Prevalence of predicted resistance to doravirine in HIV-1-positive patients after exposure to non-nucleoside reverse transcriptase inhibitors.

This study investigated the prevalence of doravirine (DOR) resistance mutations in non-nucleoside reverse transcriptase inhibitor (NNRTI)-experienced patients. DOR resistance was assessed in samples from NNRTI-experienced patients who underwent genotypic testing for virological failure from the Antiretroviral Response Cohort Analysis (ARCA) database. Intermediate DOR resistance was defined as detection of any of V106A/M, Y188C/H, V108I, and K103N+P225H. High-level DOR resistance was defined as detection of any of Y188L, M230L, G190E, V106A/M+F227L, and V106A/M+L234I. Overall, 6893 patients were included in the study: 64.2% had experienced efavirenz (EFV), 54.4% nevirapine (NVP), 6.8% etravirine (ETR), 7.7% rilpivirine (RPV) and 0.7% delavirdine. Among NNRTI-experienced patients, 12.7% and 6.1% of subjects had intermediate and high-level DOR resistance, respectively. The most common DOR resistance mutation was Y188L. In multivariable analysis, previous EFV use (OR = 1.52, 95% CI 1.15-2.02) and ETR use (OR = 1.91, 95% CI 1.34-2.73) were associated with detection of high-level DOR resistance, whilst RPV use was associated with a lower probability of high-level DOR resistance (OR = 0.39, 95% CI 0.22-0.71). Moreover, EFV use (OR = 1.76, 95% CI 1.19-2.58) and ETR use (OR = 1.72, 95% CI 1.10-2.68) were associated with detection of the Y188L mutation, whereas RPV use was not (OR = 0.16, 95% CI 0.05-0.50). In Italy, DOR resistance is uncommon among NNRTI-experienced patients, confirming a distinguishing resistance pattern within NNRTIs. However, previous EFV and ETR experience poses a higher risk of DOR resistance. These results support the use of DOR in NNRTI-experienced patients.

European type-approval test procedure for evaporative emissions from passenger cars against real-world mobility data from two Italian provinces.

This paper presents an evaluation of the European type-approval test procedure for evaporative emissions from passenger cars based on real-world mobility data. The study relies on two large databases of driving patterns from conventional fuel vehicles collected by means of on-board GPS systems in the Italian provinces of Modena and Firenze. Approximately 28,000 vehicles were monitored, corresponding to approximately 36 million kilometres over a period of one month. The driving pattern of each vehicle was processed to derive the relation between trip length and parking duration, and the rate of occurrence of parking events against multiple evaporative cycles, defined on the basis of the type-approval test procedure as 12-hour diurnal time windows. These results are used as input for an emission simulation model, which calculates the total evaporative emissions given the characteristics of the evaporative emission control system of the vehicle and the ambient temperature conditions. The results suggest that the evaporative emission control system, fitted to the vehicles from Euro 3 step and optimised for the current type-approval test procedure, could not efficiently work under real-world conditions, resulting in evaporative emissions well above the type-approval limit, especially for small size vehicles and warm climate conditions. This calls for a revision of the type-approval test procedure in order to address real-world evaporative emissions.

[Acute hepatitis C infection: epidemiological and clinical aspects, and efficacy of interferon therapy]. / Epatite acuta C: aspetti epidemiologici, clinici e impatto della terapia interferonica.

Acute hepatitis C virus infection becomes chronic in 50-80% of patients; in recent years a number of studies on acute hepatitis C have shown that interferon treatment can solve more than 80% of cases. In this study we evaluated all cases of acute hepatitis C referred to our unit from 1998 to 2005 to study the epidemiological and clinical features and the efficacy of interferon therapy during the course of the disease. Forty-three patients (28 males, 15 females) were monitored: 22 were drug-addicts, 6 patients referred from recent surgery, in 3 cases a percutaneous exposure was described, 2 patients had had a colonoscopy, 4 were partners of subjects with chronic hepatitis C and in the remaining cases the transmission route was uncertain. All subjects were symptomatic, jaundice was evident in 20 out of 43 patients and in all cases hepatic protein synthesis was unaltered. Of the 21 patients who consented to interferon therapy, in 19 cases a sustained virological response was achieved while in 2 cases the follow-up period was too short for evaluation. Four of the 22 non-treated patients had a spontaneous resolution of the infection, in 13 cases the infection became chronic, and in 4 cases the follow-up was too short for an analysis. In our study all patients were young, in 58% of subjects a parenteral exposure was described and most patients were drug-addicts. All the treated patients obtained a sustained response, while in the majority of non-treated cases the infection became chronic.

Isolation of Nocardia asiatica from cutaneous ulcers of a human immunodeficiency virus-infected patient in Italy.

A strain of Nocardia was isolated from cutaneous ulcers of a human immunodeficiency virus-infected patient in Italy. Comparative 16S rRNA gene sequence analysis revealed that the isolate represented a strain of Nocardia asiatica. Antimicrobial susceptibility testing was essential to guide the clinicians to successfully treat this infection.

Comparison between rules-based human immunodeficiency virus type 1 genotype interpretations and real or virtual phenotype: concordance analysis and correlation with clinical outcome in heavily treated patients.

We compared 2 rules-based genotype interpretation systems and real or virtual phenotype through a retrospective analysis of a prospective trial. Genotypes were determined with VircoGEN II (VIRCO) and were interpreted with either RetroGram 1.4 or TRUGENE HIV-1 (guidelines 3.0) or original virtual phenotype (Virtual Phenotype; VIRCO), as available in the year 2000. Among 188 human immunodeficiency virus (HIV) type 1 isolates, overall concordance (kappa agreement) was observed for the 2 rules-based systems, whereas striking discordances were noted between them and real and virtual phenotype interpretations for stavudine, didanosine, zalcitabine, abacavir, and amprenavir (kappa<0.4). Clinical evaluation of a subset of 173 patients showed that both rules-based sensitivity scores were independently associated with HIV RNA loads <400 copies/mL at week 16 of during-treatment analysis (TRUGENE: odds ratio [OR], 2.90; 95% confidence interval [CI], 1.52-5.52; P=.001; RetroGram: OR, 2.34; 95% CI, 1.21-4.55; P=.012), whereas, in contrast to real or virtual phenotype, interpretations according to biological cut-offs were not (OR, 1.91; 95% CI, 0.77-4.76; P=.162).

Nosocomial bloodstream infections among human immunodeficiency virus-infected patients: incidence and risk factors.

To assess the incidence of nosocomial bloodstream infections (NBSIs) in human immunodeficiency virus (HIV)-infected patients, and to analyze the main associated risk factors, we performed a 1-year multicenter prospective study of patients with advanced HIV infection who were consecutively admitted to 17 Italian infectious diseases wards. As of May 1999, a total of 65 NBSIs (4.7%) occurred in 1379 admissions, for an incidence of 2.45 NBSIs per 1000 patient-days. Twenty-nine NBSIs were catheter-related bloodstream infections, with a rate of 9.6 central venous catheter-associated infections per 1000 device-days. Multivariate analysis indicated that variables independently associated with NBSIs included active injection drug use, a Karnofsky Performance Status score of <40, presence of a central venous catheter, and length of hospital stay. Mortality rates were 24.6% and 7.2% among patients with and without NBSIs, respectively (P<.00001). In the era of highly active antiretroviral therapy, NBSIs continue to occur frequently and remain severe and life-threatening manifestations.