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Objective s : The availability of doravirine (DOR) allowed clinicians to prescribe a dolutegravir (DTG)‐based two‐drug regimen (2DR) in individuals not eligible to receive lamivudine (3TC) or rilpivirine (RPV). The aims of this study were to describe the durability of DTG + DOR compared with DTG/3TC and DTG/RPV and the rate of virological failure and target not‐detected maintenance over time. Methods: This retrospective, monocentric analysis included all subjects who started a DTG‐based 2DR from 2018 to 2022 as a simplification. Descriptive statistics and non‐parametric tests to describe and compare the groups were applied. Kaplan–Meier probability curves and Cox regression models for regimens durability were used. Results: The study enrolled 710 individuals: 499 treated with DTG/3TC, 140 with DTG/RPV, and 71 with DTG + DOR. A 2DR with DOR was prescribed to older subjects who had a longer infection, greater exposure to different antiretroviral regimens, a higher proportion of resistance‐associated mutations, and a worse immune‐virologic status. Over a cumulative follow‐up of 68 152 weeks, 42 discontinuations were registered (5.9%). DTG + DOR had a risk of treatment interruption of 7.8% at 48 weeks and 9.8% at 96 weeks, significantly higher than the other 2DRs. In the multivariate Cox model, DTG + DOR and DTG/RPV were significantly associated with discontinuation. The maintenance of target not detected during follow‐up was similar among groups. The rate of virological failure was higher for DTG + DOR through different event definitions. Conclusions: DTG + DOR durability was high over a long follow‐up albeit lower than for other 2DRs. This combination might be an effective option in people with HIV that has proven difficult to treat. [ABSTRACT FROM AUTHOR]

Background and Aims: Whether the HCV test‐and‐treat strategy impacted on the rate of new HCV infections among PLWH in Italy is unknown. Methods: Prospective study of PLWH in the ICONA network. At baseline, PLWH were tested for HCV‐Ab; HCV‐RNA (if HCV‐Ab positive) and, if positive, treated with DAA. SVR12 indicated eradication. Seroconversions and re‐infections were evaluated yearly in HCV‐Ab neg and HCV‐RNA neg at first screening. We estimated the following: HCV seroconversions, incidence of HCV reinfections, and access to DAA and SVR12 rates tighter with factors associated with each outcome. Data were analysed by Cox regression, Poisson regression and logistic regression models. Results: Sixteen thousand seven hundred and forty‐three PLWH were included; 27.3% HCV‐Ab positive; of these, 39.3% HCV‐RNA positive. HCV seroconversion incidence:.48/100 PYFU (95% CI:.36–.65); re‐infections incidence: 1.40/100 PYFU (95% CI:.91–2.04). The risk factor for HCV re‐infection was young age: aIRR 1.85, 95% CI: 1.17–2.95) per 10 years younger. 86.4% of HCV viremic in follow‐up started DAA. PWID vs. heterosexuals (aHR.75, 95% CI.62–.90), HIV‐RNA >50 copies/mL (aHR.70, 95% CI.56–.87), HCV genotype other than G1, G2, G3, G4 or with multiple/missing HCV genotype and post‐COVID‐19 calendar periods were associated with lower DAA access. 922/965 (95.5%) PLWH achieved SVR12. We estimated 72% reduction of chance to achieve SVR12 in PLWH with a CD4 count <200/mm3 (vs. CD4 ≥200/mm3 aOR.18, 95% CI:.07–.46). 95.5% of DAA‐treated individuals eradicated HCV, but they represent only 53.2% of HCV viremic PLWH and 66.4% of those in follow‐up. HCV‐RNA positivity by year decreased from 41.7% in 2017 to 11.7% in 2022. Conclusions: The screening‐and‐treat campaign implemented in Italy, even if only partially effective, resulted in a dramatic drop in HCV circulation in our cohort. [ABSTRACT FROM AUTHOR]

HCV infection could have extrahepatic manifestations due to an aberrant immune response. HCV/HIV co‐infection increases such persistent immune activation. Aim of the present study is to describe the evolution of inflammatory markers used in clinical practice, mixed cryoglobulinemia (MC) and autoantibody reactivity in co‐infected individuals who achieved sustained virological response (SVR) after DAA treatment. This prospective, observational study included all HIV/HCV co‐infected subjects who started any DAA regimen from 2015 to 2020. Samples for laboratory measurements (ferritin, C reactive protein, C3 and C4 fractions, rheumatoid factor, MC, anti‐thyroglobulin Ab, anti‐thyroid peroxidase Ab, ANCA, ASMA, anti‐LKM, anti‐DNA, AMA, ANA, T CD4+ and CD8+ cell count, and CD4/CD8 ratio) were collected at baseline, after 4 weeks, at end of treatment, and at SVR12. The analysis included 129 individuals: 51.9% with a F0–F3 fibrosis and 48.1% with liver cirrhosis. Cryocrit, C3 fraction, and rheumatoid factor significantly improved at week 4; ferritin, anti‐thyroglobulin Ab, and C4 fraction at EOT; total leukocytes count at SVR12. MC positivity decreased from 72.8% to 35.8% (p <.001). T CD4+ cell slightly increased at SVR12, but with an increase also in CD8+ resulting in stable CD4/CD8 ratio. Autoantibody reactivity did not change significantly. ANA rods and rings positivity increased from 14.8% to 28.6% (p =.099): they were observed in three subjects without exposure to RBV. DAA therapy may lead to improvement in inflammatory markers and MC clearance but without significant changes in autoantibodies reactivity and CD4/CD8 ratio over a follow up of 12 weeks. [ABSTRACT FROM AUTHOR]

Mpox is traditionally considered a zoonotic disease with endemic circulation in Africa, but the 2022–2023 outbreak reached an unprecedented high number of cases in non-endemic countries, so that it was declared a public health emergency of international concern. The reasons for this extensive global spread, characterized by sexual transmission amongst men who have sex with men (MSM), have not been fully clarified. The existence of asymptomatic carriers with viable viral shedding might be an explanation and is under-debated after retrospective studies suggested that infection without symptoms might have a prevalence of 6.5%. We aimed to prospectively assess the presence of mpox infection in asymptomatic high-risk MSM using HIV pre-exposure prophylaxis and living with HIV. We selected individuals with no signs of active infection nor suggestive symptoms in the previous 21 days. Eligible individuals collected oral and anal swabs to undergo point-of-care testing for mpox and completed a 21-days follow-up. Seventy-two individuals were enrolled, and none tested positive for mpox infection nor developed symptoms during follow-up. We selected a high-risk population with a significant history of sexual exposure, but we failed to detect any asymptomatic infection. This observation might have important consequences in terms of contact management and epidemic control. [ABSTRACT FROM AUTHOR]

Liver transplantation (LT) represents the best therapeutic option for hepatocellular carcinoma (HCC) and end-stage liver disease (ESLD). Although HIV infection does not seem to lower survival rates, HCV and HCC recurrence appear more harmful. To compare the overall survival after LT; evaluate the impact of anti-HCV direct-acting agents (DAA); assess the rate of HCC recurrence in HIV-positive and negative patients. Subjects with HCV/HBV infection who underwent LT for HCC or ESLD from 2012 to 2019 were retrospectively evaluated. Study population included 299 individuals, 31 (10.4%) were HIV-positive. Overall mortality was similar (16.1% versus 19.0%, p = 0.695). HCC recurrence was observed in 6 HIV-positive (19.4%) and in 17 negative subjects (6.3%, p = 0.022). Time to relapse was 831 days in HIV-positive and 315 days in negative patients (p = 0.046). Cox model found a significant role for HIV in univariate analysis but, after adjusting for variables, extra-hepatic tumor was the only factor associated to recurrence (aHR 56.379, p < 0.001). Post-LT survival improved after DAA availability and HIV has no impact on mortality. A higher and delayed rate of HCC recurrence was observed in co-infected individuals: surveillance protocols should be strengthened along time in this population. [ABSTRACT FROM AUTHOR]

The article discusses a study conducted in Italy on the use of human immunodeficiency virus (HIV) nucleic acid testing (NAAT) for early detection of HIV infection among high-risk men who have sex with men. It reports the results showed that NAAT detected four acute, one primary, and no chronic HIV infections, and all five individuals were linked to care and had undetectable viral loads within three months.

SARS‐CoV2 infection is a systemic disease that may involve multiple organs, including the central nervous system (CNS). Aims of our study are to describe prevalence and clinical features of neurological manifestations, mortality and hospital discharge in subjects hospitalized with COVID‐19. All individuals admitted for to our hospital COVID‐19 were retrospectively included. Patients were classified according to the symptoms at hospital entry in (1) isolated respiratory, (2) combined respiratory and neurologic, (3) isolated neurologic and (4) stroke manifestations. Descriptive statistics and nonparametric tests to compare the groups were calculated. Kaplan Meier probability curves and multivariable Cox regression models for survival and hospital discharge were applied. The analysis included 901 patients: 42.6% showed a severe or critical disease with an overall mortality of 21.2%. At least one neurological symptom or disease was observed in 30.2% of subjects ranging from dysgeusia/anosmia (9.1%) to postinfective diseases (0.8%). Patients with respiratory symptoms experienced a more severe disease and a higher in‐hospital mortality compared to those who showed only neurologic symptoms. Kaplan Meier estimates displayed a statistically significant different survival among groups (p = 0.003): subjects with stroke had the worst. After adjusting for risk factors such as age, sex and comorbidity, individuals with isolated neurologic manifestations exhibited a better survival (aHR 0.398, 95% CI [0.206, 0.769], p = 0.006). Neurologic manifestations in COVID‐19 are common but heterogeneous and mortality in subjects with isolated neurologic manifestations seems lower than in those with respiratory symptoms. [ABSTRACT FROM AUTHOR]

Background: The aim of this secondary analysis of the TESEO cohort is to identify, early in the course of treatment with tocilizumab, factors associated with the risk of progressing to mechanical ventilation and death and develop a risk score to estimate the risk of this outcome according to patients' profile. Methods: Patients with COVID-19 severe pneumonia receiving standard of care + tocilizumab who were alive and free from mechanical ventilation at day 6 after treatment initiation were included in this retrospective, multicenter cohort study. Multivariable logistic regression models were built to identify predictors of mechanical ventilation or death by day-28 from treatment initiation and β-coefficients were used to develop a risk score. Secondary outcome was mortality. Patients with the same inclusion criteria as the derivation cohort from 3 independent hospitals were used as validation cohort. Results: 266 patients treated with tocilizumab were included. By day 28 of hospital follow-up post treatment initiation, 40 (15%) underwent mechanical ventilation or died [26 (10%)]. At multivariable analysis, sex, day-4 PaO2/FiO2 ratio, platelets and CRP were independently associated with the risk of developing the study outcomes and were used to generate the proposed risk score. The accuracy of the score in AUC was 0.80 and 0.70 in internal validation and test for the composite endpoint and 0.92 and 0.69 for death, respectively. Conclusions: Our score could assist clinicians in identifying, early after tocilizumab administration, patients who are likely to progress to mechanical ventilation or death, so that they could be selected for eventual rescue therapies. [ABSTRACT FROM AUTHOR]

Objective: Through a hospital-based SARS-CoV-2 molecular and serological screening, we evaluated the effectiveness of two months of lockdown and two of surveillance, in Milan, Lombardy, the first to be overwhelmed by COVID-19 pandemics during March-April 2020. Methods: All subjects presenting at the major hospital of Milan from May-11 to July-5, 2020, underwent a serological screening by chemiluminescent assays. Those admitted were further tested by RT-PCR. Results: The cumulative anti-N IgG seroprevalence in the 2753 subjects analyzed was of 5.1% (95%CI = 4.3%-6.0%), with a peak of 8.4% (6.1%-11.4%) 60–63 days since the peak of diagnoses (March-20). 31/106 (29.2%) anti-N reactive subjects had anti-S1/S2 titers >80 AU/mL. Being tested from May-18 to June-5, or residing in the provinces with higher SARS-CoV-2 circulation, were positively and independently associated with anti-N IgG reactivity (OR [95%CI]: 2.179[1.455–3.264] and 3.127[1.18–8.29], respectively). In the 18 RT-PCR positive, symptomatic subjects, anti-N seroprevalence was 33.3% (95% CI: 14.8%-56.3%). Conclusion: SARS-CoV-2 seroprevalence in Milan is low, and in a downward trend after only 60–63 days since the peak of diagnoses. Italian confinement measures were effective, but the risk of contagion remains concrete. In hospital-settings, the performance of molecular and serological screenings upon admission remains highly advisable. [ABSTRACT FROM AUTHOR]

Background: As the novel SARS-CoV-2 pandemic occurred, no specific treatment was yet available. Inflammatory response secondary to viral infection might be the driver of severe diseases. We report the safety and efficacy (in terms of overall survival and hospital discharge) of the anti-IL6 tocilizumab (TCZ) in subjects with COVID-19.Methods: This retrospective, single-center analysis included all the patients consecutively admitted to our Hospital with severe or critical COVID-19 who started TCZ treatment from March 13th to April 03rd, 2020. A 1:2 matching to patients not treated with TCZ was performed according to age, sex, severity of disease, P/F, Charlson Comorbidity Index and length of time between symptoms onset and hospital admittance. Descriptive statistics and non-parametric tests to compare the groups were applied. Kaplan Meier probability curves and Cox regression models for survival, hospital discharge and orotracheal intubation were used.Results: Seventy-four patients treated with TCZ were matched with 148 matched controls. They were mainly males (81.5%), Caucasian (82.0%) and with a median age of 59 years. The majority (69.8%) showed critical stage COVID-19 disease. TCZ use was associated with a better overall survival (HR 0.499 [95% CI 0.262-0.952], p = 0.035) compared to controls but with a longer hospital stay (HR 1.658 [95% CI 1.088-2.524], p = 0.019) mainly due to biochemical, respiratory and infectious adverse events.Discussion: TCZ use resulted potentially effective on COVID-19 in terms of overall survival. Caution is warranted given the potential occurrence of adverse events.Financial Support: Some of the tocilizumab doses used in the subjects included in this analysis were provided by the "Multicenter study on the efficacy and tolerability of tocilizumab in the treatment of patients with COVID-19 pneumonia" (EudraCT Number: 2020-001110-38) supported by the Italian National Agency for Drugs (AIFA). No specific funding support was planned for study design, data collection and analysis and manuscript writing of this paper. [ABSTRACT FROM AUTHOR]

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. [ABSTRACT FROM AUTHOR]

Summary: Hepatitis A is a self‐limiting infection representing the most common cause of viral hepatitis worldwide. Despite being a low incidence region, in the European Union, an increasing number of cases have been reported since summer 2016, resulting in a large outbreak in 2017, involving mainly men who have sex with men (MSM). Some reports described a different clinical course of hepatitis A virus in patients infected by human immunodeficiency virus (HIV) or MSM. We consecutively collected all the hospitalized cases of hepatitis A referred to two tertiary centres in Northern Italy in 2017 and retrospectively analysed the electronic records of the 2009‐2016 period (pre‐2017). We evaluated demographics data, risk factors, comorbidities and laboratory results to see whether MSM status or HIV infection influenced the disease. Overall, 117 cases were identified in 2017:107 (91%) were male, 78 reported themselves as MSM (66%) and 17 (14.5%) were infected by HIV. For the pre‐2017 period, 48 cases were reported: 29 (60%) were male and 3 (6.2%) were infected by HIV. After stratification for HIV infection, MSM status and occurrence period, no differences were found in aspartate aminotransferase, alanine aminotransferase, γ‐glutamyl transpeptidase; bilirubin, alkaline phosphatase and bilirubin values, hospitalization length, HIV viral load and CD4 + cells count. HIV‐positive patients presented a higher number of patients with INR > 1.5 at admission. MSM status and HIV infection did not affect neither the clinical course nor the severity of hepatitis A. [ABSTRACT FROM AUTHOR]

Considering the potential benefits of CBD for several inflammatory diseases, the results proposed by Barré and colleagues need a better assessment. DATA AVAILABILITY STATEMENT The data that support the findings of this study are available from the corresponding author upon reasonable request. Substance use and CD4/CD8 ratio in HIV/HCV co-infected people receiving direct-acting antiviral treatment (ANRS CO13 HEPAVIH): Authors' reply. [Extracted from the article]

The article reports that men who have sex with men (MSM) and who are practicing oral-anal and digital-anal sex are at high risk of getting Hepatitis A Virus. Author stresses upon the need for awareness and vaccination. Topics discussed include the factors leading to spread of virus and measures to be taken to counter it and diseases which can occur when a person gets it.

This retrospective study reports the data of sofosbuvir-based anti-hepatitis C virus treatment in 24 candidates and 24 recipients of liver transplantation coinfected with human immunodeficiency virus. Sustained virologic response was cumulatively 85% (90% and 100% in those treated with optimal schedules pre- and posttransplant, respectively). [ABSTRACT FROM AUTHOR]

Background PrEP with FTC/TDF has shown great efficacy in preventing new HIV infections but issues remain (low adherence, high costs, toxicity and resistance development). No data are available about the impact of circulating Resistance-Associated Mutations (RAMs) on its efficacy. Objectives describe the prevalence of FTC and/or TDF-related RAMs in Italian HIV-infected population and their potential impact on PrEP efficacy. Study design ARCA is a national database that collects data about RAMs and epidemiological correlates from sites throughout Italy; it was queried about the prevalence of these RAMs in the last decade. PrEP efficacy was adjusted for a dynamic score based on RAMs prevalence. Absolute and relative risk increases (ARI and RRI) and number needed to harm (NNH) were calculated after this score. Results the query retrieved 3579 HAART-naïve and 5781 experienced subjects. Resistance to TDF is low and more common among naïve MSM in the area of Milan (where it topped to 14.3%), without other significant differences. If good adherence is not attained, RRI for receptive anal sex increases by 16% (in naïve) and 93.4% (in experienced MSM). NNH is largely above 10000 except for having receptive anal sex with a HAART-experienced MSM on a failing treatment (970). Conclusions according to this model, PrEP may be introduced in Italy without general concerns, but efficacy may be partly reduced in young MSM having sex in Rome and Milan. [ABSTRACT FROM AUTHOR]

Inactivated trivalent influenza vaccination is associated with lower mortality among patients with Covid-19 in Brazil [published online ahead of print December 11, 2020]. Although influenza vaccination is strongly recommended for clinical, epidemiological, and management issues,10 our data do not support its beneficial effect in terms of COVID-19-related disease severity and mortality in Italy. Influenza vaccination and COVID19 mortality in the USA. medRxiv. [Extracted from the article]

Tenofovir disoproxil fumarate (TDF) is widely used in HIV-infected patients. It is associated with tubular toxicity, but its management is controversial. A possible strategy is to switch to a dual therapy based on lamivudine or emtricitabine (XTC) and protease inhibitors (PIs). A case-control study was designed to evaluate the switch to XTC + PI therapy in patients with TDF-related renal toxicity. A case was defined as a patient who was on TDF/XTC + PI and who switched to XTC + PI. A control was defined as a patient with the same clinical features who remained on TDF/XTC + PI. Twenty-one cases and 21 controls were included. After 48 weeks, no differences in efficacy were observed. No improvement in the glomerular filtration rate as estimated with the Cockroft-Gault formula (eGFR) was seen, but the number of times that patients had values below 60 ml/min was higher with standard TDF/XTC 1 PI treatment than with dual XTC + PI treatment. A switch to dual therapy could be an option for patients at risk of TDF-related renal damage with no relevant risk of virological or immunological failure. [ABSTRACT FROM AUTHOR]

Occasionally, malaria may present with unusual signs and symptoms. We report a case of an uncommon presentation of Plasmodium falciparum infection in a 59-year-old Ethiopian immigrant, which initially presented with hyperglycaemia and multiple organ dysfunction syndrome (MODS). Reports of unusual presentations of malaria are few and cases of severe malaria with hyperglycaemia are rarely described. As hyperglycaemia is associated to most severe malaria and high mortality, our aim is to catch the attention of the physicians on this entity. [ABSTRACT FROM AUTHOR]

Direct‐acting antivirals (DAAs) demonstrated high efficacy and safety even in the post‐liver transplant (LT) setting and in HIV‐infected patients, but data are very limited in the early post‐LT period with the most recently available DAA. Two HIV/HCV‐coinfected LT recipients (both grafts from HIV/HCV‐negative donors) experienced early HCV recurrence with severe hepatitis and were treated with sofosbuvir/velpatasvir for 12 weeks. Unfortunately, both patients failed: one (genotype 4d) showed virological breakthrough at week 3 with resistance‐associated substitutions (RASs) for both NS5A and NS5B, while the other (genotype 1a) experienced virological relapse without RAS. Both progressed to fibrosing cholestatic hepatitis and were successfully retreated with glecaprevir/pibrentasvir for 16 weeks achieving sustained virological response. The higher prevalence of RAS in experienced genotype 4 patients and the long time to viral suppression observed in subjects with fibrosing cholestatic hepatitis should be taken into account, considering longer treatment duration to increase the chances of achieving sustained virological response. [ABSTRACT FROM AUTHOR]