228 research outputs found
A nucleoside-sparing regimen of dolutegravir plus ritonavir-boosted atazanavir in HIV-1-infected patients with virological failure: the DOLATAV study
No full textVincenzo Spagnuolo,1,2 Laura Galli,2 Andrea Poli,2 Alba Bigoloni,2 Luca Fumagalli,2 Nicola Gianotti,2 Silvia Nozza,2 Davide Ferrari,3 Massimo Locatelli,3 Adriano Lazzarin,2 Antonella Castagna1,2 1Vita-Salute San Raffaele University, Faculty of Medicine and Surgery, Milan, Italy; 2Clinic of Infectious Diseases, Istituto di Ricerca e Cura a Carattere Scientifico (IRCCS) San Raffaele Scientific Institute, Milan, Italy; 3Laboratory Medicine Service, IRCCS San Raffaele Hospital, Milan, Italy IntroductionThe increased exposure of dolutegravir (DTG) when given with atazanavir/ritonavir (ATV/r), as well as the acceptable safety profile, may suggest the use of this combination as a two-drug regimen both in virologically suppressed and treatment-failing subjects.1–5 This nucleoside reverse transcriptase inhibitors (NRTIs)-sparing regimen, characterized by a high genetic barrier, may represent an option in patients who have failed previous regimens and developed pharmacoresistance mutations to NRTIs and nonnucleoside reverse transcriptase inhibitors (NNRTIs). However, no data on DTG plus boosted ATV in patients with virological failure are currently available. Therefore, the aim of the DOLATAV study was to investigate the efficacy, safety, and pharmacokinetics of ATV/r 300/100 mg once-daily plus DTG 50 mg once-daily  
Advances in the Treatment of Paraproteinemic Neuropathy
No full textPurpose of review Several advances have been made on the pathogenesis and therapy of neuropathies associated with paraproteinemia (monoclonal gammopathy). It is important for the neurologist to understand the pathogenetic relevance of this association especially when the hematological disease does not require per se any therapy. Recent findings Treatment of the neuropathy in patients with malignant paraproteinemia is mainly addressed by the hematologist while the neurologist is mainly involved in the initial diagnosis and in deciding whether the neuropathy is caused by the disease or by the chemotherapy used for the disease. There is little evidence that the neuropathy is caused by the hematological condition in patients with IgG or IgA monoclonal gammopathy of undetermined significance (MGUS) unless there is an evidence of a reactivity of the paraprotein with nerve or evidence of its presence in the nerve. Patients with a chronic inflammatory demyelinating polyradiculoneuropathy (CIDP)-like presentation should be treated as CIDP while there is no evidence that immune or chemotherapy may be effective in the other patients. In most patients with IgM paraproteinemia, that is usually a MGUS or an indolent Waldenströmâs macroglobulinemia, the neuropathy is induced by an immune reactivity of the paraprotein with nerve and particularly with the myelin-associated glycoprotein. There are now consistent data also from controlled studies that the anti-CD20 monoclonal antibody rituximab may improve the neuropathy in these patients. POEMS syndrome is a severe condition characterized by a disabling neuropathy whose prognosis has improved in the last few years with therapies against the proliferating plasma cell clone or vascular endothelial growth factor including local radiotherapy and chemotherapy followed by autologous stem cell transplantation. Other therapies are also available for patients not eligible or resistant to transplantation, including lenalidomide and possibly thalidomide or bortezomib. Summary Several new therapies are now available for patients with paraproteinemic neuropathy consistently improving the prognosis of these neuropathies. In most instances, however, their efficacy needs to be confirmed in controlled trials
Siltuximab in relapsed/refractory multicentric Castleman disease: Experience of the Italian NPP program
No full textBecause of the rarity of the disease, randomized clinical trials for multicentric Castleman disease (MCD) remain a challenge and, as a consequence, there is no established standard of care. Siltuximab is a chimeric immunoglobulin G1κ monoclonal antibody against human IL-6 which was recently approved by FDA. Eligible patients in Italy were granted early access through a Named Patient Program (NPP). The aim of this observational multicenter retrospective study was to analyze outcomes and toxicity data of relapsed or refractory MCD patients treated with siltuximab in a real life context. All the 9 patients who received siltuximab in Italy under the NPP were enrolled. Median duration of treatment was 285 days (range, 104-1113 days). The global overall response rate was 33.3%. At the time of this analysis, none of the 3 responder patients had subsequently disease relapse: response duration was 20, 23, and 37 months, respectively. Grade 1 to 2 fatigue and pruritus were observed in 2 (22.2%) patients, and weight gain was reported in only 1 patient (grade 1); local edema was reported in 2 patients with a grade 2 presentation. The most common side effect was upper respiratory tract infection reported in 3 (33.3%) patients but in these cases was grades 1 to 2. No patient developed an infusion-related reaction. Our NPP data support siltuximab as single agent in the real-life experience of the treatment of relapse/refractory MCD patients in effectiveness, safety profile, and sustained disease control
How do I manage disseminated Mycobacterium avium complex disease in people with HIV?
No full textBackground: Advanced HIV disease (AHD) is increasing, with late presentation accounting for half of newly diagnosed people with HIV (PWH) in Europe. Mortality in late-presenting PWH remains high, and Mycobacterium avium complex (MAC) disease, among other opportunistic infections, presents several diagnostic and treatment challenges that lead, ultimately, to a poor clinical outcome. Objectives: We aimed to provide guidance on the diagnosis and treatment of disseminated MAC disease (dMACd) in PWH. Sources: We performed a review of original articles, meta-analyses, and systematic reviews retrieved from PubMed. Content: We reviewed and discussed the most challenging steps in the management of PWH with AHD and dMACd: the current epidemiology in the era of effective antiretroviral treatment; clinical presentation and interpretation of symptoms in the context of other opportunistic infections and immune reconstitution; diagnosis, sampling, and timing to reach a definitive diagnosis; prophylaxis, treatment options, and indications for discontinuing MAC treatment; future perspectives; and the role of rifamycins in the treatment of dMACd. Implications: Despite the widespread availability of effective antiretroviral treatment, dMACd still represents a major cause of morbidity and mortality in PWH with AHD. Residual challenges are mainly related to the difficulties and timing required to reach a definitive diagnosis, and the discussion regarding the role of rifamycins in the treatment of dMACd is still open
Recommendations of the Italian society for infectious and tropical diseases (SIMIT) for adult vaccinations
No full textVaccination prevents 2–3 million deaths worldwide every year. Nevertheless, vaccine-preventable diseases (VPDs) still cause a considerable number of deaths especially in subjects belonging to “risk groups.” These are represented by older adults, immunocompromised individuals and all subjects with underlying chronic medical conditions (cardiovascular, pulmonary, renal and liver chronic diseases, diabetes, immunodeficiency disorders). They have a weaker immune system and, if infected, are more likely to develop severe complications of their condition or of the preventable-infectious disease. This document summarizes the recommendations for vaccination of the main Global Institutional Organizations and analyses the risks of comorbidities associated with infectious disease and the benefits of vaccination for each specific group. The document provides a clear, practical and authoritative guide to adult vaccination
Efficacy of elvitegravir/cobicistat/emtricitabine/tenofovir disoproxil fumarate as treatment for primary or recent HIV infection—authors’ response
No full textEstimated Glomerular Filtration Rate Trajectories in HIV-Infected Subjects Treated With Different Ritonavir-Boosted Protease Inhibitors and Tenofovir Disoproxil Fumarate or Abacavir
No full textThe aim of the study was to evaluate in human immunodeficiency virus (HIV)-infected patients estimated glomerular filtration rate (eGFR) trajectories during treatment with different protease inhibitors (PIs) or a non-nucleoside reverse transcriptase inhibitor (NNRTI) plus tenofovir (TDF) or abacavir (ABC) and lamivudine or emtricitabine (xTC). Retrospective study of patients followed at a single clinical center; all patients who started TDF or ABC for the first time with a NNRTI or lopinavir/r (LPV/r) or atazanavir/r (ATV/r) or darunavir/r (DRV/r), for whom at least 1 eGFR value before the start and during the studied treatment was known, were included in this analysis. eGFR was calculated by means of the CKD-EPI formula. Univariate and multivariate mixed linear model (MLM) was applied to estimate eGFR slope with the considered antiretroviral treatment. In the 1658 patients treated with TDF/xTC (aged 43 [37-48] years, with an eGFR of 105 [96; 113] mL/min/1.73 m 2, 80% males, 92% Caucasians, 10% coinfected with HCV, 4% with diabetes, 11% with hypertension, 38% naive for antiretroviral therapy (ART), 37% with HIV-RNA <50copies/mL) the median follow-up was 2.5 (1.2-4.6) years. Their adjusted eGFR slopes (95% CI) were -1.26 (-1.58; -0.95), -0.43 (-1.20; +0.33), -0.86 (-1.28; -0.44), and -0.20 (-0.42; +0.02) mL/min/1.73 m 2 per year in patients treated with ATV/r, DRV/r, LPV/r, and NNRTI, respectively. Patients receiving ATV/r or LPV/r had a greater adjusted decline in eGFR compared with those receiving NNRTIs (difference -1.06 [-1.44; -0.69] mL/min/1.73 m 2 per year, P<0.001; and -0.66 [-1.13; -0.20] mL/min/1.73 m 2 per year, P=0.005, respectively); adjusted eGFR slopes were similar in patients receiving DRV/r and in those receiving NNRTIs. Patients receiving ATV/r had a greater adjusted eGFR decline than those treated with DRV/r (difference -0.83 [-1.65; -0.02] mL/min/1.73 m 2 per year; P=0.04), but not than those receiving LPV/r; no significant difference was observed in adjusted eGFR slopes between patients receiving DRV/r and those receiving LPV/r. In the 286 patients treated with ABC and lamivudine, eGFR slopes were similar, independent of the PI. In patients receiving TDF/xTC, eGFR trajectories were small for all regimens and declined less in patients receiving DRV/r or NNRTIs than in those treated with ATV/r or LPV/r
Primary Diffuse Leptomeningeal Gliomatosis in Children: A Clinical Pathologic Correlation
No full textPurpose: To describe a rare case of primary diffuse leptomeningeal gliomatosis (PDLG) presenting with progressive proptosis and direct involvement of the optic nerve sheath in a child and review of the relevant literature. Methods: Retrospective review of a single case and systematic literature review of 26 biopsy-proven cases reported in the MEDLINE-indexed English literature. A 10-year-old girl developed proptosis and progressive visual loss associated with thickening of the optic nerve sheaths and dilation of the subarachnoid spaces with multilobulated appearance of the brain meninges and thickened peripheral nerve root sheaths. Biopsy of the optic nerve sheath was diagnostic. The patient underwent chemotherapy combined with oral temozolomide and conformational radiotherapy to the brain and spine. She died 3 years after the onset of the disease. An extensive review of the published literature using the key words “primary diffuse leptomeningeal gliomatosis” and “optic nerve” confirmed the case herein reported to be the first case of primary diffuse leptomeningeal gliomatosis in which direct optic nerve infiltration was demonstrated during the course of the disease. Results: Immunohistochemistry demonstrated expression of CD56 and glial fibrillary acidic protein, and an elevated level of Ki-67; all the other markers were negative. Conclusions: According to a comprehensive literature review, we report the first case of PDLG that presented with bilateral proptosis and direct involvement of the optic nerve during the course of the disease. These new findings may explain an alternative mechanism of visual loss and proptosis in PDLG. We emphasize the importance of close collaboration between neurologists and ophthalmologists in all cases of visual symptoms associated with a neurologic condition. In case of optic nerve involvement, ophthalmologists could provide an easier route to achieve tissue specimen early in the course of this rare and fatal diseaseFil: Bernardini, Francesco P.. Ospedale Gaslini. Department of Ophthalmology; ItaliaFil: Croxatto, Juan Oscar. Consejo Nacional de Investigaciones Científicas y Técnicas; Argentina. Ospedale Gaslini. Department of Neuroradiology; Italia. Fundación Oftalmológica Argentina "J. Malbrán". Departamento de Patologia Ocular y Ultraestructura; ArgentinaFil: Nozza, Paolo. Ospedale Gaslini. Department of
Pathology; ItaliaFil: Rossi, Andrea. Ospedale Gaslini. Department of Neuroradiology; Italia. Fundación Oftalmológica Argentina "J. Malbrán". Departamento de Patologia Ocular y Ultraestructura; ArgentinaFil: Capris, Paolo. Ospedale Gaslini. Department of Ophthalmology; Itali
HIV‐DNA decrease during treatment in primary HIV‐1 infection with three different drug regimens: Italian Network of Acute HIV Infection (INACTION) clinical trial
No full textAs the introduction of antiretroviral therapy (ART) during primary HIV-1 infection (PHI) could restrict the establishment of HIV reservoirs, we aimed to assess the effect of three different ART regimens on HIV-DNA load in people living with HIV (PLWH), who started ART in PHI. Randomized, open-label, multicentric study, including subjects in PHI (defined as an incomplete HIV-1 Western blot and detectable plasma HIV-RNA) in the Italian Network of Acute HIV Infection cohort. Participants were randomly assigned (10:10:8) to a fixed-dose combination of tenofovir alafenamide fumarate (TAF) 10 mg plus emtricitabine (FTC) 200 mg, darunavir 800 mg, and cobicistat 150 mg once daily (group A), or TAF 25 mg plus FTC 200 mg, dolutegravir 50 mg once daily (group B), or an intensified four-drug regimen (TAF 10 mg plus FTC 200 mg, dolutegravir 50 mg, darunavir 800 mg, and cobicistat 150 mg once daily) (group C). The primary endpoint was the decrease of HIV-DNA copies/106 peripheral blood mononuclear cells (PBMCs) at weeks (W) 12 and 48. Secondary endpoints were increased in CD4+ cells and in CD4+/CD8+ ratio and percentage of PLWH reaching undetectable HIV-RNA. HIV-DNA was quantified by Droplet Digital PCR (Biorad QX100) and normalized to RPP30 reference gene. This study was registered in ClinicalTrials.gov (number NCT04225325). Among 78 participants enrolled, 30 were randomized to group 1, 28 to group 2, and 20 to group 3. At baseline, median CD4+ count was 658/μL (476-790), HIV-RNA 5.37 (4.38, 6.12) log10 copies/mL, without statistical difference in their change among groups at weeks 12 and 48 (p = 0.432 and 0.234, respectively). The trial was prematurely discontinued for slow accrual and for COVID-19 pandemic-associated restrictions. In the per-protocol analysis, PLWH (n = 72) with undetectable viral load was 54.3% at W12 and 86.4% at W48. Interestingly, the CD4/CD8 ratio progressively increased over time, up to normalization in almost half of the cohort by week 48, despite a deflection in group 3; no difference was observed by the Fiebig stage (I-III vs. IV-VI). HIV-DNA decreased from 4.46 (4.08, 4.81) log10 copies/106 PBMCs to 4.22 (3.79, 4.49) at week 12, and 3.87 (3.46, 4.34) at week 48, without difference among groups. At multivariable analysis, HIV-DNA delta at W48 was associated only with the increase of CD4+ count by 100 cells/mm3 but not with the Fiebig stage, the CD4+/CD8+ ratio, and treatment arm, despite a higher decrease in group 3. Six adverse events were recorded during our study, which did not cause any withdrawal from the study. We observed a decrease in HIV-DNA from baseline to W48 in PLWH treated during PHI, associated with an increase in CD4+ count, unrelated to the treatment arm
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