Search

• Risk of in-hospital COVID-19 mortality in people living with HIV (PLWH) and the general population was assessed. • PLWH <65 years with clusters of differentiation (CD)4 ≤350 cells/mm3 are at higher risk of worse COVID-19 outcomes. • This risk is further increased in PLWH <65 years with CD4 count ≤200 cells/mm3. • The evidence was insufficient for PLWH aged ≥65 years. • PLWH with low CD4 counts should be prioritized for preventive interventions. We aimed to study whether people living with HIV (PLWH) are at higher risk of in-hospital COVID-19 mortality compared to the general population (GenPop). This was a retrospective study in 19 Italian centers (February 2020 to November 2022) including hospitalized PLWH and GenPop with SARS-CoV-2 infection. The main outcome was in-hospital mortality. Competing risk analyses by Fine-Gray regression model were used to estimate the association between in-hospital mortality and HIV status/age. A total of 7399 patients with COVID-19 were included, 239 (3.2%) PLWH, and 7160 (96.8%) GenPop. By day 40, in-hospital death occurred in 1283/7160 (17.9%) among GenPop and 34/239 (14.2%) among PLWH. After adjusting for potential confounders, compared to GenPop <65 years, a significantly higher risk of death was observed for GenPop ≥65 (adjusted subdistribution hazard ratio [aSHR] 1.79 [95% CI 1.39-2.31]), PLWH ≥65 (aSHR 2.16 [95% CI 1.15-4.04]), PLWH <65 with CD4 ≤200 (aSHR 9.69 [95% CI 5.50-17.07]) and PLWH <65 with CD4 201-350 (aSHR 4.37 [95% CI 1.79-10.63]), whereas no evidence for a difference for PLWH <65 with CD4 >350 (aSHR 1.11 [95% CI 0.41-2.99]). In PLWH aged <65 years a CD4 ≤350 rather than HIV itself seems the driver for the observed higher risk of in-hospital mortality. We cannot however rule out that HIV infection per se is the risk factor in those aged ≥65 years. [ABSTRACT FROM AUTHOR]

The article offers information on the management of enzyme de-induction in a woman with HIV who was switched from a nevirapine- to bictegravir-based antiretroviral regimen. Topics include the challenges of methadone maintenance in HIV patients, drug interactions between antiretroviral medications and methadone, and the importance of monitoring and managing enzyme de-induction during antiretroviral regimen switches.

Background: SARS-CoV-2 viremia has been found to be a potential prognostic factor in patients hospitalized for COVID-19. Objective: We aimed to assess the association between SARS-CoV-2 viremia and mortality in COVID-19 hospitalized patients during different epidemic periods. Methods: A prospective COVID-19 registry was queried to extract all COVID-19 patients with an available SARS-CoV-2 viremia performed at hospital admission between March 2020 and January 2022. SARS-CoV-2 viremia was assessed by means of GeneFinderTM COVID-19 Plus RealAmp Kit assay and SARS-CoV-2 ELITe MGB® Kit using <45 cycle threshold to define positivity. Uni and multivariable logistic regression model were built to assess the association between SARS-CoV-2 positive viremia and death. Results: Four hundred and forty-five out of 2,822 COVID-19 patients had an available SARS-CoV-2 viremia, prevalently males (64.9%) with a median age of 65 years (IQR 55-75). Patients with a positive SARS-CoV-2 viremia (86/445; 19.3%) more frequently presented with a severe or critical disease (67.4% vs 57.1%) when compared to those with a negative SARS-CoV-2 viremia. Deceased subjects (88/445; 19.8%) were older [75 (IQR 68-82) vs 63 (IQR 54-72)] and showed more frequently a detectable SARS-CoV-2 viremia at admission (60.2% vs 22.7%) when compared to survivors. In univariable analysis a positive SARS-CoV-2 viremia was associated with a higher odd of death [OR 5.16 (95% CI 3.15-8.45)] which was confirmed in the multivariable analysis adjusted for age, biological sex and, disease severity [AOR 6.48 (95% CI 4.05-10.45)]. The association between positive SARS-CoV-2 viremia and death was consistent in the period 1 February 2021–31 January 2022 [AOR 5.86 (95% CI 3.43-10.16)] and in subgroup analysis according to disease severity: mild/moderate [AOR 6.45 (95% CI 2.84-15.17)] and severe/critical COVID-19 patients [AOR 6.98 (95% CI 3.68-13.66)]. Conclusions: SARS-CoV-2 viremia resulted associated to COVID-19 mortality and should be considered in the initial assessment of COVID-19 hospitalized patients. [ABSTRACT FROM AUTHOR]

Critically ill COVID-19 patients can develop invasive pulmonary aspergillosis (CAPA). Considering the weaknesses of diagnostic tests/case definitions, as well as the results from autoptic studies, there is a debate on the real burden of aspergillosis in COVID-19 patients. We performed a retrospective observational study on mechanically ventilated critically ill COVID-19 patients in an intensive care unit (ICU). The primary objective was to determine the burden of CAPA by comparing clinical diagnosis (through case definitions/diagnostic algorithms) with autopsy results. Twenty patients out of 168 (11.9%) developed probable CAPA. Seven (35%) were females, and the median age was 66 [IQR 59–72] years. Thirteen CAPA patients (65%) died and, for six, an autopsy was performed providing a proven diagnosis in four cases. Histopathology findings suggest a focal pattern, rather than invasive and diffuse fungal disease, in the context of prominent viral pneumonia. In a cohort of mechanically ventilated patients with probable CAPA, by performing a high rate of complete autopsies, invasive aspergillosis was not always proven. It is still not clear whether aspergillosis is the major driver of mortality in patients with CAPA. [ABSTRACT FROM AUTHOR]

The diagnosis of malaria in returning travellers could be a challenge in non-endemic settings. We aimed to assess the performance of LAMP in comparison with standard conventional diagnostic methods using real-time-polymerase chain reaction (PCR) in case of discordant results. All travellers returning from malaria-endemic areas who presented to our Emergency Department (ED) from January 2017 to December 2020 with signs and symptoms suggestive for malaria were included. Blood microscopy was the reference diagnostic method applied at our laboratory with LAMP implemented as an additional method to aid in malaria diagnosis. PCR was employed only in case of between test's discordant results. Sensitivity and specificity of microscopy compared to LAMP were calculated with the confidence interval of 95%. Four-hundred and eight patients (55.6% male, median age 42 years) were screened for malaria. The diagnosis was confirmed in 49 cases (12%): 44 cases (90%) caused by Plasmodium falciparum. Peripheral blood smear missed to identify three malaria cases, which tested positive with LAMP and PCR. One case of malaria caused by P. malariae in a naive tourist, one case by P. falciparum in a semi-immune pregnant women and one case by P. falciparum in a previously treated semi-immune patient. All the discordant cases were characterized by a very low parasitaemia. Microscopy when compared to LAMP showed a sensitivity of 93.9% (95% confidence interval (CI) 83.1–98.7%) and a specificity of 100% (95% CI 98.9–100%). In our non-endemic setting LAMP was able to identify malaria cases with low-level parasitaemia otherwise missed by blood microscopy. [ABSTRACT FROM AUTHOR]

A study conducted in Milan, Italy, examined the effectiveness of a two-drug regimen of doravirine plus lamivudine in people living with HIV. The study found that out of 22 patients who received this regimen, 7 discontinued it, with 3 discontinuations due to virological failure. The study concluded that this regimen should only be used as a last resort when no other options are available and both drugs are expected to be fully effective. The authors of the report have disclosed their potential conflicts of interest, which is important for readers to consider when interpreting the findings. [Extracted from the article]

Introduction: This paper describes how mortality among hospitalised COVID-19 patients changed during the first three waves of the epidemic in Italy. Methods: This prospective cohort study used the Kaplan-Meier method to analyse the time-dependent probability of death of all of the patients admitted to a COVID-19 referral centre in Milan, Italy, during the three consecutive periods of: 21 February-31 July 2020 (first wave, W1), 1 August 2020–31 January 2021 (second wave, W2), and 1 February-30 April 2021 (third wave, W3). Cox models were used to examine the association between death and the period of admission after adjusting for age, biological sex, the time from symptom onset to admission, disease severity upon admission, obesity, and the comorbidity burden. Results: Of the 2,023 COVID-19 patients admitted to our hospital during the study period, 553 (27.3%) were admitted during W1, 838 (41.5%) during W2, and 632 (31.2%) during W3. The crude mortality rate during W1, W2 and W3 was respectively 21.3%, 23.7% and 15.8%. After adjusting for potential confounders, hospitalisation during W2 or W3 was independently associated with a significantly lower risk of death than hospitalisation during W1 (adjusted hazard ratios [AHRs]: 0.75, 95% confidence interval [CI] 0.59–0.95, and 0.58, 95% CI 0.44–0.77). Among the patients aged >75 years, there was no significant difference in the probability of death during the three waves (AHRs during W2 and W3 vs W1: 0.93, 95% CI 0.65–1.33, and 0.88, 95% CI 0.59–1.32), whereas those presenting with critical disease during W2 and W3 were at significantly lower risk of dying than those admitted during W1 (AHRs 0.61, 95% CI 0.43–0.88, and 0.44, 95% CI 0.28–0.70). Conclusions: Hospitalisation during W2 and W3 was associated with a reduced risk of COVID-19 death in comparison with W1, but there was no difference in survival probability in patients aged >75 years. [ABSTRACT FROM AUTHOR]

Background: To compare differences in the probability of COVID-19-related death between native Italians and immigrants hospitalised with COVID-19.Methods: This retrospective study of prospectively collected data was conducted at the ASST Fatebenefratelli-Sacco Hospital in Milan, Italy, between 21 February and 31 November 2020. Uni- and multivariable Cox proportional hazard models were used to assess the impact of the patients' origin on the probability of COVID-19-related death.Results: The study population consisted of 1,179 COVID-19 patients: 921 Italians (78.1%) and 258 immigrants (21.9%) who came from Latin America (99, 38%), Asia (72, 28%), Africa (50, 19%) and central/eastern Europe (37, 14%). The Italians were significantly older than the immigrants (median age 70 years, interquartile range (IQR) 58-79 vs 51 years, IQR 41-60; p < 0.001), and more frequently had one or more co-morbidities (79.1% vs 53.9%; p < 0.001). Mortality was significantly greater among the Italians than the immigrants as a whole (26.6% vs 12.8%; p < 0.001), and significantly greater among the immigrants from Latin America than among those from Asia, Africa or central/eastern Europe (21% vs 8%, 6% and 8%; p = 0.016). Univariable analysis showed that the risk of COVID-19-related death was lower among the immigrants (hazard ratio [HR] 0.43, 95% confidence interval [CI] 0.30-0.63; p < 0.0001], but the risk of Latin American immigrants did not significantly differ from that of the Italians (HR 0.74, 95% CI 0.47-1.15; p = 0.183). However, after adjusting for potential confounders, multivariable analysis showed that there was no difference in the risk of death between the immigrants and the Italians (adjusted HR [aHR] 1.04, 95% CI 0.70-1.55; p = 0.831), but being of Latin American origin was independently associated with an increased risk of death (aHR 1.95, 95% CI 1.17-3.23; p = 0.010).Conclusions: Mortality was lower among the immigrants hospitalised with COVID-19 than among their Italian counterparts, but this difference disappeared after adjusting for confounders. However, the increased risk of death among immigrants of Latin American origin suggests that COVID-19 information and prevention initiatives need to be strengthened in this sub-population. [ABSTRACT FROM AUTHOR]

Invasive fungal infections (IFIs) can complicate the clinical course of COVID-19 and are associated with a significant increase in mortality, especially in critically ill patients admitted to an intensive care unit (ICU). This narrative review concerns 4099 cases of IFIs in 58,784 COVID-19 patients involved in 168 studies. COVID-19-associated invasive pulmonary aspergillosis (CAPA) is a diagnostic challenge because its non-specific clinical/imaging features and the fact that the proposed clinically diagnostic algorithms do not really apply to COVID-19 patients. Forty-seven observational studies and 41 case reports have described a total of 478 CAPA cases that were mainly diagnosed on the basis of cultured respiratory specimens and/or biomarkers/molecular biology, usually without histopathological confirmation. Candidemia is a widely described secondary infection in critically ill patients undergoing prolonged hospitalisation, and the case reports and observational studies of 401 cases indicate high crude mortality rates of 56.1% and 74.8%, respectively. COVID-19 patients are often characterised by the presence of known risk factors for candidemia such as in-dwelling vascular catheters, mechanical ventilation, and broad-spectrum antibiotics. We also describe 3185 cases of mucormycosis (including 1549 cases of rhino-orbital mucormycosis (48.6%)), for which the main risk factor is a history of poorly controlled diabetes mellitus (>76%). Its diagnosis involves a histopathological examination of tissue biopsies, and its treatment requires anti-fungal therapy combined with aggressive surgical resection/debridement, but crude mortality rates are again high: 50.8% in case reports and 16% in observational studies. The presence of other secondary IFIs usually diagnosed in severely immunocompromised patients show that SARS-CoV-2 is capable of stunning the host immune system: 20 cases of Pneumocystis jirovecii pneumonia, 5 cases of cryptococcosis, 4 cases of histoplasmosis, 1 case of coccidioides infection, 1 case of pulmonary infection due to Fusarium spp., and 1 case of pulmonary infection due to Scedosporium. [ABSTRACT FROM AUTHOR]

Background: We assessed the impact of the coronavirus disease 2019 (COVID-19) pandemic on HIV suppression rates in people living with HIV (PLWH) attending a large Italian HIV clinic. Setting: The HIV outpatient clinic of the Infectious Diseases Department of Luigi Sacco Hospital, Milan, Italy, which serves more than 5000 PLWH per year. Methods: A before and after quasi -experimental study design was used to make a retrospective assessment of the monthly trend of HIV-RNA determinations of ≥50 among the PLWH attending our clinic, with "before" being the period from January 1, 2016 to February 20, 2020, and "after" being the period from February 21, 2020 to December 31, 2020 (the COVID-19 period). Interrupted time series analysis was used to evaluate any changes in the trend. Results: During the study period, 70,349 HIV-RNA viral load determinations were made, and the percentage of HIV-RNA viral load determinations of <50 copies/mL increased from 88.4% in 2016 to 93.2% in 2020 (P < 0.0001). There was a significant monthly trend toward a decrease in the number of HIV-RNA determinations of ≥50 copies/mL before the pandemic (β −0.084; standard error 0.015; P < 0.001), and this did not significantly change after it started (β −0.039, standard error 0.161; P = 0.811). Conclusions: A high prevalence of viral suppression was maintained among the PLWH referring to our clinic, despite the structural barriers raised by the COVID-19 pandemic. The use of simplified methods of delivering care (such as teleconsultations and multiple antiretroviral treatment prescriptions) may have contributed to preserving this continuum. [ABSTRACT FROM AUTHOR]

Background: To assess the impact of syphilis infection on the risk of HIV-RNA elevation in people living with HIV (PLWH) with current HIV-RNA ≤50 copies/mL. Setting: The Italian Cohort Naive Antiretrovirals. Methods: All PLWH (2009-2020) under antiretroviral treatment with at least 2 consecutive HIV-RNA values ≤50 copies/mL before the date of syphilis diagnosis and at least 1 HIV-RNA determination after the syphilis event were enrolled. A control group of PLWH without syphilis was matched for mode of HIV transmission. Outcomes were defined using the first HIV-RNA measure in the time window ranging between -2 and +6 months of the diagnosis/index date. The primary outcome used a single value >200 copies/mL to define HIV-RNA elevation associated with risk of transmission. The association between syphilis infection and the protocol defined outcome was evaluated using logistic regression analysis. Results: Nine hundred twenty-six PLWH with a syphilis event were enrolled and matched with a random sample of 1370 PLWH without syphilis. Eighteen of the 926 (1.9%) with syphilis had ≥1 HIV-RNA >200 copies/mL in the window vs. 29/1370 (2.1%) of the not exposed (P = 0.77). In the multivariable analysis adjusted for age, year of diagnosis/index date, and clinical site, syphilis infection was not associated with the risk of HIV-RNA >200 copies/mL (adjusted odds ratio 0.81; 95% confidence interval 0.43-1.52, P = 0.508). Conclusions: We did not find any evidence for an association between syphilis infection and viral elevation >200 copies/mL. [ABSTRACT FROM AUTHOR]

The TANGO trial demonstrated the efficacy of lamivudine plus dolutegravir in virologically suppressed patients without previous virological failures (VFs). In this dataset from clinical practice investigating the impact of past nucleoside reverse-transcriptase inhibitor resistance on this strategy, the combination of M184V/I plus at least 1 thymidine analog-associated mutation significantly increased the risk of VF. [ABSTRACT FROM AUTHOR]

Background: We aimed to assess the overall cardiovascular and metabolic effect of the switch to three different single tablet regimens (STRs) [tenofovir alafenamide/emtricitabine/rilpivirine (TAF/FTC/RPV), TAF/FTC/elvitegravir/cobi (TAF/FTC/EVG/cobi) and ABC/lamivudine/dolutegravir (ABC/3TC/DTG)] in a cohort of people living with HIV/AIDS (PLWH) under effective ART.Methods: All PLWH aged above 18 years on antiretroviral treatment with an HIV-RNA < 50 cp/mL at the time of the switch to TAF/FTC/RPV, TAF/FTC/EVG/cobi and ABC/3TC/DTG were retrospectively included in the analysis. Framingham risk score modification after 12 months from the switch such as lipid profile and body weight modification were assessed. The change from baseline to 12 months in mean cardiovascular risk and body weight in each of the STR's group were assessed by means of Wilcoxon signed-rank test whereas a mixed regression model was used to assess variation in lipid levels.Results: Five-hundred and sixty PLWH were switched to an STR regimen of whom 170 (30.4%) to TAF/FTC/EVG/cobi, 191 (34.1%) to TAF/FTC/RPV and 199 (35.5%) to ABC/3TC/DTG. No difference in the Framingham cardiovascular risk score was observed after 12 months from the switch in each of the STR's groups. No significant overtime variation in mean total cholesterol levels from baseline to 12 months was observed for PLWH switched to ABC/3TC/DTG [200 (SD 38) mg/dl vs 201 (SD 35) mg/dl; p = 0.610] whereas a significant increment was observed in PLWH switched to TAF/FTC/EVG/cobi [192 (SD 34) mg/dl vs 208 (SD 40) mg/dl; p < 0.0001] and TAF/FTC/RPV [187 (SD 34) mg/dl vs 195 (SD 35) mg/dl; p = 0.027]. In addition, a significant variation in the mean body weight from baseline to 12 months was observed in PLWH switched to TAF/FTC/EVG/cobi [72.2 (SD 13.5) kilograms vs 74.6 (SD 14.3) kilograms; p < 0.0001] and TAF/FTC/RPV [73.4 (SD 11.6) kilograms vs 75.6 (SD 11.8) kilograms; p < 0.0001] whereas no difference was observed in those switched to ABC/3TC/DTG [71.5 (SD 12.8) kilograms vs 72.1 (SD 12.6) kilograms; p = 0.478].Conclusion: No difference in the cardiovascular risk after 1 year from the switch to these STRs were observed. PLWH switched to TAF/FTC/EVG/cobi and TAF/FTC/RPV showed an increase in total cholesterol levels and body weight 12 months after the switch. [ABSTRACT FROM AUTHOR]

Human histoplasmosis is a mycosis caused by two distinct varieties of a dimorphic fungus: Histoplasma capsulatum var. capsulatum and H. capsulatum var. duboisii. In Europe, it is usually imported by migrants and travellers, although there have been some autochthonous cases, especially in Italy; however, most European physicians are unfamiliar with its clinical and pathological picture, particularly among immunocompromised patients without HIV infection. This systematic review of all the cases of histoplasmosis reported in Europe and Israel between 2005 and 2020 identified 728 cases diagnosed in 17 European countries and Israel described in 133 articles. The vast majority were imported (mainly from Central and South America), but there were also seven autochthonous cases (six in Europe and one in Israel). The patients were prevalently males (60.4%), and their ages ranged from 2 to 86 years. The time between leaving an endemic region and the diagnosis of histoplasmosis varied from a few weeks to more than 40 years. Progressive disseminated histoplasmosis was the most frequent clinical picture among people living with HIV infection (89.5%) or a different immunocompromising condition (57.1%), but it was also recorded in 6.2% of immunocompetent patients. Twenty-eight cases were caused by Histoplasma duboisii. Immunocompromised patients without HIV infection had the worst outcomes, with a mortality rate of 32%. [ABSTRACT FROM AUTHOR]

• Rabies is a neglected tropical disease with a significant mortality burden. • Vaccination campaigns in wildlife animals achieved the control of rabies in Europe. • Rabies cases are still reported in Europe as imported cases. • Clinical suspicion is crucial to reach a diagnosis also in atypical manifestations. Rabies is a vaccine preventable zoonotic disease with a significant mortality burden worldwide. Several years of vaccination campaigns in wildlife animals have now achieved the control of rabies in Western Europe through a vaccination belt in front of endemic Eastern European countries. Nevertheless, rabies could be imported both by travellers from areas without an active public control of the disease or by animals coming from areas where the virus circulates in wildlife fauna. The knowledge of the current world epidemiology combined with a high index of clinical suspicion are needed to reach a diagnosis of rabies, especially in case of atypical presentation or without a history of animal exposure. The pre-travel counselling to people visiting highly endemic areas is essential to give information on how to reduce exposure to potential sources of infection and to select those subjects who could benefit from pre-travel vaccination. Rabies is almost invariably fatal, but the prompt administration of a vaccine course combined with anti-rabies immunoglobulins significantly reduces the probability to develop life-threatening consequences. In this review, we give a brief epidemiological and clinical update about rabies in Europe. [Display omitted] [ABSTRACT FROM AUTHOR]

Castiglione D'Adda is one of the municipalities more precociously and severely affected by the Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2) epidemic in Lombardy. With our study we aimed to understand the diffusion of the infection by mass serological screening. We searched for SARS-CoV-2 IgGs in the entire population on a voluntary basis using lateral flow immunochromatographic tests (RICT) on capillary blood (rapid tests). We then performed chemioluminescent serological assays (CLIA) and naso-pharyngeal swabs (NPS) in a randomized representative sample and in each subject with a positive rapid test. Factors associated with RICT IgG positivity were assessed by uni- and multivariate logistic regression models. Out of the 4143 participants, 918 (22·2%) showed RICT IgG positivity. In multivariable analysis, IgG positivity increases with age, with a significant non-linear effect (p = 0·0404). We found 22 positive NPSs out of the 1330 performed. Albeit relevant, the IgG prevalence is lower than expected and suggests that a large part of the population remains susceptible to the infection. The observed differences in prevalence might reflect a different infection susceptibility by age group. A limited persistence of active infections could be found after several weeks after the epidemic peak in the area. [ABSTRACT FROM AUTHOR]

Background: Chagas disease, as a consequence of globalization and immigration, is no more restricted to Central and Latin America. Therefore, congenital transmission represents a growing public health concern in non-endemic countries.Methods: The aim of this study was to assess the prevalence of Trypanosoma cruzi infection in pregnant Latin American (LA) women living outside endemic countries and the rate of congenital transmission. Data were extracted from studies indexed in PubMed, Scopus, Embase, Lilacs and SciELO databases without language restriction. Two investigators independently collected data on study characteristics, diagnosis, prevalence of infection in pregnant women and congenital infection rate. The data were pooled using a random effects model.Results: The search identified 1078 articles of which 29 were eligible regarding prevalence of T. cruzi infection among pregnant women and 1795 articles of which 32 were eligible regarding the congenital transmission rate. The estimated pooled prevalence of T. cruzi infection in LA pregnant women was 4.2% [95% confidence interval (CI): 3.0-5.5]. The prevalence of T. cruzi infection in pregnant women from Bolivia was 15.5% (95% CI: 11.7-19.7) and 0.5% (95% CI: 0.2-0.89) for those coming from all other LA countries. The estimated global rate of congenital transmission was 3.5% (95% CI: 2.5-4.5); excluding poor-quality studies, the rate of congenital transmission was 3.8% (95% CI: 2.4-5.1).Conclusions: Prevalence of Chagas disease among LA pregnant women living outside endemic countries is high, particularly in Bolivian women. The rate of vertical transmission of T. cruzi infection is similar to the rate reported in South and Central American countries. [ABSTRACT FROM AUTHOR]

Background: Syphilis has been associated with an increase in HIV RNA and a temporary decline in CD4 T cell counts in people living with HIV who are not receiving antiretroviral treatment (ART), and may be associated with a transient HIV RNA rebound in those who are receiving ART. Our case is the first to highlight the risk of a multidrug-resistant HIV viral rebound during the course of early syphilis even if antiretroviral drug concentrations are within the therapeutic range.Case Presentation: This 50-year-old HIV-1-positive male patient with concomitant early syphilis presented with an HIV RNA rebound (8908 copies/mL) during a scheduled visit to our clinic. He was receiving a stable ART regimen consisting of darunavir/cobicistat plus dolutegravir, and had a 15-year history of viral suppression. Good short-term drug adherence could be inferred as liquid chromatography tandem mass spectrometry showed that his trough antiretroviral drug concentrations were within the therapeutic range: darunavir 2353 ng/mL (minimum effective concentration > 500 ng/mL) and dolutegravir 986 ng/mL (minimum effective concentration > 100 ng/mL). A plasma RNA genotype resistance test revealed wild-type virus in the integrase region and protease region (PR), but extensive resistance in the reverse transcriptase (RT) region (M41L, E44D, D67N, K70R, M184V, L210W and T215Y). Phylogenetic analysis of next-generation sequences (used to investigate the presence of minor viral variants), the PR and RT sequences from plasma HIV RNA and pro-viral DNA extracted from peripheral blood mononuclear cells during the viral rebound, and a Sanger sequence obtained during a previous virological failure suggested clonal viral expression because the previous PR resistance mutations had been lost or had not been archived in pro-viral DNA.Conclusions: This case shows that early syphilis may cause an HIV RNA rebound in patients under stable virological control with the potential of transmitting an extensively drug-resistant virus. [ABSTRACT FROM AUTHOR]

Chagas disease (CD) is considered to be highly endemic in El Salvador, where its prevalence is estimated to be 1.3–3.7%. Although more than 40,000 migrants from El Salvador are currently living in Europe (particularly in Spain and Italy), there are few data regarding the prevalence of CD in this population. The aim of this study was to evaluate the prevalence of CD among Salvadorans living in Italy. A cross-sectional serological survey of CD among Salvadorans living in the metropolitan area of Milan was carried out between October 2017 and December 2019. The participants' blood samples were tested for Trypanosoma cruzi antibodies using two different serological assays. The collected demographic data included their biological sex, province of origin, the type of housing in their country of origin, and family history of CD. Of the 384 subjects who voluntarily participated in the study, five (1.3%, most coming from La Paz) were positive to both serological assays and therefore conclusively diagnosed as having CD. Five other subjects had discrepant serological results but were not positive to a third assay. Three of the five subjects with a diagnosis of CD completed medical staging, one of whom had chronic disease (digestive and cardiac involvement). The prevalence of CD among Salvadorans living in Milan is similar to that estimated by the WHO in 2010. Although they are often overlooked in CD surveys, Salvadoran migrants should be included in CD control programs in countries in which the disease is not endemic. [ABSTRACT FROM AUTHOR]

We evaluated predictive factors involved in durability and therapeutic failure of atazanavir (ATV)-based antiretroviral regimens with or without ritonavir (r) in real life setting. This retrospective study of HIV-1-positive patients evaluated the factors related to ATV continuance and the time-dependent probability of therapeutic failure (HIV-RNA >200 copies/mL and concomitant discontinuation of ATV). We also investigated the rate of therapeutic failure and the variations in total bilirubin levels from starting unboosted ATV-based regimens. The study involved 1030 patients: 183 treatment-naïve patients (17.8%) started ATV/r (17 subsequently switched to unboosted ATV); 653 (63.4%) switched to ATV/r from previous antiretroviral regimens (121 subsequently switched to unboosted ATV); and 194 (18.8%) switched to unboosted ATV from previous ATV-free regimens. The median ATV follow-up was 28 months (interquartile range 7–56). The risk of ATV discontinuation was significantly lower in patients switched to unboosted ATV from ATV/r (HR 0.45; p < 0.0001). The discontinuation of ATV correlated with female gender (HR 1.26; p = 0.035), use of a zidovudine/didanosine/stavudine containing backbone (HR 1.8; p = 0.004), and a baseline CD4+ cell counts of <200/μL (HR 1.54; p = 0.003), the last of which was also associated with a higher risk of therapeutic failure (HR 2.42; p = 0.001). Total bilirubin levels were significantly lower in the patients switching from ATV/r to unboosted ATV. Unboosted ATV-based therapies are safe and effective options in patients whose immuno-virological conditions are stable, and allow the long-term survival of ATV-containing regimeans. [ABSTRACT FROM AUTHOR]

Pre-exposure prophylaxis (PrEP) is a pivotal intervention among HIV prevention strategies. We aimed to narratively revise the topic of HIV acute infection in the setting of PrEP exposure with a focus on diagnostic options, clinical features, and future PrEP perspectives, with a particular focus on users with high adherence to PrEP. We searched the main databases (PubMed, Embase, and Scopus) with the keywords "PrEP" or "Pre-Exposure Prophylaxis" and "HIV" or "PLWH" and "breakthrough" or "acute infection" or "primary infection". We included all randomized clinical trials and non-experimental studies (both case reports and observational studies) ever published. In the present narrative review, we revise the diagnostic challenges related to HIV diagnosis in the setting of PrEP and the clinical characteristics and symptoms of breakthrough infections. We discuss the management of acute HIV infection during PrEP and the new challenges that arise from the use of long-acting drugs for PrEP. Our review underlines that although extremely rare, HIV seroconversions are still possible during PrEP, even in a context of high adherence. Efforts to promptly identify these events must be included in the PrEP follow-up in order to minimize the chance of overlooked HIV breakthrough infections and thus exposure to suboptimal concentrations of antiretrovirals. [ABSTRACT FROM AUTHOR]

Introduction: Recent studies have highlighted the prognostic value of easily accessible inflammatory markers, neutrophil-to-lymphocyte ratio (NLR), and platelet-to-lymphocyte ratio (PLR) for predicting severe outcomes in patients affected by Coronavirus disease 2019 (COVID-19). Our study validates NLR and PLR cut-off values from a prior cohort at IRCCS Policlinico San Matteo (OSM) of Pavia, Italy, across two new cohorts from different hospitals. This aims to enhance the generalizability of these prognostic indicators. Methods: In this retrospective cohort study, conducted at Milan's Ospedale Luigi Sacco (OLS) and IRCCS Ospedale Maggiore Policlinico (OMP) hospitals, we assess the predictive capacity of NLR and PLR for three main outcomes—non-invasive ventilation (NIV) or continuous positive airway pressure (CPAP) usage, invasive ventilation (IV), and death—in patients with COVID-19 at admission. For each outcome, sensitivity, specificity, positive predictive value (PPV), and negative predictive value (NPV) were computed separately for male and female cohorts. Distinct NLR and PLR cut-off values were used for men (7.00, 7.29, 7.00 for NLR; 239.22, 248.00, 250.39 for PLR) and women (6.36, 7.00, 6.28 for NLR; 233.00, 246.45, 241.54 for PLR), retrieved from the first cohort at OSM. Results: A total of 3599 patients were included in our study, 1842 from OLS and 1757 from OMP. OLS and OMP sensitivity values for both NLR and PLR (NLR: 24–67%, PLR: 40–64%) were inferior to specificity values (NLR: 64–76%, PLR: 55–72%). Additionally, PPVs generally remained lower (< 63%), while NPVs consistently surpassed 68% for PLR and 72% for NLR. Finally, both PLR and NLR exhibited consistently higher NPVs for more severe outcomes (> 82%) compared to NPVs for CPAP/NIV. Conclusions: Consistent findings across diverse patient populations validate the reliability and applicability of NLR and PLR cut-off values. High NPVs emphasize their role in identifying individuals less likely to experience severe outcomes. These markers not only aid in risk stratification but also guide resource allocation in emergencies or limited-resource situations. [ABSTRACT FROM AUTHOR]

Objective Large inter-individual variability in the pharmacokinetics of rilpivirine and cabotegravir has been reported in the first weeks after starting long-acting injectable (LAI) therapy. Here, we assessed the distribution of rilpivirine and cabotegravir trough concentrations in people with HIV (PWH) on long-term LAI treatment. Methods Adult PWH treated with LAI for at least 32 weeks with an assessment of drug plasma trough concentrations were considered. The proportion of rilpivirine and cabotegravir plasma trough concentrations below four-times the protein-adjusted concentrations required for 90% inhibition of viral replication (4×PA-IC90) was estimated. Results Sixty-seven PWH were identified. LAI treatment duration was 216 ± 80 weeks (range 32–320 weeks). Cabotegravir concentrations were associated with lower inter-individual variability compared with rilpivirine (45% versus 84%; P  < 0.05). No differences were found in rilpivirine (160 ± 118 versus 189 ± 81 ng/mL; P  = 0.430) and cabotegravir (1758 ± 807 versus 1969 ± 802 ng/mL; P  = 0.416) trough concentrations in males (n  = 55) versus females (n  = 12). A non-significant trend for lower cabotegravir concentrations was found in PWH with a body mass index >30 kg/m2 (n  = 9) versus non-obese participants (1916 ± 905 versus 1606 ± 576 ng/mL; P  = 0.131). Three out of the 67 PWH had at least one drug concentration <4×PA-IC90: 100% of PWH had undetectable HIV viral load. Conclusions At steady state, optimal systemic exposure of cabotegravir and rilpivirine was found in most PWH; cabotegravir trough concentrations were associated with lower inter-individual variability compared with rilpivirine. The study was not powered to assess the contribution of sex and/or body weight on LAI exposure due to the small number of females and obese PWH included. [ABSTRACT FROM AUTHOR]

• Despite successful antiretroviral therapy, patients with human immunodeficiency virus (HIV) could develop multi-class drug resistance (MDR) • Data about the prevalence of HIV-MDR are scanty and results are unclear • A significant decline in the prevalence of HIV-MDR over between 1998 and 2018 was observed • Nowadays, HIV-MDR still occurs, although at a lower rate • Management of patients infected by MDR viruses is a critical issue in HIV therapy Despite successful antiretroviral therapy (ART), patients infected with human immunodeficiency virus (HIV) can develop multi-class drug resistance (MDR). This retrospective study aimed to explore the prevalence of HIV-1 drug resistance over the past two decades by focusing on HIV-MDR and its predictors. ART-experienced patients with HIV with results from at least one plasma genotypic resistance test (GRT) from 1998 to 2018, from the Antiviral Response Cohort Analysis database, were included in this study. The temporal trend of resistance to any drug class was evaluated by considering all GRTs. Prevalence and predictors of HIV-MDR were analysed by consideration of cumulative GRTs. Among 15 628 isolates from 6802 patients, resistance to at least one drug class decreased sharply from 1998 to 2010 (1998–2001: 78%; 2008–2010: 59%; P <0.001) and then remained relatively constant at approximately 50% from 2011 to 2018, with the proportion of isolates with HIV-MDR also stable (approximately 9%). By evaluating factors associated with cumulative HIV-MDR, the following factors were found to be associated with increased risk of HIV-MDR on multi-variate analysis: male gender; sexual and vertical transmission; number of previous protease inhibitors, nucleoside/nucleotide reverse transcriptase inhibitors (NRTIs) and non-NRTIs; previous exposure to integrase strand transfer inhibitors, enfuvirtide and maraviroc; and co-infection with hepatitis B virus. In contrast, a nadir CD4 cell count ≥200 cells/mm3, starting first-line ART in 2008 or later and co-infection with hepatitis C virus were associated with lower risk of HIV-MDR. In conclusion, this study revealed that HIV-1 drug resistance has been stable since 2011 despite its dramatic decrease over the past two decades. HIV-MDR is still present, although at a lower rate, suggesting the need for continuous surveillance and accurate management of ART-experienced patients with HIV. [ABSTRACT FROM AUTHOR]

To theEditor - We were very interested to read the article by Lapointe et al [[1]] regarding the ability of people with human immunodeficiency virus (HIV) (PWH) to mount an efficient antibody response to coronavirus disease 2019 (COVID-19) vaccine. After 7 months, the PWH had a mean (SD) anti-S IgG titer of 309 (216) BAU/mL, whereas the mean anti-S IgG titers of the HCWs at 4 and 10 months were 1218 (649) and 361 (368) BAU/mL, respectively. Anti-S1 spike protein (anti-S) immunoglobulin (Ig) G antibody titers in people with human immunodeficiency virus (PWH) and healthy healthcare workers (HCWs) over time. [Extracted from the article]

Italy was the first European country hit by the COVID-19 pandemic and has the highest number of recorded COVID-19 deaths in Europe. This prospective cohort study of the correlates of the risk of death in COVID-19 patients was conducted at the Infectious Diseases and Intensive Care units of Luigi Sacco Hospital, Milan, Italy. The clinical characteristics of all the COVID-19 patients hospitalised in the early days of the epidemic (21 February -19 March 2020) were recorded upon admission, and the time-dependent probability of death was evaluated using the Kaplan-Meier method (censored as of 20 April 2020). Cox proportional hazard models were used to assess the factors independently associated with the risk of death. Forty-eight (20.6 %) of the 233 patients followed up for a median of 40 days (interquartile range 33–47) died during the follow-up. Most were males (69.1 %) and their median age was 61 years (IQR 50–72). The time-dependent probability of death was 19.7 % (95 % CI 14.6–24.9 %) 30 days after hospital admission. Age (adjusted hazard ratio [aHR] 2.08, 95 % CI 1.48−2.92 per ten years more) and obesity (aHR 3.04, 95 % CI 1.42−6.49) were independently associated with an increased risk of death, which was also associated with critical disease (aHR 8.26, 95 % CI 1.41−48.29), C-reactive protein levels (aHR 1.17, 95 % CI 1.02−1.35 per 50 mg/L more) and creatinine kinase levels above 185 U/L (aHR 2.58, 95 % CI 1.37−4.87) upon admission. Case-fatality rate of patients hospitalized with COVID-19 in the early days of the Italian epidemic was about 20 %. Our study adds evidence to the notion that older age, obesity and more advanced illness are factors associated to an increased risk of death among patients hospitalized with COVID-19. [ABSTRACT FROM AUTHOR]

The accumulation of drug-resistance mutations on combined antiretroviral regimens (ART) backbone could affect the virological efficacy of the regimen. Our aim was to assess the impact of previous drug resistance to nucleoside reverse transcriptase inhibitors (NRTIs) on the probability of virological failure (VF) in patients, under virological control, who switched to dolutegravir (DTG)+2NRTIs regimens. All HIV-1 positive drug-experienced patients who started a regimen composed by DTG+2NRTIs [abacavir/lamivudine or tenofovir disoproxil fumarate (TDF) or tenofovir alafenamide (TAF)/emtricitabine (FTC)] in the ARCA collaborative group with HIV-RNA <50 cp/mL were included in the analysis. Patients with a previous VF to integrase inhibitors were excluded. The impact of single and combined NRTIs mutations on the probability of VF (defined as 2 consecutive HIV-RNA >50 copies/mL or one HIV-RNA >1000 copies/mL) was assessed by Kaplan Meier curves. A multivariable Cox regression analysis was constructed to assess factors potentially related to VF. Five hundred and eighty-eight patients were included in the analysis with a median time of viral suppression before the switch of 37 months (IQR 12–78), of whom 148 (25.2%) had at least one previous NRTIs resistance mutation. In the multivariable model no association was observed between NRTIs mutations and VF. Conversely, the duration of viral suppression before switch resulted associated with a lower risk of VF (for 1 month increase, adjusted Hazard Ratio 0.98, 95%CI 0.96–0.99; p=0.024). Previous NRTIs mutations appeared to have no impact on the risk of VF in patients switched to DTG+2NRTIs, whereas a longer interval on a controlled viremia decreased significantly the risk of VF. • The switch to DTG+2NRTIs appeared to be effective with 4% (95% CI 1.6–5.5) probability of virological failure at 12 months. • Previous NRTIs resistance does not affect the efficacy of switching to DTG+2NRTIs regimens. • Time of viral suppression before the switch to DTG+2NRTIs correlates with the risk of virological failure. [ABSTRACT FROM AUTHOR]

Background: Results from clinical trials and observational studies suggest that dolutegravir plus lamivudine could be an effective and well-tolerated option for simplification in HIV-1–positive patients. We aimed to assess long-time efficacy and safety in our multicenter cohort. Methods: This was a retrospective study enrolling HIV-1–infected, virologically suppressed patients switching to dolutegravir + lamivudine. We performed survival analysis to evaluate time to virological failure (VF, defined by a single HIV-RNA ≥1000 copies/mL or by 2 consecutive HIV-RNA ≥ 50 copies/mL) and treatment discontinuation (defined as the interruption of either 3TC or dolutegravir), assessing predictors via Cox regression analyses. Results: Seven-hundred eighty-five patients were considered for the analysis: 554 were men (70.6%), with a median age of 52 years (interquartile range 45–58 years). Estimated probabilities of maintaining virological suppression at weeks 96, 144, and 240 were 97.7% (SD ±0.6), 96.9% (SD ±0.8), and 96.4% (SD ±0.9), respectively. A non-B HIV subtype (P = 0.014) and a previous VF (P = 0.037) resulted predictors of VF. We did not observe differences in probability of VF in people living with HIV with an M184V resistance mutation (P = 0.689); however, in a deeper analysis, M184V mutation was a predictor of VF (P = 0.038) in patients with time of virological suppression <88 months. Estimated probabilities of remaining on study regimen at 96, 144, and 240 weeks were 82.9% (SD ±1.4), 79.7% (SD ±1.6) and 74.3% (SD ±2.2), respectively. Conclusions: Our findings show the long-term efficacy and tolerability of dolutegravir plus lamivudine in virologically suppressed patients. [ABSTRACT FROM AUTHOR]

Oral human papillomavirus (HPV) is common among healthy individuals but causes and implications of persistent infections are under evaluation in the pathogenesis of head and neck neoplasms. This was a retrospective study evaluating the prevalence of high-risk (HR), probable HR and low-risk (LR) HPV types in patients reporting signs/symptoms of oral and upper respiratory tract lesions. Individuals attending between 2019 and 2022 a University Hospital in Milan, Italy, with risk factors for HPV (unprotected oral sex and/or previous documentation of HPV infection in oral and upper respiratory tract and/or another anatomical site) were included. Fourteen out of 110 (12.7%) individuals tested positive for HPV DNA. The prevalence of HR-HPV and LR-HPV was 3.6% (4/110) and 9.1% (10/110), respectively. No probable/possible HR-HPV was detected. Specifically, 10/110 (9.1%) were diagnosed with 1 LR-HPV genotype, 3/110 (2.7%) were infected with 1 HR-HPV and 1/110 had 3 concomitant HR-HPV types. HPV 16 (2.7%, 3/110) and 6 (4.5%, 5/110) were the most common HR and LR types, respectively. One patient positive for HPV 16, 33 and 35 was diagnosed with cancer at the base of the tongue. Two individuals among those who tested positive for HPV DNA reported previous HPV vaccination. Our data, in line with observations from previous prevalence studies, support the potential role of HPV in head and neck neoplasms. HPV DNA testing should be performed in patients presenting lesions in oral/respiratory tracts and risk factors for HPV. Improvement in HPV vaccination coverage is warranted. [ABSTRACT FROM AUTHOR]

Background: Studies of the malaria parasites infecting various non-human primates (NHPs) have increased our understanding of the origin, biology and pathogenesis of human Plasmodium parasites.This review considers the major discoveries concerning NHP malaria parasites, highlights their relationships with human malaria and considers the impact that this may have on attempts to eradicate the disease.Results: The first description of NHP malaria parasites dates back to the early 20th century. Subsequently, experimental and fortuitous findings indicating that some NHP malaria parasites can be transmitted to humans have raised concerns about the possible impact of a zoonotic malaria reservoir on efforts to control human malaria.Advances in molecular techniques over the last 15 years have contributed greatly to our knowledge of the existence and geographical distribution of numerous Plasmodium species infecting NHPs, and extended our understanding of their close phylogenetic relationships with human malaria parasites. The clinical application of such techniques has also made it possible to document ongoing spillovers of NHP malaria parasites (Plasmodium knowlesi, P. cynomolgi, P. simium, P. brasilianum) in humans living in or near the forests of Asia and South America, thus confirming that zoonotic malaria can undermine efforts to eradicate human malaria.Conclusions: Increasing molecular research supports the prophetic intuition of the pioneers of modern malariology who saw zoonotic malaria as a potential obstacle to the full success of malaria eradication programmes. It is, therefore, important to continue surveillance and research based on one-health approaches in order to improve our understanding of the complex interactions between NHPs, mosquito vectors and humans during a period of ongoing changes in the climate and the use of land, monitor the evolution of zoonotic malaria, identify the populations most at risk and implement appropriate preventive strategies. [ABSTRACT FROM AUTHOR]

Background: Nevirapine has been used as antiretroviral agent since early '90. Although nevirapine is not currently recommended in initial anti-HIV regimens, its use remains consistent in a certain number of HIV-1-positive subjects. Thus, our aim was to determine clinical and genetic factors involved in the development of severe nevirapine induced liver toxicity.Methods: We retrospectively analyzed all HIV positive patients who were followed at the Infectious Diseases Unit, DIBIC Luigi Sacco, University of Milan from May 2011 to December 2015. All patients treated with nevirapine who underwent a genotyping for the functional variants mapping into ABCB1, CYP2B6, CYP3A4 and CYP3A5 genes were included in the analysis. Severe hepatotoxicity was defined as ACTG grade 3-4 AST/ALT increase during the first three months of nevirapine treatment. The causality assessment between NVP exposure and drug-induced liver injury was performed by using the updated Roussel Uclaf Causality Assessment Methods. Hardy Weinberg equilibrium was tested by χ2 test. A multivariable logistic regression model was constructed using a backward elimination method.Results: Three hundred and sixty-two patients were included in the analysis, of which 8 (2.2%) experienced a severe liver toxicity. We observed no differences between patients with and without liver toxicity as regards gender, ethnicity, age and immune-virological status. A higher prevalence of HCV coinfection (75.0% vs 30.2%; p = .0013) and higher baseline AST (58 IU/L vs 26 IU/L; p = 0.041) and ALT (82 IU/L vs 27 IU/L; p = 0.047) median levels were observed in patients with liver toxicity vs those without toxicity. The genotypes CT/TT at ABCB1 rs1045642 single nucleotide polymorphism (SNP), showed a protective effect for liver toxicity when compared with genotype CC (OR = 0.18, 95%CI 0.04-0.76; p = 0.020) in univariate analysis. In the multivariate model, HCV coinfection was independently associated with higher risk of developing liver toxicity (aOR = 8.00, 95%CI 1.27-50.29; p = 0.027), whereas ABCB1 rs1045642 CT/TT genotypes (aOR = 0.10, 95%CI 0.02-0.47; p = 0.004) was associated with a lower risk.Conclusions: According to our findings HCV coinfection and ABCB1 rs1045642 SNP represent independent determinants of severe liver toxicity related to nevirapine. This genetic evaluation could be included as toxicity assessment in HIV-1-positive subjects treated with nevirapine. [ABSTRACT FROM AUTHOR]

The COVID‐19 pandemic has induced significant impairments, including sleep disturbances. The present study aimed to explore the impact of fear in relation to stress on sleep disorders among Italian adults and older participants in the second phase of the EPICOVID19 web‐based survey (January‐February 2021). Sleep disturbances during the pandemic were evaluated using the Jenkins Sleep Scale, perceived stress through the 10‐item Perceived Stress Scale and fear of contagion and about economic and job situation with four ad hoc items. The strength of the pathways between stress, sleep disturbances and fear was explored using structural equation modelling, hypothesising that stress was related to sleep disturbances and that fear was associated with both stress and sleep problems. Out of 41,473 participants (74.7% women; mean age 49.7 ± 13.1 years), 8.1% reported sleep disturbances and were more frequently women, employed in a work category at risk of infection or unemployed, and showed higher deprivation scores. Considering an a priori hypotheses model defining sleep and stress scores as endogenous variables and fear as an exogenous variable, we found that fear was associated with sleep problems and stress, and stress was associated with sleep problems; almost half of the total impact of fear on sleep quality was mediated by stress. The impact of stress on sleep quality was more evident in the younger age group, among individuals with a lower socioeconomic status and healthcare workers. Fear related to COVID‐19 seem to be associated with sleep disturbances directly and indirectly through stress. [ABSTRACT FROM AUTHOR]

Objectives: We aimed to assess the frequency of ICU-acquired bloodstream infections in coronavirus disease 2019 patients.Design: Retrospective observational study.Setting: The emergency expansion of an ICU from eight general beds to 30 coronavirus disease 2019 beds.Participants: Patients with coronavirus disease 2019 admitted to the ICU of Luigi Sacco Hospital (Milan, Italy) for greater than or equal to 48 hours between February 21, 2020, and April 30, 2020.Interventions: None.Measurements and Main Results: The frequency of bloodstream infections per 1,000 days of ICU stay was calculated in 89 coronavirus disease 2019 patients, and the cumulative probability of bloodstream infection was estimated using death and ICU discharge as competing events. Sixty patients (67.4%) experienced at least one of the 93 recorded episodes of bloodstream infection, a frequency of 87 per 1,000 days of ICU stay (95% CI, 67-112).The patients who experienced a bloodstream infection had a higher Sequential Organ Failure Assessment score upon ICU admission (9.5; interquartile range, 8-12 vs 8, interquartile range, 5-10; p = 0.042), a longer median ICU stay (15 d; interquartile range, 11-23 vs 8, interquartile range, 5-12; p < 0.001), and more frequently required invasive mechanical ventilation (98.3% vs 82.8%; p = 0.013) than those who did not. The median time from ICU admission to the first bloodstream infection episode was 10 days. Gram-positive bacteria accounted for 74 episodes (79.6%), with Enterococcus species being the most prevalent (53 episodes, 55.8%). Thirty-two isolates (27.3%) showed multidrug resistance.Conclusions: Coronavirus disease 2019 seemed to increase the frequency of bloodstream infections (particularly Enterococcus-related bloodstream infection) after ICU admission. This may have been due to enteric involvement in patients with severe coronavirus disease 2019 and/or limitations in controlling the patient-to-patient transmission of infectious agents in extremely challenging circumstances. [ABSTRACT FROM AUTHOR]

Introduction: A higher rate of subtherapeutic psychotropic drug concentrations was recently found in HIV-infected versus HIV-negative patients. In this study, we sought to investigate if this trend could also apply to antiepileptic drugs.Methods: Overall, 700 HIV-infected patients were screened during the first 2 years after the introduction of our outpatient polytherapy management service (Gestione Ambulatoriale Politerapie [GAP]) in the search for subjects with antiepileptic drug trough concentration assessments. The distribution of such concentrations was compared with that in HIV-negative patients monitored over the same period.Results: The search identified 97 HIV-infected patients concomitantly receiving antiretroviral and antiepileptic drugs, for a total of 310 drug measurements. Overall, 30%, 64% and 6%, versus 28%, 65% and 7%, of the antiepileptic concentrations measured in HIV-infected versus HIV-negative patients (1090 patients, for a total of 3488 antiepileptic concentrations measured) were below, within, or above the therapeutic targets, respectively. The antiepileptic drug valproate was associated with the highest risk of subtherapeutic drug concentrations, with 57% and 46% of determinations below the therapeutic range in HIV-positive and HIV-negative patients, respectively. Remarkably, the concentrations of valproate were significantly lower in HIV-infected versus HIV-negative patients (47.9 ± 21.2 versus 53.9 ± 21.6 mg/L; p < 0.05).Conclusion: In our retrospective study, most HIV-infected patients had antiepileptic drug concentrations falling within the therapeutic targets, with the exception of valproate, which was associated with a higher rate of subtherapeutic concentrations compared with other antiepileptic drugs. [ABSTRACT FROM AUTHOR]

Introduction Since antiretroviral therapy must be taken lifelong, persistence and safety have become the goals to achieve. Protease inhibitors, in particular atazanavir (ATV) with or without ritonavir (r), represent a highly prescribed class in real life long-term treatment. Methods We conducted a retrospective cohort study in HIV-1-positive patients who were followed at the Infectious Diseases Unit, DIBIC Luigi Sacco, University of Milan. Data regarding viral load, CD4 lymphocytes and the mean blood chemistry parameters were collected at baseline, first, third, sixth months from the beginning of therapy and then every six months. Factors related to persistence of therapy with ATV and time-dependent probability to reach a CD4 cells count >500 cells/µL were evaluated with Kaplan-Meier curve and Cox model. Results A total of 1030 patients were evaluated: 183 received therapy with ATV/r as naïve, 653 switched to ATV/r as a second or following line and 194 switched to unboosted ATV from previous ATV-free regimens. A total of 138 patients shifted to unboosted ATV from a previous ATV/r regimen (17 from naïve ATV/r and 121 from experienced ATV/r). The median duration of therapy was 38 months (95% CI 29-73) in ATV/r naïve patients, 36 months (95% CI 23-53) in unboosted ATV group and 35 months (95% CI 31-43) in patients switched to ATV/r. We observed no significant difference in the persistence of the three regimens (p=0.149). Female (HR=1.317; 95% CI 1.073-1.616 p=0.008) and patients with CD4<200 cells/µL at baseline (HR=1.433 95% CI 1.086-1.892 p=0.011) were at increased risk of regimen interruption, whereas starting therapy with a backbone containing abacavir (HR=0.725; 95% CI 0.533-0.987 p=0.041) resulted protective. In multivariate analysis no significant difference between the three regimens was observed regarding reaching a count of CD4 cells >500 cells/µL. Factors associated to a poor CD4 gain were each extra Log of viral load at baseline (HR=0.915; 95% CI 0.852-0.982 p=0.014) and CD4<200 cells/µL at ATV start (HR=0.197; 95%CI 0.138-0.281 p<0.0001); conversely, females (HR=1.262; 95%CI 1.032-1.543 p=0.023) had a higher probability of CD4 recovery. Conclusions Antiretroviral regimens containing atazanavir with or without ritonavir were durable and well tolerated, an elevated viral load and CD4 <200 cells/µL at baseline resulted related to regimen discontinuation and reduced CD4 recovery. [ABSTRACT FROM AUTHOR]

HCV point of care screening in people tested for SARS-CoV-2 in a social-housing neighbourhood of Milan, Italy Keywords: awareness; COVID-19; diagnosis; elimination strategy; hepatitis C; rapid test EN awareness COVID-19 diagnosis elimination strategy hepatitis C rapid test 251 255 5 01/04/23 20230101 NES 230101 Key points In our study, we assessed the antibody positivity for hepatitis C using point-of-care-testing in subjects undergoing COVID-19 screening in the San Siro social-housing neighbourhood of Milan which is characterized by a multi-ethnical population and low socio-economic status. Milestones to reach hepatitis C virus (HCV) elimination in Italy: from free-of-charge screening to regional roadmaps for an HCV-free nation. [Extracted from the article]

• A mortality gap remains for late presenters, particularly, AIDS presenters, in recent years. • Increased mortality for AIDS presenters was driven by AIDS events in the first year. • Two-year immune recovery is the key for long-term mortality in short-term AIDS survivors. • Late and AIDS presenters still show a higher risk treatment failure. • Urgent public health strategies are needed for emerging unknown HIV infections. Limited data are available on the long-term outcomes in recent years for late HIV diagnosis (LD). All subjects with HIV enrolled in the ICONA cohort in 2009-2022 who started antiretroviral treatment (ART) within 4 months from diagnosis were included and divided into: (i) pre-ART CD4 count ≥350/mm3 without AIDS (non-LD), (ii) pre-ART CD4 count <350/mm3 without AIDS (LD asymptomatic), and (iii) with AIDS events pre-ART (LD-AIDS). The estimated probability and independent risk for mortality (all-cause and cause-specific) and treatment failure were evaluated. Of 6813 participants (2448 non-LD, 3198 LD asymptomatic, and 1167 LD-AIDS), 161 (2.4%) died after ART initiation. At survival analysis, a higher probability of all-cause mortality has been identified for LD than non-LD (P <0.001) and within the former, for LD-AIDS over LD asymptomatic (P <0.001). After adjusting for confounders, LD showed a higher risk of all-cause mortality (vs non-LD adjusted hazard ratio (aHR) 5.51, P <0.001) and, in particular, being an AIDS presenter predicted a greater risk of all-cause (aHR = 4.42, P <0.001), AIDS-related (adjusted subhazard ratio [aSHR] = 16.86, P <0.001), and non-AIDS–related mortality (aSHR = 1.74, P = 0.022) than the rest of the late presenters. Among the short-term survivors in the LD-AIDS group, the long-term mortality was mediated by the lack of immune recovery at 2 years. Finally, LD compared with non-LD and, particularly, among the former, LD-AIDS over LD asymptomatic showed a greater risk of treatment failure. In recent years, LD subjects, particularly, AIDS presenters, remained at a higher risk of poorer outcomes. Public health strategies for early HIV diagnosis are urgently needed to constrain the mortality gap. [ABSTRACT FROM AUTHOR]