Background
Managing SARS‐CoV‐2 infection in frail and immunosuppressed patients still represents an open challenge, but, starting from the phase 3 PROVENT study, prophylaxis with ...tixagevimab‐cilgavimab has improved the approach in this category of patients, guaranteeing a better outcome and inferior mortality. Real‐life data in a heterogeneous cohort are few.
Methods
The aim of this study is to evaluate the benefit of prophylaxis with tixagevimab‐cilgavimab in a cohort of 202 patients affected by different hematological diseases (lymphoproliferative, myeloproliferative, autoimmune, patients recently receiving a bone marrow transplant), active (with ongoing treatment), or in watch‐and‐wait strategy, followed in our center, during a median follow‐up of 249 (45‐325) days.
Results
An incidence of 44 breakthrough infections (21.8%) is reported, with no treatment‐related adverse effects. Age ≥70 years, ongoing treatment (above all with monoclonal antibodies), baseline lymphoproliferative disorders, and prior virus exposure are identified as risk factors related to subsequent infection (p < 0.05). Moreover, the incidence is higher in low/nonresponse to prior vaccination (p = .002). Patients treated with tixagevimab‐cilgavimab had a mild course of the infection and a reduction of the duration compared with preprophylaxis infection (11 vs. 15 days, p < .001). The concurrent treatment with anti‐CD20 monoclonal antibodies and B–non‐Hodgkin lymphoma still confers a higher duration of infection despite prophylaxis. No deaths attributable to the infection occurred.
Conclusion
Prophylaxis treatment seems to be a valid and safe strategy, although not preventing breakthrough infection, but the severe complications associated with the infection and the possible delays in administering lifesaving therapies from long positivity.
The use of tixagevimab‐cilgavimab improved the management of immunocompromised patients with a high risk of severe SARS‐CoV‐2 disease. In a real‐world setting, it confirmed its role not only in preventing the occurrence of breakthrough infection, but also, above all, avoiding the severe complications associated and reducing the total days of positivity.
Despite the development of anti-COVID-19 messenger RNA vaccines, several immunocompromised patients (above all affected by hematological disorders) were unable to produce anti-SARS-CoV-2 spike ...antibodies in response to vaccination. In this context, preexposure prophylaxis with tixagevimab-cilgavimab (TIX-CIL), approved in 2022 by FSA and EMA, has resulted in an alternative strategy based on the promising results of the phase III PROVENT study.
This retrospective observational report aims to collect the clinical data of 202 patients affected by hematological diseases and treated in a single center with prophylactic therapy with TIX-CIL, evaluating the incidence of breakthrough infections and, in infected patients, the duration, the severity (potential reduction of severe forms) and the outcome.
At the end of the observation period, 44 (21.8%) patients experienced breakthrough infection after TIX-CIL prophylaxis, with a median time of occurrence of 76 days. Most of the breakthrough infections (95%) occurred in patients affected by lymphoproliferative disorders. Regarding treatment, ongoing therapy (P<0.001), above all with monoclonal antibodies (MoAb) targeting lymphocytes (P=0.001), was related to a higher frequency. Elderly patients (>70 years) reported a higher incidence (P=0.035). The median duration of infection was 11 (5–50) days, with an asymptomatic course/mild symptom in 30 (68.2%). Comparing the different duration of infection pre- with post-prophylaxis, whole days were significantly fewer after TIX-CIL therapy, with a median of 11 days (in 44 patients) vs. 15 days (in 60 patients) (P<0.001). The occurrence of breakthrough infection (P<0.05) was associated with 70 years of age and older, with an adjusted odds ratio (AOR) of 2.3, 95% confidence intervals (CI): 1.1 to 4.8, with prior SARS-CoV-2 infection (AOR 2.6, 95% CI: 1.2-5.4), and with treatment with any MoAb (AOR 2.8, 95% CI: 1.3-6). Conversely, the baseline non-lymphoid hematological disease appears as a protective condition compared to the higher risk in the lymphoid disorder (AOR 0.2, 95% CI: <0.1-0.9).
TIX-CIL is a valuable and safe prophylaxis therapy that can allow passive immunization and warrant long-term protection from severe SARS-CoV-2. Patients treated with MoAb confirmed the persistently higher risk and the difficulty in completing a rapid virus clearance due to impaired B-cell immune system.
...civic utilities tend to leverage actual popular support around causes, attaching increased political capital to them, often very quickly. ...they are well positioned to develop strategies that are ...contemporary, inherently combining online and offline tactics. Brazilian civil society succeeded in securing emergency basic income in part because many of the groups involved had already met through civic spaces such as Pacto pela Democracia, where coauthor Manoela Miklos is a founding member. Since 2015, this network has assembled Brazilian civil society organizations to defend, celebrate, and deepen democratic practice in Brazil. FUNDING CIVIC INFRASTRUCTURE An efficient civil society is one that relies upon a true division of labor among organizations. ...social impact-driven organizations function better when they focus on one of the three functions and serve as facilities, utilities, or spaces.
Invasive fungal infections (IFIs) are a leading cause of morbidity and attributable mortality in oncohematologic patients. Timely diagnosis is essential but challenging. Herein we retrospectively ...describe 221 cases of antifungal treatments (AFT) administered in a monocentric real-life cohort of hematological malignancies. Between January 2010 and July 2017, 196 oncohematologic patients were treated with AFT at our Hematology Department. Diagnosis of IFIs was carried out according to EORTC/MSG-2008 guidelines.The most represented disease was acute myeloid leukemia (104 patients). Median age was 61 years; at fever onset 177 (80%) patients had a neutrophil count<0.5x109/L. Twenty-nine (13%) patients were receiving antifungal prophylaxis (26 posaconazole, 2 fluconazole, 1 itraconazole). The incidence of AFT was 13%. Serum galactomannan antigen (GM) was positive in 20% of the tested cases, while 85% of the patients had a CT scan suggestive for IFI. Twenty-one percent of these cases had a GM positive. Sixty-five out of 196 patients (33%) showed positive culture results, in particular Candida spp. were identified in 45 isolates, while Aspergillus spp. in 16 cases. Fourteen patients presented multiple positivity. Twenty-two (10%) cases were classified as proven IFIs, 61 (28%) as probable and 81 (37%) as possible, but 57 (26%) cases could not be classified. Fifty-nine percent of the patients received single agent AFT, 37% sequential AFT, 8% a combination regimen. Liposomal-amphotericin-B was the most used AFT. IFIs attributable mortality was 20%. This epidemiologic survey underlined a persistent significant use of AFT and a high mortality rate of IFIs. We suggest that further powerful diagnostic approaches should be investigated to improve the diagnostic accuracy and potential therapeutic implication.
•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.
Tyrosine kinase inhibitors (TKIs) have dramatically changed the prognosis of patients with chronic myeloid leukemia (CML). They have a distinct toxicity profile that includes glycometabolic ...alterations: i.e. diabetes mellitus (DM), impaired fasting glucose (IFG), and the metabolic syndrome (MS). The aim of this study was to evaluate the prevalence of these alterations in a cohort of CML-chronic phase patients treated with imatinib, dasatinib or nilotinib.
The study involved 168 consecutive CML-chronic phase patients with no history of DM/IFG or MS. Anthropometric and metabolic parameters were assessed, and DM/IFG and MS were diagnosed based on the criteria of the American Diabetes Association and the National Cholesterol Education Program-Adult Treatment Panel III, respectively.
The nilotinib group had significantly higher levels of fasting plasma glucose, insulin, C-peptide, insulin resistance, and total and LDL cholesterol than the imatinib and dasatinib groups. DM/IFG were identified in 25% of the imatinib- and dasatinib-treated patients, and 33% of those in the nilotinib cohort (p = 0.39 vs imatinib and p = 0.69 vs dasatinib). A diagnosis of MS was made in 42.4% of the imatinib-treated patients, 37.5% of the dasatinib-treated patients, and 36.1% of the nilotinib-treated patients (p = 0.46 vs imatinib and p = 0.34 vs dasatinib).
Treatment with nilotinib does not seem to induce DM/IFG or the MS to a significantly higher extent than imatinib or dasatinib, though it causes a worse glycometabolic profile. These findings suggest the need for a close monitoring of glucose and lipid metabolism and a multidisciplinary approach in patients treated with nilotinib.
The study aim was to evaluate the impact on Liver and Kidney toxicity of the single tablet regimen Elvitegravir/Cobicistat/Emtricitabine/Tenofovir Disoproxil Fumarate (EVG/COBI/FTC/TDF) on ...Antiretroviral Therapy (ART) experienced or naïve patients.
Patients initiating EVG/COBI/FTC/TDF were enrolled in the SCOLTA project, a multicenter observational study reporting grade 3-4 Adverse Events in subjects beginning new antiretroviral drug regimens. In this analysis, patients were evaluated at T0 (baseline), T1 (six months) and at T2 (twelve months).
A total of 329 patients were enrolled, and 280 (85.1%) of these had at least one follow-up visit. Median observation time was 11 months (IQR 7.0-15.5). Two hundred and two patients (72.1%) were ART experienced and 78 (27.9%) ART naive. Prevalence of HCV-co-infection was 21.4%. At T1, we observed a significant decline in estimated glomerular filtration rate (eGFR), both in experienced and naive patients (mean change from T0-7.5 ± 12.8 ml/min, -15.5 ± 17.8 ml/min, respectively, p = 0.0005), which was confirmed at T2 (mean change from T0-8.2 ± 15.8 ml/min, -17.6 ± 19.4 ml/min, respectively, p = 0.001). Regarding aspartate aminotransferase (AST) and alanine transaminase (ALT) grade 1-2 modifications, no significant differences were observed between experienced and naïve subjects, but an increased prevalence of abnormal liver function test was observed in patients with chronic HCV infection (p<0.001).
A significant decline in eGFR was observed in patients initiating EVG/COBI/FTC/TDF in the first 6 months, with no significant worsening occurring at 12 months vs. 6 months of therapy. Patients with chronic HCV infection were at higher risk to develop abnormal liver tests.
Primary study outcome was absence of treatment failure (virological failure, VF, or treatment interruption) per protocol at week 48.
Patients on 3-drug ART with stable HIV-1 RNA <50 copies/mL and ...CCR5-tropic virus were randomized 1:1 to maraviroc with darunavir/ritonavir qd (study arm) or continue current ART (continuation arm).
In June 2015, 115 patients were evaluable for the primary outcome (56 study, 59 continuation arm). The study was discontinued due to excess of VF in the study arm (7 cases, 12.5%, vs 0 in the continuation arm, p = 0.005). The proportion free of treatment failure was 73.2% in the study and 59.3% in the continuation arm. Two participants in the study and 10 in the continuation arm discontinued therapy due to adverse events (p = 0.030). At VF, no emergent drug resistance was detected. Co-receptor tropism switched to non-R5 in one patient. Patients with VF reported lower adherence and had lower plasma drug levels. Femoral bone mineral density was significantly improved in the study arm.
Switching to maraviroc with darunavir/ritonavir qd in virologically suppressed patients was associated with improved tolerability but was virologically inferior to 3-drug therapy.
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