Showing papers by "Raffaele Bruno published in 2007"

Importance of baseline prognostic factors with increasing time since initiation of highly active antiretroviral therapy: Collaborative analysis of cohorts of HIV-1 infected patients

Abstract: Background: The extent to which the prognosis for AIDS and death of patients initiating highly active antiretroviral therapy (HAART) continues to be affected by their characteristics at the time of initiation (baseline) is unclear. Methods: We analyzed data on 20,379 treatment-naive HIV-1- infected adults who started HAART in 1 of 12 cohort studies in Europe and North America (61,798 person-years of follow-up, 1844 AIDS events, and 1005 deaths). Results: Although baseline CD4 cell count became less prognostic with time, individuals with a baseline CD4 count 350 cells/μL (hazard ratio for AIDS = 2.3, 95% confidence interval [CI]: 1.0 to 2.3; mortality hazard ratio = 2.5, 95% CI: 1.2 to 5.5, 4 to 6 years after starting HAART). Rates of AIDS were persistently higher in individuals who had experienced an AIDS event before starting HAART. Individuals with presumed transmission by means of injection drug use experienced substantially higher rates of AIDS and death than other individuals throughout follow-up (AIDS hazard ratio = 1.6, 95% CI: 0.8 to 3.0; mortality hazard ratio = 3.5, 95% CI: 2.2 to 5.5, 4 to 6 years after starting HAART). Conclusions: Compared with other patient groups, injection drug users and patients with advanced immunodeficiency at baseline experience substantially increased rates of AIDS and death up to 6 years after starting HAART.

Pharmacodynamics of peginterferon alfa‐2a and peginterferon alfa‐2b in interferon‐naïve patients with chronic hepatitis C: a randomized, controlled study

Abstract: Summary Background Peginterferon alfa-2a and alfa-2b, the two commercially available pegylated interferons, have different pharmacokinetic properties that produce differing abilities to suppress replication of the hepatitis C virus. Aim To compare the pharmacodynamics of peginterferon alfa-2a and peginterferon alfa-2b in interferon-naive patients with chronic hepatitis C. Methods Patients were randomized to receive peginterferon alfa-2a, 180 μg (n = 10) or peginterferon alfa-2b 1.0 μg/kg (n = 12) once weekly. The enzymatic activity of 2′5′-oligoadenylate synthetase and levels of neopterin and β2-microglobulin were measured at baseline and at 24, 48, 120 and 168 h. Results Oligoadenylate synthetase activity and serum neopterin and β2-microglobulin concentrations did not differ significantly between the two patient groups at any time point, nor was there a significant correlation between the serum area under the concentration-time curve of either peginterferon and the area under the concentration-time curve for 2′,5′-oligoadenylate synthetase, neopterin and β2-microglobulin. The area under the concentration-time curves calculated for these three markers did not correlate with body mass index stratified at <25 and ≥25 kg/m2 for either peginterferon. Conclusions Despite pharmacokinetic differences between peginterferon alfa-2a and peginterferon alfa-2b, the pharmacodynamic profiles of the two formulations appear to be comparable.

Natural history of compensated viral cirrhosis in a cohort of patients with HIV infection.

Abstract: BACKGROUND The natural history of initially compensated cirrhosis in patients with HIV and concurrent hepatitis B virus (HBV) and/or hepatitis C virus (HCV) infection is poorly defined. This study was designed to investigate the incidence and type of liver-related complications and mortality in coinfected cirrhotic patients. METHODS We retrospectively identified a cohort of patients coinfected with HIV and HCV or HBV and initially compensated viral cirrhosis. Time to decompensation and mortality from liver-related causes were recorded. RESULTS Between 1999 and 2004, 392 HIV-infected patients underwent a follow-up of > or =6 months. Sixty-nine patients (17.6%) with initially compensated cirrhosis were identified (7 HBV positive, 59 HCV positive, and 3 positive for both HBV and HCV). The most frequent complication was ascites. The mortality was 71.3 per 1000 person-years (95% confidence interval [CI], 47 to 108) in HIV-infected patients with HBV and/or HCV compensated cirrhosis, 8 (95% CI, 4 to 16) in HIV/HCV-coinfected patients without cirrhosis, and 6.5 (95% CI, 2.7 to 15.5) in HIV-monoinfected patients. After the first event of decompensation, the survival rate was 48% at 1 year and 18.1% at 3 years. Treatment with HAART after the first event of decompensation was associated with an increased survival rate (61.1% and 26.2% at 1 and 3 years, respectively, vs. 26.7% and 0%; P < 0.0001). CONCLUSIONS These results indicate significant morbidity and mortality during the 6 years after the diagnosis of compensated cirrhosis due to HBV and/or HCV in HIV-infected patients, identifying ascites as the most frequent complication.

Expression of biomarkers of interferon type I in patients suffering from chronic diseases.

Abstract: Interferons (IFNs) are used widely in the treatment of viral infections, tumours and neurological disorders. The aim of this study was to evaluate the endogenous expressions of various IFN-induced compounds [specifically: neopterin (NPT), beta2microglobulin (β2mg) and 2–5 oligoadenylate synthetase (2–5 OAS)] in patients with various chronic diseases requiring treatment with IFN type I. The results showed that patients with such chronic diseases as hepatitis C virus-associated type II mixed cryoglobulinaemia (MC), chronic hepatitis C (CHC) and relapsing–remitting multiple sclerosis (RRMS) are characterized by different activations of the IFN system. Furthermore, the interindividual variability in baseline levels of IFN-induced biomarkers was higher in patients with chronic diseases than in healthy individuals. When levels of the above biomarkers were measured 24 h after the first injection of IFN in patients with CHC or RRMS, significant increases in expression levels of IFN-induced compounds were recorded but, again, there is a broad range of variability in the degree of increase. Further, a significant inverse correlation between baseline levels of NPT, β2mg and 2–5 OAS activity and their relative increases after IFN administration was found in patients with CHC or RRMS. Together, the results are consistent with the observation that there is considerable interindividual heterogeneity in the clinical response to IFNs, which suggests that host factors other than disease markers must be taken into account in order to manage and optimize the IFN therapy.

Could tenofovir modify the model end-stage liver disease (MELD) score in patients with end-stage liver disease eligible for liver transplantation?

Abstract: To the Editor: We carefully read the letter by Buchacz et al published in the December 15, 2006 issue of this journal. Although the letter did not show clear evidence of renal impairment in patients with advanced HIV diseases treated with tenofovir, we outline some considerations about the importance of the selection of antiretroviral drugs in patients who are candidates for liver transplantation. Tenofovir is currently one of the most frequently prescribed drugs worldwide as a part of combination antiretroviral therapy and has been shown to be highly effective in the treatment of HIV-infected patients. Although it is generally well tolerated, several different kinds of kidney toxicity have been described with tenofovir, including Fanconi syndrome, diabetes insipidus, and acute renal failure. Proximal tubular damage (proximal tubular bicarbonate wasting), low-grade proteinuria, hypokalemia, and hypophosphatemia have been described. HIV coinfection accelerates the course of hepatitis viruses (hepatitis C virus [HCV] and hepatitis B virus [HBV]), inducing liver damage. The progression of liver fibrosis is faster in HIV-HBVHCV–coinfected patients, reducing the survival of patients with end-stage liver disease (ESLD), which has become the leading cause of death among coinfected subjects. HIV-infected patients are considered as candidates for orthotopic liver transplantation (OLT). They have shown a survival rate comparable to that observed in monoinfected patients. In coinfected patients, the model end-stage liver disease (MELD) score is considered the best scoring system. The system has been designed to improve the organ allocation system in liver transplantation to ensure that available organs are directed to transplant candidates based on the severity of their liver disease rather than on the length of time they have been on the waiting list. The parameters considered for the calculation of the MELD score are serum creatinine, total bilirubin, and international normalized ratio (INR). Because the availability of liver organs is limited and OLT in HIV is particularly complex and expensive, the correct allocation of livers becomes fundamental. Any factor that could influence renal function, and thus serum creatinine, should modify the MELD score and change the organ allocation. The use of tenofovir in patients with ESLD and eligible for OLT may be a cause of increased serum creatinine and a subsequent MELD score modification. Therefore, tenofovir should be used cautiously in this category of patients, and when its use is mandatory, careful monitoring of renal function is needed.