral therapy. Therefore, guidelines recommend drug resistance testing to guide the choice of initial regimen. In addition to optimizing individual patient management, these baseline resistance data enable transmitted drug resistance (TDR) to be surveyed for public health purposes. The SPREAD program systematically collects data to gain insight into TDR occurring in Europe since 2001. Methods. Demographic, clinical, and virological data from 4140 antiretroviral-naive human immunodeficiency virus (HIV)-infected individuals from 26 countries who were newly diagnosed between 2008 and 2010 were analyzed. Evidence of TDR was defined using the WHO list for surveillance of drug resistance mutations. Prevalence of TDR was assessed over time by comparing the results to SPREAD data from 2002 to 2007. Baseline susceptibility to antiretroviral drugs was predicted using the Stanford HIVdb program version 7.0. Results. The overall prevalence of TDR did not change significantly over time and was 8.3% (95% confidence interval, 7.2%-9.5%) in 2008-2010. The most frequent indicators of TDR were nucleoside reverse transcriptase inhibitor (NRTI) mutations (4.5%), followed by nonnucleoside reverse transcriptase inhibitor (NNRTI) mutations (2.9%) and protease inhibitor mutations (2.0%). Baseline mutations were most predictive of reduced susceptibility to initial NNRTI-based regimens: 4.5% and 6.5% of patient isolates were predicted to have resistance to regimens containing efavirenz or rilpivirine, respectively, independent of current NRTI backbones. Conclusions. Although TDR was highest for NRTIs, the impact of baseline drug resistance patterns on susceptibility was largest for NNRTIs. The prevalence of TDR assessed by epidemiological surveys does not clearly indicate to what degree susceptibility to different drug classes is affected. © The Author 2015.

BACKGROUND: Kaposi sarcoma (KS) remains a frequent cancer in human immunodeficiency virus (HIV)-positive patients starting combination antiretroviral therapy (cART). We examined incidence rates and risk factors for developing KS in different periods after starting cART in patients from European observational HIV cohorts. METHODS: We included HIV-positive adults starting cART after 1 January 1996. We analyzed incidence rates and risk factors for developing KS up to 90 and 180 days and 1, 2, 5, and 8 years after cART start and fitted univariable and multivariable Cox regression models. RESULTS: We included 109 461 patients from 21 prospective clinical cohorts in Europe with 916 incident KS cases. The incidence rate per 100 000 person-years was highest 6 months after starting cART, at 953 (95% confidence interval, 866-1048), declining to 82 (68-100) after 5-8 years. In multivariable analyses adjusted for exposure group, origin, age, type of first-line regimen, and calendar year, low current CD4 cell counts increased the risk of developing KS throughout all observation periods after cART initiation. Lack of viral control was not associated with the hazard of developing KS in the first year after cART initiation, but was over time since starting cART increasingly positively associated (P < .001 for interaction). CONCLUSION: In patients initiating cART, both incidence and risk factors for KS change with time since starting cART. Whereas soon after starting cART low CD4 cell count is the dominant risk factor, detectable HIV-1 RNA viral load becomes an increasingly important risk factor in patients who started cART several years earlier, independently of immunodeficiency.

Late presentation (LP) for HIV care across Europe remains a significant issue. We provide a cross-European update from 34 countries on the prevalence and risk factors of LP for 2010-2013. People aged ≥ 16 presenting for HIV care (earliest of HIV-diagnosis, first clinic visit or cohort enrolment) after 1 January 2010 with available CD4 count within six months of presentation were included. LP was defined as presentation with a CD4 count, 0, The late presenters working group in COHERE in EuroCoord, SCOPUS: ar.j, info:eu-repo/semantics/published

Introduction Chez les sujets sains, au decours de la primo-infection, le polyomavirus BK (BKv) reste present sous forme latente dans les cellules tubulaires renales et urotheliales. Apres transplantation renale, la prevalence de la nephrite a BKv (BKVAN) est de 1 a 10 %, aboutissant dans 50 % des cas a la perte du greffon renal. In vivo, chez les rongeurs, il a ete montre que le BKv etait associe au developpement de tumeurs urotheliales. L’objectif de notre etude est d’evaluer la presence du BKv dans les tumeurs de vessie survenues dans les suites d’une transplantation renale, afin de suggerer son role pro-oncogenique. Patients/Materiels et methodes Nous avons repris les 4 cas de tumeurs de vessie diagnostiques de 2007 a 2017 dans notre centre chez des patients transplantes renaux. La recherche du BKv dans les tumeurs de vessie a ete realisee par etude immunohistochimique anti-LTAg (Sv40) sur coupes de tissu fixe deparaffine. Observation/Resultats Trois des quatre patients qui ont developpe une tumeur de vessie avaient un antecedent de BKVAN (35 diagnostics de BKVAN ont ete portes sur la periode de l’etude) : un homme de 50 ans, transplante depuis 8 ans pour une polykystose renale dominante, une femme de 64 ans transplantee depuis 5 ans pour une nephroangiosclerose et un homme de 57 ans transplante depuis 4 ans pour une nephropathie indeterminee. Chez ces patients, la tumeur survenait 3 a 4 ans apres la BKVAN. Le diagnostic anatomopathologique de carcinome urothelial papillaire de haut grade etait retenu dans les 3 cas (respectivement pT2, pT1b et pT1b). Il etait observe un marquage nucleaire intense et diffus des cellules tumorales par le Sv40 alors que le tissu non tumoral etait negatif. Chez tous les patients, la proliferation tumorale a recidive apres resection ± BCGtherapie, conduisant a la cystoprostatectomie dans 2 cas et au deces dans 1 cas. Chez le patient sans antecedent de reactivation virale la tumeur etait negative pour le Sv40 en immunohistochimie. Discussion/Conclusion Des observations cliniques de plus en plus nombreuses ainsi que des travaux experimentaux suggerent un role oncogene du BKv apres transplantation renale. Notre serie reprend 4 tumeurs de vessie survenues a la suite d’une transplantation renale. Trois d’entre elles, survenues a distance d’une nephrite a BKv, exprimaient le Sv40, renforcant cette hypothese. En attendant que le role exact du BKv dans la carcinogenese urotheliale soit precise, la surveillance rapprochee des greffes renaux ayant un antecedent de BKVAN pourrait permettre le diagnostic precoce de ces tumeurs.

A striking association (>90%) between mixed cryoglobulinemia (MC) and hepatitis C virus (HCV) infection has been established by means of clinico-epidemiological and laboratory studies. However, little information is available as regards the etiopathogenesis and the actual percentage of HCV-negative MC. This latter seems to be more frequent in the same geographical areas where the overall prevalence of MC is low. In 195 Italian patients with serum mixed cryoglobulins consecutively analyzed at the laboratory of our hospital, during one year, the prevalence of HCV-negative MC was 15.9%. Moreover, we evaluated the clinico-serological characteristics of our whole series of 65 HCV-negative MC patients: “essential” MC was present in only 25%, while the majority of cases showed different connective tissue diseases or neoplastic disorders. Interestingly, patients with Sjogren's syndrome or lymphoma had higher levels of cryocrit with cryoglobulinemic syndrome comparable to that found in HCV-positive MC patients. MC is a multifactorial disorder; considering possible etiological factors and clinical associations the disease may present different subsets: the prevalent group of HCV-positive MC; HCV-positive MC associated with different autoimmune lymphoproliferative disorders; two MC subsets without any apparent causative agent: those with well-known autoimmune lymphoproliferative disorders and the rare cases of “essential” MC; and finally MC associated with other infectious agents.

Background: One out of ten newly diagnosed patients in Europe was infected with a virus carrying a drug resistant mutation. We analysed the patterns over time for transmitted drug resistance mutations (TDRM) using data from the European Spread program.Methods: Clinical, epidemiological and virological data from 4317 patients newly diagnosed with HIV-1 infection between 2002 and 2007 were analysed. Patients were enrolled using a pre-defined sampling strategy.Results: The overall prevalence of TDRM in this period was 8.9% (95% CI: 8.1-9.8). Interestingly, significant changes over time in TDRM caused by the different drug classes were found. Whereas nucleoside resistance mutations remained constant at 5%, a significant decline in protease inhibitors resistance mutations was observed, from 3.9% in 2002 to 1.6% in 2007 (p = 0.001). In contrast, resistance to non-nucleoside reverse transcriptase inhibitors (NNRTIs) doubled from 2.0% in 2002 to 4.1% in 2007 (p = 0.004) with 58% of viral strains carrying a K103N mutation. Phylogenetic analysis showed that these temporal changes could not be explained by large clusters of TDRM.Conclusion: During the years 2002 to 2007 transmitted resistance to NNRTI has doubled to 4% in Europe. The frequent use of NNRTI in first-line regimens and the clinical impact of NNRTI mutations warrants continued monitoring. © 2014 Frentz et al.; licensee BioMed Central Ltd.

Complexity of antiretroviral treatment (ART) is a reason for non-adherence and may impact treatment outcome. The association between daily dosing and pill burden and chance of virological success (VS) of first ART has been rarely assessed. 3,674 naive patients who started treatment after January 2000 were identified from the ICoNA cohort. Number of daily doses and pills were estimated on the basis of the drugs used to rank first ART complexity: 1-2 daily pills once a day (low-pills QD [lpQD]); 3-6 daily pills QD (high-pills QD [hpQD]); 2-5 daily pills BID (low-pills BID [lpBID]); >6 daily pills BID (high-pills BID [hpBID]). VS was the date of first HIV RNA

Introduction : Criteria of cART initiation after a first ADE have been modified over time based on evidence suggesting that treatment should be initiated earlier. The impact of these changes on clinical practice is unknown. Objective of this analysis was to evaluate temporal changes of time of starting cART after a first diagnosis of ADE in ART-naive patients (pts). Methods : All HIV+ enrolled in ICONA Foundation Study who presented with a diagnosis of ADE while cART-naive regardless of CD4 cell count were included. Pts were grouped according to have ADE for which additional medications that may have interactions with cART are required (Tb, atypical mycobacteriosis, non-Hodgkin lymphoma) [group A], ADE treatable only by cART (PML, isosporidiasis/cryptosporidiasis, KS, wasting syndrome) [group B] and ADE treatable with specific drugs (PCP, toxoplasmic encephalitis, CMV disease, esoph candidiasis, bacterial pneumonia, cervical cancer, cryptococcosis) [group C]. Standard survival analysis by KM was used to estimate the cumulative percentage of pts starting cART, overall and after stratification for calendar period of diagnosis (1996-2000, 2001-2008, 2009-2011) and type of ADE (groups A, B, C). Multivariable Cox regression was used to investigate association between calendar year of ADE and time to cART initiation after controlling for demographics. Summary of results : A total of 715 pts with a first ADE were observed over 1996-2011 (group A, n=187; B, n=123; C, n=405). 519 (73%) male, median age 38 (IQR:33-45), median CD4+ 64 (23-187)/mm 3 and HIV/RNA 5.25 (4.57-5.70) log 10 cps/mL, with no differences by calendar period. By 30 days from ADE, 23% (95% CI: 19-27) of those diagnosed in 1996-2000 have started cART vs. 32% (95% CI: 25-39) in 2001-2008 and 36% (28-44) after 2009 (log-rank p=0.001). After stratifying by CD4 at ADE, 45% of pts with CD4 201/mm 3 had started cART by 30 days (p

Late presentation represents a major problem for patients with HIV infection. Actually, it should be made a distinction between late testers and late presenters, since the strategies to reduce the percentage of these two group of subjects could be different. Indeed, the first population is represented by individuals unaware of their serological status, while in the second case the problem is related to engagement and retention in care. Concerning the first population, it has been shown that most of the patients had been seen by their family doctor or admitted to hospital during the year before HIV diagnosis. Indeed, this is a relevant problem and new strategies to increase the level of suspect of HIV infection among doctors non-HIV specialist, as testing in presence of indicator diseases, should be applied. Concerning the population of late presenters, American data showed a percentage of engagement in care ranging between 50 and 59%. These low percentages could be due to the American Health System, while in a public health system setting, the percentage of patients not engaged in care or lost to follow-up could be lower, even if still relevant. Another important factor that should be considered in both populations is stigma. Indeed, many patients that present late, either late testers or late presenters, are immigrants and have important cultural barriers to disclose their HIV serostatus to family members and friends. Obviously, all subjects unaware or refusing their HIV infection could potentially infect their partners. In conclusion, all efforts should be made to reduce the phenomenon of late presentation since these two populations represent not only an epidemiological problem for the prognosis of the single patient, but also for the treatment as prevention strategy. (Published: 11 November 2012) Citation: Abstracts of the Eleventh International Congress on Drug Therapy in HIV Infection Mussini C. Journal of the International AIDS Society 2012, 15 (Suppl 4):18072 http://www.jiasociety.org/index.php/jias/article/view/18072 | http://dx.doi.org/10.7448/IAS.15.6.18072

We compared the efficacy of interferon and deflazacort in the treatment of the cryoglobulinaemic syndrome and assessed the usefulness of adding a low antigen diet to drug therapy.We studied 63 patients randomly allocated to different groups who underwent clinical and laboratory examinations every two months and who received treatment for 12 months or until a significant clinical event appeared.Five of 28 patients treated with interferon showed clinical improvement whereas 4 worsened and 7 suffered untoward side effects; seven of 28 patients treated with deflazacort improved, 4 worsened and 4 suffered drug toxicity. Twenty-nine patients were assigned to combined low antigen diet and therapy, among whom 7 did not follow the diet, 5 improved and 2 worsened. Among the 34 patients who were on an unrestrained diet, 5 improved and 7 worsened. None of the treatments proved superior to the others.Our results do not confirm the suggestion that interferon should be the primary therapy in the treatment of the cryoglobulinaemic syndrome, and the usefulness of a low antigen diet seems minimal.

The aim of this study was to assess the prevalence of HBV-related markers in cryoglobulinemias and the possible association between hepatitis B virus (HBV) and essential mixed cryoglobulinemia (EMC). A retrospective survey of the prevalence of HBV infection in cryoglobulinemic patients was carried out in 596 cases of cryoglobulinemia. On the basis of clinical and laboratory criteria the cases were grouped as secondary to connective tissue disease, to lymphoproliferative disorders, to chronic liver diseases or to chronic infectious diseases. The cases in which an associated disease was not evidenced were considered as essential mixed cryogobulinemias. Subjects in which liver dysfunction was first diagnosed simultaneously with cryoglobulinemia, were considered as a separate group. A greater prevalence of HBsAg and anti-HBc antibodies was found in cryoglobulinemias secondary to chronic liver disease (p0.0001) and in those associated with liver involvement at diagnosis (p0.05) than that found in EMCs. The prevalence of anti-HBs antibodies did not differ significantly among the groups. Proven contact with the virus, documented by at least one positive marker, was evidenced more frequently in cryoglobulinemias secondary to liver disease than in the other groups (p0.01). The prevalence of HBV related markers in EMCs and in hospitalized patients not suffering from diseases associated with cryoglobulin production were similar, and seems to reflect the epidemiological situation of HBV infection in Italy. In conclusion, our findings do not support an association of HBV with EMC.

Type II essential cryoglobulinemia may be associated with a lymphoproliferative disorder of beta lineage that shows a low degree of malignancy.The authors report a case recorded of 35 patients (30 females and 5 males) affected by mixed cryoglobulinemia type II (MC II) that has been typed by immunofixation, a procedure that allows the identification of minute amounts of monoclonal components. In 20 patients with the "essential" form, the bone marrow histology revealed the presence of nodular aggregates of lymphocytes that were consistent with the diagnosis of immunocytoma in 14 cases and of early stage plasmocytoma in 1 case. The immunohistochemical analysis carried out in 5 of these cases allowed the identification of B lymphocytes in the nodules, thus confirming the diagnosis of low malignancy lymphoma. In our series the percentage of proliferative disorders of B lymphocyte lineage was 66%.Our results indicate that the cytohistological analysis of bone marrow is highly recommended in the study of essential mixed cryoglobulinemia and that histological analysis supplemented with immunohistochemistry is preferred to the simple cytological analysis of bone aspirate.

Immunoglobulin (Ig) serum levels have been assayed in 729 patients with liver cirrhosis of different etiologies, in order to evaluate their prognostic value. Serum levels of three classes of Ig resulted mainly elevated in the three etiological groups (post-hepatitic, post-alcoholic, cryptogenetic) and they were significantly related to the severity of the liver disease, evaluated according to the Child-Turcotte score. The computerized analysis of the survival curves of patients with IgG, IgM, IgA values normal or elevated demonstrated an adverse prognostic rate in those with elevated Ig values. The difference among the survival curves, compared by the Lee-Desu method, was statistically significant (p less than 0.001). Our data suggest that the Ig levels can be considered as a prognostic index in liver cirrhosis patients.

Methods ADONE is a prospective, multicenter study in patients chronically treated with FTC+TDF+EFV or 3TC+TDF+EFV, showing a stable viremia

To the Editor: We read with interest the article by Khella et al on the treatment of cryoglobulinemic neuropathy with alpha-interferon (alpha-IFN). [1] Our group has been studying the relationship between HCV and essential mixed cryoglobulinemia (EMC) since 1990. We are a collaborating center of the Italian Group for the Study of Cryoglobulinemias (GISC), and have recently published the results obtained from a large sample (654 patients with EMC). [2] In this context, we have also studied the occurrence …

Clinical, neurophysiological, histopathological and immunohistochemical features of two cases of mixed connective tissue disease (Sharp syndrome) are reported.

The authors describe the alterations of atlanto-axial joint observed in patients with rheumatoid arthritis: 16 of 86 patients = 18.6% (15 females and 1 male) showed the presence of joint luxation. The authors suggest that a "dynamic" tomographic study in lateral orthostatic projection, with indifferent position and head flexed, is essential for demonstrating the changes of this joint and that examination should be performed in all patients with rheumatoid arthritis, even if they are asymptomatic.