Evaluation of Myo-Intimal Media Thickness and Atheromatous Plaques in People Living with HIV from the Archiprevaleat Cohort vs. HIV-Negative Subjects.

BACKGROUND: Antiretroviral therapy has allowed a clear improvement in prognosis for HIV patients, but metabolic problems, such as dyslipidemia, remain. This can lead to the development of atheromatous plaques. Our study aims to evaluate whether HIV-positive (HIV+) patients show higher myo-intimal media thickness (IMT) and atheromatous plaques compared to HIV-negative (HIV-) patients. METHODS: To evaluate the association between HIV infection in experienced patients and vascular pathology, we performed a cross-sectional study, observing 1006 patients, 380 HIV+ enrolled in the Archiprevaleat cohort, and 626 HIV- as a control group. All patients underwent a Doppler scan of the supra-aortic vessels. We compared the prevalence of IMT > 1.0 mm and plaques in the two groups. RESULTS: Patients in the HIV+ group were younger than those in the HIV- group, with a lower prevalence of hypertension and diabetes and higher dyslipidemia. The prevalence of plaques in strata of age was higher in the HIV+ group than in the HIV- group and was associated with the length of ART exposure. CONCLUSIONS: Our cross-sectional, retrospective study shows that HIV+ experienced patients are at greater risk of IMT and atheromatous plaques compared to HIV-. The risk is associated with being HIV+ and with the length of ART exposure. This finding may be useful in preventing cardiovascular risk.

Subclinical atherosclerosis as detected by carotid ultrasound and associations with cardiac and HIV-specific risk factors; the Archi-Prevaleat project.

OBJECTIVES: To evaluate the prevalence of carotid intima-media thickness (IMT) and plaques in a cohort of people living with HIV (PLWH), the role of cardiovascular risk factors, the impact of the antiretroviral regimens and the difference between naïve and experienced patients in the onset of carotid lesions. METHODS: This project was initiated in 2019 and involves eight Italian centres. Carotid changes were detected using a power colour-Doppler ultrasonography with 7.5 MHz probes. The following parameters were evaluated: IMT of both the right and left common and internal carotids, data regarding risk factors for cardiovascular disease, HIV viral load, CD4 cell counts, serum lipids, glycaemia and body mass index. The associations between pathological findings and potential risk factors were evaluated by logistical regression, with odds ratios (ORs) and 95% confidence intervals (95% CI)s. RESULTS: Among 1147 evaluated PLWH, with a mean age of 52 years, 347 (30.2%) had pathological findings (15.8% plaques and 14.5% IMT). Besides the usual risk factors, such as older age, male sex and dyslipidaemia, CD4 cell nadir < 200 cells/mL (adjusted OR = 1.51, 95% CI: 1.14-1.99) and current use of raltegravir (adjusted OR = 1.54, 95% CI: 1.01-2.36) were associated with higher prevalence of pathological findings. CONCLUSIONS: Our data show that the current overall percentage of carotid impairments remains high. Colour-Doppler ultrasonography could play a pivotal role in identifying and quantifying atherosclerotic lesions among PLWH, even at a very premature stage, and should be included in the algorithms of comorbidity management of these patients.

Safety and effectiveness of a 12-week course of sofosbuvir and simeprevir ± ribavirin in HCV-infected patients with or without HIV infection: a multicentre observational study.

The combination of sofosbuvir and simeprevir ± ribavirin (SOF + SMV ± RBV) for hepatitis C virus (HCV) treatment has been associated with high rates of sustained virological response (SVR). Few data are available regarding this regimen in HIV/HCV co-infected patients. This study evaluated the effectiveness and safety of a 12-week course of SOF + SMV ± RBV in a cohort of HCV monoinfected and HIV/HCV co-infected individuals. HCV-infected patients, with or without HIV infection, receiving a 12-week course of SOF + SMV ± RBV in four Italian centres from February to October 2015, were included in this retrospective observational study. Clinical and biochemical data were retrieved for all patients. A total of 88 individuals were evaluated: 29 (33.0%) HIV/HCV co-infected and 59 (67.0%) monoinfected. Most patients were males with HCV genotype 1b (62.5%) and 1a (25%) infection. RBV was used in 41 HCV monoinfected and 6 HIV/HCV co-infected patients. Cirrhosis was found in 67 patients (76.1%). The most common adverse events (AEs) were rash and/or pruritus (23.9%), fatigue (13.6%) and anaemia (9.1%). Serious AEs occurred in three patients (3.4%). No treatment discontinuations were observed. RBV use was associated with multiple AEs (P = 0.02). An overall SVR12 of 93.2% was achieved; 96.6% in HCV monoinfected and 86.2% in HIV/HCV co-infected individuals, without significance both in univariate (P = 0.09) and multivariate analyses (P = 0.12). A baseline platelet count ≥90 000/mm3 was associated with higher rates of SVR (P = 0.005). A 12-week course of SOF + SMV ± RBV was associated with good safety and high SVR12 rate both in HCV monoinfected and HIV-HCV co-infected individuals.

Hepatitis E virus co-infection in HIV-infected patients in Foggia and Naples in southern Italy.

BACKGROUND: Hepatitis E virus (HEV) infection represents an emerging infection in developed countries and is thought to be a zoonotic infection. It has recently been described as a new causative agent of acute and chronic hepatitis in immunosuppressed subjects, including HIV-infected patients. The aim of this study was to assess the sero-virological prevalence of HEV in HIV patients and in the general population as control group. METHODS: A prospective and observational cohort study was carried out in two hospitals in southern Italy. The seroprevalence of HEV was determined in a cohort of 959 subjects, 509 (53%) of whom were HIV-positive patients and 450 were from the general population. Serum samples were tested for anti-HEV antibodies; repeatedly positive results were confirmed by a Western blot assay. In positive patients HEV RNA and genotypes were also determined. RESULTS: A total of 46 (4.8%) of the 959 serum samples examined were reactive to anti-HEV Ig and confirmed by Western blotting. The prevalence of HEV antibodies (IgG and/or IgM) was 2.7% in the control group and 6.7% in HIV-infected patients. Anti-HEV IgM was found in 6/46 (13.0%) of the anti-HEV Ig-positive serum samples, in 5/34 HIV patients and in 1/12 of the general population. No HIV-infected patient presented chronic hepatitis with HEV infection alone. CONCLUSIONS: This study indicates a higher circulation of HEV in HIV-infected patients, whereas a low prevalence of HEV antibodies in the general Italian population was shown. Chronic hepatitis with HEV alone was absent, while it was present in subjects with HIV-HEV, co-infected with hepatitis B virus (HBV) and/or hepatitis C virus (HCV).

[Hepatitis E]. / Epatite E.

Hepatitis E virus (HEV) represents the main aetiological agent of enteric non-A hepatitis and is the only member of a new virus, Hepevirus, belonging to the family of Hepeviridae. HEV is the single most important cause of acute clinical hepatitis among adults in many areas of the developing world, specifically the Indian subcontinent and Southeast Asia, the Middle East and North Africa, where it is a common cause of sporadic and epidemic waterborne outbreaks and results in a high rate of morbidity and death, especially in pregnant women. Once thought of as an infection confined to developing countries, it is now recognized as a geographically widely distributed disease. In low-endemic regions (Western countries), sporadic cases of locally-acquired HEV infection are reported, acquired possibly through zoonotic transmission from pigs, wild boars or deer. In persons with pre-existing chronic liver disease, HEV superinfection can present as acute-on-chronic liver disease. In European countries, chronic infection, which may progress to liver cirrhosis, has been reported among immunosuppressed persons. Two testing vaccines proved to be highly effective in preventing the disease; these vaccines should be of particular use in groups that are at high risk of HEV infection.

Co-receptor switch during HAART is independent of virological success.

The influence of antiretroviral therapy on co-receptor tropism remains controversial. To verify if co-receptor tropism shift was affected by HAART, the evolution of proviral DNA V3 genotype after 12 months of a new antiretroviral regimen was compared between responder and non-responder patients. Baseline blood samples were collected from 36 patients infected with HIV-1 subtype-B (18 naïve and 18 experienced) for virus isolation and env V3 genotyping from plasma HIV-1 RNA and PBMC DNA. DNA V3 genotyping was repeated after 12 months from initiating HAART. WebPSSM was used for categorizing V3 sequences into X4 or R5; for analysis purposes, dual/mixed viruses were considered as X4. From the 10 (28%) patients changing their proviral DNA V3 genotype during therapy, six shifted from R5-to-X4 and four from X4-to-R5. The lack of reaching virological suppression was not associated with an X4-to-R5 (P = 0.25) or R5-to-X4 (P = 0.14) shift; time-to-viral suppression and CD4 increase were similar in both groups. No association was found between tropism shift and patient baseline characteristics including age, sex, CDC stage, CD4 count, viral load, exposure and length of previous HAART, enfuvirtide use in the new regimen, number of reverse transcriptase and protease resistance-associated mutations. Conversely, CD4 nadir was correlated to emergence of X4 virus in proviral DNA (mean 27.2 +/- 30.6 in R5-to-X4 shifting patients vs. 161.6 +/- 150.6 in non-shifting patients, P = 0.02). The occurrence of a tropism shift in both directions was independent of HAART use, irrespective of its efficacy. The CD4 count nadir was the only baseline characteristic able to predict an R5-to-X4 viral shift.

Clinical validation and applicability of different tipranavir/ritonavir genotypic scores in HIV-1 protease inhibitor-experienced patients.

Tipranavir, a non-peptidic protease inhibitor which shows in vitro efficacy against some HIV-1-resistant strains, can be used in salvage therapies for multi-experienced HIV patients due to its peculiar resistance profile including 21 mutations at 16 protease positions according to International AIDS Society (IAS). Other genotypic scores, however, which attribute a different weight to single amino-acid substitutions, have been recently proposed. To validate the clinical utility of four different genotypic scores for selecting tipranavir responders, the baseline resistance pattern of 176 HIV heavily experienced patients was correlated with virological success (HIV-RNA<50 copies/ml) after 24 weeks of a new treatment based on tipranavir/ritonavir. Virological suppression after 24 weeks was reached by 42.5% of patients. With univariate analysis, genotypic scores were all associated with outcome but showed a low accuracy with ROC analysis, with the weighted score (WS) by Scherer et al. demonstrating the best performance with an AUC of 68%. Only 52% of patients classified as susceptible (WS< or =3) responded to the new therapy. The following variables were significantly associated (p<0.05) to failure with multivariate analysis: WS, log peak of HIV-RNA, IAS mutations: L33F, I54AMV, Q58E, and non-IAS mutation: N37DES. On the contrary, the use of T20 in T20-naïve patients and the V82AFSI and F53LY non-IAS mutations were associated with virological success. The study suggests that even if the "weighted" scores are able to interpret correctly the antiretroviral resistance profile of multi-experienced patients, it is difficult to individuate a cut-off which can be easily applied to this population for discriminating responders.

Tuberculosis and immigrants: a SIMIT (Italian Society of Infectious Diseases) clinical, epidemiological multicentric research investigation.

The aim of the study was to evaluate the epidemiology and the diagnostic, clinical and therapeutic aspects of immigrants affected by tuberculosis, hospitalized in 35 Italian Infectious Diseases Clinics during 2003. The data obtained showed that 300/2392 (12.5%) patients had active tuberculosis, 10.3% of whom had concomitant HIV infection. 53% of the patients were legal residents and were assisted by the National Health Service; 48.3% came from African regions. The mean length of residency in Italy at the time of hospitalization was 4 years. The main clinical forms were pulmonary (66%), lymph nodal (15.3%) and bone TB (5.3%). Drug resistance was demonstrated in 16% of cases with 9% cases of resistance to isoniazid, 8.2% to streptomycin, 5.1% to pyrazinamide, 2.6% to ethambutol, 2.6% to rifampicin; in 5.3% of cases a multiple resistance was demonstrated. A complete adherence to treatment was achieved in 213 patients. Statistical analysis disclosed a significant correlation between compliance with treatment and legal citizenship status. In conclusion, TB still represents an important disease among immigrants. Improved living conditions, both in countries of origin and in Italy, especially in the first few years, would certainly decrease the incidence of TB.

QuantiFERON-TB Gold In-Tube test (QFT-GIT) for the screening of latent tuberculosis in recent immigrants to Italy.

To evaluate the agreement between QuantiFERON-TB Gold In-Tube test (QFT-GIT) and tuberculin skin test (TST) for the screening of latent tuberculosis infection (LTBI) in recent immigrants to Italy, 279 subjects were submitted to concomitant TST and QFT-GIT. The agreement was analyzed using k statistics. A total of 72/279 (25.8%) individuals were TST positive, while 107/279 (38.3%) were QFT-GIT positive. The overall agreement between QFT-GIT and TST was 70.9%, with k statistic of 0.35. Using different TST and QFT-GIT cut-offs, the best concordance value was obtained for QFT-GIT at > 2.64 IU/ml and TST at > 10mm (k = 0.409). Discordant results were found for 58 subjects (21%) with QFT-GIT positive/TST negative and 23 (8%) with QFT-GIT negative/TST positive. A high amount of discordance QFT-GIT+/TST- was described. QFT-GIT might increase the identification of LTBI cases among recent immigrants.

Peg-interferon alpha-2a versus Peg-interferon alpha-2b in nonresponders with HCV active chronic hepatitis: a pilot study.

BACKGROUND: The efficacy and tolerability of Peg-Interferon alpha-2a (Peg-IFNalpha-2a) versus Peg-Interferon alpha-2b (Peg-IFNalpha-2b) were compared in a patient cohort with hepatitis C virus (HCV)-related active chronic hepatitis, unresponsive to previous antiviral treatment with standard IFN (6 MU three times/week) plus ribavirin (10.6 mg/kg/day) for a period of at least 3 months. PATIENTS AND METHODS: A total of 143 patients were enrolled and randomized into two treatment groups (A-B). Group A (71 patients) received one vial of Peg-IFNalpha-2a weekly (180 microg) subcutaneously whereas Group B (72 patients) received 1.5 microg/kg of Peg-IFNalpha-2b weekly subcutaneously. Interferon was combined with ribavirin (15 mg/kg/day) in both groups and all patients who demonstrated nondetectable HCV-RNA or a >or=2(log) reduction in viral load at week 12, were treated for 48 weeks, with a 24-week follow up. RESULTS: Group A (10/71) and Group B (8/72) patients discontinued treatment due to severe side effects. At the end of therapy, HCV-RNA was undetectable in 17/71 (23.9%) Group A and in 19/72 (26.4%) of Group B patients. When terminating follow up, a sustained virological response was observed in 14/71 in Group A (19.7%) and 13/72 in Group B (18.0%). CONCLUSIONS: Within the limits of the relatively small sample size, Peg-IFNalpha-2a and Peg-IFNalpha-2b demonstrated nonstatistically significant differences in effectiveness in patients nonresponsive to previous antiviral treatment.

Early and sustained virological response in non-responders with chronic hepatitis C: a randomized open-label study of pegylated interferon-alpha-2a versus pegylated interferon-alpha-2b.

OBJECTIVES: The purpose of this randomized open-label study was to assess the efficacy of treatment with pegylated interferon-alpha-2a versus pegylated interferon-alpha-2b, both plus ribavirin, in inducing early and sustained virological response (EVR and SVR) in chronic hepatitis C non-responders. PATIENTS AND METHODS: A total of 108 patients with chronic hepatitis C who were non-responders to previous combined therapy (standard interferon-alpha plus ribavirin for > or = 3 months) were enrolled and equally randomized into two groups in this intention-to-treat analysis. The patients exhibited similar baseline features. One group received subcutaneous pegylated interferon-alpha-2a 180 microg once weekly, while the other was treated with subcutaneous pegylated interferon-alpha-2b 1.5 microg/kg once weekly. Ribavirin 15 mg/kg/day was included in both protocols. Treatment duration for EVR was 12 weeks. Patients who demonstrated non-detectable hepatitis C virus (HCV) RNA or a > or = 2 log(10) reduction in viral load at week 12 continued therapy up to 48 weeks, with assessments every 3 months during a follow-up of 24 weeks. RESULTS: All patients in both groups completed the EVR study, then seven patients receiving pegylated interferon-alpha-2a and seven patients receiving pegylated interferon-alpha2b discontinued treatment as a result of severe adverse effects. After 12 weeks of treatment, viral load reduction was >2 log(10) with both pegylated interferon-alpha-2a (-2.53) and pegylated interferon-alpha-2b (-2.48) with no significant difference. At the end of week 48, HCV RNA was undetectable in 14 of 54 patients (25.9%) receiving pegylated interferon-alpha-2a and in 15 of 54 patients (27.7%) receiving pegylated interferon-alpha-2b. When terminating follow-up, an SVR was observed in 11 of 54 patients (20.4%) who received pegylated interferon-alpha-2a and 10 of 54 patients (18.4%) receiving pegylated interferon-alpha-2b. The incidence and severity of adverse events was similar in both groups. CONCLUSIONS: Our results seem to show that in chronic hepatitis C patients who are non-responsive to previous therapy, EVR to the two pegylated interferons did not significantly differ with a similar therapeutic efficacy defined as SVR.

Prolonged lamivudine treatment in patients with chronic active anti-HBe-positive hepatitis.

The efficacy of lamivudine (LAM) at 100 mg/d for 1 year in normalizing serum ALT levels and suppressing HBV DNA has been demonstrated in many studies. However, frequent relapses make long-term results modest. In the present study, we evaluated the efficacy of LAM administered for 3 years in patients with chronic active anti-HBe-positive hepatitis. Thirty-four patients with chronic active anti-HBe-positive hepatitis were treated with LAM (100 mg) once daily for 3 years. Before treatment, all patients demonstrated serum ALT levels >2 times normal levels for >6 months and HBV DNA positivity >5 pg/mL as determined by the sandwich hybridization test for nucleic acid. Both ALT and HBV DNA were monitored during therapy. After 12 months of therapy, 24 of 34 patients (70.6%) showed evidence of HBV DNA clearance and normal ALT levels; 22 of 34 (64.7%) and 19 of 34 (55.8%) patients maintained a complete response after 2 and 3 years of therapy, respectively. The long-term LAM therapy (>1 year) was not associated with an increase in the response of intially nonresponder patients. The YMDD variant emerged in 17.6% of patients in the first year, in 35.2% during the second year, and 52.9% during the third year of treatment. LAM was well tolerated during the 3-year therapy in all patients. Patients with chronic active anti-HBe-positive hepatitis demonstrated that the LAM response rate tends to decrease over time due to the emergence of YMDD variants.

Multiple recurrences of vertebral hydatidosis: a case report.

We present a case of an Italian man with a particularly prolonged history of hydatid disease (more than 20 years, with six recurrences) involving both osseus (costal and vertebral) and visceral (pulmonary) sites. The main clinical problems involved in the diagnosis and management of vertebral manifestations of hydatidosis are discussed in the light of the latest clinical research.

Clinical and virological response to adefovir dipovixil for lamivudine-resistant HBeAg-negative hepatitis B.

Adefovir dipivoxil (ADV), a new nucleotide analogue, has demonstrated activity against lamivudine-resistant HBV both in vivo and in vitro. Herein, we present eight lamivudine-resistant patients with chronic anti-HBe positive hepatitis B treated orally with adefovir dipivoxil at 10 mg/die to evaluate the efficacy and safety of this drug and to determine the possible development of clinical ADV resistance. After 48 weeks of therapy, 4/8 (50%) patients demonstrated a complete response with normalization of alaninoaminotransferase levels (ALT, normal value < 40 IU/L) and undetectable serum HBV- DNA (< 100 copies/ml tested by a PCR assay). In 3/8 subjects (37.5%), we observed a partial response with a > 50% reduction of both ALT and HBV DNA levels. Only one patient did not respond. Adefovir was well-tolerated and no patient presented adverse events related to treatment; there were no changes in renal parameters. We conclude that in patients with anti-HBe positive chronic hepatitis B resistant to lamivudine, a 48-week ADV treatment resulted in significant biochemical and virological improvement without major adverse effects.