Use of next-generation sequencing on HIV-1 DNA to assess archived resistance in highly treatment-experienced people with multidrug-resistant HIV under virological control: data from the PRESTIGIO Registry.

BACKGROUND: To clarify whether next-generation sequencing (NGS) can be useful for resistance assessment in virologically suppressed highly treatment-experienced (HTE) individuals with MDR HIV. METHODS: Ninety-one participants from the PRESTIGIO Registry were included. NGS was performed on HIV-DNA at 1%, 5% and 20% cut-offs; major drug resistance mutations (DRMs) were evaluated and compared with those detected in historical plasma genotypic resistance testing (h-GRT). APOBEC editing was also characterized. RESULTS: Participants had a complex and long treatment history [median 23 (IQR 21-25) years of ART exposure) and had been virologically suppressed since a median of 3 (IQR 2-5) years. Among all major DRMs detected by HIV-DNA NGS and/or h-GRT, 30% were exclusively found through NGS. The highest detection rate of historical major DRMs was reached with NGS set at 1%, but unusual substitutions and extensive APOBEC hypermutations suggest technical issues and poor clinical relevance in the 1%-5% interval. At NGS set at 5%, 67.2% of historical major DRMs were detected. The number of major DRMs detected exclusively by DNA-NGS as minority variants (frequency 5%-20%) was significantly higher in individuals who later experienced virological rebound compared with those who maintained virological control [median 2 (IQR 1-3) versus 1 (0-2), P = 0.030] and positively correlated with viraemia levels at rebound (rho = 0.474, P = 0.030). CONCLUSIONS: In non-viraemic people with an MDR virus, HIV-1 DNA NGS set at 5% is an acceptable technical cut-off that might help to reveal mutations with a potential clinical relevance. Moreover, the number of minority resistance mutations additionally detected by NGS might be associated with loss of virological control.

Trends of Antimicrobial Susceptibility of Neisseria gonorrhoeae Isolates Between 2012 and 2023: Results From an Open Italian Cohort.

BACKGROUND: Neisseria gonorrhoeae (Ng) is a public health priority because of the rapid evolution of antimicrobial resistance, the emergence of antibiotic resistance, and the absence of a vaccine against Ng. The aim of this study was to investigate trends in the minimum inhibitory concentration and resistance (R) or reduced susceptibility (DS) of Ng cases to ceftriaxone (CRO), azithromycin (AZM), tetracycline (TET), benzylpenicillin (PenG), and ciprofloxacin (CIP) during a 10-year period. METHODS: We conducted a retrospective analysis on an open cohort of Ng cases diagnosed on rectal, urethral, and pharyngeal samples at San Raffaele Scientific Institute, between September 2012 and February 2023. Minimum inhibitory concentrations of antibiotics were determined by gradient-test strips. Bivariate linear regression models were applied on logarithmic minimum inhibitory concentrations values; Cochran-Armitage test was used to determine a linear trend in the proportions of resistant strains. RESULTS: A total of 436 Ng isolates from 352 individuals were analyzed. Minimum inhibitory concentrations of CRO and PenG reduced over time ( P < 0.001, P = 0.030), AZM increased ( P = 0.001), and CIP and TET did not change ( P = 0.473, P = 0.272). The percentages of resistant strains were as follows: PenG, 89.9%; TET, 90.8%; CIP, 48.2%; AZM, and 4.4%. CRO-DS strains were 8.7%, and only 1 case of CRO-R was identified. The proportion of resistant strains increased over time for AZM ( P = 0.007), TET ( P = 0.001), and CIP ( P < 0.001), whereas it decreased for PenG ( P < 0.001) and CRO-DS/R strains ( P < 0.001). CONCLUSIONS: Ng strains showed high susceptibility to CRO, although we identified cases of DS/R and observed high levels of susceptibility to AZM. Overall, the recommended primary regimen for Ng treatment was confirmed to be effective.

High Propensity to Switch to Long-acting Injectable HIV PrEP with Cabotegravir in a Cohort of Oral PrEP Experienced Men who Have Sex with Men in Italy.

Aim was to investigate the propensity to switch to long-acting injectable HIV pre-exposure prophylaxis (PrEP) with cabotegravir among oral PrEP-experienced men who have sex with men. Out of 377 PrEP users, 325 (86.2%) were interested (would like = 210) or considering (would consider = 115) switch to long-acting PrEP. At multivariable analysis, the odds ratio of interest in long-acting PrEP in non-adherent vs. adherent individuals to oral PrEP was 5.03 (95%CI = 1.73-14.61,p = 0.003) and of consideration 1.63 (95%CI = 0.51-5.23,p = 0.410). We observed very high propensity to switch to long-acting PrEP, particularly among non-adherent users. Rapid availability of long-acting PrEP might address unmet needs of PrEP users in Italy.

Safety and pharmacokinetics of subcutaneous administration of broadly neutralizing anti-HIV-1 monoclonal antibodies (bNAbs), given to HIV-1 exposed, uninfected neonates and infants: study protocol for a phase I trial.

BACKGROUND: The ambitious goal to eliminate new pediatric HIV infections by 2030 requires accelerated prevention strategies in high-risk settings such as South Africa. One approach could be pre-exposure prophylaxis (PrEP) with broadly neutralizing anti-HIV-1 monoclonal antibodies (bNAbs). The aim of our study is to define the optimal dose(s), the ideal combination(s) of bNAbs in terms of potency and breadth, and timing of subcutaneous (SC) administration(s) to prevent breast milk transmission of HIV. METHODS: Two bNAbs, CAP256V2LS and VRC07-523LS, will be assessed in a sequential and randomized phase I, single-site, single-blind, dose-finding trial. We aim to investigate the 28-day safety and pharmacokinetics (PK) profile of incrementally higher doses of these bNAbs in breastfeeding HIV-1 exposed born without HIV neonates alongside standard of care antiretroviral (ARV) medication to prevent (infants) or treat (mothers) HIV infection. The trial design includes 3 steps and 7 arms (1, 2, 3, 4, 5, 6 and 6b) with 8 infants in each arm. The first step will evaluate the safety and PK profile of the bNAbs when given alone as a single subcutaneous (SC) administration at increasing mg/kg body weight doses within 96 h of birth: arms 1, 2 and 3 at doses of 5, 10, and 20 mg/kg of CAP256V2LS, respectively; arms 4 and 5 at doses of 20 and 30 mg/kg of VRC07-523LS, respectively. Step two will evaluate the safety and PK profile of a combination of the two bNAbs administered SC at fixed doses within 96 h of birth. Step three will evaluate the safety and PK profile of the two bNAbs administered SC in combination at fixed doses, after 3 months. Arms 1 and 6 will follow sequential recruitment, whereas randomization will occur sequentially between arms (a) 2 & 4 and (b) 3 & 5. Before each randomization, a safety pause will allow review of safety data of the preceding arms. DISCUSSION: The results of this trial will guide further studies on bNAbs to prevent breast milk transmission of HIV. PROTOCOL VERSION: Version 4.0 dated 15 March 2024. TRIAL REGISTRATION: Pan African Clinical Trial Registry (PACTR): PACTR202205715278722, 21 April 2022; South African National Clinical Trial Registry (SANCTR): DOH-27-062022-6058.

A Digital Platform for Home-Based Exercise Prescription for Older People with Sarcopenia.

Digital therapeutics refers to smartphone applications, software, and wearable devices that provide digital solutions to improve healthcare delivery. We developed a digital platform to support the GYM (Grow Your Muscle) study, an ongoing 48-week randomized, controlled trial on reduction of sarcopenia through a home-based, app-monitored physical exercise intervention. The GYM platform consists of a smartphone application including the exercise program and video tutorials of body-weight exercises, a wearable device to monitor heart rate during training, and a website for downloading training data to remotely monitor the exercise. The aim of this paper is to describe the platform in detail and to discuss the technical issues emerging during the study and those related to usability of the smartphone application through a retrospective survey. The main technical issue concerned the API level 33 upgrade, which did not enable participants using the Android operating systems to use the wearable device. The survey revealed some problems with viewing the video tutorials and with internet or smartphone connection. On the other hand, the smartphone application was reported to be easy to use and helpful to guide home exercising. Despite the issues encountered during the study, this digital-supported physical exercise intervention could provide useful to improve muscle measures of sarcopenia.

Real-life experience with remdesivir for treatment of COVID-19 among older adults: a multicentre retrospective study.

INTRODUCTION: The effect of remdesivir on COVID-19 mortality remains conflicting. Elderly individuals are at risk for poor COVID-19 outcomes. We aimed to assess the effect of remdesivir on COVID-19 mortality among elderly individuals, using real-world data. METHODS: Retrospective multinational cohort of individuals aged ≥65 years, hospitalized with COVID-19 in six medical centres between January 2020 and May 2021. Associations with in-hospital mortality were evaluated using a multivariable logistic regression model with propensity score adjustment for remdesivir therapy and while implementing generalized estimating equations to control for centre effect. Sensitivity analysis was performed by stratification according to the degree of respiratory support. RESULTS: Of 3010 individuals included, 2788 individuals required either oxygen supplementation or non-invasive/invasive mechanical ventilation, 489 (16%) were treated with remdesivir, and 836 (28%) died. Median age was 77 (IQR 70-84) years and 42% were women. Remdesivir was the only therapeutic intervention associated with decreased mortality [adjusted OR (aOR) 0.49, 95% CI 0.37-0.66, P < 0.001]. This protective effect was shown for individuals requiring oxygen support and non-invasive mechanical ventilation, while no association was found among individuals necessitating invasive mechanical ventilation.Risk factors for mortality included invasive ventilation (aOR 5.18, 95% CI 2.46-10.91, P < 0.001), higher serum creatinine (aOR 1.25, 95% CI 1.09-1.43, P = 0.001) and dyspnoea (aOR 1.40, 95% CI 1.07-1.84, P = 0.015) on presentation, and other non-modifiable factors, such as comorbidities. CONCLUSIONS: Among elderly individuals hospitalized with COVID-19, remdesivir carries survival benefit for those with moderate to severe disease. Its role among individuals with critical illness should be further assessed.

Subclinical atherosclerosis as detected by carotid ultrasound and associations with cardiac and HIV-specific risk factors; the Archi-Prevaleat project.

OBJECTIVES: To evaluate the prevalence of carotid intima-media thickness (IMT) and plaques in a cohort of people living with HIV (PLWH), the role of cardiovascular risk factors, the impact of the antiretroviral regimens and the difference between naïve and experienced patients in the onset of carotid lesions. METHODS: This project was initiated in 2019 and involves eight Italian centres. Carotid changes were detected using a power colour-Doppler ultrasonography with 7.5 MHz probes. The following parameters were evaluated: IMT of both the right and left common and internal carotids, data regarding risk factors for cardiovascular disease, HIV viral load, CD4 cell counts, serum lipids, glycaemia and body mass index. The associations between pathological findings and potential risk factors were evaluated by logistical regression, with odds ratios (ORs) and 95% confidence intervals (95% CI)s. RESULTS: Among 1147 evaluated PLWH, with a mean age of 52 years, 347 (30.2%) had pathological findings (15.8% plaques and 14.5% IMT). Besides the usual risk factors, such as older age, male sex and dyslipidaemia, CD4 cell nadir < 200 cells/mL (adjusted OR = 1.51, 95% CI: 1.14-1.99) and current use of raltegravir (adjusted OR = 1.54, 95% CI: 1.01-2.36) were associated with higher prevalence of pathological findings. CONCLUSIONS: Our data show that the current overall percentage of carotid impairments remains high. Colour-Doppler ultrasonography could play a pivotal role in identifying and quantifying atherosclerotic lesions among PLWH, even at a very premature stage, and should be included in the algorithms of comorbidity management of these patients.

Mpox DNA clearance in semen over 6-month follow-up.

Sexual intercourse is a well-established way of transmission of mpox infection. However, it is still uncertain whether semen may represent a viral reservoir. The aim of the study was to evaluate the clearance of viral DNA in semen samples from individuals diagnosed with mpox infection over 6-month follow-up. This prospective, observational, single-center study was conducted at IRCCS San Raffaele Scientific Institute, Milan, Italy, between May and October 2022 in 140 individuals who attended Sexual Health Clinic and diagnosed with mpox infection. Semen samples were collected and analyzed by real-time polymerase chain reaction assays. The baseline collection was performed in 64 (46%) of 140 men diagnosed with mpox infection. The viral DNA was detected in 43 (67%) with median cycle threshold (Ct) 34 (interquartile range [IQR] 31-36). The research was repeated in 32 (74%) and viral DNA clearance was observed in all within 6 months in a median time of 10.5 days (IQR 7-33). Viral clearance occurred in all tested individuals, mostly within 2 weeks since the first positive test. These findings suggest a transient presence of viral DNA in semen and do not support the hypothesis of reservoir. More studies on mpox DNA detection in semen with viral culture and extended follow-up are needed.

Association of high-risk sexual behaviours with sexually transmitted infections among men who have sex with men living with HIV.

OBJECTIVES: To explore different sexual behaviours as risk factors for STI among men who have sex with men (MSM) living with HIV. METHODS: This is a cross-sectional study on MSM living with HIV followed at the Infectious Diseases Unit of San Raffaele Hospital, Milan, with at least one diagnosis of gonorrhoea, syphilis, chlamydia or anal human papilloma virus (HPV), between July 2016 and February 2021. We conducted a survey on high-risk sexual behaviours with regard to (1) mean number of partners per month, (2) estimated percentage of condom use and (3) most frequent type of sexual intercourse during 2016-2021. Data on these variables were grouped as follows: (1a) ≤5 vs >5, (1b) >10 vs ≤10, (2a) 0% vs >0%, (2b) ≤50% vs >50%, (2c) 100% vs <100%, (3a) ≥50% vs <50% receptive, (3b) 100% vs <100% insertive, and (3c) 100% vs <100% receptive. A high-risk group was defined as >5 partners, <100% use of condom and ≥50% receptive intercourse. Univariate logistic regressions were applied to assess the association between sexual behaviours and the risk of each STI. RESULTS: Out of 1051 MSM with at least one STI diagnosis, 580 (55%) answered the survey. The risk of chlamydia was lower among individuals with ≤5 partners (≤5 partners vs >5 partners: OR=0.43, 95% CI 0.28 to 0.66, p=0.001) and among those using condoms more frequently (≤50% use of condom vs >50% use of condom: OR=1.55, 95% CI 1.06 to 2.27, p=0.025; 100% vs <100%: OR=0.35, 95% CI 0.20 to 0.59, p=0.001). Individuals using condoms more frequently also had lower risk of gonorrhoea (100% use of condom vs <100% use of condom: OR=0.37, 95% CI 0.17 to 0.79, p=0.011). The risks of chlamydia (OR=3.07, 95% CI 1.92 to 4.90, p<0.001) and gonorrhoea (OR=2.05, 95% CI 1.12 to 3.75, p=0.020) were higher among individuals belonging to the high-risk group. CONCLUSIONS: Chlamydia and gonorrhoea are more likely associated with high-risk sexual behaviours than syphilis and anal HPV among MSM living with HIV.

Meningococcus B Vaccination Effectiveness Against Neisseria gonorrhoeae Infection in People Living With HIV: A Case-Control Study.

BACKGROUND: We assessed the vaccination effectiveness (VE) of multicomponent meningococcal serogroup B (4CMenB) vaccine against gonorrhea among people living with HIV (PLWH) with a previous diagnosis of sexually transmitted infection. METHODS: Unmatched case-control study on men who have sex with men living with HIV, in care at San Raffaele Scientific Institute, Milan, Italy, with gonorrhea, syphilis, chlamydia, or anal human papillomavirus between July 2016 (beginning of 4CMenB vaccination) and February 2021 (date of freezing). For the analysis, cases were people with ≥1 gonorrhea infection since July 2016, and controls were people with ≥1 syphilis, chlamydia, or anal human papillomavirus infection since July 2016. Logistic regression was used to provide the estimate of 4CMenB VE against gonorrhea. RESULTS: Included people living with HIV were 1051 (103 cases, 948 controls); 349 of 1051 (33%) received 2 doses of 4CMenB vaccination. The median follow-up was 3.8 years (2.1-4.3 years). The unadjusted estimate for VE against gonorrhea was 42% (95% confidence interval, 6%-64%; P = 0.027). Logistic regression showed that VE against gonorrhea remained significant (44%; 95% confidence interval, 9%-65%; P = 0.020) after adjusting for some factors that might have a potential influence on VE or those with significant unbalanced distributions between cases and controls at univariable analysis. CONCLUSIONS: 4CMenB vaccination is associated with a lower risk of gonorrhea in the setting of men who have sex with men living with HIV with a previous sexually transmitted infection.

High-dose anakinra in addition to standard of care including corticosteroids in patients with severe COVID-19 treated with non-invasive ventilation.

Management of COVID-19 patients experiencing persisting respiratory failure despite corticosteroids remains challenging. Data on high-dose intravenous anakinra (HD-ANK) in this context are lacking. We aimed to investigate the impact of HD-ANK on mortality in COVID-19 patients progressing to non-invasive ventilation (NIV) while receiving corticosteroids. We retrospectively analyzed the impact of HD-ANK on 28-day mortality in individuals hospitalized with COVID-19 necessitating NIV after corticosteroid initiation. A total of 256 patients were identified: 146 received standard-of-care only (SOC), and 110 received HD-ANK+SOC. The groups were well-balanced at baseline. In-hospital mortality at 28 days did not differ between the two groups. HD-ANK is not beneficial in patients with severe COVID-19 deteriorating despite corticosteroids.

Risk of mortality in people with chronic liver diseases hospitalized for Coronavirus disease of 2019 (COVID-19) in a tertiary hospital in Lombardy, Italy.

The impact of severe acute respiratory syndrome-coronavirus-2 (SARS-CoV-2) infection on patients with pre-existing chronic liver diseases (CLD) remains elusive. The aim of this study was to investigate the in-hospital mortality in patients hospitalized for Coronavirus disease of 2019 (COVID-19) with CLD (CLD group) compared to those without CLD (non-CLD group). We performed a retrospective cohort study including patients with confirmed SARS-CoV-2 infection, hospitalized at San Raffaele Hospital (Milan), stratified according to the presence or absence of CLD. A propensity score was estimated and used to match the two groups by age, gender, body mass index, type 2 diabetes mellitus, and hypertension. Predictors of mortality were assessed using univariate and multivariate logistic regression model. Among 1210 patients with COVID-19, 41 (3.4%) were included in the CLD group and 1169 (96.6%) in the non-CLD group. Using a propensity score, we matched 41 patients in the CLD group with 123 in the non-CLD group. At admission, patients in the CLD group had worse liver function, lower platelets count, and lower c-reactive protein levels. By multivariate analysis, the CLD group showed a higher risk of death: OR 4.04 (95% CI 1.29-12.70; p= 0.017). Our study showed that COVID-19 with chronic liver diseases has a higher risk of mortality during hospitalization.

No need to modify treatment within the first month after rapid start of a tailored antiretroviral therapy: the TWODAY Study.

The aim of the TWODAY Study was to investigate the frequency of early treatment change after rapid start of a tailored ART regimen (a 2-drug regimen - 2DR, when clinically feasible or a 3-drug regimen - 3DR, otherwise). TWODAY was an open-label, prospective, proof-of-concept, single center study. ART-naïve patients started their first-line regimen within a few days from the first laboratory testing with a 2DR of dolutegravir (DTG) and lamivudine (3TC) if CD4+ count >200 cells/mL, HIVRNA <500,000 copies/mL, no transmitted drug resistance to DTG or 3TC and HBsAg undetectable; otherwise, ART was started with a 3DR. The primary endpoint was the proportion of patients who needed to change ART within four week from start, for any reason. Thirty-two patients were enrolled; 19 (59.3%) were deemed eligible for a 2DR. Median time from laboratory testing to ART start was 5 days (5; 5). No regimen modification occurred within one month. In conclusion, no regimen modification was needed within the first month of treatment. Starting a 2DR within a few days after HIV diagnosis was feasible, relying upon complete results of the needed laboratory tests (including resistance testing). A 2DR can be safely proposed provided full laboratory tests are readily available.

Failure of Digital Device Performance in Monitoring Physical Exercise in a Pilot Study in Sedentary Persons with HIV.

Digital devices have gained popularity in the last 10 years as a tool for exercise prescription, the monitoring of daily physical activity, and nutrition for the management of a health-related parameter. Therefore, the aim of this study was to assess the effectiveness of the use of digital devices to monitor exercise data in sedentary persons with HIV who exercise following an individualized activity pacing (AP) protocol on cardiorespiratory fitness body composition, blood lipid profile, and psychological parameters. Twenty-four PLWH were enrolled in an 18-week randomized, open-label, pilot AP exercise protocol. All participants were monitored by a Health Band connected to a mobile app that transmitted the data to a server. At week 3, they were randomized either in an experimental group (EG), in which an open device configuration enabled them to receive training data feedback (n = 12), or continued with no data feedback (control group, n = 12). The primary endpoint was improvement from the baseline of 15% of steady-state oxygen consumption (V˙O2) during a 6-min walking test. Technical issues occurred when pairing the health band with the app, which prevented EG participants from regularly receiving data feedback, and with data transmission to the server, which enabled only 40% monitoring of the total training days. Consequently, the study outcomes could not be compared between the two groups, and participants also lost confidence in the study. However, 19 out of 24 participants completed the AP program. Overall, only 6 (32%) improved steady-state V˙O2, with no significant changes at W18 from the baseline. Significant reductions were observed of BMI (p = 0.040), hip circumference (p = 0.027), and total-(p = 0.049) and HDL-cholesterol (p = 0.045). The failure of digital device performance substantially affected study procedures, monitoring, and participants' engagement, and likely limited the potential benefits of the AP exercise program.

The Life Project of People with Autism and Intellectual Disability: Investigating Personal Preferences and Values to Enhance Self-Determination.

People with autism and intellectual disabilities, much like individuals with typical development, share a fundamental right and aspiration to realise their own life projects. However, this natural pursuit is uniquely challenging for individuals with autism and intellectual disabilities due to their communication and adaptive hurdles. This growing need has prompted the development of a specific procedure for crafting life projects geared toward enhancing their quality of life. In the present work, we will describe the six key steps and the corresponding assessment, support, and verification tools essential for establishing and actualising the life project for individuals with disabilities, as conceptualised by the Italian Society of Neurodevelopmental Disorders (SIDIN). We will start by delineating diverse preference and value assessment procedures, showcasing an array of tools tailored to accommodate the distinct characteristics of adaptive and communicative functioning in individuals with disabilities. Following this, we will provide a succinct overview of support needs assessment tools. Subsequently, we will introduce the Ecological Life Balance, which serves as an integrative tool for harmonising various assessment systems. We will propose methods for defining existential goals that prioritise quality of life and suggest strategies for implementing support plans. Lastly, we will delve into the methodologies for monitoring and verifying outcomes in the final section.

Pulmonary Vascular Thrombosis in COVID-19 Pneumonia.

OBJECTIVES: During severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection, dramatic endothelial cell damage with pulmonary microvascular thrombosis have been was hypothesized to occur. The aim was to assess whether pulmonary vascular thrombosis (PVT) is due to recurrent thromboembolism from peripheral deep vein thrombosis or to local inflammatory endothelial damage, with a superimposed thrombotic late complication. DESIGN: Observational study. SETTING: Medical and intensive care unit wards of a teaching hospital. PARTICIPANTS: The authors report a subset of patients included in a prospective institutional study (CovidBiob study) with clinical suspicion of pulmonary vascular thromboembolism. INTERVENTIONS: Computed tomography pulmonary angiography and evaluation of laboratory markers and coagulation profile. MEASUREMENTS AND MAIN RESULTS: Twenty-eight of 55 (50.9%) patients showed PVT, with a median time interval from symptom onset of 17.5 days. Simultaneous multiple PVTs were identified in 22 patients, with bilateral involvement in 16, mostly affecting segmental/subsegmental pulmonary artery branches (67.8% and 96.4%). Patients with PVT had significantly higher ground glass opacity areas (31.7% [22.9-41] v 17.8% [10.8-22.1], p < 0.001) compared with those without PVT. Remarkably, in all 28 patients, ground glass opacities areas and PVT had an almost perfect spatial overlap. D-dimer level at hospital admission was predictive of PVT. CONCLUSIONS: The findings identified a specific radiologic pattern of coronavirus disease 2019 (COVID-19) pneumonia with a unique spatial distribution of PVT overlapping areas of ground-glass opacities. These findings supported the hypothesis of a pathogenetic relationship between COVID-19 lung inflammation and PVT and challenged the previous definition of pulmonary embolism associated with COVID-19 pneumonia.

Infections after Allogenic Transplant with Post-Transplant Cyclophosphamide: Impact of Donor HLA Matching.

Incidence and outcome of infections after allogeneic hematopoietic stem cell transplantation (HSCT) with post-transplant cyclophosphamide (PT-Cy) as graft-versus-host disease (GVHD) prophylaxis are largely unknown. Study aims were to estimate the incidence of pre-engraftment bloodstream infections (PE-BSIs) and viral infections (VIs; cytomegalovirus [CMV], adenovirus [ADV], human herpes virus 6 [HHV6], and BK-polyomavirus hemorrhagic-cystitis [BKPyV-HC]), their predictive factors, and infection-related mortality (IRM) after HSCT with PT-Cy. We analyzed 235 patients: 62%, 21%, and 17% received haploidentical (haplo), matched-unrelated donor (MUD), and matched-related donor, respectively. Overall, 72 patients had 77 PE-BSI episodes at a median time of 13 days after HSCT: cumulative incidence function (CIF) at 28 days was 32%, without differences among donor types (P = .988). By multivariate analysis, CIF of PE-BSI was higher in patients with severe neutropenia before HSCT (adjusted hazard ratio [AHR] = 2.90) and in multidrug-resistant Gram-negative bacteria rectal carriers (AHR = 2.68). IRM at 30 days was 5%, without differences by donor type (P = .106). Overall, 208 patients experienced ≥1 VIs (first occurrence among CMV, HHV6, ADV, BKPyV-HC) at a median time of 20 days after HSCT: CIF at 90 days was 91%, significantly higher in MUD and haplo (P = .0089). By multivariate analysis, also acute GVHD grade ≥2 (AHR = 1.32) and host/donor CMV-serology mismatch (positive/positive versus negative/negative: AHR = 2.95, positive/negative versus negative/negative: AHR = 2.41, negative/positive versus negative/negative: AHR = 2.35) affected VIs occurrence. IRM at 180 days was 8%, without differences among donor types (P = .106). In conclusion, study results did not show a significant impact of donor type on PE-BSI incidence; conversely, MUD and haploidentical transplants retained a higher occurrence of VIs in the early phase after HSCT.

Early predictors of clinical outcomes of COVID-19 outbreak in Milan, Italy.

BACKGROUND: National health-system hospitals of Lombardy faced a heavy burden of admissions for acute respiratory distress syndromes associated with coronavirus disease (COVID-19). Data on patients of European origin affected by COVID-19 are limited. METHODS: All consecutive patients aged ≥18 years, coming from North-East of Milan's province and admitted at San Raffaele Hospital with COVID-19, between February 25th and March 24th, were reported, all patients were followed for at least one month. Clinical and radiological features at admission and predictors of clinical outcomes were evaluated. RESULTS: Of the 500 patients admitted to the Emergency Unit, 410 patients were hospitalized and analyzed: median age was 65 (IQR 56-75) years, and the majority of patients were males (72.9%). Median (IQR) days from COVID-19 symptoms onset was 8 (5-11) days. At hospital admission, fever (≥ 37.5 °C) was present in 67.5% of patients. Median oxygen saturation (SpO2) was 93% (range 60-99), with median PaO2/FiO2 ratio, 267 (IQR 184-314). Median Radiographic Assessment of Lung Edema (RALE) score was 9 (IQR 4-16). More than half of the patients (56.3%) had comorbidities, with hypertension, coronary heart disease, diabetes and chronic kidney failure being the most common. The probability of overall survival at day 28 was 66%. Multivariable analysis showed older age, coronary artery disease, cancer, low lymphocyte count and high RALE score as factors independently associated with an increased risk of mortality. CONCLUSION: In a large cohort of COVID-19 patients of European origin, main risk factors for mortality were older age, comorbidities, low lymphocyte count and high RALE.

HIV-DNA undetectability during chronic HIV infection: frequency and predictive factors.

BACKGROUND: HIV-DNA is a marker of HIV reservoirs. Objectives of the study were to determine prevalence of HIV-DNA < 100 copies/106 PBMCs in blood and to identify factors associated with this in a cohort of HIV-1-infected subjects treated with ART and with undetectable viral load (VL). METHODS: This was a cross-sectional study on chronic HIV-1-infected people living with HIV (PLWH) followed up at the Department of Infectious Diseases of San Raffaele Scientific Institute on current ART without change for 12 months, with available pre-ART HIV-RNA and with undetectable VL for ≥12 months. HIV-DNA was amplified and quantified by real-time PCR (ABI Prism 7900); limit of detectability was 100 copies/106 PBMCs. Logistic regression was used to identify predictive factors for HIV-DNA < 100 copies/106 PBMCs. RESULTS: Four hundred and sixty-eight PLWH were considered in the analyses, 119 (25%) with HIV-DNA < 100 copies/106 PBMCs. At multivariate analysis, we found that PLWH with lower zenith HIV-RNA, higher nadir CD4 and a shorter time between HIV diagnosis and ART start were more likely to have HIV-DNA < 100 copies/106 PBMCs, after adjustment for age, gender, calendar year of ART start, type of current ART regimen, percentage time spent with undetectable VL since ART start, current CD4 and CD4/CD8 ratio. CONCLUSIONS: In our chronic PLWH on virological suppression for 4 years, the prevalence of HIV-DNA < 100 copies/106 PBMCs was found to be 25%. Lower zenith HIV-RNA, shorter time between HIV diagnosis and starting ART and higher CD4 nadir were independently associated with low HIV-DNA.

Dynamics of HIV-1 POL antibodies after ART in chronic HIV-1 infection.

The aim of this retrospective study was to evaluate Western Blot (WB) antibody response against HIV-1 Pol proteins in people on ≥12 months of Antiretroviral Therapy (ART) and factors associated with a negative HIV-1 Pol response or with its seroreversion from positive to negative. Multivariate logistic regression models were performed to assess factors associated with a negative HIV-1 Pol or with HIV-1 Pol seroreversion. A negative HIV-1 Pol was found in 88 (16.6%) of the 530 individuals evaluated. At multivariate analysis, a negative Pol result was associated with an early ART start [adjusted odds ratio (AOR) per 3-months longer = 0.95, 95% CI=0.90-0.99] and a greater CD4+ recovery since ART start [AOR per 100-cells/µL/year higher=1.11, 95%CI=1.01-1.24]. In a subgroup of 140 patients with WB analysis performed both at HIV-1 diagnosis and after a median of 69 months, Pol seroreverted from positive to negative in 22 (15.7%) patients and was associated with a greater CD4+ recovery [AOR per 100-cells/µL/year higher =2.50 (95%CI=1.28-4.87)]. In conclusion, a negative HIV-1 Pol and a seroreversion from positive to negative were observed in more than 15% of subjects included and were associated with a better immunological profile, suggesting a lower viral exposure to the immune system over time.