Biomedical subjects

Jacques Izopet

Publications and source records attributed to Jacques Izopet.

At least 55 records · Page 3Linked to original sources

PubMed2005

Low risk of mother-to-child transmission of hepatitis C virus in Yaounde, Cameroon: the ANRS 1262 study.

To assess mother-to-child transmission (MTCT) of hepatitis C virus (HCV) in Cameroon, 5,008 pregnant women were screened for HCV antibodies. Eighty-nine (1.8%) were HCV-antibody (HCV-Ab) positive. Among these, 7 (7.9%) were HBsAg positive, 6 (6.7%) HIV-positive, and one (1.1%) was co-infected by both hepatitis B virus (HBV) and HIV. Sixty-eight (76%) out of 89 HCV-Ab positive pregnant women were HCV-RNA positive. The HCV genotype determination indicated the predominance of genotype 4 (45.3%), followed by the genotypes 1 (28.1%) and 2 (26.6%). The mean HCV-RNA levels of 41 women at the time of delivery was 4.8 (range 0.06-34.7) x 10(6) RNA copies/mL. Finally, 35 women delivered 36 live children. None of those screened at 6 weeks and 6 months of age were HCV-RNA positive. The failure to detect HCV vertical transmission suggests that the mother-to-child transmission (MTCT) is not a major route of HCV transmission in Cameroon.

Cameroon↗

PubMed2004

Factors of intermittent HIV-1 excretion in semen and efficiency of sperm processing in obtaining spermatozoa without HIV-1 genomes.

OBJECTIVE: To study the risk factors for HIV-1 in semen according to the localization of HIV-1 in sperm cell fractions and to assess the efficiency of sperm processing in obtaining spermatozoa without HIV-1 genomes. METHODS: Ninety-four HIV-infected patients provided 281 paired blood and semen samples. Sperm cell separation was performed using two successive methods. HIV-1 RNA was quantified in blood and seminal plasma. HIV-1 RNA and DNA were detected in cell fractions. RESULTS: HIV-1 RNA was found in 14% of seminal plasma samples and up to 8.7% of native semen cells were positive for HIV-1 RNA and DNA. Ten seminal plasma samples had detectable RNA although blood viral load was undetectable. Antiretroviral treatment reduced the likelihood of RNA detection in seminal plasma. For semen with polynuclear cells and HIV-1 RNA in seminal plasma, the likelihood of detecting HIV-1 genomes in semen cells was increased fourfold and sixfold, respectively. In 25% of patients, HIV-1 excretion was intermittent. In the group of patients with systematic negative seminal plasma, HIV-1 genomes were detected in up to 10% of sperm cell samples. Our method of sperm processing always enabled us to obtain spermatozoa without detectable HIV-1 genomes. CONCLUSIONS: Polynuclear cells in semen are a risk factor for seminal HIV-1 excretion. Blood viral load was the only predictive factor for the intermittence of HIV-1 excretion in semen over time. Sperm processing using two successive methods was effective in obtaining spermatozoa without detectable HIV-1 genomes regardless of the viral load level in native semen.

Adult↗

PubMed2004

A survival method to estimate the time to occurrence of mutations: an application to thymidine analogue mutations in HIV-1-infected patients.

Virologic studies of human immunodeficiency virus type 1-infected patients have investigated either the emergence of resistance mutations according to the treatment received (type I) or their effect on subsequent regimens (type II). Type I studies provide an estimation of the frequency distribution of mutations for a given duration of therapy, but the delay to emergence of these mutations cannot be assessed. We suggest using a nonparametric estimator that generalizes the Kaplan-Meier method to data from type II studies to estimate the time to occurrence of mutations. Patients had no treatment interruption before viral genotyping. Although the curves should be interpreted with caution, they provide useful information about the kinetics of the emergence of mutations. The method was applied to the emergence of thymidine analogue mutations in patients previously treated with zidovudine (ZDV) plus didanosine or zalcitabine. Although K70R has been described as the first mutation to appear in patients receiving ZDV monotherapy, the T215Y/F mutation appeared first in patients receiving dual-nucleoside combination therapy.

Acquired Immunodeficiency Syndrome↗

PubMed2004

HIV therapy after treatment interruption in patients with multiple failure and more than 200 CD4+ T lymphocyte count.

The aim of the study was to investigate the safety and efficacy of a salvage therapy initiated after interrupting treatment in patients with virological failure and more than 200 CD4(+) T lymphocyte count. In this prospective study, 77 patients who received failing regimens had stopped completely all medication for 3 months before starting an optimised regimen consisting of 3-5 drugs. Patients were tested for HIV resistance before and after treatment interruption. Discontinuation of therapy for 3 months was associated with a median increase in HIV RNA of 1.1 log(10), a median decrease in CD4(+) T cell count of 136 x 10(6)/L and five clinical events related to HIV, but no AIDS-defining event. Eighty-seven percent of patients showed a shift from a drug resistant genotype to a wild-type genotype based on the major resistance mutations. Forty-seven percent of patients with a genotype shift reached fewer than 200 HIV RNA copies/ml of plasma 6 and 12 months after treatment resumption whereas none of those without a genotype shift did so (P = 0.03). However, the genotypic shift was not associated with a sustained virological response by multivariate analysis. The use of a new therapeutic class of compound in the salvage regimen was the only predictor of the sustained virological response. Salvage therapy with 3-5 drugs after interrupting treatment for 3 months can be a safe and effective strategy provided the HIV disease is not too advanced. Randomised trials in this population are needed to assess the clinical benefit of this strategy.

AIDS-Related Opportunistic Infections↗

PubMed2004

Hepatitis E in the south west of France in individuals who have never visited an endemic area.

A total of 431 consecutive patients from the Midi Pyrenees area with acute hepatitis with unknown etiology in 2001-2002 were tested for the presence of immunoglobulin G-class (IgG) anti-hepatitis E virus (HEV) antibodies. Forty-six (10.7%) had anti-HEV IgG, and the results were questionable for a further 17 (3.9%). Real time PCR based on TaqMan detection was used to identify HEV genome fragments in the serum of patients with positive or questionable anti-HEV serology. HEV RNA was found in 25.4% of cases. All amplification products were sequenced and analyzed. Phylogenetic analysis revealed that all the strains were genotype 3. In conclusion, virological and epidemiological data indicate that genotype 3 viruses are circulating in the south west part of France (Midi-Pyrenees) in patients with acute hepatitis and who have not visited recently areas in which HEV is endemic.

Acute Disease↗

PubMed2004

Amantadine therapy in renal transplant patients with hepatitis C virus infection.

BACKGROUND: To date, there is no safe and efficient treatment of hepatitis C virus (HCV) infection after renal transplantation. Recently, there were encouraging reports after using amantadine in HCV-positive immunocompetent patients. OBJECTIVES: In an open pilot study, we evaluated the efficacy and the safety of amantadine monotherapy in 8 HCV positive renal-transplant patients with chronic active hepatitis and increased alanine aminotransferase (ALT) levels. RESULTS: After 6 months of amantadine therapy (200 mg per day), there were no decrease in HCV viremia (5.87 +/- 0.37 log copies/ml at M6 versus 5.71 +/- 0.5 log copies/ml at baseline; P > 0.05). However, we found a significant decrease in ALT activity (71 +/- 17 IU/l at M6 versus 100 +/- 9 IU/l at baseline; P = 0.04), whereas the decrease in aspartate aminotransferase activity did not reach statistical significance. There were no significant changes in liver histology. The clinical and biological tolerance was very good. Finally, there were a significant decrease in cyclosporine A whole blood trough levels during therapy. CONCLUSIONS: Our study is the first one to demonstrate that amantadine monotherapy lack of efficacy in HCV renal-transplant patients. It is able to improve liver enzymes but it has no impact neither upon HCV viremia nor upon liver histology.

Adult↗

PubMed2004

TaqMan amplification system with an internal positive control for HCV RNA quantitation.

BACKGROUND: Quantitation of hepatitis C virus (HCV) RNA has become an essential tool for monitoring antiviral therapies in chronically infected patients. Different quantitative HCV RNA assays have been reported, mainly using techniques based on signal amplification with branched DNA (bDNA) technology or target sequence amplification by reverse-transcription PCR method (RT-PCR). OBJECTIVES AND STUDY DESIGN: An RT-PCR assay using TaqMan (fluorescence-based real-time PCR) and minor groove binding (MGB) probes was designed for the quantitative determination of HCV RNA in the clinical samples. Calculation of the concentration of HCV RNA was based on an external standard curve in the presence of an internal positive control (IPC). RESULTS: The assay detected 550 international units (IU)/mL with >95% probability of a positive result, with a linear range extending up to 10,000,000 IU/mL. The test exhibited good reproducibility with intra-assay and inter-assay coefficients of variation (CV) of 1.6% and 3.2%, respectively. All the major HCV genotypes were quantified with equivalent efficiency and accuracy. HCV genotypes 5 and 6 have also been amplified but too few samples have been tested. The performance of this new assay for quantitation of HCV viremia was evaluated with 213 anti-HCV positive sera, 120 of which corresponded to 30 patients sampled during the therapy. We used the Amplicor HCV Monitor assay (Roche Diagnostics, France) and the bDNA VERSANT HCV RNA assay (Bayer Diagnostics, France) to analyze 173 and 40 samples, respectively. The assay described here was significantly correlated with both commercial assays (R2 = 0.9535, P < 0.0001 and R2 = 0.8508, P < 0.0001, respectively). CONCLUSION: The present study illustrated the high reproducibility and reliability of our TaqMan HCV assay. Moreover, the monitoring of viral decline with our assay gave the same results as those obtained with the commercial assays indicating that this new technique provides an attractive approach for measuring HCV viral load.

Genotype↗

PubMed2004

Effects of long-term lamivudine therapy in renal-transplant patients.

BACKGROUND: Following renal transplantation (RT), chronic immunosuppression is associated in hepatitis B virus (HBV) (+) patients with a flare-up of the disease, which might be harmful in the long term. OBJECTIVES: We report on the effect of long-term lamivudine therapy given at an initial daily dose of 100mg in 18 HBV (+) RT patients. RESULTS: When lamivudine therapy was commenced, 14 patients (77%) had an increase in their aspartate (AST) and alanine (ALT) aminotransferase levels. During a mean follow-up, under treatment, of 36.5 +/- 3.5 months (up to 66 months), 10 patients (55%) had a sustained partial (HBV DNA < 4 x 10(5)copies/ml) (n = 4) or complete (HBV DNA < 400 copies/ml) (n = 6) virological response. Overall, 12 virological breakthroughs were observed. Of those who were HBe Ag(+) prior to lamivudine therapy (n = 4), one seroconverted to HBe Ab during therapy. At the last follow-up, AST and ALT levels were normal in 13 patients. When liver biopsy was repeated during treatment (n = 15), the virological responders showed a significant decrease in total Knodell score from 10 +/- 0.6 to 7 +/- 1 (P = 0.04), but no significant change in the stage of fibrosis. Conversely, in those patients with high HBV DNA titers, there were no significant changes in the total Knodell score or in the grade of fibrosis. CONCLUSION: In conclusion, lamivudine therapy is safe in HBV(+)ve renal-transplant patients. However, even if the full and partial virological response rates are still high (55%) in the long term, relapse or primary non-responses occur. The implementation of alternative efficient strategies is warranted.

Antiviral Agents↗

PubMed2004

Ribavirin pharmacokinetics in renal and liver transplant patients: evidence that it depends on renal function.

BACKGROUND: Ribavirin is approved for the treatment of chronic hepatitis C virus (HCV) infection. However, no recommendation exists for dosing patients with impaired renal function. METHODS: The authors performed a pharmacokinetic study in 21 HCV-positive renal or liver transplant patients. The mean creatinine clearance (ClCr) calculated by the Cockcroft-Gault equation was 57 mL/min (0.95 mL/s; range, 17 to 89 mL/min [0.28 to 1.48 mL/s]). Twelve blood samples were obtained during a 96-hour period after the first single administration of 1,000 mg of ribavirin. After the first pharmacokinetics (PK) and the pharmacodynamics (PD) profile was completed, the patients received ribavirin at 1,000 mg/d with or without interferon-alpha. A blood sample was taken monthly just before the oral administration of ribavirin. Plasma ribavirin concentrations were determined by high-performance liquid chromatography. RESULTS: A total of 428 plasma concentrations were analyzed by a population pharmacokinetic method using the NONlinear Mixed Effect Model program. The mean observed ribavirin apparent clearance (CL/F) was 9.1 L/h (with an interindividual variability of 39%). The influences of the age, sex, body weight (BW), serum creatinine (Scr), ClCr, hemoglobin, and graft status on CL/F were examined. CL/F was highly correlated with ClCr (r = 0.63, P < 0.01). The final regression formula was CL/F (L/h) = 32.3 x BW x (1 - 0.0094 x age) x (1 - 0.42 x sex)/Scr, where sex = 0 for men and 1 for women; Scr is in micromoles per liter. Sex had a larger influence on CL/F than that corresponding to the Cockcroft-Gault equation (ie, 15%). CONCLUSION: The authors present the parameters that determine ribavirin clearance in HCV+ transplant patients with normal or impaired renal function. Moreover, we suggest ribavirin daily doses according to various levels of renal function.

Adult↗

PubMed2004

Convenient biological assay for polyethylene glycol-interferons in patients with hepatitis C.

The vesicular stomatitis virus cytopathic effect reduction assay is suitable to quantify polyethylene glycol-alpha interferon 2a (PEG-IFN-alpha 2a) and PEG-IFN-alpha 2b. Human serum and ribavirin did not interfere with the assay. This bioassay was successfully used for assaying PEG-IFN-alpha 2a and PEG-IFN-alpha 2b in serum samples from patients undergoing combination therapy.

Animals↗

PubMed2004

Immunologically silent autochthonous acute hepatitis E virus infection in France.

Hepatitis E is an acute and self-limiting hepatitis, and the causative agent, hepatitis E virus, is excreted in feces and orally transmitted. The disease is common in Asia and Africa, causing outbreaks or sporadic cases. In Europe, the infection is generally observed after a history of travel in an area of endemicity. We report on an autochthonous case in southwestern France in which the diagnosis was based on molecular tools rather than serological testing.

Adult↗

PubMed2004

Expertise of French laboratories in detection, genotyping, and quantification of hepatitis C virus RNA in serum.

Before initiating new large-scale therapeutic trials for hepatitis C virus (HCV)-infected patients, the French Health Authorities for HCV research decided to organize an evaluation of the expertise of laboratories that could be engaged to undertake molecular biology assays in such trials; 21 experienced laboratories participated in this national evaluation of laboratory expertise, which was performed in two successive rounds. The first round evaluated the laboratories for their abilities to detect HCV RNA in serum, determine genotypes, and quantify HCV RNA loads. The results observed by qualitative assays for HCV RNA detection were 100% sensitivity and 100% specificity for all laboratories. The genotyping results were 100% concordant for 9 laboratories and greater than 90% for 10 laboratories. By contrast, large coefficients of variation were observed for quantitative determination of HCV RNA loads, leading to a second round with standardized quantitative assays only. The dispersion of the results was larger by the AMPLICOR HCV Monitor assay than by the branched-DNA assay (mean coefficients of variation, 57.4 and 16.9%, respectively). In the majority of cases, discrepancies between the results of the two tests were found for samples with high viral loads. These results indicate the usefulness of validating, by controlling for expertise, both the reliabilities of laboratories involved in multicenter work and the standardized assays chosen for use in the evaluation of the biological impacts of new therapies.

Analysis of Variance↗

PubMed2004

Genotypic determinants of the virological response to tenofovir disoproxil fumarate in nucleoside reverse transcriptase inhibitor-experienced patients.

OBJECTIVE: To assess the genotypic determinants of the virological response to tenofovir disoproxil fumarate (TDF) in a multicentre cohort of antiretroviral (ARV)-experienced patients receiving TDF as a part of a salvage therapy. METHODS: HIV-1 genotype was assessed at baseline in a subgroup of 161 patients of the French expanded access program receiving a stable TDF-including regimen for 3 months or more. Reverse transcriptase mutations associated with the viral load decrease at month 3 with a P-value <0.15 were retained for the construction of a mutation score. The score was then validated using a multivariate analysis and bootstrap resampling method. RESULTS: The strongest association with decrease in viral load was observed with a set of seven mutations (TDF mutation score) that consisted of M41L, E44D, D67N, T69D/N/S, L74V, L210W and T215Y/F RT mutations. The RT K65R mutation and the insertions at codon 69 were not included in the analysis due to low prevalences. A TDF mutation score of < or = 2 predicted the absence of resistance to TDF and > or = 6 mutations predicted resistance to TDF with corresponding reductions in viral load of -1.3 +/- 1.1, and +0.1 +/- 0.7 log10 copies/ml, respectively. In patients with a TDF mutation score of 3-5, the decrease in viral load was -0.8 +/- 1.0 log10 copies/ml and was considered possibly resistant. In the multivariate analysis, a TDF mutation score > or = 6, previous use of amprenavir, indinavir and lopinavir, and co-prescription of didanosine were associated with a worse virological response. The bootstrap analysis showed the robustness of the TDF mutation score. CONCLUSION: In ARV-experienced patients receiving TDF-containing regimens, a score derived from seven reverse transcriptase mutations was shown to be independently predictive of the virological response.

Adenine↗

PubMed2003

Stable prevalence of genotypic drug resistance mutations but increase in non-B virus among patients with primary HIV-1 infection in France.

OBJECTIVE: To evaluate the frequency of drug-resistant HIV-1 viral strains from patients presenting with primary infection in 1999-2000 and to survey the molecular epidemiology of these viruses circulating in France. METHODS: Resistance mutations were detected by sequencing the reverse transcriptase and the protease genes in plasma samples from 249 individuals. Phylogenetic analysis was performed on the reverse transcriptase genes. RESULTS: Ten per cent of patients [26/249; 95% confidence interval (CI) 7-15%] presented with virus mutations associated with resistance to at least one antiretroviral drug. The distribution of the resistance mutations was as follows: to nucleoside reverse transcriptase inhibitors in 19 (8%; 95% CI 5-12%) and to non-nucleoside reverse transcriptase inhibitors in 10 (4%; 95% CI 2-7%). Primary resistance mutations to protease inhibitors were detected in 14 (6%; 95% CI 3-9%). Twelve patients (5%; 95% CI 3-8%) presented with virus harbouring mutations associated with resistance to two or three classes of antiretroviral drugs. The median HIV RNA in plasma at enrollment was lower in patients with one or more drug resistance mutations than in patients with no mutations (5.05 log versus 5.47 log, P = 0.05). Phylogenetic analysis revealed that 19% (14-24%) of patients harboured HIV-1 non-B subtype strains; this proportion remained high when Caucasian patients only were considered (14%). CONCLUSION: This study, performed within the French network on HIV-1 primary infection survey, revealed no change in the frequency of resistant viral strains over time, but showed an increasing prevalence of non-B subtypes overall and among Caucasian individuals.

Drug Resistance, Viral↗

PubMed2003

Genetic heterogeneity of the NS5A gene of hepatitis C virus and early response to interferon-alpha.

The double-stranded RNA-activated protein kinase-binding domain (PKRbd) of the NS5A gene of hepatitis C virus (HCV) was studied by the cloning and sequencing method, in HCV-infected patients who had a primary resistance to treatment with interferon (IFN)-alpha (early nonresponders). Patients whose virus load decreased by >or=0.5 log (early responders) were similarly analyzed. In the 2 groups, the PKRbd evolved similarly over the first 24 h. Selection of resistant HCV variants is unlikely to explain primary resistance to IFN-alpha.

Antiviral Agents↗

PubMed2003

Assessment of HIV-1 subtyping for Cameroon strains using phylogenetic analysis of pol gene sequences.

Phylogenetic analysis of human immunodeficiency virus type 1 (HIV-1) pol gene is a useful method for subtyping European strains of HIV-1. The suitability of this method for genetically diverse African strains was evaluated by comparing HIV-1 subtyping of Cameroon strains using a long fragment of the pol gene sequence to the findings obtained using env gene sequences. When the pol gene could not be amplified, the reverse transcriptase (RT) or the protease (PR) genes were used. Phylogenetic analysis of the env C2/V3 gene sequences of 60 HIV-1 isolates showed 52 to be subtype A, 2 subtype G, plus one each of subtypes C, F2 and H, with 3 subtypes not determined. A long fragment of the pol gene was amplified successfully and sequenced in 23% of cases. The RT region was amplified for 42% of the samples that could not be typed by analysing the long fragment, and the PR gene was amplified for 40% of them. Thus, 63% of samples were typable. Env and pol gene subtypings were in agreement in 86% of cases. It is concluded that the phylogenetic analysis of pol gene sequences is not a practical method for HIV-1 subtyping in areas of high subtype diversity, despite the good agreement between the env and pol gene subtypings. However, it can be a useful method for HIV-1 subtyping, provided that the gene is amplifiable.

Cameroon↗

PubMed2003

Quantitation of human cytomegalovirus in recipients of solid organ transplants by real-time quantitative PCR and pp65 antigenemia.

Human cytomegalovirus (HCMV) infections and anti-HCMV treatment are usually monitored by measuring pp65 antigenemia. This method is time-consuming, labour-intensive and requires skilled operators. We have compared results obtained using real-time Light Cycler quantitative PCR (QPCR) and the pp65 antigen assay on serial samples collected from recipients of solid organ transplants. We collected 198 blood samples from 14 solid organ transplant recipients and assayed them for pp65 antigen and with Light Cycler PCR. HCMV DNA was extracted from leukocytes and measured using primers and probe located in the UL83 region. The quantity of HCMV DNA was calculated using a standard curve prepared from a plasmid containing the target sequence. There was a good correlation between the number of pp65-positive cells and the DNA copy number (r = 0.57, P < 0.0001). A clinical threshold of 50 positive polymorphonuclear leukocytes/200,000 cells was equivalent to two log10 genome copies per capillary by Light Cycler PCR. HCMV DNA was detected before pp65 antigen in three patients at a mean time of 10 days, whereas the two tests were positive simultaneously for eight patients. Both the pp65 antigen data and DNA copy number decreased over time during antiviral treatment, although the QPCR was positive 28.2 days after the pp65 antigen assay had become negative. The real-time Light Cycler quantitative PCR assay is a rapid and labour-saving technique. This molecular method could be useful for monitoring infections and antiviral treatment in recipients of solid organ transplants.

Adult↗

PubMed2003

Intermittent detection of hepatitis C virus (HCV) in semen from men with human immunodeficiency virus type 1 (HIV-1) and HCV.

HCV is usually transmitted via the blood, but HCV RNA has been detected recently in seminal fluid. This study was done to study HCV seminal shedding and factors that could influence the presence of HCV in the seminal fluid of men coinfected with HCV and HIV-1. HCV and HIV-1 genomes were assayed in multiple paired blood and semen samples obtained from 35 men enrolled in an assisted medical procreation protocol. HCV RNA was found intermittently in semen samples from 9 patients (25.7%). Samples from 9 men with HCV RNA in their semen and 26 men without were compared to further analyze these parameters. No correlation was found between HCV RNA in the seminal fluid and age, HCV virus load, the duration of HIV-1 infection, HIV treatment, the CD4(+) cell count, HIV-1 virus load or HIV-1 detection in the semen. The intermittent detection of HCV RNA in semen samples support the systematic search for HCV RNA in semen and the use of processed spermatozoa in assisted medical procreation of infertile HCV serodiscordant couples.

Adult↗