Hepatitis: Antinori A

Antonucci G, Antinori A, Boumis E, De Longis P, Gentile M, Girardi E, Lauria FN, Narciso P, Noto P, Palmieri F, Oliva A, Petrosillo N, Rosati S, Urso R, Tocci G, Tozzi V, Visco Comandini U, Ippolito G. · Istituto Nazionale per le Malattie Infettive Lazzaro Spallanzani, Istituto di Ricovero e Cura a Carattere Scientifico, Roma, Italy. · Infez Med. · Pubmed #15329524 links to  free full text

Abstract: It is crucial to ensure an optimal clinical management of HCV infection in HIV-co-infected persons. The reasons for the development of guidelines on HCV-infection treatment in HIV-infected persons arise from the need for a standardised management of HIV/HCV coinfection in our Institute. The aim of these guidelines are: to clarify principles of clinical management of HCV infection in HIV-infected patients to care-providers; to improve the awareness of HIV-infected patients cared for our Institute on current management of HCV infection; to improve the quality of care on this topic. These guidelines, based on Evidence based Medicine principles, have been developed by a panel of experts, who conducted a systematic review of the literature, mainly taking into account current international recommendations. In the present document, the most frequent clinical presentation occurring in the management of HIV/HCV co-infected patients at our Institution are discussed. The adherence to present guidelines and their effectiveness at our Institution, outcome indicators will be evaluated. The present guidelines cannot entirely substitute the judgement of an expert clinician. However, adherence to these guidelines will contribute to the improvement of the standard of care of HIV/HCV-co-infected persons.

d'Arminio Monforte A, Cozzi-Lepri A, Castagna A, Antinori A, De Luca A, Mussini C, Caputo SL, Arlotti M, Magnani G, Pellizzer G, Maggiolo F, Puoti M, Anonymous00083. · Clinic of Infectious and Tropical Diseases, Dept. of Medicine, Surgery and Dentistry, San Paolo Hospital, University of Milan, via A Di Rudinì 8-20142, Milan, Italy. · Clin Infect Dis. · Pubmed #19591597 No free full text.

Abstract: BACKGROUND: There are few data concerning the risk of specific opportunistic diseases in patients with and without hepatitis C virus (HCV) infection. We evaluated the correlation between the occurrence of different AIDS-defining illnesses (ADIs) and chronic HCV infection or HCV-related liver cirrhosis in a large Italian cohort of human immunodeficiency virus (HIV)-infected subjects. METHODS: Subjects were stratified into 2 groups: patients without HCV coinfection and with persistently normal aminotransferase levels and patients with HCV coinfection. The patients with HCV coinfection were stratified according to the diagnosis of liver cirrhosis. The incidences of new ADIs were calculated as the number of events per 1000 person-years of follow-up. The rates in the 2 groups were compared using a Poisson regression model adjusted for potential confounders. RESULTS: We observed a total of 496 ADIs among 5397 patients with 25,105 person-years of follow-up (50% tested positive for HCV). HCV coinfection was associated with increased risk of developing an ADI (adjusted relative rate [ARR], 2.61; 95% confidence interval [CI], 1.88-3.61), specifically bacterial infection (ARR, 3.15; 95% CI, 1.76-5.67), HIV-related disease (ARR, 2.68; 95% CI, 1.03-6.97), and mycotic disease (ARR, 3.87; 95% CI, 2.28-6.59) but not non-Hodgkin lymphoma (ARR, 0.88; 95% CI, 0.22-3.48). The rate of mycotic infection, bacterial infection, toxoplasmosis, and HIV-related ADI among patients with cirrhosis were significantly higher than that among HIV-monoinfected patients, and the risk was greater than that estimated for HCV antibody-positive patients without cirrhosis. CONCLUSIONS: HIV-related bacterial and mycotic infections are strongly associated with positive HCV serostatus and HCV-related cirrhosis. Clinicians should take into account these data when making decisions on initiation of antiretroviral therapy for HCV-coinfected individuals.

Torti C, Lapadula G, Antinori A, Quirino T, Maserati R, Castelnuovo F, Maggiolo F, De Luca A, Paraninfo G, Antonucci F, Migliorino G, Lazzarin A, Di Perri G, Rizzardini G, Esposito R, Carosi G. · School of Medicine, Institute of Infectious and Tropical Diseases, University of Brescia, P.le Spedali Civili, 1, 25123, Brescia, Italy. · Infection. · Pubmed #19471856 No free full text.

Abstract: BACKGROUND: Although the mechanism of atazanavir (ATV)-related hyperbilirubinemia is well identified, its prevalence, risk factors, and association with transaminase flares have rarely been assessed in a large population from the "real life" setting. METHODS: Prospectively collected data on 2,404 patients from the Italian MASTER Cohort and the Italian ATV expanded access program database were examined. Uni- and multivariable Cox proportional hazards regression models were conducted to identify risk factors for grade >or= III hyperbilirubinemia during the administration of ATV. The risk of increased levels of serum alanine aminotransferase (ALT) was compared between patients with or without grade >or= III hyperbilirubinemia in a Cox regression analysis stratified by hepatitis C virus (HCV) serostatus. RESULTS: Grade III and IV hyperbilirubinemia were observed in 1,072 (44.6%) and 174 (7.2%) of the patients, respectively. Higher CD4+ T-cell counts, abnormal bilirubinemia at baseline, and ritonavir co-administration were associated with a higher risk of developing grade >or= III hyperbilirubinemia. In contrast, female gender, clinical class C, and non-nucleoside reverse transcriptase co-administration appeared to be protective. Higher bilirubinemia at baseline and the use of ritonavir were associated with a higher risk of grade IV hyperbilirubinemia. The occurrence of grade >or= III hyperbilirubinemia was not associated with severe hepatotoxicity (hazard ratio 1.00, 95% confidence interval 0.64-1.57; p = 0.997). CONCLUSIONS: Hyperbilirubinemia is a common side effect of an ATV pharmacotherapeutic regimen. However, grade IV increase in bilirubin was rarely found. In most cases, ATV hyperbilirubinemia appeared to be an innocent phenomenon as far as the risk of a subsequent increase in liver enzyme level is concerned.

Torti C, Lapadula G, Barreiro P, Soriano V, Mandalia S, De Silvestri A, Suter F, Maggiolo F, Antinori A, Antonucci F, Maserati R, El Hamad I, Pierotti P, Sighinolfi L, Migliorino G, Ladisa N, Carosi G, Anonymous00298. · Università degli Studi di Brescia, p le Spedali Civili 1, Brescia, Italy. · J Antimicrob Chemother. · Pubmed #17434879 links to  free full text

Abstract: BACKGROUND: Tenofovir with full-dose didanosine has been associated with paradoxical CD4 + T cell decrease despite virological suppression. We investigated whether tenofovir plus didanosine at a weight-adjusted dosage could be responsible for such an effect, and factors associated with CD4 + T cell count evolution under this combination. METHODS: This was a prospective observational multicohort study (Italian MASTER and Spanish Hospital Carlos III HIV cohorts). Patients with HIV plasma viral load suppression for >/= 6 months who switched to an antiretroviral combination including tenofovir plus didanosine were studied, as long as virological success was maintained. CD4 + T cell count variations over time (slopes) were compared before and after switching to tenofovir plus didanosine using linear mixed models and segmented regression analysis. RESULTS: Annual time-weighted CD4 + T cell count slope did not change significantly after the prescription of tenofovir plus didanosine: it was 14 cells/mm(3) [95% confidence interval (CI) - 7 to 35] from month - 24 to month - 12, 12 cells/mm(3) (95% CI - 14 to 38) from month - 12 to the time of switching, 30 cells/mm(3) (95% CI 5-55) from switching to month + 12 and 15 cells/mm(3) (95% CI - 8 to 39) from month + 12 to month + 24 after switching to tenofovir plus didanosine. No significant change in the slope of the segment after the switch to tenofovir plus didanosine-containing regimens when compared with the segment preceding the intervention was found (CD4 + T cell count slope change: 24 cells/mm(3); 95% CI - 10 to 58). Similar results were obtained using CD4 + T cell percentage over total lymphocytes. The significant independent predictors of lower CD4 + T cell count slope were older age (P = 0.006), lower nadir CD4 + T cell count (P < 0.001) and positive hepatitis C virus antibody (P = 0.03). Moreover, reduced estimated creatinine clearance was an additional independent predictor of lower CD4 + T cell count slope (P = 0.02), but only after excluding nadir CD4 + T cell count. CONCLUSIONS: Tenofovir plus didanosine (weight-adjusted dosage) was not associated with paradoxical CD4 + T cell decrease in our patients maintaining undetectable HIV plasma viral load for a maximum of 24 months after switching. Several factors could explain variability in CD4 + T cell count evolution in these patients.

Guadagnino V, Trotta MP, Montesano F, Babudieri S, Caroleo B, Armignacco O, Carioti J, Maio G, Monarca R, Antinori A, Anonymous00045. · Chair of Infectious Diseases, Postgraduate School of Infectious Diseases, University Magna Graecia of Catanzaro, Italy. · Addiction. · Pubmed #17298650 No free full text.

Abstract: AIM: To evaluate the effect of a multi-disciplinary standardized management model on the efficacy of pegylated (Peg)-interferon alpha-2b plus ribavirin treatment of chronic hepatitis C in drug addicts undergoing substitutive or antagonist therapy. DESIGN: Observational prospective multi-centre study. SETTING: Six clinical infectious disease centres in collaboration with 11 drug dependency units (DDU) in five Italian regions. PARTICIPANTS: Intravenous drug users affected by chronic hepatitis C engaged in detoxification programmes. METHODS: Application of a multi-disciplinary standardized management model for HCV treatment involving DDU operators, psychologists or psychiatrists and infectious disease specialists. MEASUREMENTS: Very early, early, end-of-treatment and sustained virological response to Peg-interferon alpha-2b plus ribavirin. FINDINGS: Fifty-three subjects were studied [43.4% with hepatitis C virus (HCV) genotypes 1 or 4]. Intent-to-treat analysis showed an end-of-treatment virological response in 58.5% of patients (39.1% genotypes 1 or 4; 73.4% genotype 3) and a sustained virological response in 54.7% (34.8% genotypes 1 or 4; 70.0% genotype 3). There were 19 (35.8%) dropouts and three (5.7%) non-responders: one genotype 1 and two genotype 4. Two (3.8%) patients relapsed: genotypes 1 and 3. On-treatment analysis showed negative HCV-RNA in 40 (93.1%) of 43 subjects who completed the first 12 treatment weeks and in 35 who completed the first 24 treatment weeks. All subjects with an end-of-treatment response, except one with genotype 3 infection, had a sustained response. CONCLUSIONS: Our data show that antiviral treatment in the context of a multi-disciplinary standardized management model helps many HCV-positive drug addicts achieve a good virological response.

Carosi G, Puoti M, Antonucci G, De Luca A, Maserati R, Torti C, Bonfanti P, Bonora S, Bruno R, Gaeta GB, Antinori A, Monforte A, Orani A, Sagnelli E, Cargnel A, Cauda R, Mazzotta F, Pastore G, Suter F, Vullo V, Anonymous00062, Anonymous00063. · Department of Infectious Disease, University of Brescia, Brescia, Italy. · AIDS Rev. · Pubmed #16302464 No free full text.

Abstract: Hepatitis C virus common transmission routes and HCV coinfection is frequent in persons living with HIV. Liver enzyme elevation following the initiation of antiretroviral therapy is frequently seen in HIV-infected patients with chronic liver disease, particularly those with chronic hepatitis C. This complication may lead to treatment discontinuation, complicating HIV therapeutic management. Multiple factors influence the risk of liver toxicity under antiretroviral therapy, including the specific drug in use (e.g. use of full doses of ritonavir), and environmental factors (e.g. alcohol abuse). However a beneficial effect of antiretroviral therapy on liver disease has been supported by some studies. Despite increasing knowledge of HCV/HIV coinfection, there is no clear consensus on how to treat HIV in HCV-coinfected patients An Italian group of experts were invited to discuss in detail the current risks and implications of antiretroviral treatment in HIV-infected persons with chronic hepatitis C, and their main conclusions are summarized in this consensus document.

Guadagnino V, Trotta MP, Carioti J, Caroleo B, Antinori A, Anonymous00144. · Chair of Infectious Diseases, Postgraduate School of Infectious Diseases, University Magna Graecia of Catanzaro, Via Tommaso Campanella, 115, Catanzaro 88100, Italy. · Dig Liver Dis. · Pubmed #16297672 No free full text.

Abstract: BACKGROUND: Psychological adverse effects in intravenous drug users represent a challenge in the management of anti-HCV therapy. AIMS: To evaluate the depressive symptoms during the first weeks of anti-HCV therapy and to assess their impact on the early virological response and discontinuation of therapy. SUBJECTS: A prospective cohort study of HCV-infected drug addicts on a detoxification program at the onset of therapy with peg-interferon and ribavirin. METHODS: A self-report screening of depression (Center for Epidemiological Studies-Depression Scale) and a questionnaire investigating treatment adherence and the presence of side effects were prospectively administered. RESULTS: The mean baseline Center for Epidemiological Studies-Depression Scale score of the 43 subjects studied was 17.3. This value did not worsen significantly after 4 and 12 weeks of therapy. A higher depressive score at baseline neither significantly affected the early virological response, nor the early treatment discontinuation. Conversely, a higher symptoms score (HR 1.33; 95% CI, 1.02-1.71) was associated with a greater probability of early treatment discontinuation. CONCLUSIONS: A depressive attitude should not be considered a contraindication to the treatment of HCV-infected drug addicts on the detoxification program in which they are monitored by a multidisciplinary team. Effective management of side effects could increase the treatment adherence during the first weeks of therapy and increase the possibility of an early virological response.

Tozzi V, Balestra P, Lorenzini P, Bellagamba R, Galgani S, Corpolongo A, Vlassi C, Larussa D, Zaccarelli M, Noto P, Visco-Comandini U, Giulianelli M, Ippolito G, Antinori A, Narciso P. · National Institute for Infectious Diseases Lazzaro Spallanzani, Rome, Italy. · J Neurovirol. · Pubmed #16036806 No free full text.

Abstract: To assess prevalence and risk factors for human immunodeficiency virus (HIV)-related neurocognitive impairment (NCI), the authors performed a 7-year survey in the period 1996 to 2002. A total of 432 patients were examined. HIV-related NCI was diagnosed in 238 patients (55.1%), meeting the HIV dementia (HIV-D) criteria in 45 (10.4%). The prevalence of both NCI and HIV-D did not change significantly during the study period. Compared with patients without NCI, patients with NCI were older (40.4 versus 38.2 years; P = .003), had a higher prevalence of positive HCV serology (61.1% versus 38.9%; P = .003), and a lower nadir CD4 cell count (156 versus 222 cells/microl; P < .001). Compared with patients seen during 1996 to 1999, patients with NCI seen during 2000 to 2002 were older (40.7 versus 38.8 years; P = .004), had a less advanced disease stage (previous acquired immunodeficiency syndrome [AIDS] 28.8% versus 65.7%; P < .001) and a higher nadir CD4 count (174 versus 132 cells/microl; P = .026). This study showed an unchanged prevalence of both HIV-related NCI and HIV-D in the period 1996 to 2002. The authors found evidences for new additional potential risk factors for HIV-related NCI (older age, lower nadir CD4 count, positive hepatitis C virus [HCV] serology), and for a change of risk factors for NCI in the late highly active antiretroviral therapy (HAART) era (older age, less advanced disease, higher nadir CD4 count).

Galli M, Cozzi-Lepri A, Ridolfo AL, Gervasoni C, Ravasio L, Corsico L, Gianelli E, Vaccarezza M, Vullo V, Cargnel A, Minoli L, Coronado O, Giacometti A, Antinori A, Antonucci G, D'Arminio Monforte A, Moroni M, Anonymous00058. · Institute of Infectious Diseases and Tropical Medicine, University of Milan, "L Sacco" Hospital, Via G. B. Grassi, 74 20157 Milan, Italy. · Arch Intern Med. · Pubmed #12456235 links to  free full text

Abstract: BACKGROUND: Adipose tissue alterations (ATAs) are a frequent untoward effect of antiretroviral therapy, the causes of which remain incompletely explained. OBJECTIVES: To assess the incidence of ATAs and to identify the associated risk factors in patients infected with human immunodeficiency virus type 1 starting their first-line antiretroviral treatment. METHODS: In a multicenter investigation designed to study issues related to the treatment of patients starting antiretroviral therapy, physicians were requested to assess the presence of ATAs at enrollment and every 6 months thereafter. The ATAs were considered altogether and grouped as fat loss (lipoatrophy), adipose tissue accumulation (lipohypertrophy), and combined forms. RESULTS: A total of 655 patients were followed up for a median of 86 weeks; 128 patients (19.6%) were diagnosed as having at least 1 morphologic alteration during the study. Female gender and positivity for hepatitis C virus were independently linked to an increased risk of developing morphologic alterations. Age was another independent correlate of risk of developing ATAs. To have been infected through drug injection was a correlate of reduced risk of ATAs. Stavudine exposure was predictive at borderline statistical significance of lipoatrophy (but not of the other forms), and indinavir exposure was associated with a significantly higher risk of developing combined forms. Patients who started therapy with 2 nucleoside reverse transcriptase inhibitors and subsequently added a protease inhibitor during the follow-up had a significantly higher risk of having ATAs compared with patients who continued taking 2 nucleoside reverse transcriptase inhibitors up to the end of follow-up. CONCLUSIONS: Different types of ATAs might derive from distinct pathways and multifactorial causes. Adipose tissue alterations are a frequent and relatively early finding during first-line antiretroviral therapy.

De Luca A, Bugarini R, Lepri AC, Puoti M, Girardi E, Antinori A, Poggio A, Pagano G, Tositti G, Cadeo G, Macor A, Toti M, D'Arminio Monforte A, Anonymous00265. · Institute of Clinical Infectious Diseases, Catholic University of the Sacred Heart, Rome, Italy. · Arch Intern Med. · Pubmed #12374521 links to  free full text

Abstract: BACKGROUND: The effect of chronic coinfection with hepatitis viruses on the response to therapy against human immunodeficiency virus 1 (HIV-1) remains debated. METHODS: In a prospective cohort study, the effect of hepatitis B virus (HBV) and hepatitis C virus (HCV) serostatus on the outcome of potent HIV-1 therapy was analyzed in HIV-1-infected patients previously naive to antiretroviral therapy. Changes from baseline CD4+ cell counts and HIV RNA levels over time were analyzed by linear regression models. Time to clinical progression and time to reach virologic and immunologic response were analyzed by multivariate Cox proportional hazards regression models. RESULTS: We studied 1320 patients, among whom 600 were HCV antibody-positive and 90 were HBV surface antigen-positive. During a median follow-up of 37 months (range, 1-48 months), clinical progression was observed in 99 patients (56 new acquired immunodeficiency syndrome-defining events and 43 deaths). In multivariate models, HCV-positive HBV-negative patients showed a shorter time to clinical progression (hazard ratio, 1.55; 95% confidence interval, 1.00-2.41). Patients who were HCV-positive also showed mean CD4+ recoveries over time that were at least 30 cells/ micro L fewer than those of seronegative patients. Hepatitis virus serostatus did not affect the virologic response to HIV-1 therapy. CONCLUSIONS: Clinical progression of HIV-1 disease after starting potent antiretroviral therapy is accelerated by concomitant infection with HCV. Compared with patients without coinfection, coinfected patients showed impaired CD4+ cell recovery, despite similar virologic response to HIV-1 therapy. These findings may have important implications for the treatment of HCV and for the timing of initiation of HIV-1 therapy in coinfected individuals.

Sorà F, Antinori A, Piccirillo N, De Luca A, Chiusolo P, Cingolani A, Laurenti L, Rutella S, Ortona L, Leone G, Sica S. · Istituto di Ematologia, Università Cattolica Sacro Cuore, Rome, Italy. · Exp Hematol. · Pubmed #11882366 No free full text.

Abstract: OBJECTIVE: To evaluate the safety, feasibility, and efficacy of allogeneic stem cell transplantation (SCT) for acute myelogenous leukemia (AML) in a young female coinfected by HIV and HCV undergoing highly active antiretroviral therapy (HAART). PATIENTS AND METHODS: A 33-year-old female HIV(+), HCV(+) in complete remission after standard chemotherapy was submitted to CD34(+) selected allogeneic transplantation from her HLA-identical HIV(-) brother after myeloablative regimen. HAART was started before transplantation, achieving a reduction of HIV load to undetectable levels. GVHD prophylaxis was carried out with cyclosporine A alone. RESULTS: The patient achieved prompt and durable engraftment with acute GVHD grade II easily managed with steroids; CMV prophylaxis was prolonged, no clinically relevant infectious complications developed early after transplantation and during follow-up. HIV viremia was controlled by HAART although medication adherence was reduced early after transplantation and required drug adjustment. There was a gradual recovery of immune cells with normal CD4-cell count 39 months after engraftment, a significantly higher level than before transplantation. At 39 months post-transplantation follow-up the patient is alive and in continuous complete remission with undetectable levels of plasma HIV RNA on HAART. CONCLUSION: The introduction of HAART has recently changed the paradigm of AIDS, allowing the control of HIV replication, the reduction of opportunistic infections, and the overall improvement of survival. One may therefore reconsider the current exclusion of patients with AIDS and a concomitant lethal malignancy from programs of high-dose chemotherapy and stem cell transplantation, as suggested by this report.

Monforte Ade A, Bugarini R, Pezzotti P, De Luca A, Antinori A, Mussini C, Vigevani GM, Tirelli U, Bruno R, Gritti F, Piazza M, Chigiotti S, Chirianni A, De Stefano C, Pizzigallo E, Perrella O, Moroni M, Anonymous00114. · Institute of Infectious and Tropical Diseases, University of Milan, L Sacco H, Milan, Italy. · J Acquir Immune Defic Syndr. · Pubmed #11588504 No free full text.

Abstract: BACKGROUND: Highly active antiretroviral therapy (HAART) is strongly effective in reducing morbidity and mortality in HIV-1-positive individuals. Its main drawback is the potential toxicity. Data on the frequency and determinants of severe hepatotoxicity in a clinical setting are still sparse. METHODS: This is a prospective study of HIV-1-positive individuals with known HBsAg and HCV-Ab serology. The study end point was progression to alanine aminotransferase (ALT) levels > or =200 IU/L after HAART initiation. Cumulative probability of progression to this end point was estimated by the Kaplan-Meier method. Crude and adjusted hazard ratios (HR) were estimated by proportional hazards regression model. RESULTS: One thousand two hundred fifty-five patients were included. HBsAg was found in 91 (7.2%), HCV-Ab in 578 (46.5%) patients; almost all injection drug users (451 of 482; 93.6%) were HCV-Ab positive. Sixty-one individuals progressed to the end point with a probability of 7.9% (95% confidence interval [CI], 5.6-10.0) of progression at 24 months from starting. Independent factors predicting progression to the end point were baseline ALT levels (HR, 5.29; 95% CI, 3.24-8.65; every 10 IU/L higher), HCV-Ab positivity (HR, 4.01; 95% CI, 1.48-10.85) or both HBsAg and HCV Ab positivity (HR, 3.85, 95% CI, 1.01-14.61), and previous non-HAART therapy (HR, 1.84, 95% CI, 1.04-3.42). Patients receiving stavudine-containing regimens had a lower risk than those receiving zidovudine-containing regimens (HR, 0.30, 95% CI, 0.12-0.71). CONCLUSIONS: There was a low risk of ALT > or =200 IU/L in our cohort. Hepatitis C coinfection and elevated ALT levels at HAART initiation are important predictors of progression to ALT > or =200 IU/L; stavudine-containing regimens were associated with a lower risk compared with zidovudine-containing regimens.

Liuzzi G, Zaccarelli M, Sette P, Grisetti S, Alba L, Antinori A. · No affiliation provided · AIDS. · Pubmed #11600843 No free full text.

This publication has no abstract.