Critical role of ribavirin for the achievement of early virological response to HCV therapy in HCV/HIV‐coinfected patients

Ramos, Belén; Núñez, Marina; Rendón, Ana; Berdún, Miguel Angel; Losada, Elena; Santos, Ignacio; Echevarría, S.; Ocampo, Antonio; Miralles, Celia; Arazo, Piedad; Barreiro, Pablo; Romero, Míriam; Labarga, Pablo; Guardiola, Josep M.; García‐Samaniego, J.; Soriano, Vincent

doi:10.1111/j.1365-2893.2006.00806.x

Cited by 36 publications

(29 citation statements)

References 31 publications

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“…Virologic response at weeks 4 and 12 were superior with the use of 1000-1200 mg of RBV compared to 800 mg/d of RBV (Figure 2). Improved SVR rates, similar to that seen in HCV monoinfection, were observed when RBV was used at a dose of 1000-1200 mg [49,64,65] . Based on the current data, it is recommended that weight-based RBV (1000 mg/d for < 75/kg and 1200 mg/d for 75 kg and above) should be used in co-infected patients.…”

Section: Drug Dosesmentioning

confidence: 69%

Management of hepatitis C virus infection in HIV/HCV co-infected patients: Clinical review

Singal¹,

Anand²

2009

WJG

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N e a r l y o n e fo u r t h o f i n d i v i d u a l s w i t h h u m a n immunodeficiency virus (HIV) infection have hepatitis C virus (HCV) infection in the US and Western Europe. With the availability of highly active antiretroviral therapy and the consequent reduction in opportunistic infections, resulting in the prolongation of the life span of HIV-infected patients, HCV co-infection has emerged as a significant factor influencing the survival of HIV patients. Patients with HIV/HCV co-infection have a faster rate of fibrosis progression resulting in more frequent occurrences of cirrhosis, end-stage liver disease, and hepatocellular carcinoma. However, the mechanism of interaction between the two viruses is not completely understood. The treatment for HCV in co-infected patients is similar to that of HCV monoinfection; i.e., a combination of pegylated interferon and ribavirin. The presence of any barriers to anti-HCV therapy should be identified and eliminated in order to recruit all eligible patients. The response to treatment in co-infected patients is inferior compared to the response in patients with HCV mono-infection. The sustained virologic response rate is only 38% for genotype-1 and 75% for genotype-2 and -3 infections. Liver transplantation is no longer considered a contraindication for end-stage liver disease in coinfected patients. However, the 5 year survival rate is lower in co-infected patients compared to patients with HCV mono-infection (33% vs 72%, P = 0.07). A better understanding of liver disease in co-infected patients is needed to derive new strategies for improving outcome and survival.

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Section: Drug Dosesmentioning

confidence: 69%

Management of hepatitis C virus infection in HIV/HCV co-infected patients: Clinical review

Singal¹,

Anand²

2009

WJG

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“…This is particularly true for the large number of subjects infected with HCV genotypes 1 or 4, which show particularly poor response to therapy [5]. Low baseline serum HCV-RNA levels [6,30,31] and elevated ribavirin exposure [32][33][34] have been associated with increased response rates in this subset of patients. Host genetic factors, such as SNPs nearby the IL28B gene at chromosome 19, have recently been associated with an increased likelihood of viral response in HCV-monoinfected patients [14][15][16][17], as well as in HIV-HCV-coinfected patients [18].…”

Section: Discussionmentioning

confidence: 97%

Influence of a Single Nucleotide Polymorphism at the Main Ribavirin Transporter Gene on the Rapid Virological Response to Pegylated Interferon–Ribavirin Therapy in Patients with Chronic Hepatitis C Virus Infection

Morello¹,

Cuenca²,

Soriano³

et al. 2010

J INFECT DIS

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The equilibrative nucleoside transporter 1 (ENT1) is the main protein involved in ribavirin cellular uptake. Polymorphisms at the ENT1 gene may influence ribavirin activity as part of hepatitis C virus (HCV) therapy. A retrospective study was conducted in 109 human immunodeficiency virus (HIV)-infected patients who were infected with HCV genotypes 1 or 4 who had received pegylated interferon (pegIFN)-ribavirin. Single nucleotide polymorphisms (SNPs) at the ENT1 gene were examined using TaqMan 5'-nuclease assays. In the study population, allelic frequencies at rs760370 were as follows: A3 (43 [39%] of 109 patients), AG (50 [46%] of 109 patients), and GG (16 [15%] of 109 patients). Achievement of rapid virological response was more frequent in GG carriers than in AA/AG carriers (50% vs 17%, respectively; P = .007). In multivariate analysis, the GG genotype (odds ratio [OR], 15.9; 95% confidence interval [CI], 2.8-92.2; P < .002), a baseline serum HCV-RNA level <600,000 IU/mL (OR, 45.7; 95% CI, 8.7-240.5; P <.001) and a serum ribavirin trough concentration >2.5 μg/mL (OR, 4.8; 95% CI, 1.3-17.1; P < .016) were associated with rapid virological response. When 2 or more of these factors were present, positive and negative predictive values of rapid virological response were 65% and 91%, respectively. In summary, a SNP rs760370A→G at the ENT1 gene influences the chance of rapid virological response to pegIFN-ribavirin therapy in HIV-infected patients with chronic HCV infection due to HCV genotypes 1 or 4, most likely modulating intracellular ribavirin exposure within hepatocytes.

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“…The association between RBV C trough and relapse supports the essential role of RBV exposure in the clearance of HCV and highlights the idea that besides influencing the early decay of HCV clearance (18,19), it may influence as well the risk of HCV relapse independently of any effect on RVR, as recently shown in trials testing HCV protease inhibitors (9,10). This observation is important since monitoring of RBV C trough at week 4 might allow adaptation strategies to maximize the chances of cure with standard HCV therapy.…”

mentioning

confidence: 99%

Plasma Ribavirin Trough Concentrations at Week 4 Predict Hepatitis C Virus (HCV) Relapse in HIV-HCV-Coinfected Patients Treated for Chronic Hepatitis C

Morello

Soriano²,

Barreiro³

et al. 2010

Antimicrob Agents Chemother

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The standard treatment for chronic hepatitis C virus (HCV) infection is the combination of pegylated alpha interferon (pegIFN) and ribavirin (RBV), which allows cure of HCV in around 50 to 60% of HCV-monoinfected patients (8, 12) and 30 to 40% of HIV-HCV-coinfected individuals (4, 21). Although new drugs for treating HCV infection, such as HCV protease inhibitors, are currently being developed, preliminary evidence (9, 10) suggests that the use of RBV seems unavoidable for maximizing the chances of sustained virological response (SVR).RBV is a synthetic guanosine analogue. Several mechanisms of action have been proposed to explain its anti-HCV effect, including direct inhibition of the viral RNA polymerase, IMP dehydrogenase inhibition, hypermutagenesis, and immunomodulation (7). Pharmacokinetic-pharmacodynamic studies conducted in HCV-monoinfected and HIV-HCV-coinfected patients have found an association between RBV concentrations and achievement of early and sustained virological responses (reviewed in references 5 and 15 and a recent paper [3]), indirectly supporting a role for therapeutic drug monitoring of RBV concentrations to tailor RBV dosage early in treatment and in this way to try to enhance the chances of SVR.In addition to a lower initial response to hepatitis C therapy, a higher rate of HCV relapse (range, 15% to 37%) (4,6,16,20,21,23) could contribute to the lower rate of SVR seen in HIV-HCV-coinfected patients than in HCV-monoinfected patients. Several factors such as high baseline HCV RNA and lack of rapid virological response (RVR) have been associated with HCV relapse (16). However, the impact of RBV concentrations on the risk of HCV relapse is unknown. If a significant association exists, adjustment of RBV dosages based on early RBV concentrations could be very useful to minimize the risk of HCV relapse.A retrospective study was performed in HIV-HCV-coinfected patients who achieved end-of-treatment (EOT) response with pegIFN-␣ 2a or 2b (180 g/week or 1.5 g/kg of body weight/week) plus weight-based RBV (1,000 or 1,200 mg/day for patients weighting Ͻ75 or Ͼ75 kg, respectively) since 2004 at our clinic. The duration of treatment was based on HCV genotype and the achievement of undetectable HCV RNA at week 4 (RVR), ranging from 6 to 18 months (11,17).Demographics and other clinical characteristics were recorded in a case report form specially designed for this study. Serum HCV RNA was measured at baseline, every 4 to 12 weeks of therapy, and 24 weeks after completion of treatment by TaqMan (Roche), with a limit of detection of 10 IU/ml. HCV genotyping was examined using a hybridization assay (InnoLipa-HCV; Bayer). RBV plasma trough concentrations (RBV C trough ) were measured before the intake of the first daily dose of RBV at week 4 of therapy by high-performance liquid chromatography with ultraviolet detector (HPLC-UV) (14).EOT response was defined as undetectable HCV RNA at the end of therapy. HCV relapse was defined as detectable HCV RNA within the next 24 weeks after achieving EOT response.S...

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Critical role of ribavirin for the achievement of early virological response to HCV therapy in HCV/HIV‐coinfected patients

Cited by 36 publications

References 31 publications

Management of hepatitis C virus infection in HIV/HCV co-infected patients: Clinical review

Management of hepatitis C virus infection in HIV/HCV co-infected patients: Clinical review

Influence of a Single Nucleotide Polymorphism at the Main Ribavirin Transporter Gene on the Rapid Virological Response to Pegylated Interferon–Ribavirin Therapy in Patients with Chronic Hepatitis C Virus Infection

Plasma Ribavirin Trough Concentrations at Week 4 Predict Hepatitis C Virus (HCV) Relapse in HIV-HCV-Coinfected Patients Treated for Chronic Hepatitis C

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