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Biomedical subjects

G Angarano

Publications and source records attributed to G Angarano.

At least 19 recordsLinked to original sources

Key questions in antiretroviral therapy: Italian Consensus Workshop (2005).

A panel of leading Italian specialists in infectious diseases, virologists and immunologists met in Rome in 2005 to review critical data and discuss recommendations for each of the key questions in antiretroviral therapy today: When to start treatment? How to start? When to switch? What to switch to? Whether to stop or not to stop treatment, and how? The method of a nominal group meeting was used and recommendations were graded for their strength and quality using a system based on the one adopted by the Infectious Diseases Society of America. Main conclusions are summarized and critically discussed in this consensus statement, as well as some of the most recent data supporting these recommendations are provided.

Anti-HIV Agents↗

Impact of unreported HIV-1 reverse transcriptase mutations on phenotypic resistance to nucleoside and non-nucleoside inhibitors.

An extended spectrum of HIV-1 reverse-transcriptase (RT) mutations in HAART-treated patients has been recently described. To verify the possible association of previously unreported RT mutations with a decrease of phenotypic susceptibility to nucleoside (NRTIs) and non-nucleoside (NNRTIs) RT inhibitors, the RT sequence of 328 HIV-1-positive patients (102 naïve and 226 treated with HAART participating in either the PhenGen or Genpherex study) was analyzed. All treated patients were tested at the time of therapeutic failure with both phenotypic (Antivirogram, Virco) and genotypic analyses (VircoGen); the frequency of RT substitutions (positions 1-240) with respect to consensus B was compared to that of naïve patients using a Chi-square test. Amino acid changes at 13 positions not included in the IAS list of resistance-associated mutations were detected more frequently in treated than in naïve subjects. The mutations involving 10 of these positions were associated with a reduced susceptibility to antiretroviral drugs; K20R, T39A, K43EQN, E203KD, H208Y, and D218E were correlated with NRTI resistance while mutations K101EQP, H221Y, K223EQ, L228HR were associated to NNRTI resistance. A correlation was found between K20R and lamivudine resistance (P = 0.006) while T39A (P = 0.005), K43EQN (<0.001), E203KD (P = 0.010), and H208Y (P = < 0.001) seemed to be associated with a previous use of zidovudine and stavudine and with the development of thymidine analog resistance. For H208Y, an association with use/resistance to abacavir (P = 0.004) was also noted. D218E showed a weak association to didanosine resistance (P = 0.013). The data confirm that previously unreported mutations are associated with antiretroviral drug experience and, more importantly, with a reduced susceptibility to NRTIs and NNRTIs.

Adult↗

Extended lamivudine treatment in patients affected by chronic active anti-Hbe positive hepatitis.

The aim of the study was to evaluate the biochemical and virological response and the histological changes in 34 chronic hepatitis B anti-Hbe-positive patients treated with lamivudine at 100 mg/day orally for five years. Liver biopsies were performed in all patients at least 6 months before starting therapy and 3 months after the stop of treatment. After 12 months of therapy, 70.6% of patients showed evidence of HBV DNA clearance and normal ALT levels; 64.7% and 55.8% of patients maintained a complete response after two and three years of therapy, respectively, 47% after four years and 44.1% after five years. The histological activity index improved in 13%, remained unchanged in 61% and worsened in 26% of patients with tyrosine-methionine-aspartate-aspartate (YMDD) variants compared to 63, 27 and 0% without variants, respectively. The authors conclude that the clinical benefit of lamivudine is greatest for patients without YMDD variants after 5 years of extended treatment.

Administration, Oral↗

Cryoglobulinemia in subjects with HCV infection alone, HIV infection and HCV/HIV coinfection.

OBJECTIVES: To assess the prevalence of cryoglobulinemia in three groups of patients: HCV-positive/HIV-negative, HCV/HIV co-infected and HIV mono-infected. METHODS: From September 2002 to December 2003, 58 patients with documented HCV infection, 70 subjects with HIV/HCV co-infection, and 48 subjects with HIV infection alone were enrolled. Serum samples were tested for detectable cryoglobulins, liver enzymes, HCV viral load and HCV genotypes. Plasma HIV-RNA levels and CD4+ cell count were also evaluated in HIV-positive subjects. RESULTS: Cryoglobulinemia was detected in 24.1% HCV mono-infected, 14.2% HCV/HIV co-infected and 6% HIV mono-infected patients. A significant statistical correlation was found between the presence of cryoglobulins and HCV infection (P = 0.03), while cryoglobulins were unrelated to HIV mono-infection (P = 0.16) and HCV/HIV co-infection (P=0.7). No significant correlation was observed between the presence of cryoglobulinemia and alanine transaminase (ALT) levels, HCV viremia and duration of HCV infection. Circulating cryoglobulins in HIV patients were not correlated with plasma HIV viral load, CD4+ cell count or duration of HIV infection. Only two HCV mono-infected patients complained of arthralgia. CONCLUSION: A similar rate of cryoglobulinemia prevalence was detected in the patient groups with an HCV-related infection. HIV infection does not appear to play a significant role in cryoglobulin production.

Adult↗

Simit epidemiological multicentric study on hospitalized immigrants in Italy during 2002.

The aim of this article is to retrospectively evaluate the patient characteristics and the most common infectious diseases in immigrant patients hospitalized in 46 Italian infectious disease clinics during 2002. The main Italian infectious disease clinics were invited to fill in a questionnaire that regarded the number and type of hospital admissions, the country of origin, and demographic features (age, sex, and resident state) of immigrants. A total of 46 clinics including 2255 patients participated in the study. Most patients were men (63%) with an age between 16 and 40 years (63.4%) covered by the National Health Service (71%) and coming from Africa (44.3%). The main infectious diseases observed were: 378 (16.76%) cases of HIV infection, 303 (13.43%) cases of tuberculosis diseases, 282 (12.5%) cases of various forms of viral hepatitis, 177 (7.84%) cases of respiratory diseases, and 196 (8.69%) gastrointestinal diseases. Tropical diseases found were 134 (5.94%) including 95 cases of malaria (70.9%). In conclusion, a broad range of diseases was noted in immigrants which were directly correlated with conditions of poverty. Only a few tropical diseases were diagnosed and therefore the immigrant should not be considered as an infectious disease carrier.

Adolescent↗

Peginterferon alfa-2b treatment for patients affected by acute hepatitis C: presentation of six case reports.

Acute hepatitis C often progresses to chronic infection (70%). In this clinical study, we evaluated if early treatment with peginterferon alfa-2b can prevent acute hepatitis C from developing into a chronic disease. Six patients with acute hepatitis C, based on a well-documented hepatitis C virus (HCV) seroconversion with high alanine aminotransferase (ALT) levels (> 10 x ULN) and persistent HCV RNA titers after 3 months from disease onset, were consecutively treated with peginterferon alfa-2b at 1.5 microg/kg/weekly/sc for 24 weeks. The viral load was quantified by PCR assay. Response was defined as undetectable HCV RNA and normal ALT levels at the end of therapy and after a 6-month follow-up. All patients completed therapy; at the end of therapy, 5/6 patients (83%) responded and no relapses were observed during follow-up. No correlation was found between treatment response and pretreatment viral load, viral genotype, and interval between acute infection diagnosis and start of therapy.

Acute Disease↗

Access to HAART in HIV-infected immigrants: a retrospective multicenter Italian study.

Since 1996, AIDS has declined in the Italian population, but cases in foreign patients, including both recent immigrants and long-term residents, have increased from 3.9% in 1995-1996 to 15.4% in 2001-2002. This increase can only be partly explained by a higher migratory flow and might reflect a delayed access to health facilities and to antiretroviral therapy in migrants. We performed a survey for the year 2003 of HIV-infected immigrants to Italy from countries outside the European Union to verify which factors might influence a lack of access to highly active antiretroviral therapy (HAART). Italian centers of infectious diseases were requested to send sociodemographic and clinical data of HIV-infected immigrant patients. A total of 553 HIV-infected immigrants (49.9% women) were evaluated, representing 6.5% of all HIV-infected patients from these centers. The mean duration of residency in Italy was 6.6 +/- 5.0 years. The country of origin was Africa (64.5%), North and South America (24.2%), Eastern Europe (7.0%), and Asia (3.8%). A total of 407 of 553 patients (73.6%) were taking antiretroviral drugs at the time of screening. Females presented a younger age (p = 0.001), a lower frequency of Centers for Disease Control (CDC) stage B/C (p = 0.008) and a more frequent heterosexual exposure to HIV (p < 0.001), while no differences were observed for time of first positive serology (p = 0.7). CD4 cell count (p = 0.9) and log plasma HIV-RNA (p = 0.1). Characteristics of HAART patients were compared to those of nontreated patients, despite a CD4 cell count less than 350 cells/mm(3). No significant difference was found for gender, country of origin, risk factor, and years of Italian residence, while legal immigrants (p = 0.018) and registered in the National Health Service (p = 0.014) were significantly more likely to receive HAART compared to illegal immigrants.

Adult↗

Prevalence of HIV infections in hospitalised immigrants in Clinics of Infectious Diseases in Italy: a multicentric survey.

Our aim was to evaluate the prevalence of HIV infection in immigrants hospitalised in infectious disease settings in Italy during 2002. Each participating centre filled in a CRF which regarded the number of immigrants hospitalised in ordinary regime or in day-hospital during 2002 and, for HIV-positive patients only, some demographic (age, sex, origin) and clinical features (only HIV positivity or AIDS, new diagnosis or not, diagnosis of opportunistic infections). A total of 46 Infectious Diseases Units participated in the study and a total number of 2255 patients were tested for anti-HIV, irrespective of the cause of hospitalization, with 378 (16%) cases of positivity. Women accounted for 47.9%; the mean age of the population was 34.5 years. African patients showed a higher prevalence of HIV infections than subjects from other geographical areas (61.9% of all cases). Most HIV-infected patients were unaware of their positivity. In conclusion, HIV infection represents one of the main health problems among immigrants, particularly of African origin.

Adult↗

Intrabiliary rupture of a hydatid liver cyst: a case report.

Intrabiliary rupture of a hydatid liver cyst is a rare occurrence which may result in the development of obstructive jaundice and cholangitis. In this report we discuss the diagnostic and therapeutic management of a patient in whom the parasitic nature of cholangitis was underestimated due to the small size and site of the cyst, and to the misleading concomitant presence of cholelithiasis.

Cholangiography↗

Secondary mutations in the protease region of human immunodeficiency virus and virologic failure in drug-naive patients treated with protease inhibitor-based therapy.

The role of mutations in protease (PR) and reverse-transcriptase (RT) of human immunodeficiency virus (HIV) in predicting virologic failure was assessed in 248 antiretroviral-naive HIV-positive patients who began a PR inhibitor-containing antiretroviral regimen. Genotypic testing was performed on plasma samples stored before the start of therapy. Twenty-seven patients (10.9%) had mutations in the RT, 5 (2%) carried primary mutations in the PR, and 131 (52.8%) showed only secondary PR mutations. Virologic failure at week 24 occurred in 62 (25.0%) of 248 patients. There was a statistically significant correlation between virologic failure and the number of PR mutations (P= .04, chi(2) test). Mutations at codons 10 and 36 of PR (present in 39.3% and 40.0% of patients in whom treatment failed, respectively) were identified by stepwise logistic regression as the strongest predictors of virologic failure (odds ratio, 2.20; 95% confidence interval, 1.30-3.75; P= .004). If confirmed in independent studies, this result may justify the increased use of HIV genotyping in drug-naive patients requiring antiretroviral therapy.

Acute Disease↗

Intracellular and cell-free (infectious) HIV-1 in rectal mucosa.

The intestinal mucosa contains most of the total lymphocyte pool and plays an important role in viral transmission, but only slight attention has been given to the immunological and virological aspects of human immunodeficiency virus-1 (HIV-1) infection at this site. In this study, before initiating or changing antiretroviral therapy, paired blood samples and rectal biopsies (RB) were obtained from 26 consecutive HIV-infected subjects. HIV-1 isolation and biological characterization, DNA, and HIV-1 RNA titration were assessed, as were in vitro tumor necrosis factor-alpha (TNF-alpha) and interleukin-beta (IL-1beta) spontaneous production. The rate of HIV-1 isolation from peripheral blood mononuclear cells (PBMCs) and RBs was 75% and 58%, respectively. All RB-derived isolates were nonsyncytium inducing (NSI), independent of the phenotype of blood-derived isolates. Proviral DNA and detectable HIV-1 RNA levels were measured in 100% and 77% of RBs, respectively. A statistical correlation was observed between HIV-1 DNA and HIV-1 RNA levels in rectal mucosa (P = 0.0075), whereas no correlation was found between these levels in blood samples (P > 0.05). Antiretroviral treatment did not seem to influence HIV-1 detection in RBs. Higher levels of in vitro proinflammmatory cytokine production were found in the RBs of most infected patients when compared with healthy controls. Therefore, the rectal mucosa is an important HIV-1 reservoir that demonstrates a discordant viral evolution with respect to blood. Both the virus type and the mucosa pathway of immunoactive substances might have important implications for therapeutic decision-making and monitoring and could influence the bidirectional transmission of HIV-1 in mucosal surfaces.

Adult↗

Response of severe HIV-associated thrombocytopenia to highly active antiretroviral therapy including protease inhibitors.

OBJECTIVE: To investigate the response of HIV-associated severe thrombocytopenia (STP) to highly active antiretroviral therapy (HAART) including protease-inhibitors. METHODS: In this retrospective study, 15 patients with HIV-associated STP (platelet count < 50 x 10(9)/l mostly antiretroviral experienced (13/15), underwent HAART for at least 6 months (median 21; range 6-41 months) during which the platelet (PLT) count and plasmatic HIV-RNA were monitored. The PLT response was compared to that observed in 19 patients previously treated with zidovudine (AZT) monotherapy. RESULTS: HAART induced a significant increase in the PLT count (chi(2)=10.53, P=0.01) within the third month which was sustained up to the sixth month of therapy. No STP relapse was observed among eight PLT responders followed for longer than 6 months (median 27; range 7-41 months). The PLT increase after HAART was similar to that observed with AZT monotherapy, but a greater number of HAART patients were antiretroviral-experienced. HAART determined a PLT response in 10/13 subjects whose thrombocytopenia had not improved after previous AZT monotherapy. After 6 months of HAART, a complete platelet response occurred more frequently in patients with undetectable plasma HIV-RNA levels (P=0.01). CONCLUSIONS: HAART induces a sustained PLT response in HIV-associated STP, even in antiretroviral-experienced subjects and in those with AZT-resistant thrombocytopenia. An undetectable plasma HIV viraemia induced by HAART is necessary for STP recovery.

Adolescent↗

Guidelines of tuberculosis preventive therapy for HIV-infected persons: a prospective, multicentre study. GISTA (Gruppo Italiano di Studio Tubercolosi e AIDS).

The aim of this study was to assess the degree of implementation of national guidelines for isoniazid preventive therapy (IPT) among human immunodeficiency virus (HIV)-infected individuals and factors affecting the impact of the programme. Twenty-eight infectious disease hospital units in Italy participated in this observational, multicentre, prospective cohort study. A number of HIV-infected subjects, (n=1,705) seen for the first time as outpatients, were included in this analysis. Of the subjects considered, 1,215 out of the 1,705 completed purified protein derivative (PPD) screening. Variables independently associated with offering and completion of PPD screening included having acquired immune deficiency syndrome (AIDS), higher educational levels and currently receiving therapy. Overall, 103 subjects were identified as candidates for IPT. Of these subjects, five had tuberculosis and 15 had contraindications to IPT. Forty subjects agreed to start IPT, and 29 completed a full-course regimen. The incidence of tuberculosis among IPT candidates who either did not begin or discontinued IPT was 6.1 per 100 person-yrs, while no cases of tuberculosis were observed in subjects completing IPT. Several factors may limit the implementation of an isoniazid preventive therapy programme for human immunodeficiency virus-infected persons. Physicians fail to offer purified protein derivative screening to patients with high degrees of immunodeficiency, and those with a more intense workload seem to pay less attention to this test. The high number of contraindications among patients and their low level of acceptance further affects the impact of isoniazid preventive therapy.

AIDS-Related Opportunistic Infections↗

"In vitro" spontaneous production of B-chemokines by endocervical and endometrial short-term bioptic cultures.

Several studies indicate that HIV-1 is present in the cervico-vaginal tissues and secretions of infected women representing an important determinant of both sexual and mother-to-child transmission. HIV-1 genital shedding is influenced by various factors; among these, proinflammatory cytokines, in particular the beta/C-C chemokine group (RANTES, MIP-1alpha and MIP-1beta), are known to suppress HIV-1 replication and thus might affect both sexual and vertical transmission. This study aimed to standardize a procedure to measure "in vitro" uterine spontaneous chemokine production by means of short-term cultures of endocervical and endometrial bioptic fragments. In most cases, "in vitro" chemokine production was observed in both fragment cultures. These results further confirm that beta/C-C chemokines exist in the female genital tract and that uterine mucosa actively produces basal levels of these immuno-active substances. This method constitutes a useful approach to evaluate cytokine production and expression in the female genital tract, their influence on HIV-1 expression and infectivity in this site, and their possible role in viral transmission.

Adult↗