[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.
European review for medical and pharmacological sciences 04/2014; 18(8):1277-85. · 1.09 Impact Factor
[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.
PLoS ONE 01/2014; 9(2):e89861. · 3.73 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: Leishmaniasis is endemic in Sardinia but only cutaneous and visceral cases have been reported to date. We report a case of mucocutaneous leishmaniasis as presentation of HIV infection in a Sardinian patient who had never visited endemic areas. Serological and clinical diagnosis were cytologically and histopathologically confirmed. The patient had a good response to treatment with liposomal amphotericine combined with highly active antiretroviral therapy without recurrences after four years. Our case report highlights the need to better assess the circulation of species, risk factors and clinical spectrum of Leishmania infection in the Italian Mediterreanean islands.
Parasitology International 10/2013; · 2.30 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: Lipid pathway impairment, decrease in the antioxidant pool and downregulation in amino-acid metabolism are just some of the metabolic variations attributed to chronic HCV infection. All of them have been studied separately, mainly in animal models.
Thanks to proteomic analysis we managed to describe (for the fist time to the best of our knowledge), in vivo and in humans, the metabolic alterations caused by HCV, and the recovery of the same alterations during HCV treatment.
We performed proteomic analysis on liver specimens of a 28-year-old woman affected by hepatitis C genotype 1a, alcoholism and diabetes mellitus type 1, before and after antiviral treatment with pegylated interferon alpha 2b and ribavirin. The subject, thanks to a patient-tailored therapy, reached Sustained Virological Response. Throughout the treatment period the patient was monitored with subsequent biochemical, clinical and psychological examinations.
The data obtained by the patient's close monitoring suggest a direct interaction between insulin resistance and an active HCV genotype 1 infection, with a leading role played by the infection, and not by insulin resistance, as demonstrated by the sharp fall of the insulin units needed per day during treatment.
The proteomic analysis showed that after therapy, a downregulation of enzymes involved in amino acid metabolism, glycolysis/gluconeogenesis and alcohol catabolism takes place, the latter probably due to cessation of alcohol abuse. On the contrary, the metabolic pathways linked to metabolism of the reactive oxygen species were upregulated after therapy. Finally, a significant alteration in the pathway regulated by peroxisome proliferator-activated receptor alpha (PPARA), a major regulator of lipid metabolism in the liver, was reported.
These “real time” data confirm in vivo, in humans, that during HCV infection, the pathways related to fatty acids, glucose metabolism and free radical scavenging are inhibited. The same enzyme deficit is completely recovered after HCV eradication.
Journal of Clinical Virology 03/2013; · 3.29 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: The etiology of multiple sclerosis (MS) is still unclear. The immuno-pathogenic phenomena leading to neurodegeneration are thought to be triggered by environmental (viral?) factors operating on predisposing genetic backgrounds. Among the proposed co-factors are the Epstein Barr virus (EBV), and the potentially neuropathogenic HERV-W/MSRV/Syncytin-1 endogenous retroviruses. The ascertained links between EBV and MS are history of late primary infection, possibly leading to infectious mononucleosis (IM), and high titers of pre-onset IgG against EBV nuclear antigens (anti-EBNA IgG). During MS, there is no evidence of MS-specific EBV expression, while a continuous expression of HERV-Ws occurs, paralleling disease behaviour. We found repeatedly extracellular HERV-W/MSRV and MSRV-specific mRNA sequences in MS patients (in blood, spinal fluid, and brain samples), and MRSV presence/load strikingly paralleled MS stages and active/remission phases. Aim of the study was to verify whether HERV-W might be activated in vivo, in hospitalized young adults with IM symptoms, that were analyzed with respect to expression of HERV-W/MSRV transcripts and proteins. Healthy controls were either EBV-negative or latently EBV-infected with/without high titers of anti-EBNA-1 IgG. The results show that activation of HERV-W/MSRV occurs in blood mononuclear cells of IM patients (2Log10 increase of MSRV-type env mRNA accumulation with respect to EBV-negative controls). When healthy controls are stratified for previous EBV infection (high and low, or no anti-EBNA-1 IgG titers), a direct correlation occurs with MSRV mRNA accumulation. Flow cytometry data show increased percentages of cells exposing surface HERV-Wenv protein, that occur differently in specific cell subsets, and in acute disease and past infection. Thus, the data indicate that the two main links between EBV and MS (IM and high anti-EBNA-1-IgG titers) are paralleled by activation of the potentially neuropathogenic HERV-W/MSRV. These novel findings suggest HERV-W/MSRV activation as the missing link between EBV and MS, and may open new avenues of intervention.
PLoS ONE 01/2013; 8(11):e78474. · 3.73 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: PURPOSE: The prevalence of anti-hepatitis E virus (HEV) and anti-hepatitis A virus (HAV), as well as the possible links with socio-demographic and other viral risks factors, were evaluated in an inmates population. METHODS: The study population consisted of 973 consecutively recruited inmates of eight Italian prisons. RESULTS: The anti-HEV prevalence was 11.6 % (113/973). It increased significantly by age (χ(2) for linear trend: p = 0.001) and was significantly higher among non-Italian compared to Italian inmates (15.3 vs. 10.7 %, respectively). Age >40 years [odds ratio (OR) 2.1; 95 % confidence interval (CI) 1.4-3.1], non-Italian citizenship (OR 1.8; 95 % CI 1.1-2.9) and anti-HIV seropositivity (OR 2.2; 95 % CI 1.2-4.2) were the only factors independently associated to anti-HEV positivity by logistic regression analysis. The overall anti-HAV prevalence was 86.4 %, and was significantly higher in non-Italian compared to Italian prisoners (92.6 vs. 84.9 %, respectively; p = 0.02). Age older than 40 years (OR 3.6; 95 % CI 2.2-5.9), <5 years formal education (OR 2.1; 95 % CI 1.3-3.2) and non-Italian nationality (OR 2.7; 95 % CI 1.5-4.8) were factors independently associated to anti-HAV positivity by the logistic regression analysis. CONCLUSIONS: Compared to the general population, significantly higher anti-HEV and anti-HAV prevalences were observed in an inmates population in Italy. Old age and non-Italian nationality were factors independently related to both HEV and HAV exposures. This data suggest the important role of low socio-economic factors in the transmission of both infections in high-risk populations. The possible epidemiological and/or pathogenetic links between HEV and HIV exposures need to be studied further.
[Show abstract][Hide abstract] ABSTRACT: Central nervous system (CNS) symptoms have been reported in clinical trials and case reports in patients receiving raltegravir. We investigated CNS symptoms in 453 HIV-infected patients. Of these 47 (10.4%) developed at least one drug related CNS symptom. Predictors of CNS symptoms were concomitant therapy with tenofovir or with proton pump inhibitors which can increase raltegravir concentration. Thus, our data suggest a possible correlation between high raltegravir plasma concentrations and CNS symptoms and therefore their monitoring in clinical practice.
AIDS (London, England) 10/2012; · 4.91 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: In Italy, HIV-1 epidemic is still mainly sustained by subtype B genetic form, although other and novel subtypes and circulating recombinant forms (CRFs) have been reported. A total of 215 HIV-1 pol gene sequences were collected between 1992 and 2010. Multiple alignments spanning subtype specific HIV-1 B pol sequences were analyzed by Bayesian phylogenetic methods. Subtype B represented 90.7% (n=195) of the sequences. Three main clusters were detected. The root of the tree dated 1987. Most of the observed viral gene flow events occurred from heterosexual to IDUs. Phylogenetic and molecular clock analysis showed an early HIV-1 subtype B introduction in the mid1980s and dissemination within local risk-specific clusters. This is the first study described in detail HIV-1 molecular epidemiology in one of the largest islands in the European basin. The future potential of the Sardinian epidemic as a hub between Southern and Northern Europe have to been considered.
AIDS research and human retroviruses 09/2012; · 2.18 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: OBJECTIVES: To define the impact of coinfection with hepatitis B virus (HBV) or hepatitis C virus (HCV) on viroimmunological response to raltegravir-based salvage regimens that also include new HIV inhibitors such as maraviroc, darunavir and etravirine. METHODS: We used data from a national observational study of patients starting raltegravir-based regimens to compare virological suppression and CD4 cell change from baseline in patients with and without concomitant HBV or HCV infection. RESULTS: Overall, 275 patients (107 coinfected and 168 non-coinfected) were evaluated. Coinfected patients were more commonly former intravenous drug users and had a longer history of HIV infection and higher baseline aminotransferase levels. Both HIV-RNA and CD4 response were similar in the two groups. Mean time to first HIV-RNA copy number <50 copies/mL was 4.1 months (95% CI 3.5-4.6) in non-coinfected patients and 3.9 months (95% CI 3.3-4.5) in coinfected patients (hazard ratio 1.039, 95% CI 0.761-1.418, P = 0.766, log-rank test). The risk of developing new grade 3-4 hepatic adverse events was significantly higher in coinfected patients (hazard ratio 1.779, 95% CI 1.123-2.817, P = 0.009). The two groups of coinfected and non-coinfected patients had similar rates of interruption of any baseline drug (hazard ratio 1.075, 95% CI 0.649-1.781, P = 0.776) and of raltegravir (hazard ratio 1.520, 95% CI 0.671-3.447, P = 0.311). Few AIDS-defining events and deaths occurred. CONCLUSIONS: Viroimmunological response to regimens based on raltegravir and other recent anti-HIV inhibitors is not negatively affected by coinfection with HBV or HCV. Liver toxicity, either pre-existing or new, is more common in coinfected patients, but with no increased risk of treatment interruption.
Journal of Antimicrobial Chemotherapy 09/2012; · 5.34 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: PURPOSE: The objective of our study was to evaluate the presence of respiratory symptoms and chronic obstructive pulmonary disease (COPD) in a human immunodeficiency virus (HIV)-infected outpatient population and to further investigate the role of highly active antiretroviral therapy (HAART) and other possibly associated risk factors. METHODS: We consecutively enrolled in a cross-sectional study HIV-infected patients and HIV-negative age, sex and smoking status matched controls. All participants completed a questionnaire for pulmonary symptoms and underwent a complete spirometry. RESULTS: We enrolled 111 HIV-infected patients and 65 HIV-negative age- and sex-matched controls. HIV-infected patients had a significantly higher prevalence of any respiratory symptom (p = 0.002), cough (p = 0.006) and dyspnoea (p = 0.02). HIV-infected patients also had a significantly higher prevalence of COPD in respect of HIV-negative controls (p = 0.008). Furthermore, HIV-infected individuals had significantly (p = 0.002) lower forced expiratory volume at one second (FEV1) and FEV1/forced vital capacity (FVC) ratio (Tiffeneau index) (p = 0.028), whereas the total lung capacity (TLC) was significantly higher (p = 0.018). In the multivariate analysis, significant predictors of respiratory symptoms were current smoking [adjusted odds ratio (AOR) 11.18; 95 % confidence interval (CI) 3.89-32.12] and previous bacterial pneumonia (AOR 4.41; 95 % CI 1.13-17.13), whereas the only significant predictor of COPD was current smoking (AOR 5.94; 95 % CI 1.77-19.96). HAART receipt was not associated with respiratory symptoms nor with COPD. CONCLUSIONS: We evidenced a high prevalence of respiratory symptoms and COPD among HIV-infected patients. HIV infection, current cigarette smoking and previous bacterial pneumonia seem to play a significant role in the development of respiratory symptoms and COPD. Thus, our results suggest that the most at-risk HIV-infected patients should be screened for COPD to early identify those who may need specific treatment.
[Show abstract][Hide abstract] ABSTRACT: TO THE EDITOR: Prisons represent a crucial setting for tuberculosis (TB) control. Worldwide, reported TB rates for correctional system populations have been 10-100× higher than rates for the local civilian populations, and TB outbreaks with a high number of TB multidrug-resistant cases have been documented (1,2). Prisons are known as social and sanitary pathology reservoirs in which TB is often associated with chronic infectious diseases caused by HIV, hepatitis B virus (HBV), or hepatitis C virus (HCV) (2).
[Show abstract][Hide abstract] ABSTRACT: TO THE EDITOR: Rickettsia conorii, the etiologic agent of Mediterrenean spotted fever (MSF), is transmitted to humans by the brown dog tick (Rhipicephalus sanguineus). MSF is endemic to Italy; incidence is highest in the south and on the islands of Sardinia and Sicily (1). Recently, the use of molecular methods has enabled identification of other rickettsiae of the spotted fever group (SFG) from Ixodes ricinus ticks in northeastern Italy and in other areas of Europe (2-6). R. monacensis was identified as an etiologic agent of MSF-like illness in Spain (7).
[Show abstract][Hide abstract] ABSTRACT: Criteria of cART initiation after a first ADE have been modified over time based on evidence suggesting that treatment should be initiated earlier. The impact of these changes on clinical practice is unknown. Objective of this analysis was to evaluate temporal changes of time of starting cART after a first diagnosis of ADE in ART-naïve patients (pts). Methods: All HIV+ enrolled in ICONA Foundation Study who presented with a diagnosis of ADE while cART-naïve regardless of CD4 cell count were included. Pts were grouped according to have ADE for which additional medications that may have interactions with cART are required (Tb, atypical mycobacteriosis, non-Hodgkin lymphoma) [group A], ADE treatable only by cART (PML, isosporidiasis/cryptosporidiasis, KS, wasting syndrome) [group B] and ADE treatable with specific drugs (PCP, toxoplasmic encephalitis, CMV disease, esoph candidiasis, bacterial pneumonia, cervical cancer, cryptococcosis) [group C]. Standard survival analysis by KM was used to estimate the cumulative percentage of pts starting cART, overall and after stratification for calendar period of diagnosis (1996-2000, 2001-2008, 2009-2011) and type of ADE (groups A, B, C). Multivariable Cox regression was used to investigate association between calendar year of ADE and time to cART initiation after controlling for demographics. Summary of results: A total of 715 pts with a first ADE were observed over 1996-2011 (group A, n=187; B, n=123; C, n=405). 519 (73%) male, median age 38 (IQR:33-45), median CD4+64 (23-187)/mm3 and HIV/RNA 5.25 (4.57-5.70) log10 cps/mL, with no differences by calendar period. By 30 days from ADE, 23% (95% CI: 19-27) of those diagnosed in 1996-2000 have started cART vs. 32% (95% CI: 25-39) in 2001-2008 and 36% (28-44) after 2009 (log-rank p=0.001). After stratifying by CD4 at ADE, 45% of pts with CD4<50/mm3, 30% of those with 51-200/mm3 and 16% of those>201/mm3 had started cART by 30 days (p<0.0001). Restricting the analysis to pts diagnosed after 2009, the percentages of cART initiation were 9% for group A, 52% for group B and 39% for group C (p=0.05). The table shows the relative hazards of starting cART from fitting a multivariable Cox regression model. Conclusions: In our 'real-life' setting, time from AIDS diagnosis to cART was significantly shorter in pts diagnosed in more recent years, although for most ADE cART initiation was less prompt than expected, even in pts with severe immunodeficiency.
Journal of the International AIDS Society 01/2012; 15(6):18200. · 3.94 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: The clinical severity of human infection with the novel influenza virus A/H1N1v has not been completely defined, especially in HIV/hepatitis C virus (HCV) infected patients. Although most patients develop mild to moderate symptoms, severe disease may occur in a limited proportion of cases. We report the case of a 44-year-old man infected with HIV and HCV with a high CD4 cell count who developed acute respiratory distress syndrome associated with influenza virus A/H1N1v infection. The patient recovered completely after oseltamivir therapy and mechanical ventilation.
International Journal of STD & AIDS 04/2011; 22(4):234-5. · 1.00 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: International HIV treatment guidelines recommend HLA-B*57:01 typing before abacavir administration, in order to reduce the incidence of abacavir hypersensitivity reactions, the major cause of early therapy discontinuation. A fast, sensitive and specific test for HLA-B*57:01 detection has been developed in the present study.
Two sets of sequence-specific primers were designed, and amplification rapidly detected by real-time PCR.
A total of 108 samples were analyzed in a single-blind fashion, and 41 samples were identified as positive. Complete agreement, with κ = 1 (standard error = 0.0962, p < 0.0001), was found, with a validated methodology used in the EPI109367 clinical trial funded by GlaxoSmithKline, and consisting of low-resolution sequence-specific oligonucleotide PCR, followed by high-resolution sequence-specific oligonucleotide PCR carried out on the HLA-B*57-positive samples.
We provided a detailed characterization of a novel HLA-B*57:01 screening test, which can be easily implemented by those laboratories already involved in the detection of viral load and virus genotyping. Original submitted 26 October 2010; Revision submitted 13 December 2010.
[Show abstract][Hide abstract] ABSTRACT: Background: CXCR4 phenotype has been associated with increased severity of HIV disease, higher viral load, and decreased CD4 T-cell counts. We thus evaluated whether a genotypic analysis of core-ceptor tropism impacts on HIV-related markers such as CD4-cell counts. Methods: 960 HIV-1 B subtype infected patients (all maraviroc-naive) with an available V3 sequence were analyzed. Tropism determination was performed by using Geno2Pheno algorithm. All V3 mutations, including the mutations used for tropism prediction (Sing T et al., Antiviral Therapy 2007), with prevalence [1% were considered. The associations of CD4 cell counts with false positive rate (FPR) ranges and V3 mutations were evaluated by Mann– Whitney test, Chi-squared test for trend and Fisher exact test, as appropriate. The Benjamini–Hochberg method was used to identify results that were statistically significant in the presence of multiple-hypothesis testing. A false discovery rate of 0.05 was used to deter-mine statistical significance. Results: Overall, 26% of patients (either drug-naive or drug-expe-rienced) were infected by X4 tropic viruses (using the classical 10% FPR cutoff). Among patients with available CD4 cell-counts at V3 genotypic test, 321 were drug-naive and 490 drug-experienced (median [IQR] CD4-cell counts: 331 [201–448] vs. 282 [138–422] cells/mm 3 , p = 0.004). CD4 cell-count \\200 cells/mm 3 was observed in 80 drug-naive patients and in 169 drug-experienced patients. For different CD4 cell count ranges, FPR \\2% was mostly associated, in experienced patients, with CD4 cell-counts \\200 cells/mm 3 (\\200 vs. 200–350 vs. 350–500 vs. [500 cells/ mm 3 : 21.3 vs. 7.6 vs. 9.0 vs. 8.0%, respectively, p = 0.0005). This finding was also observed in drug-naive patients, even if with less significance (11.3 vs. 6 vs. 2.6 vs. 1.5%, respectively, p = 0.040). A deeper analysis showed that patients with FPR \\2% (both naive and drug-experienced) carried a significantly greater risk of having CD4 counts \\200 cells/mm 3 (see figure). Among all V3 mutations analyzed (87 in naive patients and 88 in experienced patients), in drug-experienced patients the X4-related S11R was the only mutation found associated with CD4 cell count \\200 cells/mm 3 (17.8 vs. 5.6% in \\200 vs. [200 CD4, respectively, p \\ 0.001). This significance was confirmed after correction for multiple comparisons. Conclusions: Within the context of genotypically-defined CXCR4 tropism, FPR \\2% and the X4-related mutation S11R are associated with low CD4 rank, and thus may be related with a greater risk of disease progression. These findings suggest that FPR, beyond tropism prediction, can be used also as a marker to evaluate the immuno-logical status of HIV-1 infected patients.