Search

Objectives Being COVID-19 convalescent plasma (CCP) a therapeutic option that can have a potential impact on the normalization of immunological parameters of COVID-19 affected patients, a detailed analysis of post-infusion immunological changes was conducted in CCP treated patients, aiming to identify possible predictive hallmarks of disease prognosis. Methods This prospective observational study describes a cohort of 28 patients who received CCP shortly after being hospitalized for COVID-19 and diagnosed for Acute Respiratory Distress Syndrome. All patients were subjected to a detailed flow cytometry based evaluation of immunological markers at baseline and on days +3 and +7 after transfusion. Results At baseline almost all patients suffered from lymphopenia (25/28 on T-cells and 16/28 on B-cells) coupled with neutrophil-lymphocyte ratio exceeding normal values (26/28). Lymphocyte subsets were generally characterized by increased percentages of CD19+CD20-CD38hiCD27+ plasmablasts and reduction of CD4+CD45RA+CCR7+CD31+ recent thymic emigrants, while monocytes presented a limited expression of CD4 and HLA-DR molecules. Amelioration of immunological parameters began to be evident from day +3 and became more significant at day +7 post-CCP transfusion in 18 patients who recovered within 30 days from hospitalization. Conversely, baseline immunological characteristics generally persisted in ten critical patients who eventually progressed to death (6) or long-term care (4). Conclusions This study demonstrates that proper immunophenotyping panels can be potentially useful for monitoring CCP treated patients from the first days after infusion in order to presume higher risk of medical complications.

to describe the course of COVID-19 epidemic in the hospitals of the ASST of Mantua (Lombrady Region, Northern Italy) from February 2020 to April 2021.observational study.data from hospital discharging chart of all patients admitted to the hospitals of ASST were collected from 26.02.2020 to 30.04.2021 with COVID-19 diagnosis. Data from Emergency Rooms for patients evaluated but not admitted to departments were also collected.the data from hospital discharging were crossed for diagnosis with data from laboratory. The department were classified into 'low intensity' and 'middle/high intensity'. The comparison was according to the different periods of epidemic.patients admitted to the hospitals were 2,738: 510 died (17.3%) and 1,736 patients were evaluated in the Emergency Rooms but not admitted to departments. Among these patients, 166 died (9.6%). The prevailing age class were=65 years, with a trend to reduction in the third wave. The proportion of admission in middle/high intensity departments was significantly higher in the second wave than in the first. N. 510 deaths by 2,738 (17.3%) were observed, with significant reduction in the second and third waves in the low intensity departments (from 21.9% to 14.3% and 12.7%) (p0.001), while mortality was substantially unchanged in the middle/high intensity departments (28.0%, 29.6%, and 28.3%). The mortality for patients with=65 years was 26.7%. Females showed lower mortality (OR 0.690; CI95% 0.560-0.840) and lower incidence of admissions in middle/high intensity departments (OR 0.556; CI95% 0.459-0.673) in the three waves. Finally, including also the patients not admitted, the general mortality was 15.1%.a worse outcome by mortality and severity of disease was observed for male gender compared to female and for older age classes. Moreover, a significant improvement of outcomes in the second and third waves, compared to the first, was pointed out.

BACKGROUNDHyperimmune plasma from Covid-19 convalescent is a potential treatment for severe Covid-19.METHODSWe conducted a multicenter one arm proof of concept interventional study. Patients with Covid-19 disease with moderate-to-severe Acute Respiratory Distress Syndrome, elevated C-reactive Protein and need for mechanical ventilation and/or CPAP were enrolled. One to three 250-300 ml unit of hyperimmune plasma (neutralizing antibodies titer ≥1:160) were administered. Primary outcome was 7-days hospital mortality. Secondary outcomes were PaO2/FiO2, laboratory and radiologic changes, as well as weaning from mechanical ventilation and safety.RESULTSThe study observed 46 patients from March, 25 to April, 21 2020. Patients were aged 63, 61% male, 30 on CPAP and 7 intubated. PaO2/FiO2 was 128 (SD 47). Symptoms and ARDS duration were 14 (SD 7) and 6 days (SD 3). Three patients (6.5%) died within 7 days. The upper one-sided 90%CI was 13.9%, allowing to reject the null hypothesis of a 15% mortality. PaO2/FiO2 increased by 112 units (95%CI 82 to142) in survivors, the chest radiogram severity decreased in 23% (95%CI 5% to 42%); CRP, Ferritin and LDH decreased by 60, 36 and 20% respectively. Weaning from CPAP was obtained in 26/30 patients and 3/7 were extubated. Five serious adverse events occurred in 4 patients (2 likely, 2 possible treatment related).CONCLUSIONSHyperimmune plasma in Covid-19 shows promising benefits, to be confirmed in a randomized controlled trial. This proof of concept study could open to future developments including hyperimmune plasma banking, development of standardized pharmaceutical products and monoclonal antibodies.

Atazanavir (300 mg) boosted by ritonavir (100 mg) is the preferred third drug in pregnancy. However, there is still discordance on atazanavir dose increase during the third trimester.To evaluate plasma and intracellular atazanavir and ritonavir concentrations in HIV-infected women during pregnancy and after delivery.This was an observational study. HIV-infected pregnant patients treated with atazanavir/ritonavir plus either tenofovir/emtricitabine or abacavir/lamivudine had been prospectively enrolled after having signed a written informed consent form. Plasma and intracellular atazanavir and ritonavir Ctrough (24 ± 3 h after drug intake) were measured at each visit during the first, second and third trimesters and post-partum using validated HPLC-MS and HPLC-photodiode array methods (with direct evaluation of cellular volume). Data are described as median (IQR) and compared through non-parametric tests.Twenty-five patients were enrolled; at baseline, the median age was 32 years (27-35). All patients had plasma HIV RNA50 copies/mL; the median CD4+ count was 736 cells/mm3 (542-779). Atazanavir plasma concentrations were 441 ng/mL (261-1557), 710 ng/mL (338-1085), 556 ng/mL (334-1022) and 837 ng/mL (608-1757) during the first, second and third trimesters and post-partum, respectively; intracellular concentrations were 743 ng/mL (610-1928), 808 ng/mL (569-1620), 756 ng/mL (384-1074) and 706 ng/mL (467-2688), respectively. Atazanavir intracellular/plasma ratios were 1.32 (0.98-2.77), 1.34 (1.13-1.88), 1.38 (0.61-2.63) and 1.07 (0.56-2.69), respectively. Atazanavir intracellular concentrations and intracellular/plasma ratios showed non-significant changes over time (P 0.05).This is the first demonstration that intracellular atazanavir exposure remains unchanged during pregnancy supporting the standard 300/100 mg atazanavir/ritonavir dosing throughout pregnancy.

Progressive disseminated histoplasmosis (PDH) is an AIDS-defining illness with a high lethality rate if not promptly treated. The wide range of its possible clinical manifestations represents the main barrier to diagnosis in non-endemic countries. Here we present a case of PDH with haemophagocytic syndrome in a newly diagnosed HIV patient and a comprehensive review of disseminated histoplasmosis focused on epidemiology, clinical features, diagnostic tools and treatment options in HIV-infected patients.

OBJECTIVES Lymphoproliferative disorders are often observed in HIV-positive patients. Combination antiretroviral treatment (cART) during antineoplastic chemotherapy is beneficial, but little is known about the clinical outcome according to different antiretroviral combinations. The aim of the study was to address this gap in current knowledge. METHODS A retrospective study was conducted in five large Italian centres for the period from 1998 to 2015; HIV-positive patients diagnosed with lymphoma were included and demographic, clinical and therapeutic variables were recorded and associated with clinical outcomes. Bivariate and multivariate analyses were performed, including Cox proportional hazard models for survival. RESULTS A total of 399 patients were included in the study. The most common types of lymphoma were diffuse large B-cell lymphoma (DLCLB; n = 164), Hodgkin lymphoma (HL; n = 99) and Burkitt lymphoma (BL; n = 57), followed by plasmablastic lymphoma (PBL; n = 38), T-cell lymphoma (TCL; n = 17), indolent lymphoma (n = 10) and other less common types (n = 14). cART was given to 327 (out of 387 evaluable) patients: in 216 subjects it was protease inhibitor (PI)-based, in 73 it was nonnucleoside reverse transcriptase inhibitor (NNRTI)-based and in 18 it was integrase strand transfer inhibitor (INSTI)-based (the remaining 20 individuals received other regimens). The 5-year overall survival was 57.5% (52.8% for DLCLB, 67.8% for HL, 42.3% for BL, 60.6% for PBL and 64.7% for TCL). PI-based ART compared with other compounds was associated with worse survival in non-Hodgkin lymphoma (NHL) and HL patients combined (P ≤ 0.001) and in NHL patients alone (P

Kidney transplantation was recently introduced for the treatment of end stage renal disease (ESRD) in HIV-infected patients. We report the results of the first 28 procedures at our centre. A retrospective study was conducted on HIV-infected patients evaluated for kidney transplantation between January 2005 and October 2016. Patients were selected and monitored by the kidney transplantation and infectious diseases teams, according to the national protocol. 60 patients were evaluated; 32 entered the list and 28 were transplanted. Median CD4+ count was 337 cell/μL at transplantation and 399 cell/μL 12 months thereafter. HIV RNA was undetectable at transplantation in 27/28 patients and became undetectable within 24 weeks in the only patient starting antiretroviral combination therapy (cART) after surgery. Four patients experienced virological failure, but reached again undetectability after cART regimen change. At last available point of follow-up (median 126.1 weeks), HIV RNA was undetectable in all patients. Three patients experienced AIDS-defining events. We observed a cumulative number of 19 acute rejections in 16 patients (median time from transplantation to first rejection 5.2 weeks). Survival rate was 82.1%. To avoid pharmacokinetics (PK) interactions, cART regimen was changed from a protease inhibitor (PI)/non-nucleoside reverse transcriptase inhibitor (NNRTI)-based to an integrase inhibitor (InSTI)-based regimen in 11/20 alive patients with functioning graft. Kidney transplantation appears to be safe in HIV-infected patients carefully selected. As previously reported, we observed a high incidence of acute rejection. We expect that the recent implementation of the immunosuppressive protocols will allow a better immunologic control. Moreover, the introduction of InSTI permits a better strategy of cART, with lower incidence of PK interactions with immunosuppressive drugs.

With the development of combination antiretroviral therapy (cART), the first generation of perinatally HIV-infected children has reached young adulthood. A retrospective study was conducted on perinatally HIV-infected young adults after transition to adult care in Brescia (Northern Italy). Twenty-four patients were transferred to Infectious Disease outpatient Clinic from Pediatric Clinic between 2004 and 2016. Median age at transition was 18 years. 37.5% were male, and 75% were Italian. Median CD4+ T-cell count was 534 cell/μL, and 9/24 presented detectable HIV-RNA at the time of transition. At month 12 after transition, median CD4+ T-cell count was 626 cell/μL, and HIV-RNA was still detectable in 25% of patients. Nineteen patients were still in care at the end of follow-up (median of 52 months); 100% on cART, with undetectable HIV-RNA and a median CD4+ T-cell count of 716 cell/μL. After transition, cART regimen was modified in 14/19 patients (in 13 of them it was modified at least twice). Resist...

Early consolidation with high-dose therapy and autologous stem cell transplantation is a feasible and effective treatment option in HIV-associated non-Hodgkin lymphoma at high risk

Reactivation of the hepatitis B virus (HBV) has been reported in patients with occult infection (OBI), i.e. HBV surface antigen (HBsAg) negative, HBV core antibody (anti-HBc) positive ± antibodies against HBsAg (anti-HBs) and detectable HBV DNA in serum or liver, receiving immunosuppressive or cytotoxic therapies. Recently, concerns have been raised regarding the risk of HBV reactivation in OBI patients treated with direct acting antiviral agents (DAAs) for chronic hepatitis C (CHC). Here we describe a case of HBV reactivation in a 72-year-old woman with OBI as a possible consequence of effective treatment with sofosbuvir (SOF) and ribavirin (Rbv) for genotype 2a/2c CHC.

New Direct-acting Antiviral Agents (DAA)-based anti-HCV therapies currently provide extraordinary opportunities to cure patients. Drug-drug interactions are however a real challenge during treatment. In particular, in HIV-infected patients in cART, DAA choice is limited by such interactions, which can result both in reduced efficacy and toxicity. We report the case of a HIV-infected patient on cART with atazanavir/ritonavir/abacavir/lamivudine, who presented kidney and biliary lithiasis, the latter treated with endoscopic retrograde cholangiopancreatography and endoscopic biliary sphincterotomy, after beginning anti-HCV treatment with daclatasvir/sofosbuvir/ribavirin. Hyperbilirubinemia with or without jaundice is a well known side effect of atazanavir, because of its inhibition of uridine diphosphate-glucuronosyl transferase. We speculate that in this case hyperbilirubinemia worsening was due to atazanavir/ribavirin co-administration. However, pharmacokinetic data are lacking about atazanavir/daclatasvir concomitant administration in real life setting.

Background Two biomarkers, the neutrophil to lymphocyte ratio (NLR) and platelet to lymphocyte ratio (PLR), have been shown to be indicative of systemic inflammation and predictive of mortality in general population. We aimed to assess the association of NLR and PLR, with risk of death in HIV-infected subjects when also taking account of HIV-related factors. Methods We conducted a multicenter Italian cohort study from 2000 to 2012 including HIV-infected subjects naïve at antiretroviral treatment. The associations of NLR and PLR with all-cause mortality were tested by univariate and multivariate analyses using both time independent and dependent Cox proportional hazard models. We also fitted models with a cubic-spline for PLR and NLR to evaluate the possible non-linear relationship between biomarkers values and risk of death. Results Eight-thousand and two hundred thirty patients (73.1% males) with a mean age of 38.4 years (SD 10.1) were enrolled. During a median follow-up of 3.9 years, 539 patients died. PLR

Summary Background Dolutegravir is a once-daily integrase strand transfer inhibitor with no need for pharmacokinetic boosting that is approved for the treatment of HIV-1 infection. Because women are often under-represented in HIV clinical trials, we addressed the safety and efficacy of dolutegravir in women with HIV-1. Methods The ARIA study is a randomised, open-label, multicentre, active-controlled, parallel-group, non-inferiority phase 3b study done in 86 hospital and university infectious disease clinics, local health clinics, and private infectious disease clinics in 12 countries and one US territory, in North America, South America, Europe, Africa, and Asia. Eligible participants were women aged 18 years or older who had HIV-1 RNA viral loads of 500 copies per mL or greater, had received 10 days or less of previous antiretroviral therapy, and had tested negative for the HLA-B*5701 allele. Pregnant women were excluded. Eligible women were randomly assigned (1:1) to receive either a single-tablet regimen of dolutegravir plus abacavir and lamivudine once a day (dolutegravir group) or a three-tablet combination of ritonavir-boosted atazanavir plus coformulated tenofovir disoproxil fumarate and emtricitabine once a day (atazanavir group). Random treatment group assignment was stratified by plasma HIV-1 RNA viral loads and CD4 cell count at baseline. The primary endpoint was the proportion of participants with HIV-1 RNA viral loads of less than 50 copies per mL at week 48 in all participants who received at least one dose of study medication (intention-to-treat exposed population). We used a non-inferiority margin of −12%. Investigators monitored adverse events to assess safety. This study is registered with ClinicalTrials.gov, number NCT01910402. Findings Between Aug 22, 2013, and Sept 22, 2015, of 705 women assessed, 499 were randomly assigned to either the dolutegravir group (n=250) or the atazanavir group (n=249); two participants from each group were randomised to treatment but did not receive study medication. At week 48, 203 (82%) of 248 participants in the dolutegravir group compared with 176 (71%) of 247 in the atazanavir group had HIV-1 RNA viral loads of less than 50 copies per mL (mean difference 10·5%, 95% CI 3·1–17·8, p=0·005). One participant in the atazanavir group had nucleoside reverse transcriptase inhibitor–associated resistance that led to reduced emtricitabine susceptibility. Adverse events were similar between the dolutegravir and atazanavir groups; the most common were nausea (46 [19%] of 248 in the dolutegravir group vs 49 [20%] of 247 in the atazanavir group) and headache (28 [11%] vs 32 [13%]). Fewer participants in the dolutegravir group than the atazanavir group reported drug-related adverse events (83 [33%] vs 121 [49%]) or adverse events that led to discontinuation (ten [4%] vs 17 [7%]). One death was reported in each treatment group, but neither was considered related to the study medications. Interpretation The non-inferior efficacy and similar safety profile of the dolutegravir combined regimen compared with the atazanavir regimen support the use of dolutegravir for HIV-1 infection in treatment-naive women. Funding ViiV Healthcare.

Background. Phase I/II studies in human immunodeficiency virus (HIV)–infected patients receiving antiretroviral therapy have shown that a single cycle of 3 weekly subcutaneous (s/c) injections of recombinant human interleukin 7 (r-hIL-7) is safe and improves immune CD4 T-cell restoration. Herein, we report data from 2 phase II trials evaluating the effect of repeated cycles of r-hIL-7 (20 µg/kg) with the objective of restoring a sustained CD4 T-cell count >500 cells/µL. Methods. INSPIRE 2 was a single-arm trial conducted in the United States and Canada. INSPIRE 3 was a 2 arm trial with 3:1 randomization to r-hIL-7 versus control conducted in Europe and South Africa. Participants with plasma HIV RNA levels 63% of their follow-up time with a CD4 T-cell count >500 cells/µL. Conclusions. Repeated cycles of r-hIL-7 were well tolerated and achieved sustained CD4 T-cell restoration to >500 cells/µL in the majority of study participants. Clinical Trials Registration. INSPIRE II: clinicaltrials.gov ({"type":"clinical-trial","attrs":{"text":"NCT01190111","term_id":"NCT01190111"}}NCT01190111) and INSPIRE III: EudraCT (No. 2010-019773-15) and clinicaltrials.gov ({"type":"clinical-trial","attrs":{"text":"NCT01241643","term_id":"NCT01241643"}}NCT01241643).

Pseudomonas aeruginosa is a well-known cause of severe and potentially life-threatening infections among hematological patients. A prospective epidemiological surveillance program ongoing at our Hematology Unit revealed an increase over time of P. aeruginosa bloodstream infections (BSI). Their impact on outcome and antibiotic susceptibility was analyzed. BSI which consecutively occurred at our institution during a 70-month period were evaluated and correlated with type of pathogen, status of underlying disease, neutropenia, previous antibiotic therapy, resistance to antibiotics, and outcome. During the observation period, 441 BSI were recorded. Frequency of Gram-negative BSI was higher than that of other pathogens (57.3%). Overall, 66 P. aeruginosa BSI were recorded; 22 out of 66 were multiresistant (MR P. aeruginosa). Thirty-day mortality for all BSI was 11.3%; it was 27.3% for P. aeruginosa BSI and 36.4% for MR P. aeruginosa. At multivariate analysis, only active hematological disease and P. aeruginosa BSI were associated to an increased risk of death. For MR P. aeruginosa, BSI mortality was 83.3% vs. 18.8% when empiric therapy included or not an antibiotic with in vitro activity against P. aeruginosa (p = 0.011). Together with active disease, the emergence of P. aeruginosa BSI, particularly if multiresistant, was responsible for an increased risk of death among hematological patients at our institution. In this scenario, reconsidering the type of combination antibiotic therapy to be used as empiric treatment of neutropenic fever was worthwhile.

Introduction: Autologous stem cell transplantation (ASCT) is considered safe and effective in patients with HIV-associated lymphoma (HIV-Ly). The reported studies usually analyze togheter different histological subtypes, including classical Hodgkin lymphoma (HL) and a variety of aggressive non Hodgkin lymphoma (NHL), and different indications for ASCT, and report composite outcomes. Aim: We report our single center experience on a large single institution series of patients (pts) with HIV-Ly undergoing ASCT and analyse efficacy according to histology subtypes, indications for ASCT, previous therapy and lymphoma status at transplant, to understand the settings where this treatment approach is most effective and useful. Methods: Retrospective analysis of clinical characteristics and outcome of all consecutive pts with HIV-Ly transplanted at our Institution from March 2001 to February 2018. Results: 62 pts with HIV-Ly underwent ASCT during the study period. Ninety-four % were male; median age was 46 years (range, 29-62). Lymphoma histology was HL in 11 (18%), diffuse large B-cell lymphoma in 22 (35%), Burkitt or Burkitt-like in 13 (21%) , plasmablastic in 10 (16%), T-cell aggressive NHL (3 anaplastic large cell lymphoma, ALK negative, and 1 extranodal NK/T-cell lymphoma, nasal type) in 4 (6%), and indolent B-cell lymphoma (1 follicular lymphoma, and 1 extranodal marginal zone lymphoma) in 2 (3%) pts, respectively. Median CD4+ cells count at ASCT was 208/mL (range, 55-720); 8 pts (13%) had detectable HIV viral load. Eighteen pts (29%) had concomitant hepatitis C and 2 (3%) hepatitis B infection. Indications for ASCT were primary refractory disease (26%), first or subsequent relapse (37%), and consolidation after first line therapy for partial remission (PR) or high risk complete remission (CR) (37%). At the time of ASCT, 10 pts (16%) were in first CR, 45 (73%) had chemosensitive disease (i.e. first PR, chemosensitive relapse/refractory disease), and 7 (11%) had disease refractory to the last chemotherapy (CT) received. Twenty-three patients (37%) had received only 1 line of CT before ASCT, 29 (47%) 2 lines, and 10 (16%) 3 or more lines. Conditioning regimen was BEAM in 47 patients (76%), FEAM in 13 (21%), and 1 each Mitoxantrone-Melphalan and BiCNU-Thiotepa. All pts were receiving cART throughout ASCT except 3 who suspended cART for at least 1 week, due to toxicity and/or oral mucositis. Neutrophil engraftment (neutrophils > 500/mcl) occurred in all pts at a median of 10 days (range, 8-12), and platelet engraftment (platelet count > 20.000/mcl) occurred in all pts at a median of 13 days (range, 9-46), except in one with refractory disease who died of sepsis early after ASCT (treatment-related mortality 1.6%). Twenty-three pts (70%) experienced grade 3-4 toxicity, including oral mucositis (17 patients), gastrointestinal toxicity (8), hepatic toxicity (1), and seizures (1). Twenty-five pts (41%) had an episode of fever of unknown origin. Before engraftment, 22 documented bacterial infections, 1 fungal infection, 2 herpes zoster infections and 5 CMV reactivations were recorded. After a median follow-up of 59 months (range, 1-177) from ASCT, the 5 years-progression free survival (5y-PFS) and OS (5y-OS) were 66.6% and 69.7% respectively, with no significant differences according to different histologies (figure 1). The outcome was satisfactory regardless of the indication for transplant (primary refractory disease, 5y-PFS 50% and 5y-OS 49% , relapse, 5y-PFS 62.6% and 5y-OS 70.7%, and first line consolidation, 5y-PFS 80.3% and 5y-OS 80.1%, P=NS), and number of CT lines before ASCT (1 line, 5y-PFS 80.3% and 5y-OS 80.1%, 2 lines, 5y-PFS 61.3% and 5y- 63.4%, and 3 or more lines, 5y-PFS 53.3% and 5y-OS 66.7%, P=NS). According to the status of lymphoma at the time of ASCT, pts in first CR had a 5y-PFS of 77.8% and 5y-OS of 77.8% and pts with chemosensitive disease 73.7% and 80.3%, while all chemorefractory pts died within 5 months from ASCT, with median PFS and OS of 2 and 3 months respectively (P< 0.001) (figure 2). Conclusion: This is the largest single institution series of HIV-Ly receiving ASCT. We confirm the feasibility and long-term efficacy of this treatment approach in different histological subtypes. ASCT was beneficial also in primary refractory disease and heavily pre-treated pts, provided that lymphoma proved chemosensitive to the last CT received before ASCT. Disclosures Rossi: ABBVIE: Other: ADVISORY BOARD; PFIZER: Other: ADVISORY BOARD; SANDOZ: Honoraria; GILEAD: Other: ADVISORY BOARD; AMGEN: Other: ADVISORY BOARD; SANOFI: Other: ADVISORY BOARD; JANNSEN: Other; JAZZ: Other: ADVISORY BOARD; TEVA: Other: ADVISORY BOARD; CELGENE: Other: ADVISORY BOARD; ROCHE: Other: Advisory Board; NOVARTIS: Honoraria; MUNDIPHARMA: Honoraria; BMS: Honoraria.

After the introduction of highly active antiretroviral therapy (HAART), intensive treatment, including high-dose therapy (HDT) and peripheral blood stem cell transplantation (PBSCT), has become feasible in HIV-positive patients with Hodgkin (HL) and non-Hodgkin (NHL) lymphoma. Herein, we report the long-term results, on an intention-to-treat basis, of a prospective study on HDT and PBSCT in 50 HIV-positive HAART-responding patients with refractory/relapsed lymphoma. After debulking therapy, 2 patients had early toxic deaths, 10 had chemoresistant disease, 6 failed stem cell mobilization, 1 refused collection, and 4 progressed soon after PBSC harvest. Twenty-seven actually received transplant. Twenty-one patients are alive and disease-free after a median follow-up of 44 months (OS, 74.6%; PFS, 75.9%). Only lymphoma response significantly affected OS after transplantation. In multivariate analyses both lymphoma stage and low CD4 count negatively influenced the possibility to receive transplant. Median OS of all 50 eligible patients was 33 months (OS, 49.8%; PFS, 48.9%). Low CD4 count, marrow involvement, and poor performance status independently affected survival. PBSCT is a highly effective salvage treatment for chemosensitive AIDS-related lymphoma. It seems rational to explore its use earlier during the course of lymphoma to increase the proportion of patients who can actually receive transplant.

Background Regular monitoring of bacterial epidemiology allows evaluation of antibacterial strategies adopted. The aim of this study was to disclose evolving trends in the epidemiology of infections and emerging antibiotic resistance in unselected inpatients with haematological cancers. Methods Febrile/infectious episodes occurring in 823 patients consecutively admitted to a single institution during a 16 month period were analysed. Levofloxacin prophylaxis was used in patients with >7 days expected neutropenia. Results Fever developed in 364 patients (44.2%) and an infection was documented in 187 (22.7%), either clinically (6.1%) or microbiologically (16.6%). Levofloxacin prophylaxis, used in 39.4% of cases, caused a reduction in febrile episodes only among neutropenic patients and no difference in the frequency of documented infections. Among 164 pathogens isolated, gram-negative (49.4%) outweighed gram-positive bacteria (40.9%), Escherichia coli being most frequent (23.2%). Fluoroquinolone resistance and methicillin resistance were the most frequent types of antibiotic resistance, occurring in 56.1% of bacterial isolates and in 66.7% of staphylococci, respectively. Fluoroquinolone-resistant E. coli accounted for 20.1% of all isolates and for 86.8% of E. coli. Multivariate analysis of risk factors for fluoroquinolone resistance identified prophylaxis (P 7 days (P = 0.02) as independent. Methicillin resistance was independently associated with prophylaxis (P = 0.041) and central venous catheters (P = 0.036). Infections by fluoroquinolone-resistant strains did not show a worse outcome. Conclusions A shift towards gram-negative bacteria has been occurring in recent years in the bacterial epidemiology of haematological patients. Fluoroquinolone resistance is emerging as a major type of antibacterial resistance, particularly among E. coli strains. Further investigation is needed to explore the consequences of such epidemiological changes.

Since 2014 several direct-acting antivirals (DAAs) have been made available, allowing interferon-free antiviral treatments with high sustained virological response rates. Side effects are, however, a real challenge during treatment. Sarkar et al. recently published a case of colitis following initiation of sofosbuvir and simeprevir for genotype 1 hepatitis C. We report the case of a patient with no prior history of inflammatory bowel disease, who developed significant bloody diarrhea within 3 weeks of sofosbuvir/simeprevir/ribavirin initiation. Colonoscopy and biopsy suggested a drug-induced colitis.

Early detection of undiagnosed HIV infected patients is of paramount importance. The attitude of Italian hospital-based Internal Medicine physicians to prescribe HIV testing following the detection of HIV-associated signs, symptoms and behaviours (triggers) has been reported to be poor. The aim of the study is to quantify the extent of the missed opportunities for early HIV diagnosis in Internal Medicine Departments (IMD).Patients admitted to IMD of a General University Hospital in Italy in March-June 2013 were interviewed using a structured questionnaire investigating the presence of triggers for HIV testing, including patient's characteristics, symptoms and conditions associated with HIV infection. HIV tests performed during hospitalisation were recorded.HIV testing was performed in 73 (6.6%) out of 1113 hospitalisations (1072 patients), providing positive results in three cases (4.1%). All of them presented ≥1 triggers. Conversely, 853 triggers were identified in 528 hospitalisations with at least one trigger (47.4%). The proportion of hospitalisations where an HIV testing was prescribed was 3.1%, 9.5% and 16.0% in the presence of zero, one-to-two or more triggers, respectively. Age70 years, female gender, length of hospital stay, haematological disease, HBV infection, multiple sexual partners and lymphadenopathy were predictors of HIV testing by logistic regression analysis.Although chances of an HIV test being performed in patients hospitalised in IMD increases along with the number of triggers, the number of tests being performed in people presenting with triggers is unacceptably low and requires educational interventions in order to obtain individual and public health advantages.

Background We aimed at evaluating frequency and factors associated with late presentation and advanced HIV disease and excess risk of death due to these conditions from 1985 to 2013 among naïve HIV infected patients enrolled in the Italian MASTER Cohort. Methods All antiretroviral naive adults with available CD4+ T cell count after diagnosis of HIV infection were included. Multivariable logistic regression analysis investigated factors associated either with late presentation or advanced HIV disease. Probabilities of survival were estimated both at year-1 and at year-5 according to the Kaplan-Meier method. Flexible parametric models were used to evaluate changes in risk of death overtime according to late presentation and advanced HIV disease. The analyses were stratified for calendar periods. Results 19,391 patients were included (54 % were late presenters and 37.6 % were advanced presenters). At multivariable analysis, the following factors were positively associated with late presentation: male gender (OR = 1.29), older age (≥55 years vs.

Neurocognitive disorders are emerging, probably underestimated, complications in HIV-infected people. The aim of the study was to assess neurocognitive profiles of newly detected HIV-infected patients. We performed an observational retrospective single-cohort study. Illiterates and patients with neurologic symptoms or previous psychiatric diagnosis were excluded. Neuropsychological profiles were assessed using a validated battery of neuropsychological tests. We included 206 patients; with males representing the majority of them (85%). Risk factors for HIV acquisition were unprotected sexual intercourse (homo/bisexual in 39.8% and heterosexual in 60.2%). Thirty-nine patients (18.9%) were previous injection drug users, while 41 (19.9%) were alcohol abusers. Mean education was 11.1 years (SD--standard deviation--3.7). A high prevalence of HIV-associated neurocognitive disorders (HAND, 47.1%) was present in HIV-infected patients: particularly, asymptomatic neurocognitive impairment (ANI) was found in 30.6%, mild neurocognitive disorder (MND) in 15% and HIV-associated dementia (HAD) in 1.5%. Male gender, low degree of education, AIDS diagnosis and gepatitis B virus (HBV) co-infection were factors independently associated with HAND in a multivariable logistic regression model. Our data suggest that patient-specific factors and AIDS diagnosis have a certain kind of impact in HAND occurrence. A complete neuropsychological screening must be recommended in all patients at HIV-infection diagnosis.

Background Baseline and follow-up predictors of new AIDS-defining events (ADE) or death among patients who started HAART with CD4+ T-cell counts ≥200 cells/mm3 have rarely been assessed simultaneously. Methods A prospective observational cohort study (1996–2002) is reported. HIV-infected patients initiating HAART with a CD4+ T-cell count ≥200 cells/mm3 were studied. Baseline and time-varying factors were tested for the prediction of new ADE/death using Cox regression models. Results A total of 896 subjects were studied over a median of 5.1 years. The incidence of a new ADE was 1.6 (95% confidence interval 1.3–2.1) per 100 person-years. Among baseline factors, higher CD4+ T-cell counts before HAART were associated with lower risk of ADE/death, but not after adjustment for time-varying factors. On a multivariable analysis including both baseline and time-varying covariates, longer delay from HIV diagnosis to HAART was an independent predictor of ADE/death (per year, hazard ratio [HR] 1.06; P=0.025) and was independent of CD4+ T-cell count before treatment. Longer time spent with HIV RNA + T-cell count (per log2 cells/mm3, HR 0.65; PConclusions Patients with higher CD4+ T-cell counts before HAART initiation had a better prognosis. However, except for the delay in starting HAART, viro-immunological evolution outweighed the effect of baseline factors. Moreover, suppressing HIV replication for as long as possible could improve the clinical outcome. Prospective randomized clinical trials to assess the optimal timing of HAART initiation are both feasible and urgently needed.

Background HIV infection, with an estimated prevalence be between 2 and 50 times those of the general adult population is a major health challenge for prison authorities worldwide. Since no nationwide surveillance system is present in Italy, data on HIV prevalence and treatment in prisons are limited to only a few and small observational studies. We aimed to estimate HIV prevalence and obtain an overview on diagnostic and therapeutic activities concerning HIV infection in the Italian penitentiary system. Methods We piloted a multi-centre cross-sectional study investigating the prevalence of HIV infection and assessing HIV-related medical activities in Italian correctional institutions. Results A total of 15,675 prisoners from 25 institutions, accounting for approximately one-fourth of the prison inmates in Italy, were included in the study, of whom, 97.7 % were males, 37.1 % foreigners and 27 % had a history of intravenous drug addiction. HIV-tests were available in 42.3 % of the total population, with a known HIV Infection proportion of 5.1 %. In the month prior to the study, 604 of the 1,764 subjects who entered prison were tested for HIV, with a HIV-positive prevalence of 3.3 %. Among the 338 HIV-positive prisoners, 81.4 % were under antiretroviral treatment and 73.5 % showed undetectable HIV-RNA. In 23/338 (6.8 %) a coinfection with HBV and in 189/338 (55.9 %) with HCV was also present. Among the 67 (19.8 %) inmates with HIV who did not receive HIV treatment, 13 (19.5 %) had T-CD4+ count

Background: The independent role of hepatitis C virus (HCV) genotype 3 in liver transaminase elevation following highly active antiretroviral regimens is still controversial. Methods: Analysis of data from a cohort of 492 HIV/HCV-coinfected patients was conducted using an intention-to-treat approach. Incidence of grade ≥III liver transaminase elevation was estimated per 100 patient-years of follow-up. Univariate and multiple proportional hazards regression analysis of factors that may predict liver enzyme elevation was performed. Results: The incidence of grade ≥III hepatotoxicity was 25 per 100 patient-years among patients coinfected with HCV genotype 3 and 11 per 100 patient-years among those with other genotypes. On multiple proportional hazard regression analysis, time-to-grade ≥III liver enzyme elevation was directly correlated with HCV genotype 3 (hazards ratio [HR]: 2.0, 95% CI: 1.3 to 2.9; P = 0.001), male gender (HR: 2.7; 95% CI: 1.3 to 5.7; P = 0.007), chronic hepatitis B virus infection (HR: 2.9, 95% CI: 1.5 to 5.9; P = 0.002), and alanine aminotransferase level at baseline (per 10 IU/L HR: 1.10; 95% CI: 1.06 to 1.15; P < 0.001). In the same model, higher CD4 + T-cell counts at baseline were inversely correlated with risk of hepatotoxicity (HR: 0.998; 95% CI: 0.997 to 0.999; P = 0.036). Moreover, among patients experienced to antiretroviral drugs, previous grade ≥III hepatotoxicity (HR: 2.8; 95% CI: 1.8 to 4.3; P < 0.001) was an adjunctive independent risk factor. Conclusions: HIV-positive patients coinfected with HCV genotype 3 displayed a higher risk of relevant hepatotoxicity, independently from other clinical variables. The impact of HCV genotype outweighed the role of drugs in determining hepatotoxicity. Copyright © 2006 by Lippincott Williams & Wilkins.

Oral cavity lymphoma (OCL) seems to occur more frequently in HIV-positive patients, but it is presently unknown whether HIV-related immune deficit plays a role in modifying the prevalence and the characteristics of these lymphomas. To clarify this issue, we compared OCL occurring in immunocompetent and HIV-positive patients. A comparison was made between cases of OCL occurring among 543 and 123 NHL consecutively diagnosed at a single center in immunocompetent and HIV-positive patients respectively. The prevalence of oral cavity involvement at diagnosis was significantly lower in the immunocompetent subgroup (HIV-negative: 1.66%; HIV-positive: 7.3%, P = 0.002). Extranodal T/NK nasal-nasal-type lymphoma (ET/NK-NL) was observed in 3 of 9 immunocompetent patients, whereas plasmablastic lymphoma (PBL) was observed in 3 of 9 HIV-positive patients. EBV expression correlated with HIV-positivity. Response to treatment was similar between the two subgroups, but the overall prognosis was significantly worse among HIV-positive patients. Median survival was 34 months in immunocompetent vs. 9 months in HIV-positive patients (P0.01). A higher frequency of oral cavity lymphoma was associated with HIV infection. ET/NK-NL and PBL seemed to be clinical entities characteristically related to immunocompetent and HIV-positive subgroups, respectively. Chemotherapy was feasible and effective in both subgroups, although a poor prognosis was associated with immunodeficiency.

We describe the clinical characteristics of 12 HIV-infected patients who suffered from myocardial infarction (MI) in our clinical cohort. They were compared with a control group matched (1:2) for factors related to cardiovascular risk (age, gender, smoking habit, risk factor for HIV acquisition, hypertension, family history for relevant cardiovascular events, and body mass index) by conditional (fixed-effect) logistic regression analysis. Among patients with MI, 6/12 had never used protease inhibitors (PIs) or were antiretroviral therapy naïve. The only variables marginally associated with MI were nadir CD4+ T-cell count 3 (odds ratio (OR): 7.2; 95% confidence interval (CI) 0.81–64.2; P: 0.077) and zenith >100,000 HIV RNA copies/mL (OR: 7; 95% CI 0.81–60.2; P: 0.076) at univariate analysis. Moreover, the use of PIs did not result in being associated with the risk of MI. Our data show that in HIV-infected patients, PI use does not seem to have any negative impact on MI while the possible impact of advanced HIV infection itself needs further investigations.

Clinical and in vitro studies have suggested that nelfinavir (NFV)‐containing regimens may not preclude the use of other protease inhibitors (PIs) in treatment sequencing. We have studied the prevalence of 30N mutation in a human immunodeficiency virus–1 (HIV‐1)‐infected cohort and the virological response to a PI‐containing regimen in patients who had previously failed NFV. A total of 335 patients were included in the study; 32 of them were antiretroviral‐naïve and 303 were antiretroviral‐experienced (251 were PI‐experienced). Mutations 30N and/or 90M were not detected in sequences obtained either from the antiretroviral naïve or non‐PI‐experienced patients. The 30N mutation was detected in 21/251 (8.3%) of PI‐experienced patients and 90M in 103/251 (41%). Moreover, we have observed that the 88D and 77I mutations were present in more than 75% of patients harbouring the 30N HIV‐1 variant and the 71T mutation was present in almost 50% of them. Finally, mutations 30N+90M were never detected together in the same HIV‐1 strain. The 30N and 90M mutations were not observed together. The presence of mutations at positions 36, 46, 71, 77, and/or 88 in a 30N background, increases the risk of the cross‐resistance to other PIs. The use of NFV as a first‐line PI, as an application of drug sequencing strategies, may help preserve future PI options. J. Clin. Lab. Anal. 19:26–29, 2005. © 2005 Wiley‐Liss, Inc.

SEN virus (SENV) is a new family of single-stranded DNA viruses with eight different strains, A–H. The modifications in SENV DNA detection and subtype distribution were studied over a long-term follow-up (48 ± 32.5 months) in 52 HIV-infected patients. 46% of the patients in the first sample and 34.6% in the second sample were found to have detectable SENV viremia. While the most prevalent variant in the first sample was found to be genotype A (83.3%), the second sample revealed a broader subtype diversification. Several epidemiological and clinical variables were tested in univariate model for clearance of detectable SENV viremia, but none of them reached statistical significance. In conclusion, a high degree of instability of both SENV DNA detection and subtype distribution in a cohort of HIV-infected patients was suggested, which may have important implications for further studies on both SENV epidemiology and its clinical impact.

Purpose: High-dose therapy (HDT) and peripheral-blood stem-cell transplantation (PBSCT) in HIV-associated lymphoma (HIV-Ly) has been recently reported in selected patients. We describe the results of a multi-institutional program of HDT and PBSCT as salvage therapy in HIV-Ly responsive to highly active antiretroviral therapy (HAART) in unselected patients. Patients and Methods: Patients with resistant or relapsed HIV-Ly after first-line chemotherapy (CT) underwent PBSC collection after a course of second-line CT or cyclophosphamide and granulocyte colony-stimulating factor. Patients with chemotherapy-sensitive disease received carmustine, etoposide, cytarabine, and melphalan (BEAM regimen) and PBSC reinfusion. Effective HAART was maintained during the entire program. Results: Sixteen consecutive patients entered the program. Adequate collection of PBSC was obtained in 80% of patients (median CD34+ cells 6.8 × 106/kg). Three patients had early progression. Ten patients (62%) received PBSCT with prompt engraftment in all patients (neutrophils and platelet engraftment after a median of 10 days [range, 8 to 10 days] and 13 days [range, 8 to 18 days], respectively). No patients died as a result of opportunistic or other infections or treatment-related complications. Eight of nine assessable patients achieved complete remission (one patient after radiotherapy for residual disease) and one patient achieved partial remission. Two patients experienced relapse and died at +10 and +14 months. Six patients are alive and disease free at a median of 8 months after transplantation. Conclusion: Our data confirm that HDT plus PBSCT is feasible and active as salvage therapy in HIV-Ly on a multi-institutional basis and in unselected HAART-responding patients. HIV infection should no longer preclude the opportunity of HDT in patients with lymphoma.

Objectives: To assess incidence, risk factors, histology, and outcome of severe hepatotoxicity (SH) during antiretroviral treatment (ART). Methods: Seven hundred fifty-five HIV-seropositive patients consecutively prescribed new ART were selected. Liver function tests were assessed at baseline, after I month, and every 4 months thereafter. Liver biopsy was recommended in case of SH (i.e., increase in liver enzymes ≥ 10 times the upper limit of normal or 5 times baseline if markedly abnormal). Results: Twenty-six cases of SH were observed with an incidence of 4.2% person-years. Liver failure (LF) was rarely seen (1.1 per 100 person-years). Liver damage was invariably observed in patients with chronic viral hepatitis. Liver histology showed exacerbation of viral hepatitis in all 16 patients for whom a liver biopsy was available at the time of SH. A direct correlation was found between alanine aminotransferase increase and increase in CD 4+ T-cell count in patients with SH (r = 0.53, p

Summary One of the main concerns associated with renal transplantation in HIV-infected patients is the high risk of acute rejection, which makes physicians reluctant to use steroid-free immunosuppressive therapy in this subset of patients. However, steroid therapy increases cardiovascular morbidity and mortality. The aim of this study was to define the efficacy of a steroid-sparing regimen in HIV-infected renal transplant recipients. Thirteen HIV-infected patients were consecutively transplanted. The induction therapy consisted of basiliximab and methylprednisolone for 5 days followed by a calcineurin inhibitor plus mycophenolate acid. The mean follow-up was 50 ± 22 months. Eight patients (61.5%) experienced acute rejection, and 75% of the first episodes occurred within 2 months after transplantation. The probability of first acute rejection was 58% after 1 year and 69% after 4 years. Seven of eight patients recovered or maintained their kidney function after antirejection therapy and steroid resumption. At the last follow-up, seven of 13 patients (54%) had resumed steroid therapy. The 4-year patient and graft survivals were 100% and 88.9%, respectively. The benefits of this steroid-free regimen in HIV-infected renal recipients must be reconsidered because of the high rate of acute rejection. New immunosuppressive steroid-free strategies should be identi-fied in this set of patients.