Giuseppe Ferrea

The ligurian human immunodeficiency virus clinical network: a web tool to manage patients with human immunodeficiency virus in primary care and multicenter clinical trials.

Background In recent years, Highly-Active Anti-Retroviral Therapies (HAARTs) have modified the Human Immunodeficiency Virus (HIV) life-cycle and the disease is now considered chronic. Consequently, a longitudinal and complex follow-up is now required for HIV positive patients during their lifetime. Moreover, patients often encounter various complications due to comorbidities, related to the immunodeficiency state and HAARTs’ side effects. Thus, HIV positive patients are involved in multicenter clinical trials (MCTs) to improve treatments and discover a preventive vaccine. Therefore, physicians require proper instruments to access comprehensive patient data for managing patients during follow-ups, and tools for data collection and analysis in MCTs. Objective The Ligurian HIV Clinical Network aims to provide physicians with a Web-tool to administrate HIV positive patients’ data within primary-care and to reuse the collected clinical information to perform MCTs in Northern Italy. Methods The key aspect of the system is a relational database which allows the storage of various types of clinical information (eg, related to HIV, cardiovascular, or hepatic diseases) in multiple formats. The modular design of the database permits a rapid insertion of new parameters without requiring any changes in the database structure. Furthermore, codes from biomedical ontologies controlled vocabularies (“Logical Observation Identifier Names and Codes”, and “International Classification of Diseases 9”) and ontologies (“Systematized Nomenclature of Medicine Clinical Terms”), units and normality ranges used by all partners participating in the project were collected to achieve a complete semantic interoperability. Accordingly, data can be automatically normalized through the z score formula and physicians can extract and correctly compare information with external statistical tools. Moreover, to respect patients’ privacy and legal issues, a local identifier, determined through an HASH cryptography algorithm, is assigned to each patient during the registration process. The database is managed by a user-friendly Web-platform which allows quick access to information during medical examinations and the reusing of the collected data for present and future MCTs. Furthermore, a bidirectional middleware was created in order to import/export information through HL7 messaging. Hence, data can be manually entered by physicians or automatically collected within HL7-compliant Hospital Information systems. Results Presently, the direct storage of patients’ information from the San Paolo Hospital (Savona, Italy), and San Martino and Galliera hospitals in Genoa is in a test phase. Currently, 8 centers of Infectious Diseases (located in Liguria and Piedmont) are participating in the project and almost 400 HIV positive patients have been recorded in the system. Patient data has been used for primary care and research purposes. Currently, there are 4 on-going MCTs and preliminary results have already been presented at International HIV congresses. Conclusions The Web-platform allows effective management, sharing and reuse of information within primary care and clinical research. In the future it is planned to share the clinical information from this network with other HL7-compliant workgroups and to extend the platform to other infective diseases (eg, hepatitis).

Listeria monocytogenes brain abscesses in a girl with acute lymphoblastic leukaemia after late central nervous system relapse

A case of Listeria monocytogenes bacteraemia and meningitis with intracerebral abscesses in a girl with acute lymphoblastic leukaemia in relapse is reported. The clinical features included subacute onset with fever and marked irritability followed by seizures, meningism and confusion. The pathogen was isolated from blood and cerebrospinal fluid. Computerised tomography of the brain showed two intracerebral parenchymal localisations, in the left frontal lobe and in the right occipital lobe, respectively. The patient survived this severe infection without neurological sequelae. 2 months later she underwent allogeneic bone marrow transplantation without major complications. This case report should alert pediatric oncologists about the possible occurrence of severe intracerebral listerial infections in the immunocompromised child and suggests that this infection can be treated successfully and should not necessarily preclude continuation of antineoplastic treatments.

Visceral leishmaniasis due to Leishmania infantum with renal involvement in HIV-infected patients

BackgroundWe describe histological, clinical findings and outcomes of renal involvement during Leishmania infantum infection in four HIV-infected patients in South France and North Italy hospital settings.Cases presentationFour HIV-infected Caucasian patients (age 24-49) performed renal biopsy during episodes of visceral leishmaniasis. They presented severe immunosuppression, frequent relapses of visceral leishmaniasis during a follow-up period of several years and partial or complete recovery of renal function after anti-parasitic treatment. Main clinical presentations were nephrotic or nephritic syndrome and/or acute renal failure secondary to membranoproliferative type III glomerulonephritis or acute interstitial nephritis. Clinical outcome was poor, probably as a consequence of insufficient immuno-virological control of the HIV infection.ConclusionsOur findings suggest that the main histological findings in case of renal involvement due to Leishmania infantum infection in HIV-infected patients are type III MPGN and acute interstitial nephritis, with a histological specificity similar to that observed in canine leishmaniasis. Poor immune status in HIV-infected patients, altering the capacity for parasite clearance, and prolonged course of chronic active VL in this population may lead to the development of specific renal lesions.

Clinically Stable Treatment-Experienced Adults Receiving Tenofovir and Didanosine

Abstract Method: Analysis of virological, immunological, and clinical data over 24 weeks of treatment of drug-experienced patients administered didanosine (ddI) and tenofovir (TDF) plus either PI or NNRTI (17 patients) compared to 14 patients on ddI plus lamivudine and to 19 patients on ddI plus stavudine. Results: Patients treated with TDF and ddI do not have a higher risk of early immunological or virological failure. Conclusion: Treatment success and increase in CD4+ lymphocytes may depend, among other factors, on historical CD4+ nadir. These data agree with previous work and argue against preemptive switches for fear of side effects or immunological/virological failure away from a successful ddI-TDF combination in clinically stable drug-experienced patients.

Use of maraviroc in clinical practice: a multicenter observational study

Promising research suggest that maraviroc (MVC) has favourable clinical outcome in HIV‐infected patients (pts). Aim of the study is to assess: durability, safety profile and immunovirological recovery in a large MVC‐based cohort.

Relationship between innate immunity, soluble markers and metabolic-clinical parameters in HIV+ patients ART treated with HIV-RNA<50 cp/mL.

The persistence of immune activation and inflammation in HIV patients with HIV‐RNA (VL) undetectable causes many co‐morbidities [ 1 – 3 ]. The aim of this study is to correlate monocytes (m) and NK cell activation levels, soluble markers and oxidative stress with clinical, biochemical and metabolic data in HIV‐1 infected patients with VL≤50 copies (cp)/mL on antiretroviral therapy.

Conserved T cell and natural killer cell function in treatment-experienced adults receiving tenofovir plus didanosine as nucleoside reverse transcription inhibitor backbone

Anti‐retroviral treatment (ART) usually results in efficient control of virus replication and in immune reconstitution. Among potential adverse effects, impairment of immune responses in terms of CD4+ T cell counts has been attributed to some ART regimens, as with didanosine–tenofovir. We studied the functional integrity of adaptive and innate immunity during didanosine–tenofovir‐containing ART. Two groups of extensively pretreated patients completing at least 48 weeks of ART containing either lamivudine–didanosine (n = 21) or tenofovir–didanosine (n = 25) were identified. In addition to standard clinical immune and virological parameters, we performed a flow cytometric analysis of natural killer (NK) cells, of memory and naive CD4+ T cells and of T cell receptor αβ+ T cells co‐expressing inhibitory NK receptors. Functional analysis consisted in specific and total interferon‐γ production by NK cells and of recall antigen proliferation of peripheral blood mononuclear cells. Comparable clinical immunological reconstitution and virological control were confirmed in the two groups of patients in the absence of clinically relevant adverse effects. The proportion of CD4+CD45RA+ T cells and of functionally inhibited killer immunoglobulin‐like receptor T cell receptor αβ+ cells, the proliferation to recall antigens as well as NK cell phenotype and function as determined by interferon‐γ production in patients treated with tenofovir–didanosine were comparable to those treated with a different regimen. Thus, no differences in functional innate or adaptive immune reconstitution are detected in drug‐experienced human immunodeficiency virus‐infected patients on tenofovir–didanosine nucleoside reverse transcription inhibitor regimens.