May some HCV genotype 1 patients still benefit from dual therapy? The role of very early HCV kinetics.

When treating HCV patients with conventional dual therapy in the current context of rapidly evolving HCV therapy, outcome prediction is crucial and HCV kinetics, as early as 48 hours after the start of treatment, may play a major role. We aimed at clarifying the role of HCV very early kinetics. We consecutively enrolled mono-infected HCV patients at 7 treatment sites in Central Italy and evaluated the predictive value of logarithmic decay of HCV RNA 48 hours after the start of dual therapy (Delta48). Among the 171 enrolled patients, 144 were evaluable for early and sustained virological response (EVR, SVR) prediction; 108 (75.0%) reached EVR and 84 (58.3%) reached SVR. Mean Delta 48 was 1.68 ± 1.22 log10 IU/ml, being higher in patients with SVR and EVR. Those genotype-1 patients experiencing a Delta 48 >2 logs showed a very high chance of success (100% positive predictive value), even in the absence of rapid virological response (RVR). Evaluation of very early HCV kinetics helped identify a small but significant proportion of genotype-1 patients (close to 10%) in addition to those identified with RVR, who could be treated with dual therapy in spite of not reaching RVR. In the current European context, whereby sustainability of HCV therapy is a crucial issue, conventional dual therapy may still play a reasonable role in patients with good tolerance and early prediction of success.

A simple rule to personalize standard dual therapy across all genotypes in naive chronic hepatitis C patients: the TT4 randomized trial.

BACKGROUND: Rapid and early virological responses to peginterferon-alpha and ribavirin are predictive of sustained virological response (SVR) in hepatitis C virus (HCV) infection. We aimed at finding a simple rule to determine the shortest duration of dual therapy for all HCV genotypes, obtained by multiplying time to Initial Viral Response, IVR (first undetectable HCV-RNA) by 4 (Tailored Therapy-4, or TT4). METHOD: 267 naïve HCV-infected patients with compensated liver disease were randomized (2:1) to the TT4 (n=180) or current standard-of-care (SoC, n=87) and received peginterferon-alpha plus ribavirin. Patients with HCV-RNA decrease ≤2log10 at week 12 or detectable HCV-RNA at week 24 discontinued treatment. RESULTS: Both groups had comparable baseline characteristics, SVR rates were similar in the whole population (60.6% vs. 60.9%) and within each genotype subgroup (G1: 46.6% vs. 55.6%; G2: 90.2% vs. 94.4%; G3: 74.1% vs. 58.3%; G4: 45.8% vs. 33.3%). Relapse rate was higher in G1-TT4 than G1-SoC. Treatment duration in SVR patients was shorter in TT4 compared to SoC, both overall [25±15 vs. 36±12.1 weeks], and for subgroups: G1 [35.3±16.7 vs. 47.3±2.6 weeks], G2 [18.3±7.5 vs. 24±2.8 weeks], G3 [15.2±8.7 vs. 22.8±3 weeks] and G4 [26.9±13 vs. 48 weeks]. CONCLUSIONS: In HCV-naive patients, TT4-rule treatment yields similar SVR rates compared to SoC but with shorter treatment duration and remarkable cost reduction.

[Epidemiological, clinical and therapeutical aspects of HIV/HCV coinfection in a series of HIV seropositive Umbrian patients]. / Epidemiologia, clinica e terapia della coinfezione HIV-HCV in una casistica di pazienti umbri.

Because hepatitis C virus (HCV) and human immunodeficiency virus (HIV) share common transmission pathways, HIV-HCV co-infection is frequent, involving about 40% of seropositive subjects particularly injection drug users and patients with hemophilia. We performed a retrospective analysis on clinical, epidemiological and therapeutical aspects in a population of HIV-HCV coinfected patients, observed in our Department during the period 2001-2003. Forty per cent of 404 observed patients had a co-infection; 90% of those were drug addicts and most (90.2%) were on HAART treatment. Seventy-three per cent of co-infected patients showed transaminases alterations, and 85% had detectable viremia. Prevalent genotypes were 1 (44.6%) and 3 (36.4%). The association PEG-IFN and ribavirine obtained sustained responses in 55% of 9 treated patients.