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Pascale Trimoulet

Publications and source records attributed to Pascale Trimoulet.

15 recordsLinked to original sources
PubMed2006

Outbreak of hepatitis C virus infection during sclerotherapy of varicose veins: long-term follow-up of 196 patients (4535 patient-years).

BACKGROUND/AIMS: The aim of this study was to describe the natural history of a HCV infection outbreak in 196 patients who had sclerotherapy by a same physician and to confirm patient-to-patient transmission using phylogenetic analysis in a large series of patients. METHODS: Demographic information included clinical and biological parameters. Fibrosis evaluation was performed using liver biopsy or transient elastography. Follow-up was maintained until death, or the end of the observation period. In order to determine if the virus had been transmitted between the HCV genotype 2 patients, sequence analysis was undertaken of a part of the NS5b region of the genomes in samples of patients. RESULTS: The mean duration of follow-up was 23.1+/-6.7 years (4535 patient-years). In patients with fibrosis evaluation, 55.7% had no or mild fibrosis and 44.3% had significant fibrosis. No patient died from HCV-related disease. Nucleotide sequence analysis of a part of the NS5b region revealed that patients were all infected with the same HCV subtype (genotype 2d). The most evident feature of the tree is the clustering of all patients involved in the outbreak without any unrelated isolates. CONCLUSION: This study emphasizes the risk for nosocomial spread of HCV during intravenous therapy.

Adult↗
PubMed2006

Estimation of dynamical model parameters taking into account undetectable marker values.

BACKGROUND: Mathematical models are widely used for studying the dynamic of infectious agents such as hepatitis C virus (HCV). Most often, model parameters are estimated using standard least-square procedures for each individual. Hierarchical models have been proposed in such applications. However, another issue is the left-censoring (undetectable values) of plasma viral load due to the lack of sensitivity of assays used for quantification. A method is proposed to take into account left-censored values for estimating parameters of non linear mixed models and its impact is demonstrated through a simulation study and an actual clinical trial of anti-HCV drugs. METHODS: The method consists in a full likelihood approach distinguishing the contribution of observed and left-censored measurements assuming a lognormal distribution of the outcome. Parameters of analytical solution of system of differential equations taking into account left-censoring are estimated using standard software. RESULTS: A simulation study with only 14% of measurements being left-censored showed that model parameters were largely biased (from -55% to +133% according to the parameter) with the exception of the estimate of initial outcome value when left-censored viral load values are replaced by the value of the threshold. When left-censoring was taken into account, the relative bias on fixed effects was equal or less than 2%. Then, parameters were estimated using the 100 measurements of HCV RNA available (with 12% of left-censored values) during the first 4 weeks following treatment initiation in the 17 patients included in the trial. Differences between estimates according to the method used were clinically significant, particularly on the death rate of infected cells. With the crude approach the estimate was 0.13 day-1 (95% confidence interval [CI]: 0.11; 0.17) compared to 0.19 day-1 (CI: 0.14; 0.26) when taking into account left-censoring. The relative differences between estimates of individual treatment efficacy according to the method used varied from 0.001% to 37%. CONCLUSION: We proposed a method that gives unbiased estimates if the assumed distribution is correct (e.g. lognormal) and that is easy to use with standard software.

AIDS-Related Opportunistic Infections↗
PubMed2006

Anti-hepatitis B virus efficacy of tenofovir disoproxil fumarate in HIV-infected patients.

Tenofovir disoproxil fumarate (TDF) has shown in vitro activity against both HIV and hepatitis B virus (HBV). We retrospectively evaluated the efficacy of TDF (300 mg/d), administered as a part of anti-retroviral therapy, in a large cohort of HIV/HBV-coinfected patients. Sixty-five HIV/HBV-coinfected patients who received TDF for at least 6 months with serum HBV DNA levels above 2.3 log10 copies/mL at TDF initiation and who had stored serum samples before and during TDF therapy were included. Serum HBV DNA was measured on stored samples. The median follow-up period was 12 (Q1-Q3: 8-17) months. Serum hepatitis B e antigen (HBeAg) was positive in 54 patients (83.1%). Fifty-two patients (80.0%) were receiving lamivudine (LAM) (150 mg twice a day), and 68.8% had documented LAM resistance at baseline. Among HBeAg-positive patients, the median reduction from baseline (8.17; Q1-Q3 = 7.30-8.30 log10 copies/mL) of serum HBV DNA was 4.56 log10 copies/mL (Q1-Q3 = 3.33-5.55) (P < .0001). In HBeAg-negative patients, serum HBV DNA decline from baseline (4.83; Q1-Q3 = 2.69-6.40 log10 copies/mL) was 2.53 log10 copies/mL (Q1-Q3 = 0.39-4.10). At the end of the study, HBV DNA became undetectable in 29.6% and 81.6% of the HBeAg-positive and HBeAg-negative patients, respectively. Serum HBeAg became negative in 4 patients, 2 of whom acquired serum hepatitis B e antibody. In conclusion, this retrospective analysis demonstrates the efficacy of TDF against wild-type, presumed precore mutants and LAM-resistant HBV when used as a part of anti-retroviral therapy in HIV-coinfected patients.

Adenine↗
PubMed2006

Plasma and liver hepatitis C virus variability in patients coinfected with human immunodeficiency virus.

Liver and plasma hepatitis C virus (HCV) variability was compared by E2 cloning and sequencing in three patients coinfected with HCV and human immunodeficiency virus (HIV) before and after interferon treatment and in three patients solely infected with HCV. The plasma and liver samples contained unique sequences. In the patients coinfected with HIV, accumulated random mutations produced mostly nonsynonymous substitutions in contrast to the reduced HCV genetic variability seen after treatment.

Case-Control Studies↗
PubMed2005

Epidemiological and phylogenetic evidence for patient-to-patient hepatitis C virus transmission during sclerotherapy of varicose veins.

The aim of this study was to provide evidence for patient-to-patient nosocomial hepatitis C virus (HCV) transmission during sclerotherapy of varicose veins. Forty-three patients who had evidence of current infection by genotype 2 HCV have had sclerotherapy by the same physician. Based on this observation, a detailed epidemiological questionnaire on risk factors for HCV in genotype 2 infected patients was conducted. Seventeen sequences in the hypervariable region 1 (HVR1) of the HCV genome obtained from 17 HCV RNA positive patients with a past history of sclerotherapy, were compared with 17 sequences derived from genotype 2 patients with no past history of sclerotherapy, and with 25 sequences sampled from GenBank. Two hundred seven genotype 2 HCV infected patients were included. The main risk factors for HCV infection were transfusion (n = 76), drug use (n = 6), and sclerotherapy of varicose veins (n = 62 including 43 (20.8%) by the same physician), other or unknown (n = 76). These sclerotherapy sessions were carried out in the 1980s for many years. Five of these 43 patients had jaundice within a few weeks after a sclerotherapy session. Sequence analysis of HVR1 from 17 patients who had sclerotherapy by the same physician revealed that they were all infected with HCV genotype 2c. The phylogenetic tree indicated clustering of the patients with a past history of sclerotherapy. The method by which infection was likely to have been transmitted was probably the use of a single vial for multiple patients. This study provides strong evidence that sclerotherapy of varicose veins is a risk factor for HCV infection.

Adolescent↗
PubMed2004

Predictive value of early HCV RNA quantitation for sustained response in nonresponders receiving daily interferon and ribavirin therapy.

The prognostic value of early hepatitis C virus (HCV)-RNA load was evaluated among nonresponder patients to previous interferon (IFN) therapy treated with daily IFN and ribavirin. One hundred-six nonresponders (83 men), mean age 44.8 +/- 11 years, were treated with IFN-alpha 2b 3 MU/day for 24 weeks, followed by 3 MU x 3/week for 24 weeks plus ribavirin 1-1.2 g/day for 48 weeks. HCV RNA was quantified by Versant HCV RNA 3.0 assay (Bayer). The predictive values of the baseline and the change in viral load at week 1, 4, and 12 for sustained virological responses were analyzed using receiver operating characteristic (ROC) curves, as well as predictive values of >2 log(10) drop from baseline by weeks 1, 4, and 12 in combination with undetectable HCV RNA for sustained virological response. Thirty-two patients (30.2%) were sustained virological responders. The highest area under the curve was obtained at week 4. The unquantifiable HCV RNA level, in combination with at least a 2 log(10) drop in viral load by week 4 and week 12, had a negative predictive value of 96% and 97%, respectively. Nonresponse can be predicted as early as week 4 or week 12 in nonresponders treated with daily IFN and ribavirin.

Adult↗
PubMed2004

Fibrosis is worse in HIV-HCV patients with low-level immunodepression referred for HCV treatment than in HCV-matched patients.

Hepatitis C virus (HCV) infection is frequent in human immunodeficiency virus (HIV)-infected patients. It is known to have an aggressive course in significantly immunosuppressed patients, and cirrhosis C has become one of the main causes of mortality in HIV-HCV coinfected patients since the improvement of antiretroviral therapy. The reasons for this severe fibrotic evolution are unclear. This prospective study compared chronic HCV lesions, liver immunocompetent cells, fibrosis and liver HCV loads in 2 cohorts of naive patients referred for HCV treatment: 33 HIV-HCV coinfected patients with CD4 >250/microL and 33 HCV-infected patients matched for the main risk factors of fibrosis. Fibrosis, particularly perisinusoidal fibrosis, was more marked in the coinfected patients. This occurred in the absence of a significant difference in disease activity. The number of CD3+ cells in the liver was higher in the HIV-HCV patients than in the HCV patients. Conversely, the number of liver CD4+ cells was lower in HIV-HCV patients than in HCV patients. The numbers of CD8+ and CD68+ cells were similar in the 2 groups. Finally, liver HCV load, assessed by immunostaining and reverse-transcription polymerase chain reaction, was similar in the 2 groups. We conclude that in the population of HIV-HCV coinfected patients with low-level immunosuppression referred for HCV treatment, fibrosis is worse than in HCV patients and the proportion of CD4+ lymphocytes among CD3+ cells is markedly decreased in the liver, whereas intrahepatic viral load is similar. Our data confirm the need to treat such patients against HCV, and suggest that HIV infection could favor fibrosis via the modulation of the intrahepatic immune response.

Antigens, CD↗
PubMed2003

Comparison of 2 regimens that include interferon-alpha-2a plus ribavirin for treatment of chronic hepatitis C in human immunodeficiency virus-coinfected patients.

An open-label, randomized trial was conducted to compare the efficacy and safety of 2 regimens of interferon-alpha-2a (IFN-alpha-2a) plus ribavirin for management of chronic hepatitis C virus (HCV) infection in human immunodeficiency virus (HIV)-coinfected patients. Sixty-eight patients were randomized to receive IFN-alpha-2a at a dosage of either (1) 6 MU given 3 times per week for 24 weeks, followed by 3 MU 3 times per week for an additional 24 weeks (group A; 31 patients); or (2) 9 MU per day for 2 weeks, followed by 3 MU per day for 22 weeks, followed by 3 MU 3 times per week for 24 weeks (group B; 37 patients). Ribavirin was added at week 16 of therapy if HCV RNA remained detectable at week 12. Sustained virological response was achieved in 10 patients (15%; 6 in group A and 4 in group B). HCV genotypes 2 or 3 and a decrease in the HCV load of >or=3 log(10) copies/mL between inclusion and week 4 were associated with virological response. In conclusion, the combination of conventional IFN-alpha-2a and ribavirin has poor virological efficacy in HCV-HIV-coinfected patients.

Adolescent↗
PubMed2003

HIV and HCV co-infection: situation at six French university hospitals in the year 2000.

The aims of this study were to assess the sociodemographic, epidemiological, clinical, and biological characteristics of French patients co-infected with human immunodeficiency virus-hepatitis C virus (HIV-HCV), as well as the management of their HCV infection. Data on 509 HIV-HCV co-infected patients, followed up at six French University Hospitals, were collected using a questionnaire. Student's t-test, Pearson's chi-square, Fisher's exact, and Fisher-Freeman-Halton's exact tests were used. The mean age of the patients was 38.3 years, and the male to female sex ratio 2.08; 88% of patients were born in Metropolitan France, and 20% were dependent on health benefits; 74% were intravenous drug users and 14% blood or blood product recipients. Forty-seven percent were in CDC classification stage A, 18% had a CD4+ count of <200, and 79% were undergoing current antiretroviral treatment. HCV RNA was positive in 84% (50% type 1, 13% untypable). Forty-four percent had normal alanine aminotransferase (ALT) levels, 24% alcohol consumption >15 g/day, and 51% had undergone liver biopsy (10% of which had cirrhosis). Histological grade was not related to ALT level or CD4+ count. Overall, 40% of patients had been treated for HCV infection. HCV treatment was significantly associated with performance of liver biopsy, histological grade, ALT level, CD4+ count, Centers for Disease Control (CDC) classification, but not with age or alcohol consumption. Rate of early response to treatment was fifty percent among patients treated with bitherapy. Eighty-nine percent of all patients with previous or current anti-HCV treatment had undergone liver biopsy. In conclusion, despite the difficulties in managing hepatitis C in HIV-infected patients, almost one-half of all patients in this study had received anti-HCV treatment.

Adult↗
PubMed2003

Hepatitis C virus genetic variability in 52 human immunodeficiency virus-coinfected patients.

The aim of this study was to examine whether hepatitis C virus (HCV) pretreatment quasispecies complexity was linked to virological response or other clinical and biological parameters, in human immunodeficiency virus (HIV)-coinfected patients undergoing anti-HCV treatment. In addition, HCV quasispecies composition is described longitudinally in these patients before, during, and after treatment. The 52 HIV-coinfected patients were included in a randomized therapeutic trial. At inclusion, they had CD4(+) counts of >250/micro l, HIV plasma load of <10,000 copies/ml, and chronic HCV infection with genotype 1 (n = 27), 2 (n = 2) or 3 (n = 23). These values were compared at baseline with 32 HCV-only-infected, interferon-naive patients who were infected with genotype 1, 2, or 3 (n = 16, 1, or 15, respectively). HCV complexity was studied by single-strand conformation polymorphism (SSCP) in E2 hypervariable region 1 (HVR1), and diversity was evaluated at inclusion in 20 coinfected patients by sequencing four major SSCP bands. The baseline number of SSCP bands was identical in HIV-infected and control patients. In HIV-infected patients, HCV complexity was not predictive of sustained virological response to anti-HCV treatment and was unrelated to epidemiological factors, immunological parameters linked to HIV infection (CD4(+) counts, T CD4(+) proliferative responses to HIV-1 p24), protease inhibitor treatment, HCV plasma load, or genotype. HCV diversity was lower in genotype 2- and 3-infected patients. Six months after completion of the anti-HCV treatment, in comparison with baseline, SSCP profiles were modified in 13 of the 21 nonresponding coinfected patients with analyzable samples. In conclusion, in HIV-infected patients, HCV variability had no significant influence on virological response to anti-HCV treatment.

AIDS-Related Opportunistic Infections↗
PubMed2002

CD4 T lymphocyte proliferative responses to hepatitis C virus (HCV) antigens in patients coinfected with HCV and human immunodeficiency virus who responded to anti-HCV treatment.

CD4 T lymphocyte proliferative responses to hepatitis C virus (HCV) antigens were evaluated before and during an anti-HCV regimen (interferon-alpha2a and ribavirin) in 36 patients coinfected with HCV and human immunodeficiency virus (HIV), to determine whether immune responses against HCV antigens are present in such patients, whether these responses are modified by anti-HCV treatment, and whether they are correlated with treatment efficacy. The CD4 responses against HCV antigens (primarily core antigens) detected at study entry in one-half of the patients did not correlate with anti-HCV treatment efficacy. Of 36 patients, 8 had patterns of persistent immune response to infection by genotypes 3 or 4 that were significantly correlated with sustained virologic response. Persistent immunologic reactivity and sustained virologic response coexisted only in patients infected with genotype 3. These findings suggest that HCV genotype may influence specific immune response, which, in turn, is implicated in virologic control.

Adult↗
PubMed2002

Daily or three times a week interferon alfa-2b in combination with ribavirin or interferon alone for the treatment of patients with chronic hepatitis C.

BACKGROUND/AIMS: Data on hepatitis C virus (HCV) viral dynamics and on the effect of interferon in blocking virion production have suggested a rationale for daily administration of interferon in patients with chronic hepatitis C infection. We compared the efficacy and safety of daily interferon alfa-2b in combination with ribavirin with those of interferon alfa-2b three times a week alone or in combination with ribavirin. METHODS: We randomly assigned 321 patients with chronic hepatitis C to receive standard-dose interferon alfa-2b alone or in combination with ribavirin for 48 weeks or daily interferon alfa-2b (3 million units per day for 12 weeks then 3 million units three times per week for 24 weeks) and ribavirin (36 week treatment). RESULTS: The rate of sustained virologic response (defined as an undetectable serum HCV-RNA level 72 weeks after initiation of treatment) was higher in patients who received combination therapy with three times weekly interferon (51.7%) or daily interferon (46.1%) than in patients who received interferon alone (25%) (P=0.0001 and P=0.002, respectively). Independent predictive factors for sustained virologic response were combination therapy, weight, genotype and viral load. In conclusion, in patients with chronic hepatitis C, combination therapy with induction treatment (daily interferon for 12 weeks) and shorter duration of treatment was not different from combination therapy for 48 weeks without induction treatment. CONCLUSIONS: Induction treatment with interferon for 12 weeks and combination therapy for a total duration of 36 weeks could therefore be cost effective.

Adult↗
PubMed2002

Daily or three times per week interferon alpha-2b in combination with ribavirin or interferon alone for the treatment of patients with chronic hepatitis C not responding to previous interferon alone.

BACKGROUND/AIMS: We compared the efficacy and safety of the combined therapy of daily interferon alpha-2b and ribavirin with those of interferon alpha-2b three times per week alone or in combination with ribavirin in non-responder patients with hepatitis C virus (HCV) infection. METHODS: A total of 376 patients were randomly assigned to receive interferon alpha-2b (6 MU three times per week for 24 weeks followed by 3 MU three times per week for 24 weeks) alone (group A) or in combination with ribavirin for 48 weeks (group B), or daily interferon alpha-2b (3 MU per day for 24 weeks followed by 3 MU three times per week for 24 weeks) and ribavirin (group C). RESULTS: After 24 weeks of therapy, HCV RNA was undetectable in 11.7, 24.0, and 37.8% for groups A, B, and C, respectively. Sustained virological response was more frequent in patients who received combination therapy with three times weekly interferon (20.9%) or daily interferon (26.0%) than in patients who received interferon alone (5.8%) (P<0.001). The predictive HCV parameters for sustained response were a low viral load on day 7 and a negative HCV RNA on week 12. CONCLUSIONS: In conclusion, in non-responder patients with chronic hepatitis C, virological response with daily interferon and ribavirin, compared to interferon monotherapy, was significantly improved during treatment, although sustained virological response was similar for both combination therapies with ribavirin and three times a week or daily interferon.

Adult↗
PubMed2002

Evaluation of the VERSANT HCV RNA 3.0 assay for quantification of hepatitis C virus RNA in serum.

We assessed the performance of a new assay (VERSANT HCV RNA 3.0 [bDNA 3.0] assay [Bayer Diagnostics]) to quantitate HCV RNA levels and compared the results of the bDNA 3.0 assay to results of the Quantiplex HCV RNA 2.0 (bDNA 2.0) assay. Samples used in this study included 211 serum specimens from hepatitis C virus (HCV)-infected persons from two sites (Bordeaux and Marseille, France) with different genotypes; 383 serum specimens from HCV antibody-negative, HCV RNA-negative persons; and serial dilutions of World Health Organization (WHO) HCV RNA standard at a titer of 100,000 IU/ml. The specificity of the bDNA 3.0 assay was 98.2%. A high correlation was observed between expected and observed values in all dilutions of WHO standard (r = 0.9982), in serial dilutions of pooled samples (r = 0.9996), and in diluted sera from different HCV genotypes (r = 0.9930 to 0.9995). The standard deviations (SD) for the within-run and between-run reproducibility of the bDNA 3.0 assay were <or=0.2 and <or=0.14, respectively. The intersite SD ranged from 0.03 to 0.14. The bDNA 3.0 assay results were positively correlated with the bDNA 2.0 assay results (r = 0.9533). Taking in account the overall performance, this assay could be used as a routine tool for the HCV RNA quantification.

Branched DNA Signal Amplification Assay↗