[Show abstract][Hide abstract] ABSTRACT: Acute B19 virus infection is classically associated with a widespread benign and self-limiting childhood rash
illness, known as erythema infectiosum (EI) or fifth disease. The clinical presentation associated with B19
infection may vary greatly, ranging from benign forms of arthralgias to life-threatening conditions, depending
on age and immunologic status. A case of polymyalgia rheumatica (PMR) in a 74-years-old woman
affected by B19 virus infection is reported here, presenting with evening low-grade fever, shoulder and
pelvic girdle arthralgia and functional impairment. A comprehensive review of the literature showed that
B19 virus has been hypothetically implicated as the causative or precipitating agent of several autoimmune
and rheumatic diseases, including PMR. Some molecular mechanisms underlying the autoimmune phenomena
have been described, involving the inflammatory response due to cytokine activation, the formation
and deposition of immune complexes and molecular mimicry mechanisms. Nowadays, the reports in
the literature, which have focused on the possible role of Parvovirus B19 in the pathogenesis of PMR, are
few and discordant. Therefore, further and more in deep investigations are needed, hopefully leading to
a final consensus between researchers.
[Show abstract][Hide abstract] ABSTRACT: Background: Chronic Fatigue Syndrome (CFS) is a complex illness with different clinical definition, etiological
models and treatments. A lot of studies have focused on the concomitance with herpesviridae infections,
especially Epstein-Barr Virus (EBV). We report a clinical case highlighting the correlation between
chronic EBV infection and CFS.
Results: The patient met the CDC criteria for the diagnosis of CFS and presented a high level of EBV-DNA
Conclusions: Although some studies suggest that subjects with viral infections are not more likely to develop
CFS than controls, the possible connection between EBV and CFS remains unclear. EBV-DNA shows
the presence of an actively replicating virus, which is known to be associated with several cancers. Whether
its replication is the cause or the consequence of CSF needs further investigations.
[Show abstract][Hide abstract] ABSTRACT: Objectives:
This study aims to evaluate the reliability and clinical utility of NS3 sequencing in hepatitis C virus (HCV) 1-infected patients who were candidates to start a PI-containing regimen.
NS3 protease sequencing was performed by in-house-developed HCV-1 subtype-specific protocols. Phylogenetic analysis was used to test sequencing reliability and concordance with previous genotype/subtype assignment by commercial genotyping assays.
Five hundred and sixty-seven HCV plasma samples with quantifiable HCV-RNA from 326 HCV-infected patients were collected between 2011 and 2014. Overall, the success rate of NS3 sequencing was 88.9%. The success rate between the two subtype protocols (HCV-1a/HCV-1b) was similarly high for samples with HCV-RNA >3 log IU/mL (>92% success rate), while it was slightly lower for HCV-1a samples with HCV-RNA ≤3 log IU/mL compared with HCV-1b samples. Phylogenetic analysis confirmed the genotype/subtype given by commercial genotyping assays in 92.9% (303/326) of cases analysed. In the remaining 23 cases (7.1%), 1 was HCV-1g (previously defined as subtype 1a), 1 was HCV-4d (previously defined as genotype 1b) and 1 was HCV-1b (previously defined as genotype 2a/2c). In the other cases, NS3 sequencing precisely resolved the either previous undetermined/discordant subtype 1 or double genotype/subtype assignment by commercial genotyping assays. Resistance-associated variants (RAVs) to PI were detected in 31.0% of samples. This prevalence changed according to PI experience (17.1% in PI-naive patients versus 79.2% in boceprevir/telaprevir/simeprevir-failing patients). Among 96 patients with available virological outcome following boceprevir/telaprevir treatment, a trend of association between baseline NS3 RAVs and virological failure was observed (particularly for HCV-1a-infected patients: 3/21 failing patients versus 0/22 achieving sustained virological response; P = 0.11).
HCV-NS3 sequencing provides reliable results and at the same time gives two clinically relevant pieces of information: a correct subtype/genotype assignment and the detection of variants that may interfere with the efficacy of PI.
Full-text · Article · Dec 2015 · Journal of Antimicrobial Chemotherapy
[Show abstract][Hide abstract] ABSTRACT: Premessa: La terapia con NRTI è stata associata allo sviluppo di tossicità a breve e a lungo termine che può
rappresentare una minaccia al successo a lungo termine della HAART. L’utilizzo di regimi di terapia
antiretrovirale NRTI-sparing è frequente anche se le evidenze scientifiche a sostegno sono scarse
soprattutto in casistiche di pratica clinica.
Obiettivo: Abbiamo voluto studiare l’efficacia e la tollerabilità della dual therapy includente raltegravir
(RAL) + darunavir (DRV)/ritonavir (r) nella pratica clinica tramite uno studio multicentrico retrospettivo in
quattro centri di riferimento di Malattie Infettive in Sardegna. Sono stati inclusi pazienti con infezione da
HIV che avessero iniziato un regime di terapia dual includente RAL+DRV/r.
Risultati: Sono stati arruolati 53 pazienti con infezione da HIV di cui 33 (62,3%) maschi. Ventotto (52,8%)
erano ex-tossicodipendenti e 31 (58%) erano in stadio CDC B. La conta mediana dei CD4 era di 610 (IQR
395-801), e del nadir era di 232 (IQR 81-418). L’HIV-RNA era negativo in 40 (75%) pazienti. Solo un paziente
era naive. La mediana di esposizione alla HAART era di 173 (IQR 130-223) mesi e quella dei regimi HAART
praticati era di 6 (IQR 4-8). Dei 53 pazienti arruolati, inoltre, 22 (41,5%) avevano mutazioni maggiori di
resistenza, 7 (13,2%) per NRTI+NNRTI, 5 (9,4%) per NRTI+PI mentre 6 (11,3%) per NRTI+NNRTI+PI. Due
pazienti su 53 (3,8%) erano coinfetti con HBV e 26/53 (49%) erano con HCV.
La percentuale di pazienti con HIV-RNA <50 cp/ml era di 38/45 (84,4%) a 6 mesi, a 12 mesi 43/45 (95,5%;
p=0,006), a 18 mesi 36/40 (90%) e a 24 mesi 30/35 (85,7%). La percentuale di pazienti con HIV RNA <200
cp/ml rispetto al baseline era di 44/45 (97,7%; p=0,0014) a 6 mesi, di 46/47 (97,9%, p=0,0011) a 12 mesi,
39/40 (97,5%; p=0,003) a 18 mesi e 34/35 (97,1%; p=0,0067) a 24 mesi. La conta mediana dei CD4 è
aumentata nel tempo e significativamente rispetto al baseline fino al mese 24 (p=0,015).
Nei pazienti con HIV-RNA <50 cp/ml al basale la percentuale di pazienti soppressi a 6 mesi era 27/33
(81,8%, p=0,006), a 12 mesi 32/35 (91,4%), a 18 mesi 25/28 (89,3%) e a 24 mesi 20/23 (86,9%, p=0,045).
Negli stessi pazienti la percentuale di pazienti con HIV-RNA <200 cp/ml era di 33/33 (100%) a 6 mesi, di
34/35 (97,1%) a 12 mesi, 27/28 (96,4%) a 18 mesi e 22/23 (95,6%) a 24 mesi. In questi pazienti la conta
mediana dei CD4 è aumentata in maniera statisticamente significativa al mese 3 (p=0,031) e 12 (p=0,007).
Soltanto 1 (1,8%) paziente ha presentato un fallimento virologico. I valori di AST e ALT hanno mostrato una
riduzione nel tempo e l’eGFR non ha mostrato modificazioni significative.
XIV Congresso Nazionale SIMIT
Società Italiana di Malattie Infettive e Tropicali
Conclusioni: La terapia con RAL+DRV/r si è dimostrata altamente efficace e ben tollerata in una coorte di
pazienti multi drug-experienced. Tale strategia potrebbe rappresentare una valida opzione di
ottimizzazione del trattamento antiretrovirale anche in pazienti difficili da trattare.
[Show abstract][Hide abstract] ABSTRACT: Gastrointestinal L' infezione acuta da Parvovirus B19 è la causa di una diffusa patologia generalmente benigna ed autolimitantesi nota come eritema infettivo o quinta malattia. Tipica dell'infanzia, in cui può presentarsi asintomatica o con esantema, artralgie e crisi aplastiche transitorie, può colpire anche la popolazione adulta dove talvolta è causa di artralgie croniche non facilmente ascrivibili a causa distinta. Le sincrone variazioni dell'incidenza della polimialgia reumatica sono state, già in passato, associate ad epidemie di infezioni virali come il Parvovirus B19. Riportiamo il caso clinico di una paziente di 74 anni con infezione da Parvovirus B19 alla quale è stata diagnosticata, dopo circa un mese dall'esordio sintomatico, una polimialgia reumatica.
[Show abstract][Hide abstract] ABSTRACT: Background and purpose:
Infectious mononucleosis (IM) caused by Epstein-Barr virus (EBV) has been associated with increased risk of multiple sclerosis (MS). However, the mechanism linking these pathologies is unclear. Different reports indicate the association of EBV, and recently Mycobacterium avium subsp. paratuberculosis (MAP), with MS. For a better understanding of the role of these pathogens, the host response induced by selected antigenic peptides in subjects with a history of IM that significantly increases the risk of MS was investigated.
Both humoral and cell-mediated response against peptides able to induce a specific immune activation in MS patients deriving from lytic and latent EBV antigens BOLF1305-320 , EBNA1400-413 , from MAP MAP_402718-32 , MAP_0106c121-132 and from human proteins IRF5424-434 and MBP85-98 in subjects with current and past IM were examined.
EBNA1 and MAP_0106c peptides were able to induce a humoral immune response in subjects with a history of clinical IM in an independent manner. Moreover, these peptides were capable of inducing pro-inflammatory cytokine interferon γ by CD4+ and CD8+ T lymphocytes and interleukin 6 and tumour necrosis factor α by CD14+ monocyte cells.
Our results highlight that EBV and MAP may be involved independently in the same causal process leading to MS in subjects with a history of IM.
Full-text · Article · Oct 2015 · European Journal of Neurology
[Show abstract][Hide abstract] ABSTRACT: This study aimed to evaluate inducible protein-10 (IP-10) as a biomarker besides interferon-gamma (IFN-γ) to improve the identification of active tuberculosis (TB) and latent tubercular infection (LTBI) in a country with a low incidence of TB.
Whole blood from Mycobacterium tuberculosis-infected subjects was stimulated with region-of-difference-1 (RD1)-specific peptides and with heparin-binding hemagglutinin (HBHA) to determine the release of IP-10 and IFN-γ.
No statistically significant difference was observed between positive rates of IP-10 and IFN-γ after RD1-specific peptide stimulation in the TB and LTBI groups; a different response was detected in QuantiFERON TB-gold test-negative (QFT-) subjects. A significantly different proportion of positive responses was observed between IP-10 and IFN-γ following HBHA stimulation in the TB group and in the QFT- group but not in the LTBI group.
The IP-10 test seemed to identify false-negative QFT results in some subjects with a positive IFN-γ/IP-10/HBHA pattern.
[Show abstract][Hide abstract] ABSTRACT: Chronic kidney disease (CKD) is a major health issue for HIV-positive individuals, associated with increased morbidity and mortality. Development and implementation of a risk score model for CKD would allow comparison of the risks and benefits of adding potentially nephrotoxic antiretrovirals to a treatment regimen and would identify those at greatest risk of CKD. The aims of this study were to develop a simple, externally validated, and widely applicable long-term risk score model for CKD in HIV-positive individuals that can guide decision making in clinical practice.
[Show abstract][Hide abstract] ABSTRACT: To identify the presence of Human Papilloma Virus (HPV) infection and evaluate the role of Highly Active Antiretroviral Treatment (HAART) in patients with HIV-HPV co-infection. We also compared cytological screening results with HPV-DNA detection to implement screening programs and prevention of invasive cervical cancer (ICC) in HIV-infected females.
We enrolled HIV-infected females presenting for routine clinical evaluation. HPV-DNA of high/intermediate and low-risk types was detected from cervical specimens by nucleic acid hybridization assay with signal-amplification. Patients were divided into two groups according to the presence of HPV co-infection (HPV+) or not (HPV-).
We enrolled 57 HIV-infected females. Median age was 40 (IQR 35-44) years, mean CD4 count was 547 ± 227 cells/mm3, 45 (78.9%) had undetectable HIV-RNA and 52 (91.2%) received HAART. Globally, 19/57 (33.3%) patients were HPV-infected, 16/57 (28.1%) with high/intermediate and 3/57 (5.3%) with low-risk types. Five of the 19 (26.3%) HPV+ patients carried both types. Correlating high-risk genotype HPV-DNA detection with cytology, 17.5% of women with negative cytology, 36.4% with ASCUS (Atypical Squamous Cells of Uncertain Significance) and 83.4% of women with positive cytology (50% of LSIL: low-grade squamous intraepithelial lesion and 100% of HSIL: high grade SIL) were HPV positive. No statistical difference when comparing HPV+ and HPV-patients in age, CD4 cell count, in the proportion of previous intravenous-drug use, previous AIDS and of those receiving HAART with undetectable HIV-RNA was observed.
Cervical cancer screening including HPV-DNA detection should be implemented in HIV infected females across Europe, also when receiving successful HAART, to early identify the HIV patients at risk for ICC to be submitted to more frequent follow up and proper treatment.
Full-text · Article · Apr 2014 · European review for medical and pharmacological sciences
[Show abstract][Hide abstract] ABSTRACT: Time of starting antiretroviral therapy (ART) after diagnosis of specific AIDS-defining event (ADE) is a crucial aspect. Objectives of this study were to evaluate if in patients diagnosed with ADE the time to ART initiation may vary according to year of diagnosis and type of ADE.
All HIV+ persons diagnosed with an ADE over the 6 months prior to or after enrolment in the Icona Foundation study cohort and while ART-naive were grouped according to type of diagnosis: Those with ADE requiring medications interacting with ART [group A], those with ADE treatable only with ART [B] and other ADE [C]. Survival analysis by Kaplan-Meier was used to estimate the percentage of people starting ART, overall and after stratification for calendar period and ADE group. Multivariable Cox regression model was used to investigate association between calendar year of specific ADE and time to ART initiation.
720 persons with first ADE were observed over 1996-2013 (group A, n = 171; B, n = 115; C, n = 434). By 30 days from diagnosis, 27% (95% CI: 22-32) of those diagnosed in 1996-2000 had started ART vs. 32% (95% CI: 24-40) in 2001-2008 and 43% (95% CI: 33-47) after 2008 (log-rank p = 0.001). The proportion of patients starting ART by 30 days was 13% (95% CI 7-19), 40% (95% CI: 30-50) and 38% (95% CI 33-43) in ADE groups A, B and C (log-rank p = 0.0001). After adjustment for potential confounders, people diagnosed after 2008 remained at increased probability of starting ART more promptly than those diagnosed in 1996-1999 (AHR 1.72 (95% CI 1.16-2.56).
In our "real-life" setting, the time from ADE to ART initiation was significantly shorter in people diagnosed in more recent years, although perhaps less prompt than expected.