Giovanna Orlando

Combined surgery and cidofovir is an effective treatment for genital warts in HIV-infected patients.

Objective To evaluate the efficacy of surgical-cidofovir (SCT), surgical (ST) and cidofovir (CT) treatment of genital warts in HIV-infected patients. Design Open randomized prospective pilot study. Setting Outpatients attending the sexually transmitted disease service of the II Dept of Infectious Diseases, L Sacco Hospital, Milan-Italy. Patients Consenting HIV-positive patients with anal–genital warts recruited from January 2000 to March 2001. Interventions Three treatment arms: surgical excision by electrocautery, topical 1% cidofovir-gel (5 days per week, maximum 6 weeks) and electrocautery–cidofovir treatment with 1% cidofovir-gel applied within 1 month of surgical treatment (5 days per week for 2 weeks). Main outcome measures Rate of wart clearance and time and rate of relapses within a 6-month follow-up period. Results Complete response was achieved in 93.1% of 29 patients treated by ST, 76.2% of 26 treated by CT and in 100% of 19 patients treated by SCT (P = 0.0033). The relapse rate in 49 patients followed-up was 73.68% in ST, 35.29% in CT and 27.27% in SCT patients (P = 0.018). Median time to relapses in ST patients was 66 days (Kaplan–Meyer, P = 0.0012). Human papillomavirus DNA was cleared in 52.63% of 19 patients evaluated. The rate of clearance of high risk and low risk genotypes was 0% and 57.14% 25% and 50% 100% and 71.42% in ST, CT and SCT patients, respectively. Conclusions A combination of surgical and medical treatment was most effective in clearing lesions completely and in reducing the relapse rate. Human papillomavirus DNA clearance can be attributed to the antiviral effect of cidofovir and could explain the low relapse rate observed. Larger studies are required to determine the most appropriate medical treatment for viral eradication after surgery.

Linezolid plasma concentrations and occurrence of drug-related haematological toxicity in patients with Gram-positive infections

Retrospective studies have documented a significant association between linezolid (LNZ) plasma concentrations and drug-related haematological toxicity. However, the safe upper threshold level for LNZ plasma trough concentrations (Cmin values) has not been defined with certainty. A prospective observational study was performed aimed at comparing LNZ Cmin values in patients developing drug-related side effects with those measured in patients not experiencing LNZ toxicity. LNZ Cmin values were measured from the first week after starting therapy and were repeated periodically up to the end of treatment. Fifty patients, for a total of 210 LNZ Cmin evaluations, were considered. All patients (n=9) who developed drug-related haematological toxicity also had significantly higher plasma LNZ Cmin values during the first week of therapy (9.0±6.4 mg/L vs. 4.9±3.7 mg/L; P<0.01) and thereafter (9.3±5.4 mg/L vs. 4.4±3.4 mg/L; P<0.01). The significant association between LNZ plasma concentrations and haematological toxicity was also confirmed by multivariate logistic regression analysis including age, serum creatinine and concomitant medications as independent variables. A causal relationship between LNZ concentrations and the risk of developing drug-related haematological toxicity was observed. Accordingly, application of therapeutic drug monitoring may improve the safety outcome of patients receiving LNZ therapy.

High performance of a new PCR-based urine assay for HPV-DNA detection and genotyping†

Human papillomavirus (HPV) testing has been proposed as a means of replacing or supporting conventional cervical screening (Pap test). However, both methods require the collection of cervical samples. Urine sample is easier and more acceptable to collect and could be helpful in facilitating cervical cancer screening. The aim of this study was to evaluate the sensitivity and specificity of urine testing compared to conventional cervical smear testing using a PCR‐based method with a new, designed specifically primer set. Paired cervical and first voided urine samples collected from 107 women infected with HIV were subjected to HPV‐DNA detection and genotyping using a PCR‐based assay and a restriction fragment length polymorphism method. Sensitivity, specificity, Positive Predictive Value (PPV), and Negative Predictive Value (NPV) were calculated using the McNemars test for differences. Concordance between tests was assessed using the Cohens unweighted Kappa (k). HPV DNA was detected in 64.5% (95% CI: 55.1–73.1%) of both cytobrush and urine samples. High concordance rates of HPV‐DNA detection (k = 0.96; 95% CI: 0.90–1.0) and of high risk‐clade and low‐risk genotyping in paired samples (k = 0.80; 95% CI: 0.67–0.92 and k = 0.74; 95% CI: 0.60–0.88, respectively) were observed. HPV‐DNA detection in urine versus cervix testing revealed a sensitivity of 98.6% (95% CI: 93.1–99.9%) and a specificity of 97.4% (95% CI: 87.7–99.9%), with a very high NPV (97.4%; 95% CI: 87.7–99.9%). The PCR‐based assay utilized in this study proved highly sensitive and specific for HPV‐DNA detection and genotyping in urine samples. These data suggest that a urine‐based assay would be a suitable and effective tool for epidemiological surveillance and, most of all, screening programs. J. Med. Virol. 85:91–98, 2012.

Risk factors for indinavir-related renal colic in HIV patients: predictive value of indinavir dose/body mass index.

In a prospective study evaluating risk factors for indinavir-related renal colic in 555 HIV-infected patients receiving highly active antiretroviral therapy, followed-up fir 24 months, 23.6% developed one or more renal colic episodes, and 50 patients stopped indinavir. No correlation was observed between renal colic onset and sex, age, CD4 cell count, history, and hepatitis B or C virus co-infection, but baseline anthropometric values were significantly related to the onset of renal colic.

The cost of HIV disease in Northern Italy: the payer's perspective

Background:Healthcare expenditures incurred by the Health Service for HIV-infected patients have not been reported in Italy. Objective:To present health care costs for HIV-infected patients in the Lombardy Region, in 2004-2007, to determine the clinical characteristics of HIV infection associated with costs. Methods:Retrospective, observational, budget impact study, based on information collected for the period 2004-2007, including hospitalizations, outpatient services, highly active antiretroviral therapy (HAART) and non-HAART drug utilization. Inclusion criteria includes: confirmed HIV infection, age ≥18 years, resident in Lombardy Region, and followed at the “L. Sacco” Hospital in Milan from 2004 to 2007. Results:The mean total cost per year to provide healthcare to HIV-positive patients was rather stable (&U20AC;9658.36 in 2004 and &U20AC;9745.65 in 2007 (+0.90%)); HAART represented more than 60% of the total cost. We found that hepatitis C virus coinfection was related to higher costs (&U20AC;11,003.45 vs. &U20AC;8896.06), as well as CD4 cell count <200 cells/mm3 (&U20AC;12,681.36 vs. &U20AC;9594.11 and &U20AC;9450.36 in 200-499 and ≥500 cells/mm3, respectively). The mean total cost of HIV health care was higher in patients who initiated antiretroviral treatment before 1997 than in those who started after 1996. Conclusions:The mean total cost per year to provide health care to HIV-positive patients was stable during the period 2004-2007, with an increase of HAART percentage impact on the total cost. Several clinical characteristics of HIV-infected patients were significantly associated with cost variation.

Profile of infective endocarditis observed from 2003 - 2010 in a single center in Italy.

BackgroundThis study aimed to provide a contemporary picture of the epidemiologic, clinical, microbiologic characteristics and in-hospital outcome of infective endocarditis (IE) observed in a single center in Italy.MethodsWe performed a retrospective study of patients with definite or probable IE observed at the “L. Sacco” Hospital in Milan, Italy, from January 1, 2003 through December 31, 2010.Results189 episodes of IE in 166 patients were included. The mean number of incident IE in the study period was of 1.27 (range 0.59-1.76) cases per 1000 patients admitted. The median age of the cohort was 57 (interquartile range, 43-72) years, 63% were male and 62.5% had native valve IE. Twenty-six percent were active intravenous drug users (IVDU), 29% had a health care-associated IE and 5% chronic rheumatic disease. Twenty-nine percent of the cases occurred in patients affected by chronic liver disease and 19% in HIV positive subjects. Staphylococcus aureus was the most common pathogen (30%), followed by streptococci. The mitral (34%) and aortic (31%) valves were involved most frequently. The following complications were common: stroke (19%), non-stroke embolizations (25%), heart failure (26%) and intracardiac abscess (9%). Surgical treatment was frequently employed (52%) but in hospital mortality remained high (17%). Health care-associated IE and complications were independently associated with an increased risk of in-hospital death, while surgery was associated with decreased mortality.ConclusionS. aureus emerged as the leading causative organism of IE in a University hospital in northern Italy. Our study confirmed the high in-hospital mortality of IE, particularly if health care associated, and the protective role of surgery.

Fungal Endocarditis Observed Over an 8-Year Period and a Review of the Literature

BackgroundFungal endocarditis (FE) is a “modern” disease that is considered an emerging cause of infective endocarditis (IE). The most frequently identified fungal pathogens are Candida spp., which are responsible for up to two-thirds of all cases; the remaining cases are due to Aspergillus spp., Histoplasma capsulatum or, more rarely, other yeasts and moulds.ObjectivesTo describe the prevalence, clinical characteristics and outcome of FE diagnosed in a single tertiary centre and review the literature concerning FE.Design and settingAn 8-year retrospective review of the case records of patients attending a single Italian University Centre and diagnosed as having definite or probable IE as defined by the modified Duke criteria.ResultsSix patients were identified from 229 episodes of IE: five cases involved a prosthetic valve, and one a native valve of an intravenous drug user. Five cases were caused by Candida spp. (two by C. albicans, one each by C. lusitaniae, C. dubliniensis and C. glabrata) and one by Aspergillus flavus. Three patients were treated by means of surgery plus antifungal therapy; two received antifungal therapy alone. Three patients survived, but only the patient with Aspergillus endocarditis was followed up for a long time.ConclusionsFE is difficult to diagnose but generally associated with healthcare infections. The optimal treatment is poorly characterised, and international collaborative studies are urgently needed to evaluate newer antifungal agents.

Human papillomavirus genotypes and phylogenetic analysis of HPV-16 variants in HIV-1 infected subjects in Italy

A cross-sectional study was carried out to improve the state of evidence regarding the spectrum of HPV types and HPV-16 LCR variants circulating among men and women infected with HIV-1 in Italy. This study, conducted in 518 HIV-positive subjects (346 males and 172 females), showed a high prevalence of HPV anal infections (88.7%) in men and of cervical infections (65.1%) in women. A wide spectrum of HPV genotypes has been observed, as both single and multiple infections. Low-risk HPV types 6, 11 and 61 were frequently detected. HPV-16 was the prevalent high-risk type. Fourteen different HPV-16 LCR variants were found. Ten belonged to the European lineage (78.7% were detected in Italian subjects and 21.3% in foreign-born, all homo/bisexual men), two to the Asiatic lineage and two to the African-2 lineage. This study underlines the great genotypic heterogeneity characterizing anal and cervical HPV infections and the marked polymorphism of the predominant HPV-16 in this high-risk population in Italy.

Cost-effectiveness analysis of HIV treatment in the clinical practice of a public hospital in northern Italy.

Introduction We carried out an economic analysis to assess the cost-effectiveness of highly active antiretroviral therapy (HAART) regimens in Italy for the management of human immunodeficiency virus (HIV)-infected patients according to clinical practice in the Infectious Diseases Department of “L. Sacco” Hospital, Milan, Italy. Patients and methods The incremental cost-effectiveness analysis was completed by means of a Markov model. Through a decision-analytic approach, this enabled us to compare the studied antiretroviral regimens. The model considered a population of adult HIV subjects who received HAART therapy for the first time according to clinical practice in the Infectious Diseases Department of “L. Sacco” Hospital, Milan. Data were investigated from the standpoint of the Lombardy Regional Health Service. We considered the following outcome measures: quality-adjusted life-years (QALYs), and direct health costs calculated for the years 2008 and 2009. The time horizon adopted in the model was 2 years. Results The model revealed that, in terms of cost per gained QALY, the tenofovir disoproxil fumarate + emtricitabine + efavirenz (TDF+FTC+EFV) once-a-day treatment strategy seems to be the most cost-effective therapeutic choice (€34,965); the incremental cost-effectiveness ratio (ICER) values for the remaining strategies ranged from €53,000 to around €62,000 per QALY. The validity of the base case scenario was then confirmed by means of a sensitivity analysis on the main variables. Conclusion The TDF+FTC+EFV treatment strategy (TDF/FTC+EFV fixed-dose combination then switched to single-tablet regimen [STR]) in this setting is the most cost-effective treatment strategy compared with the other therapeutic regimens. The ICER value for the TDF+FTC+EFV once-a-day then switched to STR treatment was lower than the internationally generally accepted threshold value of €50,000. The developed model is a tool for policy makers and health care professionals for creating short- and long-term cost projections, with the aim of assessing their impact on the available budgets for HIV patients.

Malaria clusters among illegal Chinese immigrants to Europe through Africa.

Between November 2002 and March 2003, 17 cases of malaria (1 fatal) were observed in illegal Chinese immigrants who traveled to Italy through Africa. A further cluster of 12 was reported in August, 2002. Several immigrants traveled by air, making the risk of introducing sudden acute respiratory syndrome a possibility should such illegal immigrations continue.