Andrea Beltrame

Clinical and virological survey of patients with hepatitis B surface antigen in an Italian region: clinical considerations and disease burden.

The aim of this study was to determine the prevalence of hepatitis B virus (HBV) infection in an Italian region, Liguria (1,572,000 inhabitants), by means of a network of 12 referral centers for liver diseases. All patients with HBV surface antigen followed throughout 2006 were included. Personal data, infectious status with risk factors, other non‐infectious risk factors for liver disease, clinical status, and treatment were the questionnaire. Four hundred forty‐five patients (71% male) were evaluated. Their median age was 48 years (range 5–84), and 83.4% were of Italian origin. Community‐acquired infection was the principal mode of HBV transmission (82.5%), followed by previous intravenous drug use (9.4%), perinatal transmission (6.3%), and transfusion‐associated transmission (1.8%). Hepatitis B e‐antigen was present in 20.4% of the patients, while co‐infections with hepatitis D virus and/or hepatitis C virus and/or human immunodeficiency virus (HIV) were observed in 18.7% of the patients. Chronic active hepatitis was present in 62.5% of the patients, cirrhosis in 13.5%, hepatocellular carcinoma in 2.2%, and 21.8% of the patients were inactive carriers of HBV. In all, 42.5% of the patients were treated with interferon or lamivudine and/or adefovir‐dipivoxil. Forty‐nine patients were co‐infected with HIV (86% on highly active antiviral therapy). Nevertheless, this study identified only 2.2% of the expected patients with HBV. Hence, it has to be reasoned that few potential infectious or treatable patients are referred to liver disease centers. HBV infection is still an underestimated health problem, and few potential infectious or treatable patients are referred to tertiary centers. J. Med. Virol. 81:1882–1886, 2009.

Effectiveness of a project to prevent HIV vertical transmission in the Republic of Congo

OBJECTIVES To evaluate the effectiveness of a prevention programme against the vertical transmission of HIV in a resource-limited setting and to investigate variables associated with compliance. PATIENTS AND METHODS The Kento-Mwana project (2005-2008) provided counselling, serological and biomolecular testing and prophylaxis/therapy to HIV-positive pregnant women and their children attending four antenatal clinics in Pointe Noire, Republic of Congo. Expected and actual rates of vertical transmission of HIV were compared. Univariate and multivariate analyses were performed in order to identify variables associated with non-compliance. RESULTS The observed transmission rate in the group who completed follow-up was 5/290 (1.7%, 95% CI 0.6%-4.1%). The overall estimated transmission rate in the target population, computed taking into account the expected vertical transmission of HIV among drop-outs, was 67-115/638 (10.5%-18.0%). A comparison between this rate and the expected transmission rate in the absence of intervention (25%-40%) showed that the programme was able to prevent approximately 50% of vertical transmissions. Older age (OR 0.33, 95% CI 0.16-0.66, P = 0.002), telephone availability (OR 0.42, 95% CI 0.24-0.72, P = 0.002) and occupation (OR 0.57, 95% CI 0.29-1.10, P = 0.092) were associated with better compliance. CONCLUSIONS Despite the vast majority of women accepting counselling and testing, many of them refused prophylaxis or dropped out, thus reducing the effectiveness of the intervention from an ideal 2% to a still important but less impressive median transmission rate of 15% (range 10.5%-18%). Promoting participation and compliance, rather than increasing the potency of antiretroviral regimens, is crucial for preventing the vertical transmission of HIV in Africa.

Therapeutical aspects and outcome of HIV/HCV coinfected patients treated with pegylated interferon plus ribavirin in an Italian cohort.

Background:One-third of HIV-infected individuals suffer from chronic hepatitis C virus infection (HCV) in Europe. Recommendations from HCV–HIV International Panel advise current treatment with pegylated interferon plus ribavirin. We assessed the impact of interferon and ribavirin combination in 43 patients between 2002 and 2006.Patients and Methods:All coinfected patients treated for HCV during the 5-year period were included in retrospective data collection. CD4+ T-lymphocyte count, HAART discontinuation, reasons for treatment interruption and factors correlated to sustained virological response (SVR) were monitored.Results:The mean age was 41 ± 6.7 years; the risk factor for coinfection was intravenous drug abuse in 32/43 (74%). The baseline CD4+ T-lymphocytes cell count was > 500 in 51% (22/43). Genotype 3a represented 51% (22/43); 37% were on HAART at baseline (16/43) and half of patients showed high HCV RNA levels (> 800,000 IU/ml). High rates of treatment discontinuation were observed (27/43, 63%), caused by voluntary interruptions in 52% (14/27) and virological failure in 26% (7/27). The overall population had an SVR of 30%; genotypes 3a and 1 had SVR of 38% and 24%, respectively. The SVR was significantly lower in three groups: high HCV RNA viral load (χ2 = 6, p < 0.0025), CD4+ T-lymphocyte historical nadir <350 cells/mm3 (χ2 = 3.26, p < 0.01) and genotype 1 with high viral load (χ2 = 4.8, p < 0.005).Conclusions:Although factors such as HCV viral load rates and genotype 1 have been confirmed to threaten the response to therapy, we observed a significant response rate when patients had a history of CD4+ T-lymphocyte nadir >350 per mm3. The high dropout rates due to voluntary discontinuations complicated the patients’ case management.

Role of linezolid in the treatment of orthopedic infections.

Gram-positive organisms, particularly staphylococci and streptococci, are responsible for the majority of bone and joint infections. The rising incidence of antimicrobial resistance among Staphylococcus aureus, coagulase-negative staphylococci and enterococci means that novel antibiotics with unique mechanisms of antimicrobial activity are needed, especially in orthopedic infections. Linezolid is the first of the oxazolidinones, a new class of antibacterial agents particularly effective against Gram-positive infections including methicillin- and vancomycin-resistant strains. With an excellent oral bioavailability and acceptable safety profile, linezolid offers a valuable alternative to more traditional therapies, such as glycopeptides. No large randomized trials have been published on its use in patients with orthopedic infections, but early results are encouraging. Reported adverse events, especially bone marrow suppression and optic neuropathy seen with prolonged administration, mean that treatment of such patients must be undertaken with careful follow-up of laboratory tests. Until now, little resistance has been reported.

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.

Therapeutic management of chronic hepatitis B in clinical practice: A region-wide survey

Goals: To characterize the clinical and treatment pattern in a large population of hepatitis B virus (HBV) patients managed at tertiary referral centers in clinical practice. Background: Successful treatment, either with interferon (IFN) or nucleos(t)ide analogs (NUCs), of chronic HBV infection is associated with improved long-term patient outcome. However, in clinical practice, the actual management of these patients is not well characterized, and data regarding treatment pattern in this setting are lacking. Methods: In this cross-sectional study, we evaluated 505 patients chronically infected with HBV alone and who had at least 1-year follow-up. We assessed indication to, rate of, and type of treatment as well as the characteristics of treated patients. Results: Overall prevalence of positivity for HBe antigen was 19.3%, and the majority of patients had chronic hepatitis (47.5%). Non-Italian patients represented approximately one third of the population (27.1%). Among patients with indication to antiviral therapy (n=318), treatment was actually carried out in 264 patients (83.0%), prevalently with NUCs (65.9%). IFN-treated patients were younger (P<0.001), more frequently male (P=0.025) and HBeAg positive (P=0.003), and less frequently cirrhotics (P<0.001) as compared with patients treated with NUCs. Conclusions: In a geographical area with a low positivity for HBe antigen, antiviral therapy is actually carried out in the majority of patients who have indication to treatment, prevalently with NUCs, whereas IFN treatment is more frequently carried out in young, HBe antigen–positive patients who do not have advanced liver disease.

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.

Sepsis in frail patient

Frailty is defined as a clinical syndrome in which three or more of the following criteria are present: unintentional weight loss, self-reported exhaustion, weakness (grip strength), slow walking speed and low physical activity. Sepsis is defined as an inflammatory response to infection, with severe sepsis and septic shock being the most severe forms. The incidence of severe sepsis increases with older age and several studies have shown that there are many risk factors that predispose the elderly to a higher incidence of sepsis. Pre-existing co-morbidities such as cancer, diabetes, obesity, human immunodeficiency virus, and renal or pulmonary disease can cause sepsis, but other factors including poor lifestyle habits ( i.e ., smoking, drug or alcohol abuse), malnutrition, and endocrine deficiencies, which are frequent in the elderly, may also predispose to severe infections. Other risk factors for sepsis include recurrent hospitalization, especially in the Intensive Care Unit, and nursing home residence, where interventions such as urinary catheterization or multiple drug use are quite frequent and many studies reported that people above 65 years of age are three times more likely to be admitted to hospital than those aged 16-64 years, and have a higher risk of prolonged hospital stays, institutionalization and death. Clinical evaluation of the frail patient with sepsis poses some challenges. The immune response becomes progressively less efficient with increasing age thereby causing an altered response to infection and it is important to know that the clinical evaluation of the so-called fragile patient with severe infection should take into account the sometimes unusual signs and symptoms that, if identified, can lead to early diagnosis. Laboratory diagnostics can also be of great help in this setting. The treatment of sepsis in the fragile patient can be empirical or based on microbiological culture. Moreover, frail patient population presents many clinical problems with numerous comorbidities, therefore anti-infective treatment is difficult, so the physician’s armamentarium must include many antibiotic drugs, of which there are far more available for the treatment of sepsis caused by Gram-positive bacteria than for sepsis caused by Gram-negative ones or fungi.