Malattie Infettive Research Articles

Reduced risk of death in people with SARS-CoV-2 infection treated with remdesivir: a nested case–control study

Introduction Since the start of the SARS-CoV-2 pandemic, several treatment options have been proposed (e.g. steroids, heparin, antivirals and monoclonal antibodies). Remdesivir was the first antiviral approved for the treatment of COVID-19, even though controversial evidence exists concerning the efficacy. Therefore, we aimed to conduct a study to evaluate whether the use of remdesivir was associated with lower mortality in patients with COVID-19. Methods We conducted a nested case–control study of a retrospective cohort collecting medical records of people with SARS-CoV-2 infection admitted in the infectious Disease Unit of Sassari University Hospital (S.C. Clinica di Malattie Infettive, AOU di Sassari, Italy), or in the Infectious Disease Unit of Foggia (AOU “Ospedali Riuniti” Foggia), between 1 July 2020 and 10 November 2021. The outcome considered was death; thus, we matched death (cases) to survivors (controls) by sex and age (1:1). Results We included in the study 342 patients, with 171 deaths (cases) and 171 survivors (controls). Remdesivir was administered to 60 people in the control group and to 18 people in the case group (35.1% vs. 10.5%, p < .0001). In the multivariate analysis, treatment with remdesivir and heparin was associated with lower mortality (OR: 0.19 [95% CI :0.10–0.38], p <.0001; OR: 0.39 [95% CI: 0.21–0.74] p = .004, respectively). On the contrary, diabetes, oxygen therapy and CPAP/NIV were associated with higher mortality. Conclusion Our study showed lower mortality in people with SARS-CoV-2 infection treated with remdesivir.

Transmission of infection from non-isolated patients with COVID-19 to healthcare workers

Insufficiently protected healthcare workers (HCWs), defined as high-risk contacts of patients with coronavirus disease 2019 (COVID-19), are routinely quarantined. This study evaluated the transmission of infection from a symptomatic patient with COVID-19 to 60 HCWs exposed at ≤2 m for ≥15 min or during aerosol-generating procedures. Following ≥106 unique high-risk contacts, none of the HCWs tested positive for severe acute respiratory syndrome coronavirus-2 RNA or developed antibodies. The HCWs reported adherence to basic infection control procedures. These results are in accordance with other reports, and should reassure HCWs and further stimulate broader evaluation of the foundation for the current practice of home quarantining non-symptomatic HCWs.

The impact of the COVID-19 outbreak on liver transplantation programs in Northern Italy.

In January 2020, Novel Coronavirus Disease 2019 (COVID‐19) resulted in a global pandemic, creating uncertainty toward the management of liver transplantation (LT) programs. Lombardy has been the most affected region in Italy: the current mortality rate of COVID‐19 patients is 18.3% (10 022 deaths; April 10th) with hospitals in Lombardy having to expand the total number of ICU beds from 724 to 1381 to accommodate infected patients. There has been a drastic decrease in liver donors. From February 23rd until April 10th, 17 LTs were performed in Lombardy. Mean donor age was 49 years (range 18‐74) whereas mean recipient age was 55 (13‐69); mean MELD score was 12 (6‐24). All donors underwent screening for SARS‐CoV‐2 prior to LT. Two patients tested positive after LT, and one patient died for COVID on POD 30. Sixteen patients are alive after an average of 30 days post‐LT (range 3‐46). 10 patients have been discharged. This study has found no specific reason concerning the safety of recipients, to stop LT programs. Several key lessons from our experience are reported. However, due to the complex circumstances which surround the viral outbreak, the cessation or a reduction in LT activity is a pragmatic requirement.

Italian recommendations for influenza and pneumococcal vaccination in adult patients with autoimmune rheumatic diseases

To provide evidence-based recommendations for vaccination against influenza virus and S. pneumoniae in patients with autoimmune rheumatic diseases (ARDs). A Consensus Committee including physicians with expertise in rheumatic and infectious diseases was established by two Italian scientific societies, Società Italiana di Reumatologia (SIR) and Società Italiana di Malattie Infettive e Tropicali (SIMIT). The experts were invited to develop evidence-based recommendations concerning vaccinations in ARDs patients, based on their clinical status before and after undergoing immunosuppressive treatments. Key clinical questions were formulated for the systematic literature reviews, based on the clinical pathway. A search was made in Medline (via PubMed) according to the original MeSH strategy from October 2009 and a keyword strategy from January 2016 up to December 2017, updating existing EULAR recommendations. Specific recommendations were separately voted and scored from 0 (no agreement with) to 100 (maximal agreement) and supporting evidence graded. The mean and standard deviation of the scores were calculated to determine the level of agreement among the experts' panel for each recommendation. Total cumulative agreement ≥70 defined consensus for each statement. Nine recommendations, based on 6 key clinical questions addressed by the expert committee, were proposed. The aim of this work is to integrate the 2011 EULAR recommendations on vaccination against influenza and S. pneumoniae in ARDs patients. An implementation plan was proposed to improve the vaccination status of these patients and their safety during immunosuppressive treatments. Influenza and pneumococcus vaccinations are effective and safe in patients with ARDs. More efforts should be made to translate the accumulated evidence into practice.

Hepatitis B and immigrants: a SIMIT multicenter cross-sectional study

The continuing migration of individuals from geographic areas with high/medium endemicity has determined the arrival of new chronic hepatitis B virus (HBV) carriers in Italy. The magnitude of this phenomenon and clinical/virological features of HBsAg-positive migrants remain not very well defined. To evaluate the proportion of HBsAg-positive immigrants enrolled in this multicenter Società Italiana di Malattie Infettive e Tropicali (SIMIT) cross-sectional study and to compare the characteristics of chronic hepatitis B infection in migrants to those of Italian carriers. From February 1 to July 31 2008, anonymous data were obtained from all HBsAg-positive patients aged ≥ 18 years observed at 74 Italian centers of infectious diseases. Of the 3,760 HBsAg-positive subjects enrolled, 932 (24.8 %) were immigrants, with a prevalent distribution in central to northern Italy. The areas of origin were: Far East (37.1 %), Eastern Europe (35.4 %), Sub-Saharan Africa (17.5 %), North Africa (5.5 %), and 4.5 % from various other sites. Compared to Italian carriers, migrants were significantly younger (median age 34 vs. 52 years), predominantly female (57.5 vs. 31 %), and most often at first observation (incident cases 34.2 vs. 13.3 %). HBeAg-positives were more frequent among migrants (27.5 vs. 14 %). Genotype D, found in 87.8 % of Italian carriers, was present in only 40 % of migrants, who were more frequently inactive HBV carriers, with a lower prevalence of chronic hepatitis, cirrhosis, and hepatocellular carcinoma (HCC). Only 27.1 % of migrants received antiviral treatment compared to 50.3 % of Italians. Twenty-five percent of all HBV carriers examined at Italian centers was composed of immigrants with demographic, serological, and virological characteristics that differed from those of natives and appeared to have an inferior access to treatment.

Self-reported adherence supports patient preference for the single tablet regimen (STR) in the current cART era

ObjectiveTo analyze self-reported adherence to antiretroviral regimens containing ritonavir-boosted protease inhibitors, nonnucleoside reverse transcriptase inhibitors (NNRTI), raltegravir, and maraviroc.MethodsOverall, 372 consecutive subjects attending a reference center for HIV treatment in Florence, Italy, were enrolled in the study, from December 2010 to January 2012 (mean age 48 years). A self-report questionnaire was filled in. Patients were defined as “nonadherent” if reporting one of the following criteria: <90% of pills taken in the last month, ≥1 missed dose in the last week, spontaneous treatment interruptions reported, or refill problems in the last 3 months. Gender, age, CD4, HIV-RNA, years of therapy, and type of antiretroviral regimen were analyzed with respect to adherence.ResultsAt the time of the questionnaire, 89.8% of patients had <50 copies/mL HIV-RNA and 14.2% were on their first combined antiretroviral therapy. 57% of patients were prescribed a regimen containing ritonavir boosted protease inhibitors (boosted PI), 41.7% NNRTI, 17.2% raltegravir, and 4.8% maraviroc; 49.5% of the subjects were on bis-in-die regimens, while 50.5% were on OD regimens, with 23.1% of these on the single tablet regimen (STR): tenofovir/emtricitabine/efavirenz. The nonadherence proportion was lower in NNRTI than in boosted-PI treatments (19.4% vs 30.2%), and even lower in STR patients (17.4%). In multivariable logistic regression, patients with the NNRTI regimen (OR: 0.56, 95% CI: 0.34–0.94) and the STR (OR: 0.45, 95% CI: 0.22–0.92) reported lower nonadherence. Efavirenz regimens were also associated with lower nonadherence (OR: 0.42, 95% CI: 0.21–0.83), while atazanavir/ritonavir regimens were associated with higher nonadherence. No other relation to specific antiretroviral drugs was found. A higher CD4 count, lower HIV-RNA, and older age were also found to be associated with lower nonadherence, while a longer time on combined antiretroviral therapy was related to higher nonadherence.ConclusionSTR maintains an advantage in improving adherence with respect to other combined antiretroviral therapies, even though new antiretroviral drugs and drug classes have become available in recent years.

Dear readers of INFECTION

It was a great honour for me to be nominated as the new Editor-in-Chief of INFECTION and it is my privilege to address you with these salutatory lines. I have known INFECTION for more than 20 years, I have published many times in INFECTION and I served on the Editorial Board for 12 years. My own commitment to the journal also has a personal connotation: I am well acquainted with the honoured founder of our journal, Prof. Walter Marget, now Editor Emeritus, who encouraged me to take on the new task as a follower of Prof. Christian Ruef, who steered INFECTION successfully for more than a decade. Under his leadership, the journal’s scientific impact was increased and the transition to a full-scale online journal along with the transition to a new publisher was accomplished. This is the time and opportunity to express gratitude and admiration for him and his work! And thank you Prof. Ruef as well for staying on the Section Editors board. As we state in the aims and scope declaration of INFECTION, the first aim of the journal is to be ‘‘a peerreviewed forum for the presentation and discussion of clinically relevant information on infectious diseases for readers and contributors from all over the world’’. As the new Editor-in-Chief, I will be supported by Section Editors in seven Sections. Two major European societies of clinical infectious diseases (Italy: Societa Italiana di Malattie Infettive e Tropicali, SIMIT; Germany: Deutsche Gesellschaft fur Infektiologie, DGI) have a cooperation with INFECTION as their scientific publication organ. This is a basis for a Europe-based journal that, however, receives papers from all over the world, including Asia and Africa. According to the new style of editorial work, we now have the opportunity to strengthen our diversity in the direction of international travel medicine and tropical diseases, as well as emerging infectious diseases (Section ‘‘Parasitic infections & international health’’). Submitted and accepted articles deal with the aetiology, pathogenesis, diagnosis and treatment of infectious diseases. We will continue to cover public health issues of the most regional or international importance. This will increasingly relate to infectious diseases caused by multi-resistant organisms encountered in the community and in the hospital. One of the new Sections will be called ‘‘Healthcare-associated infections, Antimicrobial use, Healthcare quality’’. All kinds of infections due to organisms will continue to be represented (Sections ‘‘Clinical microbiology’’, ‘‘Fungal infections’’ and ‘‘Viral infections’’) and also ‘‘Pediatric infectious diseases’’ will be covered in an extra Section. We will continue to publish interesting case reports and papers of general interest and on the use of anti-infective compounds (Section ‘‘Clinical infectious diseases’’). I was the board member who suggested to introduce a new publication type, IMAGES in INFECTION, and I will pay special attention to this. Maybe we will succeed in showing how colourful and exciting infectious diseases can look like? Over the years, we will end up with an images series depicting all areas of diseases. Please present your exciting IMAGES in INFECTION. May I express my respect and gratitude to the members of the Board of Section Editors for their acceptance to serve on the Board as well as the Editorial Board members in continuation of the existing group of advisors. I am looking forward to continuing the excellent teamwork with the Publisher’s team headed by S. Ibkendanz and C. Lodge at Springer. J. Bogner (&) Sektion Klinische Infektiologie, Klinik und Poliklinik IV, Klinikum der Universitat Munchen, Pettenkoferstr. 8a, 80336 Munich, Germany e-mail: Johannes.Bogner@med.uni-muenchen.de

Critical reappraisal of risk factors for occurrence of hepatocellular carcinoma in patients with hepatitis C virus

More than one and half of current cases of hepatocellular carcinoma in the US, Europe, and Japan are attributable to hepatitis C virus (HCV) infection. HCV is also the primary cause of death in patients with HCV-related cirrhosis, with annual incidences of 0.5%–5% in Europe and 4%–10% in Asia. Screening is based on serum alpha-fetoprotein determination and liver ultrasound scan, but the sensitivity of the former is far less than optimal, and screening intervals are still poorly defined for the latter. Risk factors related to the host or environment, or both, appear to be more relevant than viral factors, such as HCV genotype, in determining disease progression to cirrhosis and cancer, and include age, male gender, severity of liver disease at presentation, coinfection with hepatitis B virus or human immunodeficiency virus, and alcohol abuse. Early liver transplantation in selected cases can be curative, but most patients are not eligible for liver grafting and are treated with locoregional ablative therapies, after which recurrence is common. Recently, orally available inhibitors of the vascular endothelial growth factor receptor have shown a significant, albeit modest, increment of survival in patients with advanced hepatocellular carcinoma, thus paving the way for modern molecular approaches to treatment of this highly malignant tumor.

16 PREVALENCE AND RISK FACTOR OF HBV INFECTION AMONG 4959 IMMIGRANTS FROM NON EU COUNTRIES IN ITALY

16 PREVALENCE AND RISK FACTOR OF HBV INFECTION AMONG 4959 IMMIGRANTS FROM NON EU COUNTRIES IN ITALY

The Role of Immune Reconstitution in the Onset of Subclinical Atheromasic Lesions

To the Editors: In recent studies,1-3 patients with low CD4+ cell count showed an increased risk for cardiovascular disease (CVD). A hyperproduction of proinflammatory cytokines (interleukin-6, high sensitivity C-reactive protein [hsPCR]) have been hypothesized in these patients.4 Few data exist regarding the role of immune reconstitution in the onset of CVD, another condition that could be related to an increase of circulating proinflammatory factors. Aimed at the detection of subclinical atheromasic lesions in patients who experienced immune reconstitution, in the present study, we evaluated 263 patients starting antiretroviral therapy (ART) at baseline and after 12 months, with color Doppler ultrasonography of the epiaortic vessels, a well-validated technique, considered the gold standard for the detection of premature vascular lesions. The patients were subjected to color Doppler ultrasonography of the epiaortic vessels using a last-generation power color Doppler instrument with 7.5 mgHz probes (ACUSON sequoia 512). Ultrasonography was performed by physicians specifically trained on carotid vessels and had at least 15 years experience with the ultrasound color Doppler technique and about 10,000 documented epiaortic examinations. They were blinded to the patient's treatment history and status and unaware of the diagnosis of the other colleagues. The patients were placed in a supine position after at least 10 minutes of acclimatization in a comfortable room. They were informed that the investigation was noninvasive. The 2 common carotids, the bifurcations and at least the first 2 cm of the internal and external carotid vessels were examined in the short and long axis during the telediastolic phase (T wave of the electrocardiogram). During the investigation, the head of the patient was hyperextended and extrarotated from the opposite side. The morphological investigation of the plaques was performed using both ultrasonography and the ultrasound power color Doppler to better characterize the profile of the plaque and the intima media thickness. An intima media thickness >0.9 mm and/or the presence of atherosclerotic plaques were considered pathologic findings. After 12 months of ART, patients with <50 CD4+ cell count per cubic millimeter at baseline were divided into 3 groups based on CD4+ at follow-up: group A: patients with <100 CD4+ (# 41); group B: patients with 100-200 CD4+ (# 50); and group C: patients with >200 CD4+ (# 62). The CD4+ cell count was detected on 2 separate occasions, measured sequentially at least 4 weeks apart. The data were compared with those observed in 110 patients starting their ART with >200 CD4+ and remaining at follow-up, over this value (group D). The 4 groups were comparable for gender, mean age, and other risk factors for CVD. All patients were treated with a PI-based therapy. Backbone drugs were well balanced among the groups (Table 1). Statistical analysis was performed using χ2 test. The Ethics Committee of the hospital approved the study, and the patients provided informed consent.TABLE 1: Distribution of Demographics, Risk Factors for CVD, and Antiretroviral Therapies Among the GroupsAs showed in Figure 1, patients with <50 CD4+ cell count at baseline that reached values >200 (group C) showed a significant increase in the number of carotid lesions at follow-up. Moreover, comparing patients with <50 cells at baseline (groups A + B + C) with patients with >200 cells (group D), the first group had a significant increase of lesions with respect to group D (P = 0.00001).FIGURE 1: Distribution of subclinical carotid lesions at baseline and at follow-up with statistical analysis.In a previous issue, Williams et al5 observed a higher rate of myocardial infarctions and other symptomatic cardiovascular events in patients experiencing immune reconstitution. Our data show that patients starting ARV with a high degree of immune depression tend to develop more subclinical carotid lesions with respect to patients starting ARV in a relatively better immunologic condition. Moreover, patients experiencing a more rapid immune reconstitution develop a significantly higher number of subclinical vascular lesions. These data suggest that inflammatory events characterizing both immune deficiency and immune reconstitution could play a role in the onset of CVD. Paolo Maggi, MD* Anna Volpe, BD* Chiara Bellacosa, MD* Giuseppe Pastore, MD* Francesco Perilli, MD† Antonio Lillo, MD† Guido Regina, MD† *Clinica delle Malattie Infettive, Università degli Studi di Bari, Italy †Cattedra di Chirurgia Vascolare, Università degli Studi di Bari, Italy

O332 Opportunistic infections in immunocompromised but virologically suppressed HIV-1 infected patients

Address: 1Royal Free and University College Medical School, London, UK, 2Copenhagen HIV Programme, Panum Institute, Copenhagen, Denmark, 3Academisch Medisch Centrum bij de Universiteit van Amsterdam, Amsterdam, Netherlands, 4Istituto Di Clinica Malattie Infettive e Tropicale, Milan, Italy, 5Hospital Clinic i Provincial, Barcelona, Spain, 6Royal Sussex County Hospital, Brighton, UK, 7Medical University, Gdansk, Poland and 8Medical Academy Botkin Hospital, St Petersburg, Russian Federation * Corresponding author

Chronic Coinfection With Hepatitis B and Hepatitis C Viruses in an Italian Population of HIV-Infected Patients

Chronic Coinfection With Hepatitis B and Hepatitis C Viruses in an Italian Population of HIV-Infected Patients

Absence of New Thymidine-Associated Mutations and Evidence of an Immune Virologic Response Over a 12-Month Period in a Cohort of Antiretroviral-Experienced HIV-1-Infected Subjects Treated With Tenofovir Combination Therapy

Absence of New Thymidine-Associated Mutations and Evidence of an Immune Virologic Response Over a 12-Month Period in a Cohort of Antiretroviral-Experienced HIV-1-Infected Subjects Treated With Tenofovir Combination Therapy

Partnership of HIV-Infected Women and Health Status

To the Editor: Social and psychological characteristics of partners may influence a person's health status1,2 or even survival.3 According to a recently published paper on HIV-infected persons,4 lack of a stable partnership may be considered an important determinant of clinical progression. In a study we conducted on women with HIV infection enrolled in the Italian Cohort Naive to Antiretrovirals (ICONA Study), we found that having a current partner who was an intravenous drug user (IDU) was associated with significantly lower levels of psychological well-being even when adjusted for several confounders. ICONA is an Italian multicenter observational study on the natural history of HIV disease among adults who are naive to antiretrovirals at the time of enrollment. Within the ICONA cohort, the Behavioural Epidemiology (BEHEPI) Study investigates behavioral profile and health status of the enrolled HIV-infected persons. Participants were asked to complete a self-administered questionnaire including items on psychological well-being, personal behavior (self-reported HIV acquisition modality, lifetime number of sex partners, sexual intercourse in the previous 2 weeks, having a current IDU partner) as well as demographic characteristics.5 Psychological well-being was measured through a 5-item scale with 5-point responses (BEHEPI Psychologic Well-Being scale or B-PWBS). Answers to the scale were summed and the result was linearly transformed in a 0-100 score. The scale included the most frequently used items for measuring the psychological well-being and was designed after a focus discussion with HIV experts and people living with HIV infection. We aimed to create a very brief tool for the screening of impaired psychological well-being. From March 1998 to March 2000, 746 women participated in the BEHEPI Study. Mean age of women enrolled was 32 years (interquartile range [IQR] 28-36), 33% were unemployed, 37% were IDUs, 8% had Centers for Disease Control-defined AIDS: mean of CD4 was 460 (IQR 300-633), and median log of plasma HIV RNA was 4.1 (IQR 3.4-4.7). At enrollment, no woman was receiving antiretroviral therapy. Fifty-five of 746 women (9.7%) reported a current IDU partner. Women with a current IDU partner has a 17-fold probability (95% CI 7.6-38.8; P < 0.0001) of being currently IDU themselves compared with women who did not report a current IDU partner. Fifty-three percent of women had not sexual intercourse in the 2 weeks before the survey. Missing data for the B-PWB Scale ranged from 4.6% to 5.5% among the 5 items and 7.4% for the whole scale. The validity of the B-PWB scale, evaluated through internal consistency, was good (Cronbach α: 0.81). Median of the B-PWB Scale was 55 (IQR 35-70); 0.5% of patients scored 0 (minimum) and 1.1% scored 100 (maximum). A multiple linear regression analysis was performed to identify variables independently associated with the B-PWB Scale scores (Table 1). Having a current IDU partner was associated with lowest values on the psychological well-being scale. The multivariate analysis suggested that this association was independent of past or current use of drugs. Results were similar when we considered as IDU only current IDU women (n = 37) (data not shown).TABLE 1: Variables Associated with the B-PWB Scale Scores: Multiple Linear Regression AnalysisOur results suggest that a focused analysis of familiar and social characteristics of women may be helpful in identifying determinants of health status because even a stable partnership may be associated with a mental health impairment if the partner is a current IDU. Particularly, we suggest that a gender-oriented approach should be used when analyzing social and psychological factors that may influence health outcomes. We did not analyze the potential association of type of partner with clinical course of HIV infection. However, several published papers have demonstrated that depression and mental health impairment are associated with a suboptimal adherence to drugs6 and thus with worse outcomes of therapy. Maria Stella Aloisi, PhD* Rita Murri, MD† Antonella D'Arminio Monforte, MD‡ Davide Bertelli, MD§ Vincenzo Colangeli, MD∥ Francesco Leoncini, MD¶ Giuseppe Ippolito, MD* Enrico Girardi, MD* *Istituto Nazionale Malattie Infettive, Spallanzani, Rome, Italy, †Istituto di Clinica delle Malattie Infettive, Università Cattolica S. Cuore, Rome, Italy, ‡Istituto di Malattie Infettive e Tropicali, Università di Milano, Milan, Italy, §Divisione Malattie Infettive, Spedali Civili di Brescia, Brescia, Italy, ∥Clinica Malattie Infettive, Università di Bologna, Bologna, Italy, ¶Divisione Malattie Infettive, Ospedale Careggi di Firenze, Florence, Italy

Genotyping for Guiding Drug Choice in Human Immunodeficiency Virus-Infected Children Failing Multiple Antiretroviral Treatment Regimens

To the Editors: The use of human immunodeficiency virus (HIV) genotyping for identifying the most effective regimens in HIV-infected adults failing highly active antiretroviral therapy led to improved virologic response as compared with regimens selected on the basis of antiretroviral exposure history. In contrast, similar studies conducted in small cohorts of HIV-infected children failed to demonstrate a clear advantage of antiretroviral resistance testing over antiretroviral exposure history. In this study, we have genotyped HIV reverse transcription and protease genes in 17 children (ages 4.5–11.3 years) between 2000 and 2001, at treatment failure and have changed antiretroviral drugs according to HIV genotype profiles. All 17 children who were included showed an elevated viral load (>1000 copies/mL) for at least 9 months during the last year before genotyping and had failed from 1–5 regimens during that time. All the HIV-infected children had received a combination of at least 2 nucleoside reverse transcriptase inhibitors (NRTIs) (17 of 17) and while 8 of 17 had been treated with a PI containing regimen; none of them was previously treated with non-NRTIs (Table 1). Adherence to therapy was based on reports from children and caretakers and on calculation of quantities of drugs that were requested at each visit. At the time of treatment failure, we identified substitutions in both the reverse transcription and the protease genes in samples from 94% of children.TABLE 1: Nucleoside Reverse Transcription Inhibitors Used in HIV TreatmentWild-type sequences could not be identified in any sample from this cohort of HIV-infected children. Drug-specific genotypic resistance, identified on the basis of the IAS mutation list,4 was commonly observed for all the NRTIs as shown in detail in Table 1. Antiretroviral therapy was changed by substitution of at least one antiretroviral medication in all patients, except in patient 17. Since none of the patients had been previously exposed to non-NRTI drugs whereas 8 of 17 had received a drug of the protease inhibitor class, we introduced efavirenz in the therapeutic regimens of 11 children. Virologic and immunologic data were collected at 2- to 3-month intervals for at least 12 months. We observed a significant suppression of viral load (<1000 copies) 3-6 months after treatment change. HIV suppression was detected in 8 of the 17 patients from 6 to 35 months (stably undetectable in 5 cases), whereas in another 5 children viral load remained elevated through 12 months of follow-up. CD4+ percentages showed a significant increase from baseline levels in the same children who showed virologic suppression, except in patient 10 who had already started the treatment with 44% of CD4, suggesting that their treatment regimens were effective to induce immunologic reconstitution. The remaining patients (patients 1, 3, 4 and 13) showed a rapid, but transient, decline of viral load after treatment change. Because of the high risk of false negatives, we have performed an additional HIV genotyping in the remaining 9 patients who showed an unsatisfactory response to medication changes. In patients 1 and 13, we detected additional mutations in reverse transcription gene (Table 1) that conferred resistance to efavirenz, thereby accounting for the inadequate response to the previous change of antiretroviral treatment. HIV genotyping did not reveal any resistance-associated mutation in 7 children who had failed 2 changes of treatment regimens, suggesting that limited adherence may account for this observation. Our study demonstrates that HIV genotyping based treatment choices in 17 infected pretreated children led to persistent viral suppression and immunologic reconstitution in 10 children, suggesting that use of this assay improves clinical outcome of antiretroviral-experienced children. A previous study failed to show benefit of HIV resistance testing in a cohort of 18 children. We believe that the limited availability of novel antiretroviral medications and variable adherence to therapeutic regimens may account the different results that are observed in these studies. Drs Badolato and Schumacher contributed equally to this work. Raffaele Badolato, MD, PhD R. Fabian Schumacher, MD Elisabetta Rodella, MD Franco Gargiulo, MD Carlo Torti, MD Luigi D. Notarangelo, MD Marzia Duse, MD Istituto di Medicina Molecolare “Angelo Nocivelli” Clinica Pediatrica Cattedra di Malattie Infettive Laboratorio di Microbiologia University of Brescia Brescia, Italy

Lipodystrophy Is Associated With a Low Rate of Treatment Failure in HIV-Positive Patients Switched to Atazanavir

Lipodystrophy Is Associated With a Low Rate of Treatment Failure in HIV-Positive Patients Switched to Atazanavir

Hospital preparedness and management of patients affected by viral haemorrhagic fever or smallpox at the Lazzaro Spallanzani Institute, Italy.

The US cases of anthrax in 2001 and the recent severe acute respiratory syndrome outbreak have heightened the need for preparedness and response to naturally emerging and re-emerging infections or deliberately released biological agents. This report describes the response model of the Istituto Nazionale per le Malattie Infettive Lazzaro Spallanzani (INMI), Rome, Italy for managing patients suspected of or affected by smallpox or viral haemorrhagic fever (VHF) either in the context of an intentional release or natural occurrence. The INMI is Italy's leading hospital in its preparedness and response plan to bioterrorism-related infectious agents. All single and double rooms of INMI are equipped with negative air pressure, sealed doors, high efficiency particulate air (HEPA) filters and a fully-equipped anteroom; moreover, a dedicated high isolation unit with a laboratory next door for the initial diagnostic assays is available for admission of sporadic patients requiring high isolation. For patient transportation, two fully equipped ambulances and two stretcher isolators with a negative pressure section are available. Biomolecular and traditional diagnostic assays are currently performed in the biosafety level 3/4 (BSL 3/4) laboratories. Continuing education and training of hospital staff, consistent application of infection control practices, and availability of adequate personnel protective equipment are additional resources implemented for the care of highly infectious patients and to maintain the readiness of an appropriately trained workforce to handle large scale outbreaks.

Adherence to antiretroviral therapy: where are we, and where do we go from here?

*Department of Health Policy and Management, Johns Hopkins Bloomberg School of Public Health and Department of Medicine. School of Medicine, Johns Hopkins University, Baltimore, Maryland, U.S.A.; †Clinica delle Malattie Infettive, Università Cattolica del S. Cuore, Roma; ‡Istituto Nazionale per le Malattie Infettive, L. Spallanzani IRCCS, Roma, Italy ??nded in part by the National Institute of Allergy and Infectious ??ase. Adult AIDS Clinical Trials Group (U01 AI27668). Address correspondence and reprint requests to Albert W. Wu. M.D., ??H. Health Services Research and Development Center, N. Broadway. Room 633, Baltimore, MD 21205, U.S.A.; e-mail:[email protected]

Core gene heterogeneity in HBV-DNA isolated from children with chronic HBV infection: [formula omitted]. Dtp. Medicina Interna, Università di Messina and ∗Ist. Malattie Infettive Universitá di Bologna - Italy

Core gene heterogeneity in HBV-DNA isolated from children with chronic HBV infection: [formula omitted]. Dtp. Medicina Interna, Università di Messina and ∗Ist. Malattie Infettive Universitá di Bologna - Italy

Relations among HCV genotype and serotype patterns and route, time and outcome of infections in patients from the same geographic area: [formula omitted] Dept. of Gastroenterol. Molinette Hosp. Torino, 2 Clinica Medica II, Istituto di Clinica Medica e Malattie Infettive, Bari, Italy

Relations among HCV genotype and serotype patterns and route, time and outcome of infections in patients from the same geographic area: [formula omitted] Dept. of Gastroenterol. Molinette Hosp. Torino, 2 Clinica Medica II, Istituto di Clinica Medica e Malattie Infettive, Bari, Italy