Publications by authors named "Andrea Costantini"

38 Publications

The effect of dupilumab in an HBV-HIV coinfected atopic patient: a case report.

Acta Dermatovenerol Alp Pannonica Adriat 2021 Jun;30(2):71-73

Dermatology Unit, Department of Clinical and Molecular Sciences, Marche Polytechnic University, Ancona, Italy.

Atopic dermatitis (AD) is a chronic immune-mediated inflammatory disease typical of childhood that can also affect adults. AD is clinically characterized by intensely pruritic eczematous lesions. The burden of this disease and its impact on quality of life are often substantial. Dupilumab is a fully humanized monoclonal antibody against interleukin 4 (IL-4) receptor α, capable of blocking IL-4 and IL-13 signaling. This novel therapy represents the first biologic approved for the treatment of moderate to severe AD. Our report describes the case of a 39-year-old adult patient affected by severe chronic AD with associated allergic and viral comorbidities for whom conventional systemic therapies proved ineffective or contraindicated. The main source of interest in this case is hepatitis B virus (HBV) and human immunodeficiency virus (HIV) coinfection because, to our knowledge, this is the first case of an adult atopic patient treated with dupilumab in the simultaneous presence of these comorbidities. Regarding coinfections, the patient was on antiretroviral therapy for HBV and HIV before starting dupilumab. Efficacy and safety data after 24 weeks of therapy are reported in detail.
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June 2021

Inflammation and microbial translocation measured prior to combination antiretroviral therapy (cART) and long-term probability of clinical progression in people living with HIV.

BMC Infect Dis 2021 Jun 12;21(1):557. Epub 2021 Jun 12.

Clinic of Infectious Diseases, Department of Health Sciences, University of Milan, "ASST Santi Paolo e Carlo, Milan, Italy.

Background: Despite the effectiveness of cART, people living with HIV still experience an increased risk of serious non-AIDS events, as compared to the HIV negative population. Whether pre-cART microbial translocation (MT) and systemic inflammation might predict morbidity/mortality during suppressive cART, independently of other known risk factors, is still unclear. Thus, we aimed to investigate the role of pre-cART inflammation and MT as predictors of clinical progression in HIV+ patients enrolled in the Icona Foundation Study Cohort.

Methods: We included Icona patients with ≥2 vials of plasma stored within 6 months before cART initiation and at least one CD4 count after therapy available. Circulating biomarker: LPS, sCD14, EndoCab, hs-CRP. Kaplan-Meier curves and Cox regression models were used. We defined the endpoint of clinical progression as the occurrence of a new AIDS-defining condition, severe non-AIDS condition (SNAEs) or death whichever occurred first. Follow-up accrued from the data of starting cART and was censored at the time of last available clinical visit. Biomarkers were evaluated as both binary (above/below median) and continuous variables (logescale).

Results: We studied 486 patients with 125 clinical events: 39 (31%) AIDS, 66 (53%) SNAEs and 20 (16%) deaths. Among the analyzed MT and pro-inflammatory markers, hs-CRP seemed to be the only biomarker retaining some association with the endpoint of clinical progression (i.e. AIDS/SNAEs/death) after adjustment for confounders, both when the study population was stratified according to the median of the distribution (1.51 mg/L) and when the study population was stratified according to the 33% percentiles of the distribution (low 0.0-1.1 mg/L; intermediate 1.2-5.3 mg/L; high > 5.3 mg/L). In particular, the higher the hs-CRP values, the higher the risk of clinical progression (p = 0.056 for median-based model; p = 0.002 for 33% percentile-based model).

Conclusions: Our data carries evidence for an association between the risk of disease progression after cART initiation and circulating pre-cART hs-CRP levels but not with levels of MT. These results suggest that pre-therapy HIV-driven pro-inflammatory milieu might overweight MT and its downstream immune-activation.
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http://dx.doi.org/10.1186/s12879-021-06260-yDOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8196504PMC
June 2021

Quantification of the HIV-1 total reservoir in the peripheral blood of naïve and treated patients by a standardised method derived from a commercial HIV-1 RNA quantification assay.

Clin Chem Lab Med 2021 Feb 28;59(3):609-617. Epub 2020 Apr 28.

Department of Biomedical Sciences and Public Health, Polytechnic University of Marche, Ancona, Italy.

Objectives: HIV-1 DNA can persist in host cells, establishing a latent reservoir. This study was aimed to develop an extraction and amplification protocol for HIV-1 DNA quantification by modifying a quantitative commercial assay.

Methods: HIV-1 DNA was extracted on an Abbott m2000 instrument, using an open-mode protocol. Two calibrators, spiked with a plasmid containing HIV-1 genome (10 and 10 cps/mL), were extracted and amplified to generate a master calibration curve. Precision, accuracy, linear dynamic range, limit of quantification (LOQ) and limit of detection (LOD) were determined. A cohort of patients, naïve or chronically infected, was analysed.

Results: Calibration curve was obtained from 42 replicates of standards (std); precision was calculated (coefficients of variability [CVs] below 10%); accuracy was higher than 90%. Linearity covered the entire range tested (10-10 copies per reaction), and LOD (95%) was 12 copies per reaction. HIV-1 DNA was significantly higher (p < 0.0001) in drug-naïve (62) than in chronically treated patients (50), and proviral loads correlated with lymphocytes (p = 0.0002) and CD4 (p < 0.0001) counts only in naïve patients. Both groups displayed a significant inverse correlation between CD4 nadir and proviral loads. A significant correlation (p < 0.0001) between viraemia and HIV-1 reservoir was disclosed. No significant difference was obtained from the comparison between proviral loads on whole blood and peripheral blood mononuclear cells (PBMCs) from the same patient.

Conclusions: The novelty of our approach relies on the selection of appropriate reference standard extracted and amplified as clinical specimens avoiding any underestimation of the reservoir. Results confirm HIV-1 DNA as a marker of disease progression, supporting the relationship between the width of latent reservoir and the immunological status of the patient.
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http://dx.doi.org/10.1515/cclm-2020-0142DOI Listing
February 2021

Evaluation of HIV Transmission Clusters among Natives and Foreigners Living in Italy.

Viruses 2020 07 23;12(8). Epub 2020 Jul 23.

Clinical Epidemiology Unit, National Institute for Infectious Diseases "Lazzaro Spallanzani" IRCCS, 00149 Rome, Italy.

We aimed at evaluating the characteristics of HIV-1 molecular transmission clusters (MTCs) among natives and migrants living in Italy, diagnosed between 1998 and 2018. Phylogenetic analyses were performed on HIV-1 polymerase () sequences to characterise subtypes and identify MTCs, divided into small (SMTCs, 2-3 sequences), medium (MMTCs, 4-9 sequences) and large (LMTCs, ≥10 sequences). Among 3499 drug-naïve individuals enrolled in the Italian Cohort Naive Antiretroviral (ICONA) cohort (2804 natives; 695 migrants), 726 (20.8%; 644 natives, 82 migrants) were involved in 228 MTCs (6 LMTCs, 36 MMTCs, 186 SMTCs). Migrants contributed 14.4% to SMTCs, 7.6% to MMTCs and 7.1% to LMTCs, respectively. HIV-1 non-B subtypes were found in 51 MTCs; noteworthy was that non-B infections involved in MTCs were more commonly found in natives ( = 47) than in migrants ( = 4). Factors such as Italian origin, being men who have sex with men (MSM), younger age, more recent diagnosis and a higher CD4 count were significantly associated with MTCs. Our findings show that HIV-1 clustering transmission among newly diagnosed individuals living in Italy is prevalently driven by natives, mainly MSM, with a more recent diagnosis and frequently infected with HIV-1 non-B subtypes. These results can contribute to monitoring of the HIV epidemic and guiding the public health response to prevent new HIV infections.
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http://dx.doi.org/10.3390/v12080791DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7472346PMC
July 2020

A novel method to evaluate prethawing viability of cryopreserved CD34+ hematopoietic stem cells for autologous transplantation.

Transfusion 2020 07 2;60(7):1529-1535. Epub 2020 Jun 2.

Dipartimento di Scienze Cliniche e Molecolari, Università Politecnica delle Marche, Ancona, Italy.

Background: Cryopreservation of CD34+ hematopoietic stem cells (HSCs) is associated with variable loss of viability. Although postfreezing CD34+ cell viability can be assessed on the sampling tube (bag tail) directly connected to the main bag (mother bag), results often underestimate the actual viability observed when the mother bag is thawed and reinfused. We assessed a novel method to measure postfreezing CD34+ cell viability, based on small bag (minibag) samples; results were compared with those obtained on the corresponding mother bags and bag tails.

Study Design And Methods: Sixty-one apheresis procedures of 42 patients undergoing autologous HSC transplant were analyzed. Viable CD34+ cells were quantified with flow cytometry before controlled rate freezing (ICE-CUBE14M system, SY-LAB- IceCube, SIAD), after 10 days of storage (mini-bag and bag tail), and before reinfusion (aliquot from a thawed mother bag). Results were compared using Student's t test and Spearman's rho correlation test.

Results: The mean CD34+ cell viability before cryopreservation was 99.3% (confidence interval [CI], 98.94-99.65%); the mean amount of CD34+ cells, white blood cells and neutrophils in the mother bag was 0.8 ± 1.1 × 10 /L, 63.4 ± 23.5 × 10 /L, and 25.7 ± 15.5 × 10 /L, respectively. Mother bags postthawing CD34+ cell viability was 72.3% (CI, 67.74-76.85%; p < 0.01 compared to prefreezing); no difference was observed with respect to minibags (73.7%; CI, 69.80-77.59%; p = NS), whereas significantly lower values were found for bag tails (58.6%; CI, 54.19-63.00%; p < 0.01 vs. both mini- and mother bags).

Conclusion: Compared to bag tails, minibags represent a more accurate tool to measure the CD34+ cell viability of the apheresis mother bag prior to reinfusion; in addition, minibags may could be of help for case-by-case calculation of the amount of apheresis to be infused to patients undergoing autologous HSC transplant.
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http://dx.doi.org/10.1111/trf.15825DOI Listing
July 2020

Gut epithelial impairment, microbial translocation and immune system activation in inflammatory bowel disease-associated spondyloarthritis.

Rheumatology (Oxford) 2021 01;60(1):92-102

Dipartimento di Scienze Cliniche e Molecolari, Clinica Medica, Università Politecnica delle Marche, Ancona, Italy.

Objectives: Gut microbiota has been widely reported to be involved in systemic inflammation through microbial translocation and T cell activation in several diseases. In this work we aimed to investigate bacterial infiltration and epithelial impairment in the gut of patients with IBD-associated SpA (SpA-IBD), as well as the relationship of microbial translocation with immune system activation and their putative role in the pathogenesis of joint inflammation in IBD patients.

Methods: Tight-junction proteins (TJPs) occludin and claudin-1/-4 and bacteria were assessed by real-time PCR analysis and immunohistochemical staining of the ileum. Intestinal fatty acid binding protein (I-FABP), lipopolysaccharides (LPS), soluble CD14 (sCD14), sclerostin and anti-sclerostin antibodies (anti-sclerostin-IgG) were assayed with ELISAs and peripheral mononuclear blood cells with flow cytometry. LPS and sCD14 were used in vitro to stimulate a human osteoblast cell line.

Results: Compared with IBD, ileal samples from SpA-IBD patients showed bacterial infiltration, epithelial damage and downregulation of TJPs. In sera, they showed higher serum levels of I-FABP, LPS, sCD14 (the latter correlating with sclerostin and anti-sclerostin-IgG) and higher CD80+/CD163+ and lower CD14+ mononuclear cells. In vitro experiments demonstrated that only the LPS and sCD14 synergic action downregulates sclerostin expression in osteoblast cells.

Conclusion: SpA-IBD patients are characterized by gut epithelium impairment with consequent translocation of microbial products into the bloodstream, immune system activation and an increase of specific soluble biomarkers. These findings suggest that gut dysbiosis could be involved in the pathogenesis of SpA-IBD and it could hopefully prompt the use of these biomarkers in the follow-up and management of IBD patients.
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http://dx.doi.org/10.1093/rheumatology/keaa164DOI Listing
January 2021

Nilotinib Treatment of Patients Affected by Chronic Graft-versus-Host Disease Reduces Collagen Production and Skin Fibrosis by Downmodulating the TGF-β and p-SMAD Pathway.

Biol Blood Marrow Transplant 2020 05 30;26(5):823-834. Epub 2020 Jan 30.

Department of Clinical and Molecular Science, Università Politecnica delle Marche, Ancona, Italy; Hematology Unit, AUO Ospedali Riuniti di Ancona, Ancona, Italy. Electronic address:

The present study was conducted to investigate cellular and molecular features of chronic graft-versus-host disease fibroblasts (GVHD-Fbs) and to assess the effectiveness of nilotinib as a fibrosis modulator. Growth kinetics, phenotype, and differentiation of cultured skin biopsy-derived GVHD-Fbs were compared with normal fibroblasts from both a dermal cell line (n-Fbs) and healthy individuals undergoing cosmetic surgery (n-skin-Fbs). Collagen genes (COL1α1/COL1α2) and p-SMAD2 expression were assessed by real-time PCR and immunofluorescence. The in vivo effects of nilotinib on chronic GVHD (cGVHD)-affected skin were investigated by immunohistochemistry; the relationship to TGF-β plasma levels was assessed. Although the morphology, phenotype, and differentiation of cultured GVHD-Fbs were comparable to normal fibroblasts, growth was slower and senescence was reached earlier. The expression of COL1α1 and COL1α2 mRNAs was respectively 4 and 1.6 times higher in cGVHD-Fbs (P = .02); the addition of TGF-β increased n-Fbs, but not GVHD-Fbs, collagen gene expression. Compared with the baseline, the addition of 1 μM nilotinib induced 86.5% and 49% reduction in COL1α1 and COL1α2 expression in cultured GVHD-Fbs, respectively (P< .01). In vivo immunohistochemistry analysis of skin biopsy specimens from patients with cGVHD showed strong baseline staining for COL1α1 and COL1α2, which decreased sharply after 180 days of nilotinib; immunofluorescence revealed TGF-β inhibition and p-Smad2 reduction at the intracellular level. Of note, nilotinib treatment was associated with normalization of TGF-β levels both in culture supernatants and in plasma. In general, the data show that cGVHD fibroblasts promote fibrosis through abnormal collagen production induced by hyperactive TGF-β signaling. TGF-β inhibition at the intracellular and systemic level represents an essential antifibrotic mechanism of nilotinib in a clinical setting.
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http://dx.doi.org/10.1016/j.bbmt.2020.01.014DOI Listing
May 2020

Poem Versus Laparoscopic Heller Myotomy in the Treatment of Esophageal Achalasia: A Case-Control Study from Two High Volume Centers Using the Propensity Score.

J Gastrointest Surg 2020 03 17;24(3):505-515. Epub 2019 Dec 17.

Digestive Endoscopy Unit, Fondazione Policlinico Universitario Agostino Gemelli IRCCS, Università Cattolica del Sacro Cuore, Center for Endoscopic Research, Therapeutics and Training (CERTT), Rome, 00168, Italy.

Background: POEM has recently had a widespread diffusion, aiming at being the treatment of choice for esophageal achalasia. The results of ongoing RCTs against laparoscopic myotomy are not available, yet. We, therefore, designed this propensity score (PS) case-control study with the aim of evaluating how POEM compares to the long-standing laparoscopic Heller myotomy + Dor fundoplication (LHD) and verifying if it may really replace the latter as the first-line treatment for achalasia.

Methods: Two groups of consecutive patients undergoing treatment for primary achalasia from January 2014 to November 2017 were recruited in two high-volume centers, one with extensive experience with POEM and one with LHD. Patients with previous endoscopic treatment were included, whereas patients with previous LHD or POEM were excluded. A total of 140 patients in both centers were thus matched. LHD and POEM were performed following established techniques. The patients were followed with clinical (Eckardt score), endoscopic, and pH-manometry evaluations.

Results: The procedure was successfully completed in all the patients. POEM required a shorter operation time and postoperative stay compared to LHD (p < 0.001). No mortality was recorded in either group. Seven complications were recorded in the POEM group (five mucosal perforations) and 3 in the LHD group (3 mucosal perforations)(p = 0.33). Two patients in the POEM group and one in the LHD were lost to follow-up. One patient in both groups died during the follow-up for unrelated causes. At a median follow-up of 24 months [15-30] for POEM and 31 months [15-41] for LHD (p < 0.05), 99.3% of the POEM patients and 97.7% of the LHD patients showed an Eckardt score ≤ 3 (p < 0.12). Four years after the treatment, the probability to have symptoms adequately controlled was > 90% for both groups (p = 0.2, Log-rank test). HR-Manometry showed a similar reduction in the LES pressure and 4sIRP; 24-h pH-monitoring showed however an abnormal exposure to acid in 38.4% of POEM patients, as compared to 17.1% of LHD patients (p < 0.01) and esophagitis was found in 37.4% of the POEM and 15.2% of LHD patients (p < 0.05).

Conclusion: POEM provides the same midterm results as LHD. This study confirms, however, a higher incidence of postoperative GERD with the former, even if its real significance needs to be further evaluated.
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http://dx.doi.org/10.1007/s11605-019-04465-wDOI Listing
March 2020

Impact of NRTI resistance mutations on virological effectiveness of antiretroviral regimens containing elvitegravir: a multi-cohort study.

J Antimicrob Chemother 2020 01;75(1):194-199

Infectious Diseases, IRCCS San Raffaele, Via Olgettina 60, 20132, Milan, Italy.

Background: Antiretroviral drug resistance mutations remain a major cause of treatment failure.

Objectives: To evaluate the impact of NRTI resistance mutations on virological effectiveness of elvitegravir-containing regimens.

Materials And Methods: We selected treatment-experienced HIV-1-infected patients starting elvitegravir/cobicistat/emtricitabine/tenofovir alafenamide (E/C/F/TAF) or elvitegravir/cobicistat/emtricitabine/tenofovir disoproxil fumarate (E/C/F/TDF), with at least one protease/reverse transcriptase genotype available before switching and at least one HIV-1 RNA viral load (VL) measurement during follow-up. The primary endpoint was virological failure (VF), defined as one VL value of ≥1000 copies/mL or two consecutive VL values of >50 copies/mL.

Results: We included 264 ART regimens: 75.6% male, median (IQR) age 47 years (39-53), 7 years (3-16) of HIV infection, nadir CD4+ 247 cells/mm3 (105-361), 81.5% with VL ≤50 copies/mL and 11.7% with at least one NRTI mutation at baseline. Eleven (5.2%) VFs occurred in virologically suppressed patients versus eight (15.1%) in viraemic patients. The estimated probability of VF at 48 weeks with versus without any NRTI mutation was 7.4% (95% CI 2.3-12.5) versus 3.8% (2.1-5.5) in virologically suppressed patients and 66.7% (39.5-93.9) versus 11.2% (6.5-15.9) (P<0.001) in viraemic patients. The only predictor of VF was time on therapy (per 1 year more, adjusted HR 1.14, 95% CI 1.02-1.27, P=0.024) in viraemic patients.

Conclusions: A switch to E/C/F/TDF or E/C/F/TAF is safe for virologically suppressed patients without documented NRTI resistance, but not recommended in viraemic patients with a history of NRTI resistance. Although we did not detect a detrimental effect of past NRTI resistance in virologically suppressed patients, a fully active regimen remains preferred in this setting due to possible rebound of drug-resistant virus in the long term.
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http://dx.doi.org/10.1093/jac/dkz424DOI Listing
January 2020

Durability of first-line regimens including integrase strand transfer inhibitors (INSTIs): data from a real-life setting.

J Antimicrob Chemother 2019 05;74(5):1363-1367

HIV/AIDS Department, INMI 'L. Spallanzani' IRCCS, Rome, Italy.

Objectives: To evaluate the durability of three integrase strand transfer inhibitors (INSTIs) and two NRTIs in ART-naive individuals.

Methods: The study design was observational. Patients were HIV-positive, ART-naive subjects starting raltegravir, elvitegravir/cobicistat or dolutegravir with two NRTIs. The primary endpoint was time to treatment failure, i.e. occurrence of virological failure (first of two consecutive plasma HIV RNAs  ≥200 copies/mL after 24 weeks) or INSTI discontinuation for any reason apart from simplification. Secondary endpoints were INSTI discontinuation due to toxicity/intolerance and CD4 count response. Survival analysis was done using Kaplan-Meier and Cox regression.

Results: Two thousand and sixteen patients were included: 310 (15.4%) started raltegravir-based regimens, 994 (49.3%) started dolutegravir-based regimens and 712 (35.3%) started elvitegravir/cobicistat-based regimens. Over a median of 11 months, 167 patients experienced treatment failure; the 1 year probability of treatment failure was 6.5% for raltegravir, 5.4% for dolutegravir and 6.7% for elvitegravir/cobicistat (P = 0.001). Sixty-eight patients (3.4%) discontinued INSTIs owing to toxicity/intolerance. By multivariable analysis, patients starting raltegravir had a 2.03-fold (95% CI = 1.2-3.2) higher risk and patients on elvitegravir/cobicistat a 1.88-fold (95% CI = 1.2-2.9) higher risk of treatment failure versus dolutegravir; there was no difference in risk of discontinuation due to toxicity/intolerance when comparing dolutegravir and raltegravir and marginal evidence for a difference when comparing elvitegravir/cobicistat and dolutegravir (adjusted relative hazard = 1.94 for elvitegravir/cobicistat versus dolutegravir, 95% CI = 1.00-3.76, P = 0.05).

Conclusions: In our real-life setting, INSTI-based regimens showed high potency and durability. Among regimens currently recommended in Europe, those including dolutegravir are associated with a lower risk of treatment failure.
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http://dx.doi.org/10.1093/jac/dky566DOI Listing
May 2019

A Thousand and One Laparoscopic Heller Myotomies for Esophageal Achalasia: a 25-Year Experience at a Single Tertiary Center.

J Gastrointest Surg 2019 01 20;23(1):23-35. Epub 2018 Sep 20.

Clinica Chirurgica 3, Department of Surgical, Oncological and Gastroenterological Sciences, Università ed Azienda Ospedaliera di Padova, 2, via Giustiniani, 35128, Padua, Italy.

Background: The aim of this study was to assess the long-term outcome of laparoscopic Heller-Dor (LHD) myotomy to treat achalasia at a single high-volume institution in the past 25 years.

Methods: Patients undergoing LHD from 1992 to 2017 were prospectively registered in a dedicated database. Those who had already undergone surgical or endoscopic myotomy were ruled out. Symptoms were collected and scored using a detailed questionnaire; barium swallow, endoscopy, and manometry were performed before and after surgery; and 24-h pH monitoring was done 6 months after LHD.

Results: One thousand one patients underwent LHD (M:F = 536:465), performed by six staff surgeons. The surgical procedure was completed laparoscopically in all but 8 patients (0.8%). At a median of follow-up of 62 months, the outcome was positive in 896 patients (89.5%), and the probability of being cured from symptoms at 20 years exceeded 80%. Among the patients who had previously received other treatments, there were 25/182 failures (13.7%), while the failures in the primary treatment group were 80/819 (9.8%) (p = 0.19). All 105 patients whose LHD failed subsequently underwent endoscopic pneumatic dilations with an overall success rate of 98.4%. At univariate analysis, the manometric pattern (p < 0.001), the presence of a sigmoid megaesophagus (p = 0.03), and chest pain (p < 0.001) were the factors that predicted a poor outcome. At multivariate analysis, all three factors were independently associated with a poor outcome. Post-operative 24-h pH monitoring was abnormal in 55/615 patients (9.1%).

Conclusions: LHD can durably relieve achalasia symptoms in more than 80% of patients. The pre-operative manometric pattern, the presence of a sigmoid esophagus, and chest pain represent the strongest predictors of outcome.
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http://dx.doi.org/10.1007/s11605-018-3956-xDOI Listing
January 2019

Day-On, Day-Off emtricitabine, tenofovir disoproxil fumarate and efavirenz single tablet regimen (DODO) as maintenance therapy in HIV-infected patients.

Infez Med 2018 Jun;26(2):126-132

Azienda Ospedaliero Universitaria Ospedali Riuniti, Ancona, Italy.

Reduced dose schedules may be feasible options to simplify antiretroviral therapy (ART) in selected HIV-1-infected individuals. Efficacy and safety of a Day-on, Day-off (DODO) schedule of tenofovir disoproxil fumarate, emtricitabine and efavirenz (FTC/TDF/EFV) single tablet regimen (STR) was assessed. Twenty-seven patients were prescribed the DODO schedule and were monitored for 48 weeks. Switching criteria were: no previous ART failure, no AIDS-defining illnesses, T CD4 cell nadir >200/mmc, and HIV-RNA below detection limit (40 copies/mL) for at least six months. Clinical and laboratory data, including plasma HIV-RNA levels, T CD4 and CD8 counts, liver and kidney function, lipid levels and ultrasensitive C-reactive protein (us-CRP) were assessed at baseline, week 4, 12, 24, and 48. Statistical analysis was performed by paired Student's T-test for comparison between baseline and each time point and Chi square test for CD4/CD8 ratio comparison. In all, 26 out of 27 patients maintained plasma HIV-RNA levels below the detection limit through the entire follow-up. One patient experienced low level plasma HIV-RNA rebound at week 36 (47 copies/ml) and immediately reverted to the conventional dose schedule of FTC/TDF/EFV; plasma HIV-RNA was undetectable after four weeks. No major changes on liver and kidney function tests, lipid levels and us-CRP were observed. Although no profound modifications of T CD4 count were observed during follow-up, the CD4/CD8 ratio increased significantly at week 48 compared to the baseline (p<0.05). In conclusion, 48-week DODO administration of the fixed dose FTC/TDF/EFV STR combination was safe and effective in maintaining HIV viral replication below the detection limit in a selected group of HIV-1-infected individuals.
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June 2018

Age-related M1/M2 phenotype changes in circulating monocytes from healthy/unhealthy individuals.

Aging (Albany NY) 2018 Jun;10(6):1268-1280

Department of Experimental, Diagnostic and Specialty Medicine, DIMES, Alma Mater Studiorum, Bologna, Italy.

Macrophage polarization is a candidate biomarker of disease-related inflammatory status, but its modulation during aging has not been investigated. To do this, the M1/M2 profile was assessed by CD80/CD163 gating in classical (CD14CD16), intermediate (CD14CD16), and non-classical (CD14CD16) monocytes from 31 healthy subjects (CTRs) of different ages. Cytofluorimetric analysis showed a significantly different CD80/CD163 distribution in the three subsets, as more than 80% of classical and intermediate monocytes were CD80CD163, whereas most non-classical monocytes were CD80CD163 and CD163. Non-classical CD163 monocytes were significantly higher whereas classical CD163 and CD80CD163 monocytes significantly lower in older than younger CTRs (cut-off, 65 years), suggesting different age-related trends for M2 subsets. To establish whether an M1/M2 imbalance could be associated with disease, 21 patients with acute myocardial infarction (AMI) were compared with older CTRs. The AMI patients showed a significantly decreased proportion of CD163CD80 and an increased proportion of CD163 and CD163CD80 cells among classical monocytes, opposite trends to those observed in healthy aging. Moreover, a significantly greater proportion of intermediate and non-classical CD80 monocytes suggested a shift to a pro-inflammatory phenotype. Overall, CD163/CD80 cytofluorimetric characterization of circulating monocytes provides additional information about their polarization and could be an innovative tool to monitor aging.
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http://dx.doi.org/10.18632/aging.101465DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6046240PMC
June 2018

Incidence and predictors of single drug discontinuation according to the presence of HCV coinfection in HIV patients from the ICONA Foundation Cohort Study.

Eur J Clin Microbiol Infect Dis 2018 May 9;37(5):871-881. Epub 2018 Jan 9.

Department of Health Sciences, Clinic of Infectious and Tropical Diseases, ASST Santi Paolo e Carlo, University of Milan, Milan, Italy.

To evaluate incidence rates of and predictors for any antiretroviral (ART) drug discontinuation by HCV infection status in a large Italian cohort of HIV infected patients. All patients enrolled in ICONA who started combination antiretroviral therapy (cART) containing abacavir or tenofovir or emtricitabine or lamivudine plus efavirenz or rilpivirine or atazanavir/r or darunavir/r (DRV/r) or lopinavir/r or dolutegravir or elvitegravir or raltegravir were included. Multivariate Poisson regression models were used to determine factors independently associated with single ART drug discontinuation. Inverse probability weighting method to control for potential informative censoring was applied. Data from 10,637 patients were analyzed and 1,030 (9.7%) were HCV-Ab positive. Overall, there were 15,464 ART discontinuations due to any reason in 82,415.9 person-years of follow-up (PYFU) for an incidence rate (IR) of 18.8 (95% confidence interval [95%CI] 18.5-19.1) per 100 PYFU. No difference in IR of ART discontinuation due to any reason between HCV-infected and -uninfected patients was found. In a multivariable Poisson regression model, HCV-infected participants were at higher risk of darunavir/r discontinuation due to any reason (adjusted incidence rate ratio = 1.5, 95%CI 1.01-2.22, p value = 0.045) independently of demographics, HIV-related, ART and life-style factors. Among DRV/r treated patients, we found that HCV-viremic patients had twice the risk of ART discontinuation due to any reason than HCV-aviremic patients. In conclusion, HIV/HCV coinfected patients had a marginal risk increase of DRV/r discontinuation due to any reason compared with those without coinfection.
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http://dx.doi.org/10.1007/s10096-017-3180-8DOI Listing
May 2018

The natural history of achalasia: Evidence of a continuum-"The evolutive pattern theory".

Dig Liver Dis 2018 Apr 26;50(4):342-347. Epub 2017 Nov 26.

Department of Surgical, Oncological and Gastroenterological Sciences, University of Padova, School of Medicine, Padova, Italy.

Background: It is currently unclear if the three manometric patterns of esophageal achalasia represent distinct entities or part of a disease continuum. The study's aims were: a) to test the hypothesis that the three patterns represent different stages in the evolution of achalasia; b) to investigate whether manometric patterns change after Laparoscopic-Heller-Dor (LHD).

Methods: We assessed the patients diagnosed with achalasia who underwent LHD as their first treatment from 1992 to 2016. Their symptoms were scored using a detailed questionnaire for dysphagia, food-regurgitation, and chest pain. Barium-swallow, endoscopy, and esophageal-manometry were performed before and 6 months after surgery.

Results: The study population consisted of 511 patients (M:F=283:228). Patients' demographic and clinical data showed that those with pattern III had a shorter history of symptoms, a higher incidence of chest pain, and a less dilated gullet (p<0.001). All patients with a sigmoid-shaped mega-esophagus had pattern I achalasia. One patient with a diagnosis of pattern III achalasia developed pattern II at a follow-up manometry before surgery. At a median follow-up of 30 months (IQR 12-56), the outcome of surgery was positive in 479 patients (91.7%). All patients with pattern I preoperatively had the same pattern after LHD, whereas more than 50% of patients with pattern III before treatment showed pattern I or II after surgery.

Conclusions: This study supports the hypothesis/theory that the different manometric patterns represent different stages in the evolution of the disease-where pattern III is the earliest stage, pattern II an intermediate stage, and pattern I the final stage.
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http://dx.doi.org/10.1016/j.dld.2017.11.012DOI Listing
April 2018

Immunomodulatory Effects of Tyrosine Kinase Inhibitor In Vitro and In Vivo Study.

Biol Blood Marrow Transplant 2018 02 8;24(2):267-275. Epub 2017 Nov 8.

Dipartimento di Scienze Cliniche e Molecolari, Università Politecnica delle Marche, Ancona, Italy; Clinica di Ematologia, Azienda Ospedaliero Universitaria Ospedali Riuniti, Ancona, Italy. Electronic address:

Pathogenesis of chronic graft-versus-host disease (cGVHD) is incompletely defined, involving donor-derived CD4 and CD8-positive T lymphocytes as well as B cells. Standard treatment is lacking for steroid-dependent/refractory cases; therefore, the potential usefulness of tyrosine kinase inhibitors (TKIs) has been suggested, based on their potent antifibrotic effect. However, TKIs seem to have pleiotropic activity. We sought to evaluate the in vitro and in vivo impact of different TKIs on lymphocyte phenotype and function. Peripheral blood mononuclear cells (PBMCs) from healthy donors were cultured in the presence of increasing concentrations of nilotinib, imatinib, dasatinib, and ponatinib; in parallel, 44 PBMC samples from 15 patients with steroid-dependent/refractory cGVHD treated with nilotinib in the setting of a phase I/II trial were analyzed at baseline, after 90, and after 180 days of therapy. Flow cytometry was performed after labeling lymphocytes with a panel of monoclonal antibodies (CD3, CD4, CD16, CD56, CD25, CD19, CD45RA, FoxP3, CD127, and 7-amino actinomycin D). Cytokine production was assessed in supernatants of purified CD3 T cells and in plasma samples from nilotinib-treated patients. Main T lymphocyte subpopulations were not significantly affected by therapeutic concentrations of TKIs in vitro, whereas proinflammatory cytokine (in particular, IL-2, IFN-γ, tumor necrosis factor-α, and IL-10) and IL-17 production showed a sharp decline. Frequency of T regulatory, B, and natural killer (NK) cells decreased progressively in presence of therapeutic concentrations of all TKIs tested in vitro, except for nilotinib, which showed little effect on these subsets. Of note, naive T regulatory cell (Treg) subset accumulated after exposure to TKIs. Results obtained in vivo on nilotinib-treated patients were largely comparable, both on lymphocyte subset kinetics and on cytokine production by CD3-positive cells. This study underlines the anti-inflammatory and immunomodulatory effects of TKIs and supports their potential usefulness as treatment for patients with steroid-dependent/refractory cGVHD. In addition, both in vitro and in vivo data point out that compared with other TKIs, nilotinib could better preserve the integrity of some important regulatory subsets, such as Treg and NK cells.
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http://dx.doi.org/10.1016/j.bbmt.2017.10.039DOI Listing
February 2018

Brief Report: Soluble CD163 in CMV-Infected and CMV-Uninfected Subjects on Virologically Suppressive Antiretroviral Therapy in the ICONA Cohort.

J Acquir Immune Defic Syndr 2017 03;74(3):347-352

*Sapienza University of Rome, Rome, Italy; †Sapienza University of Rome, Polo Pontino, Latina, Italy; ‡University of Milan, Milan, Italy; §University of Bologna, Bologna, Italy; and ‖Polytechnic University of Marche, Ancona, Italy.

Aims: To contribute to the understanding of the role played by cytomegalovirus (CMV) in sustaining monocyte/macrophage-mediated immune activation in antiretroviral therapy treated HIV-infected subjects.

Design And Methods: We selected 23 CMV-uninfected and 46 CMV-infected HIV+ subjects, matched for age, CD4 nadir, HIV infection duration, and viral hepatitis serostatus. All subjects were on successful antiretroviral therapy since at least 1 year. A group of 16 healthy donors with similar age and sex was also included. Plasma levels of tumor necrosis factor-alpha, interleukin-6, sCD163, sCD14, and CMV immunoglobulin G levels were measured in duplicate with human enzyme-linked immunosorbent assay kits.

Results: We found significantly higher sCD163 plasma levels in HIV+CMV+ compared with HIV+CMV- subjects and healthy donors. This augmentation was confirmed also when subjects positive for hepatitis C virus-Ab were excluded from analysis. Interestingly, a correlation between anti-CMV immunoglobulin G levels and sCD163, tumor necrosis factor-alpha, interleukin-6, and sCD14 in HIV+CMV+ subjects was found.

Conclusions: CMV coinfection could be a major driver of monocyte/macrophage activation in virally suppressed HIV+ individuals and might explain the increased risk of non-AIDS morbidity/mortality in HIV/CMV-coinfected subjects.
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http://dx.doi.org/10.1097/QAI.0000000000001232DOI Listing
March 2017

Validation of a self-reported HIV symptoms list: the ISS-HIV symptoms scale.

AIDS Res Ther 2016 9;13:18. Epub 2016 Apr 9.

Istituto Superiore di Sanità, Rome, Italy.

Background: To describe the development and the psychometric properties of the Istituto Superiore di Sanità-HIV symptoms scale (lSS-HIV symptoms scale).

Methods: The ISS-HIV symptom scale was developed by an Italian working team including researchers, physicians and people living with HIV. The development process went through the following steps: (1) review of HIV/AIDS literature; (2) focus group; (3) pre-test analysis; (4) scale validation.

Results: The 22 symptoms of HIV-ISS symptoms scale were clustered in five factors: pain/general discomfort (7 items); depression/anxiety (4 items); emotional reaction/psychological distress (5 items); gastrointestinal discomfort (4 items); sexual discomfort (2 items). The internal consistence reliability was for all factors within the minimum accepted standard of 0.70.

Conclusions: The results of this study provide a preliminary evidence of the reliability and validity of the ISS-HIV symptoms scale. In the new era where HIV infection has been transformed into a chronic diseases and patients are experiencing a complex range of symptoms, the ISS-HIV symptoms scale may represent an useful tool for a comprehensive symptom assessment with the advantage of being easy to fill out by patients and potentially attractive to physicians mainly because it is easy to understand and requires short time to interpret the results.
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http://dx.doi.org/10.1186/s12981-016-0102-2DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4826516PMC
September 2016

Discontinuation of Initial Antiretroviral Therapy in Clinical Practice: Moving Toward Individualized Therapy.

J Acquir Immune Defic Syndr 2016 Mar;71(3):263-71

*Infectious Diseases Unit, IRCCS AOU S. Martino-IST, National Institute for Cancer Research, Genoa, Italy;†Department of Infection and Population Health, Division of Population Health, UCL Medical School, Royal Free Campus, London, United Kingdom;‡Department of Biomedical Science and Human Oncology, University of Bari, Bari, Italy;§Clinic of Infectious Diseases, San Gerardo Hospital, University of Milano-Bicocca, Monza, Italy;‖Infectious Diseases Unit, Busto Arsizio Hospital, Busto Arsizio (VA), Italy;¶Infectious Diseases Unit, Siena University Hospital, Siena, Italy;#Department of Health Sciences, University of Ancona, Ancona, Italy;**Infectious Diseases Clinic, Policlinico of Modena, University of Modena and Reggio Emilia, Modena, Italy;††Infectious Diseases Unit, Sacco Hospital, Milan, Italy;‡‡Infectious Diseases Unit, Vita-Salute University, San Raffaele Scientific Institute, Milan, Italy;§§National Institute for Infectious Diseases IRCCS L. Spallanzani, Rome, Italy; and‖‖Clinic of Infectious and Tropical Diseases, Department of Health Sciences, S Paolo Hospital, University of Milan, Milan, Italy.

Background: Study aim was to estimate the rate and identify predictors of discontinuation of first combination antiretroviral therapy (cART) in recent years.

Methods: Patients who initiated first cART between January 2008 and October 2014 were included. Discontinuation was defined as stop of at least 1 drug of the regimen, regardless of the reason. All causes of discontinuation were evaluated and 3 main endpoints were considered: toxicity, intolerance, and simplification. Predictors of discontinuation were examined separately for all 3 endpoints. Kaplan-Meier analysis was used for the outcome discontinuation of ≥ 1 drug regardless of the reason. Cox regression analysis was used to identify factors associated with treatment discontinuation because of the 3 reasons considered.

Results: A total of 4052 patients were included. Main reason for stopping at least 1 drug were simplification (29%), intolerance (21%), toxicity (19%), other causes (18%), failure (8%), planned discontinuation (4%), and nonadherence (2%). In a multivariable Cox model, predictors of discontinuation for simplification were heterosexual transmission (P = 0.007), being immigrant (P = 0.017), higher nadir lymphocyte T CD4 cell (P = 0.011), and higher lymphocyte T CD8 cell count (P = 0.025); for discontinuation due to intolerance: the use of statins (P = 0.029), higher blood glucose levels (P = 0.050). About toxicity: higher blood glucose levels (P = 0.010) and the use of zidovudine/lamivudine as backbone (P = 0.044).

Conclusions: In the late cART era, the main reason for stopping the initial regimen is simplification. This scenario reflects the changes in recommendations aimed to enhance adherence and quality of life, and minimize drug toxicity.
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http://dx.doi.org/10.1097/QAI.0000000000000849DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4770376PMC
March 2016

Cost of HAART in Italy: multicentric evaluation and determinants from a large HIV outpatient cohort.

Clinicoecon Outcomes Res 2015 22;7:27-35. Epub 2014 Dec 22.

Infectious Diseases Unit, Pescara General Hospital, Pescara, Italy.

Background: As HIV infection turned into a chronic treatable disease, now ranking as one of the most costly in medicine, long-term sustainability of highly active antiretroviral treatment (HAART) expenses became a major issue, especially in countries with universal access to care. Identification of determinants of higher HAART costs may therefore help in controlling costs of care, while keeping high levels of retention in care and viral suppression.

Methods: With this aim, we enrolled a large multicentric sample of consecutive unselected human immunodeficiency virus (HIV) patients followed at five sites of care in Italy, and evaluated annual individual HAART costs in relation to a number of sociodemographic, clinical, and laboratory variables.

Results: We enrolled 2,044 patients, including 1,902 on HAART. Mean HAART costs were €9,377±€3,501 (range 782-29,852) per year, with remarkable site-based differences, possibly related to the different composition of local assisted populations. Percentages of patients on viral suppression were homogeneously high across all study sites. The factors identified by cross-validation were line of HAART, diagnosis of acquired immune deficiency syndrome, current CD4 T-cell count, and detectable HIV viremia >50 copies/mL. In the final multivariable model, HAART costs were independently directly associated with more advanced HAART line (P<0.001) and inversely correlated with current CD4 T-cell count (P=0.024). Site of care held independent prediction of higher costs, with marked control of expenses at sites 2 (P=0.001) and 5 (P<0.001).

Conclusion: Higher costs of HAART were strongly associated with previous treatment failures, detectable HIV viremia, and lower CD4 T-cell count at the time of evaluation, with no correlation at all with sex, age, hepatitis C virus coinfection, and nadir CD4 T-cell counts. Newer drugs, which are typically those associated with high prices, at the time of the analysis were still prevalently prescribed to rescue and maintain viral suppression in patients with more complex treatment history. Further analyses of the contribution of the single drug/regimen to the estimated cost are warranted.
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http://dx.doi.org/10.2147/CEOR.S69183DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4278727PMC
January 2015

Treatment discontinuation in HIV-1-infected individuals starting their first-line HAART after 2008: data from the ICONA Foundation Study Cohort.

J Int AIDS Soc 2014 2;17(4 Suppl 3):19825. Epub 2014 Nov 2.

Infectious Diseases, University of Milan, San Paolo Hospital, Milano, Italy; Health Sciences, University of Milan, San Paolo Hospital, Milano, Italy.

Introduction: The aim of this study was to analyze the likelihood and the predictors of discontinuation of first-line regimen in the late HAART era.

Methodology: An observational multi-center analysis of HIV-positive patients enrolled in ICONA. Patients eligible were those starting a first-line HAART after 1 January 2008. Discontinuation was defined as stop and/or switch of at least one drug of the regimen. All causes of discontinuation, as reported by the treating physician, were evaluated and cumulative risk of stopping was investigated according to age, gender, co-morbidity, years since starting HAART, immuno-virological status, third drug and backbone of the first regimen. Kaplan Meier (KM) analysis and Cox proportional hazards model were used for the outcome discontinuation of ≥1 drug regardless of the reason. For the KM estimates a competing risk approach was used to estimate the contribution of each of the reasons over time to the cumulative risk of stopping over time.

Results: Data of 1759 patients who started first HAART and had at least one month of clinical follow-up were analyzed. The overall discontinuation risk was 33% over a median follow-up of 12 months. The likelihood of discontinuation by KM was 27% by one year (95% CI 25-29) and 41% by two years (95% CI 38-44). Main reason for stopping at least one drug in regimen was simplification (10%), followed by intolerance (7%), toxicity (5%), failure (2%) and other causes (8%). Estimates of the cumulative risk of discontinuation of ≥1 drug over time and according to reason are shown in Figure 1. In a multivariable Cox model independent predictors of discontinuation regardless of the reason were: longer time from HIV diagnosis to date of starting HAART (hazard ratio [HR] 0.96; 95% CI 0.93-1.00; p=0.039), regimens containing ZDV/3TC (HR 2.86; 95% CI 1.42-5.76; p=0.003 vs TDF/FTC) and an NNRTI-based regimen (HR 2.47; 95% CI 0.91-6.72; p=0.07 vs regimens not NNRTI-based).

Conclusions: In a previously reported analysis of the ICONA data (1), the overall risk of discontinuation of first-line HAART was 36% with 21% due to intolerance/toxicity. In this updated analysis, the main reason for stopping is simplification (accounting for 32% of stops), reflecting the recent changes in recommendations aimed to minimize drug toxicity, enhancing adherence and quality of life.
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http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4225385PMC
http://dx.doi.org/10.7448/IAS.17.4.19825DOI Listing
January 2016

Pregnancy outcomes among ART-naive and ART-experienced HIV-positive women: data from the ICONA foundation study group, years 1997-2013.

J Acquir Immune Defic Syndr 2014 Nov;67(3):258-67

*Department of Health Sciences, Clinic of Infectious and Tropical Diseases, University of Milan, Milan, Italy; †Infectious Diseases, San Raffaele Hospital, Milan, Italy; ‡Infectious Diseases, Bagno a Ripoli Hospital, Florence, Italy; §Department of Health and Infectious Diseases, University La Sapienza, Polo Pontino, Rome, Italy; ‖Infectious Diseases, INMI "L. Spallanzani," I.R.C.C.S, Rome, Italy; ¶Infectious Diseases, Galliera Hospital, Genova, Italy; #Infectious Diseases, University of Perugia, Perugia, Italy; **Clinical Immunology, University of Ancona, Ancona, Italy; ††Infectious Diseases, University Sacro Cuore, Rome, Italy; ‡‡Division of Infectious and Tropical Diseases, Spedali Civili, University of Brescia, Brescia, Italy; and §§INMI "L. Spallanzani," I.R.C.C.S, Epidemiology, Rome, Italy.

Background: We analyzed antiretroviral therapy (ART) regimens and pregnancy outcomes in naive and ART-experienced HIV-positive women from Italian Cohort Naive Antiretrovirals cohort and investigated frequency and predictors of detectable viral load (VL) at delivery.

Methods: All pregnancies resulting in live births were included. Based on ART at the beginning of pregnancy, pregnancies were allocated either to the ART-naive or ART-experienced group. Analyses were stratified according to calendar periods. Multivariate logistic regression was used to describe predictors of detectable VL at delivery.

Results: One hundred fifty-eight of 2862 women experienced 169 pregnancies (88 in naives and 81 in 70 ART-experienced women). ART regimens varied according to calendar periods; mono-dual combination regimens progressively decreased over time (P value for trend <0.0001). Protease inhibitor-including regimens were the most frequently used regimens at delivery (71.6% vs 63.0% in naives and in ART experienced, P = 0.2). VL was detectable in 35.6% of women at delivery; this was less likely with increasing calendar periods (adjusted odds ratio per 1-year longer: 0.8, 95% confidence interval: 0.7 to 0.9, P = 0.007) and more likely in women with HIV RNA >50 copies per milliliter at pregnancy ascertainment (adjusted odds ratio: 7.1, 95% confidence interval: 1.9 to 33.3, P = 0.006). Nevertheless, no cases of vertical transmission were diagnosed. Preterm birth rate of 17.3% (11.9% vs 22.6% naive and ART experienced, P = 0.1) was reported; this was not associated with ART duration or protease inhibitor-including regimens; 27.2% of infants had <2500 g birth weight.

Conclusions: Antiretroviral regimens prescribed during pregnancy changed over time according to guidelines. Although undetectable VL was not always achieved, no vertical transmission occurred; preterm delivery and low birth weight occurred in some cases and still remain key issues.
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http://dx.doi.org/10.1097/QAI.0000000000000297DOI Listing
November 2014

Durability of lopinavir/ritonavir monotherapy in individuals with viral load ≤50 copies/ml in an observational setting.

Antivir Ther 2014 13;19(3):319-24. Epub 2013 Sep 13.

Department of Health Sciences, Institute of Infectious Diseases, University of Milan, Milan, Italy.

Background: The main objective is to evaluate the efficacy and durability of lopinavir-ritonavir monotherapy (LPV/r-MT) in virologically controlled HIV-positive individuals switching from combination antiretroviral therapy (cART).

Methods: Criteria to be included in this observational study were to have initiated for the first time LPV/r-MT after ≥2 consecutive HIV RNA≤50 copies/ml achieved on a ≥3-drug-including regimen. The main end points were time to virological rebound (VR; defined in two ways: time of first of two consecutive viral load [VL]>50 and >200 copies/ml), time to discontinuation/intensification and time to experience either a single VL>200 copies/ml or discontinuation/intensification (treatment failure [TF]). Individuals' follow-up accrued from the date of starting LPV/r-MT to event or last available VL. Kaplan-Meier curves and Cox regression analyses were used.

Results: A total of 228 individuals were included: median age 46 years (IQR 40-50), 36% females, 36% intravenous drug users and 25% HCV-coinfected. Median CD4(+) T-cell count at nadir was 215 cell/mm(3) (IQR 116-336) and at baseline was 615 cell/mm(3) (IQR 436-768). By 36 months after switching to LPV/r-MT, the proportion of individuals with VR (confirmed VL>200 copies/ml) was 11% and with TF was 35%. In the multivariable Cox model the factors associated with a lower risk of TF was the duration of viral suppression <50 copies/ml prior to baseline (ARH=0.92; 95% CI 0.85, 0.99; P=0.024, per 6 months longer) and having LPV/r as part of last cART (ARH=0.45; 95% CI 0.21, 0.95; P=0.037).

Conclusions: In daily clinical practice, we confirm a relatively safe approach of treatment simplification to LPV-MT in a selected population with long-lasting virological control.
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http://dx.doi.org/10.3851/IMP2687DOI Listing
January 2015

Polyclonal serum-free light chains elevation in HIV-infected patients.

AIDS 2012 Oct;26(16):2107-10

National Institute for Infectious Diseases, Lazzaro Spallanzani, IRCCS, Rome, Italy.

We investigated the association between polyclonal serum-free light chains and prognostic biomarkers routinely used in the setting of HIV infection. For this purpose serum samples of 182 HIV-infected patients from the Italian Cohort of Antiretroviral Naive Patients foundation cohort were analysed. We found that polyclonal serum free light chains above the upper normal limit are strongly correlated in HIV-infected patients with advancing age, shorter time of undetectable HIV viremia, higher viral load and with lower CD4 cell count at sample.
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http://dx.doi.org/10.1097/QAD.0b013e328358d54bDOI Listing
October 2012

Molecular analysis of hepatitis B virus (HBV) in an HIV co-infected patient with reactivation of occult HBV infection following discontinuation of lamivudine-including antiretroviral therapy.

BMC Infect Dis 2011 Nov 4;11:310. Epub 2011 Nov 4.

Department of Biomedical Sciences and Public Health, Università Politecnica Marche, Ancona, Italy.

Background: Occult hepatitis B virus (HBV) infection (OBI) is characterized by HBV DNA persistence even though the pattern of serological markers indicates an otherwise resolved HBV infection. Although OBI is usually clinically silent, immunocompromised patients may experience reactivation of the liver disease.

Case Presentation: We report the case of an individual with human immunodeficiency virus (HIV) infection and anti-HBV core antibody positivity, who experienced severe HBV reactivation after discontinuation of lamivudine-including antiretroviral therapy (ART). HBV sequencing analysis showed a hepatitis B surface antigen escape mutant whose presence in an earlier sample excluded reinfection. Molecular sequencing showed some differences between two isolates collected at a 9-year interval, indicating HBV evolution. Resumption of ART containing an emtricitabine/tenofovir combination allowed control of plasma HBV DNA, which fell to undetectable levels.

Conclusion: This case stresses the ability of HBV to evolve continuously, even during occult infection, and the effectiveness of ART in controlling OBI reactivation in HIV-infected individuals.
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http://dx.doi.org/10.1186/1471-2334-11-310DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3239326PMC
November 2011

Hepatitis C virus core antigen: analytical performances, correlation with viremia and potential applications of a quantitative, automated immunoassay.

J Clin Virol 2011 Aug 28;51(4):264-9. Epub 2011 May 28.

Virology Unit, Section of Microbiology, University of Parma, Italy.

Background: Testing for hepatitis C virus core antigen (HCV Ag) may represent a complementary tool to anti-HCV and HCV-RNA in the diagnosis and monitoring of HCV infection.

Objective: To evaluate the performance characteristics of the automated Abbott ARCHITECT HCV Ag assay.

Study Design: Five sites analyzed over 3000 routine serum samples from populations at different risk, comparing HCV Ag results with anti-HCV screening and supplemental assay results and with HCV-RNA.

Results: The HCV Ag assay showed a specificity of 100%, a good precision (CV<10%) and excellent dilution linearity (r>0.999). The sensitivity (3 fmol/L) corresponds to 700-1100 IU/mL of HCV-RNA. A non-linear correlation with HCV-RNA was found: r=0.713 vs. Siemens bDNA (523 specimens), r=0.736 vs. Roche Cobas TaqMan (356 specimens) and r=0.870 vs. Abbott Real-Time PCR (273 specimens). HCV Ag quantitation was equally effective on different HCV genoypes (239 for genotype 1/1a/1b/1c, 108 for genotype 2/2a/2c, 86 for genotype 3/3a, 50 for genotype 4/4a/4c/4d). Testing of subjects at high risk for HCV and with potential or actual impairment of the immune system identified 2 cases negative for anti-HCV and positive for HCV Ag on 361 hemodialyzed (0.6%) and 7 cases on 97 (7.2%) among transplant recipients. HCV Ag positivity anticipated anti-HCV seroconversion in all three cases of acute hepatitis C.

Conclusions: HCV Ag may be used as reflex testing on anti-HCV positive individuals to confirm or exclude an active infection, and on subjects with acute hepatitis or belonging to high risk groups.
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http://dx.doi.org/10.1016/j.jcv.2011.05.003DOI Listing
August 2011
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