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H Fleury

Publications and source records attributed to H Fleury.

At least 19 recordsLinked to original sources
PubMed2006

HIV-1 reverse transcriptase (RT) genotypic patterns and treatment characteristics associated with the K65R RT mutation.

BACKGROUND: The K65R HIV-1 reverse transcriptase (RT) mutation is a multidrug resistance mutation which may be correlated with specific antiretroviral combinations and with the presence or absence of other RT resistance mutations. OBJECTIVES: The aims of this study were: (i) to determine the prevalence of the K65R mutation in a cohort of antiretroviral-treated patients; (ii) to study genotypic patterns and treatment characteristics in patients in whom the K65R mutation was present. STUDY DESIGN: We included in the study all antiretroviral-experienced patients followed up at the Bordeaux University Hospital in 2003 and 2004 for whom an HIV-1 genotypic resistance analysis was available. Information on RT resistance mutations was reported from a hospital database including therapeutic and biological parameters. The prevalence of K65R was investigated for all patients. Genotypic patterns and treatment characteristics were examined at the time of detection of the K65R mutation. RESULTS: The prevalence of K65R was 1.9% (26 of 1404 patients). K65R was associated with nucleoside RT inhibitor-based regimens in 22 patients, and with tenofovir disoproxil fumarate, lamivudine, didanosine and abacavir in 23, 17, 17 and eight patients, respectively. The M184V and Q151M mutations were the most commonly co-selected substitutions. Thymidine analogue mutations (TAMs) were rarely co-selected with K65R and inversely associated with K65R. CONCLUSION: The K65R mutation may emerge preferentially in the absence of zidovudine and TAMs, suggesting the possibility of an antagonistic interaction between K65 and TAMs.

Anti-HIV Agents↗
PubMed2004

Surveillance network for herpes simplex virus resistance to antiviral drugs: 3-year follow-up.

Herpes simplex virus (HSV) infections are very common in the general population and among immunocompromised patients. Acyclovir (ACV) is an effective treatment which is widely used. We deemed it essential to conduct a wide and coordinated survey of the emergence of ACV-resistant HSV strains. We have formed a network of 15 virology laboratories which have isolated and identified, between May 1999 and April 2002, HSV type 1 (HSV-1) and HSV-2 strains among hospitalized subjects. The sensitivity of each isolate to ACV was evaluated by a colorimetric test (C. Danve, F. Morfin, D. Thouvenot, and M. Aymard, J. Virol. Methods 105:207-217, 2002). During this study, 3900 isolated strains among 3357 patients were collected; 55% of the patients were immunocompetent. Only six immunocompetent patients excreted ACV-resistant HSV strains (0.32%), including one female patient not treated with ACV who was infected primary by an ACV-resistant strain. Among the 54 immunocompromised patients from whom ACV-resistant HSV strains were isolated (3.5%), the bone marrow transplantation patients showed the highest prevalence of resistance (10.9%), whereas among patients infected by human immunodeficiency virus, the prevalence was 4.2%. In 38% of the cases, the patients who excreted the ACV-resistant strains were treated with foscarnet (PFA), and 61% of them developed resistance to PFA. The collection of a large number of isolates enabled an evaluation of the prevalence of resistance of HSV strains to antiviral drugs to be made. This prevalence has remained stable over the last 10 years, as much among immunocompetent patients as among immunocompromised patients.

Acyclovir↗
PubMed2004

Detection of human immunodeficiency virus type 1 antiretroviral resistance mutations by high-density DNA probe arrays.

Genotypic resistance testing has become an important tool in the clinical management of patients infected with human immunodeficiency virus type 1 (HIV-1). Standard sequencing methodology and hybridization-based technology are the two principal methods used for HIV-1 genotyping. This report describes an evaluation of a new hybridization-based HIV-1 genotypic test of 99 clinical samples from patients infected mostly with HIV-1 subtype B and receiving treatment. This test combines RNA extraction with magnetic silica particles, amplification by nested reverse transcriptase PCR, and detection with high-density probe arrays designed to detect 204 antiretroviral resistance mutations simultaneously in Gag cleavage sites, protease, reverse transcriptase, integrase, and gp41. The nested reverse transcriptase PCR success rates at viral loads exceeding 1,000 copies/ml were 98% for the 2.1-kb amplicon that covers the Gag cleavage sites and the protease and reverse transcriptase genes, 92% for the gp41 amplicon, and 100% for the integrase amplicon. We analyzed 4,465 relevant codons with the HIV-1 DNA chip genotyping assay and the classic sequence-based method. Key resistance mutations in protease and reverse transcriptase were identified correctly 95 and 92% of the time, respectively. This test should be a valuable alternative to the standard sequence-based system for HIV-1 drug resistance monitoring and a useful diagnostic tool for simultaneous multiple genetic analyses.

Anti-HIV Agents↗
PubMed2003

T-lymphocyte populations in hepatitis C and HIV co-infected patients treated with interferon-alfa-2a and ribavirin.

OBJECTIVE: The effects on T-lymphocyte populations of two interferon-alfa-2a (IFN) regimens associated with ribavirin were evaluated in 36 HCV-HIV co-infected patients with chronic hepatitis C, T-CD4 cell count > 250 cells/ micro L and a plasma viral load of < 10 000 HIV RNA copies/mL. METHODS: Patients were given IFN for 48 weeks. Group A (18 patients) received 6 mega units (MU) subcutaneously three times a week for 24 weeks, then 3 MU three times a week for the last 24 weeks. Group B (18 patients) received 9 MU daily for 2 weeks, 3 MU daily for 22 weeks, then 3 MU three times a week for the last 24 weeks. Serum HCV RNA was evaluated at weeks 12 and 72. Ribavirin was added at week 16 for virologic nonresponders at week 12. CD3, CD3 CD4, CD3 CD8, CD3 CD4 human leucocyte antigen (HLA)-DR and CD3 CD8 HLA-DR lymphocyte subsets were evaluated before, during and after treatment by cytofluorometry. Controls were healthy and HCV mono-infected patients. RESULTS: CD3 CD4 and CD3 CD8 T-cells counts were both impaired during anti-HCV therapy, but returned to baseline value after treatment completion. Lymphopenia concerned mainly CD8 T-cells, the percentage of which decreased, whereas that of CD4 increased. Three patients displayed reversible CD4 lymphopenia < 200 cells/ micro L. HIV infection at inclusion was responsible for higher CD3 CD8 HLA-DR T-cell percentages in co-infected patients than in healthy and HCV mono-infected subjects. T-cell sequestration in lymphoid tissues and enhanced apoptosis may account for lymphopenia. CONCLUSION: High-dosed IFN anti-HCV therapy induced only moderate and transient CD4 lymphopenia in HIV co-infected patients.

Adult↗
PubMed2002

Intrahepatic HCV RNA loads in 37 HIV-HCV co-infected patients with controlled HIV infection.

Serum and intrahepatic hepatitis C virus (HCV) RNA were measured in 37 HIV-HCV co-infected patients with controlled human immunodeficiency virus (HIV) infection and correlated with clinical, biological, and histological parameters. Thirty-seven interferon-naive patients underwent liver biopsy. HCV-induced activity (A) and fibrosis (F) were evaluated with METAVIR score. The 37 patients included had HIV plasma loads < 10,000 copies/ml, CD4(+) count > 250/microl. All the patients but two were receiving antiretroviral treatment. Liver tissue and sera were used for measurement of HCV RNA by the Cobas Amplicor HCV Monitor. All patients had serum and liver HCV RNA, and both levels were correlated (r = 0.47; P = 0.003). Intrahepatic HCV load did not depend on age, sex, duration of HCV infection, CD4(+), HCV genotype, or fibrosis. AST levels correlated with intrahepatic HCV load (r = 0.52; P = 0.001). Patients with METAVIR A1/A2 had significantly lower levels of liver HCV-RNA than were found in patients with METAVIR A3 (P = 0.026). Highly active antiretroviral therapy (HAART) including protease inhibitors(PI)-treated patients had significantly lower intrahepatic HCV load (P = 0.04). A weak but significant correlation between serum and liver HCV RNA was found. The amount of hepatic HCV RNA was correlated with AST levels, histological activity, but not with HCV genotype or fibrosis. The immune improvement associated with PI regimens could help reduce HCV load, supporting a protective effect of PI-induced immune restoration.

Adult↗
PubMed2002

Human immunodeficiency virus type 1 genotypic and pharmacokinetic determinants of the virological response to lopinavir-ritonavir-containing therapy in protease inhibitor-experienced patients.

The response to regimens including lopinavir-ritonavir (LPV/r) in patients who have received multiple protease (PR) inhibitors (PI) can be analyzed in terms of human immunodeficiency virus type 1 (HIV-1) genotypic and pharmacokinetic (pK) determinants. We studied these factors and the evolution of HIV-1 resistance in response to LPV/r in a prospective study of patients receiving LPV/r under a temporary authorization in Bordeaux, France. HIV-1 PR and reverse transcriptase sequences were determined at baseline LPV/r for all the patients and at month 3 (M3) and M6 in the absence of response to treatment. pK measurements were determined at M1 and M3. Virological failure (VF) was defined as a plasma viral load >or=400 copies/ml at M3. A multivariate analysis of the predictors of VF, including clinical and biological characteristics and the treatment history of the patients, was performed. The PR gene sequence at M0, including individual mutations or a previously defined LPV mutation score (D. J. Kempf, J. D. Isaacson, M. S. King, S. C. Brun, Y. Xu, K. Real, B. M. Bernstein, A. J. Japour, E. Sun, and R. A. Rode, J. Virol. 75:7262-7269, 2001), and the individual exposure to LPV were also included covariates. Sixty-eight patients were enrolled. Thirty-four percent had a virological response at M3. An LPV mutation score of >5 mutations, the presence of the PR I54V mutation at baseline, a high number of previous PIs, prior therapy with ritonavir or indinavir, absence of coprescription of efavirenz, and a lower exposure to LPV or lower LPV trough concentrations were independently associated with VF on LPV/r. Additional PI resistance mutations, including primary mutation I50V, could be selected in patients failing on LPV/r. Genotypic and pK parameters should be used to optimize the virological response to LPV/r in PI-experienced patients and to avoid further viral evolution.

Adult↗
PubMed2001

Impact of protease inhibitors on intrahepatic hepatitis C virus viral load.

During chronic hepatitis C, hepatitis C virus (HCV) load in plasma was shown to be higher in HIV-co-infected than in immunocompetent patients [1]. The reason for this increased HCV replication is not known. It may be as a result of HIV-induced immune deficiency [2], although some authors did not find any correlation with the CD4 cell count [3]. A direct interaction between HCV and HIV was also hypothesized [4]. Protease inhibitors (PI) used in highly active antiretroviral therapy (HAART) have no HCV reduction effect during the first months of treatment [5-8]. However, a decrease in HCV plasma load was recently described in patients treated with HAART for a year [9,10]. We therefore investigated the potential impact of HAART on intrahepatic HCV load.

Adult↗
PubMed2001

Zidovudine genotypic resistance in HIV-1-infected newborns in the French perinatal cohort.

A retrospective study was set up to investigate the frequency of zidovudine (ZDV)-resistant HIV-1 in infected newborns after ZDV prophylaxis in the French Perinatal Cohort study. Nucleotide sequence analysis was carried out from 34 infants' isolates and 18 maternal plasma samples. Mutations related to ZDV resistance were found in the HIV-1 reverse transcriptase in 7 of 34 children (20%). Evidence of mother-child transmission of ZDV-resistant HIV-1 was found in 4 cases. Phylogenetic analysis showed that 14 of 34 HIV-1 isolates from the infants belonged to non-B subtypes. The presence of ZDV resistance-encoding mutations in the newborn isolates was associated with a longer total duration of exposure to ZDV. In a context of a wide HIV-1 variability, ZDV resistance can be one of the factors contributing to mother-child transmission.

Anti-HIV Agents↗
PubMed2001

Comparison of capillary electrophoresis sequencing with the new CEQ 2000 DNA Analysis System to conventional gel based systems for HIV drug resistance analysis.

To date the majority of sequencing technologies have been based on use of gel plates. In this study sequencing by capillary electrophoresis for HIV-1 genotyping on the CEQ 2000 sequencer (Beckman Coulter Inc.) has been investigated and compared to an 'in house' protocol on the Prism-377 sequencer (Applied Biosystems) and to the HIV-1 TruGene kit (Visible Genetics Inc.), two gel plate-based systems. Plasma from 20 HAART-treated patients with virological failure were analyzed for protease (PR) and reverse transcriptase (RT) genes. A total of 520 RT codons (26/patient) and 360 PR codons (18/patient) related to antiretroviral drug resistance were evaluated. The overall agreement between CEQ 2000 and Prism-377 results was 100% for the RT and PR primary and secondary mutations. The overall agreement between CEQ 2000 and TruGene was 100% for primary and > or =97% for secondary mutations. Discrepant results would have never led to errors in genotype interpretation. Performances for a 24 patients/week/one technician genotyping throughput were analyzed. For Prism-377, TruGene and CEQ 2000, manual processing required 5, 4 and 2,5 days, sequence data analysis needed additional 3, 1 and 2 days and cost/patient was approximately 49, 214 and 39 $, respectively. The CEQ 2000 sequencer offers a reliable alternative for fast and cost effective HIV drug resistance analysis.

Anti-HIV Agents↗
PubMed2001

High variability of HTLV-I in a remote population of Gabon as compared to that of a similar population of French Guiana.

An anomalous high frequency of ATL was observed in a remote 'noir maroons' village of French Guiana. Since it is not clear if HTLV-I is responsible for different frequencies of disease in different geographical areas, we undertook a comparison of the population with a similar one located in Gabon. We found a much higher degree of gp46 surface envelope glycoprotein sequence conservation in the Guianese village than in the Gabonese one.

Base Sequence↗
PubMed2001

Genotypic and phenotypic resistance patterns of human immunodeficiency virus type 1 variants with insertions or deletions in the reverse transcriptase (RT): multicenter study of patients treated with RT inhibitors.

Genomic rearrangements in the 5' part of the human immunodeficiency virus type 1 (HIV-1) reverse transcriptase (RT) have been involved in multidrug resistance to nucleoside RT inhibitors (NRTI). We carried out a retrospective, multicenter study to investigate the prevalence, variability, and phenotypic consequences of such rearrangements. Data concerning the HIV-1 RT genotype and the biological and clinical characteristics of NRTI-treated patients were collected from 10 virology laboratories. Sensitivities of the different HIV-1 variants to RT inhibitors were analyzed in a single-cycle recombinant virus assay. Fifty-two of 2,152 (2.4%) RT sequences had a rearrangement in the 5' part of the RT, with an extensive molecular variation. The number of codons inserted between positions 68 and 69 ranged from 1 (3 samples) or 2 (41 samples) to 5 and 11 in one case each. In four cases, codon 67 was deleted. High levels of phenotypic resistance to zidovudine (AZT), lamivudine (3TC), stavudine (d4T), abacavir (ABC), and didanosine (ddI) were found in 95, 92, 72, 62, and 15% of the 40 samples analyzed, respectively. Resistance to AZT, d4T, and ABC could be found in the absence of the T215Y/F mutations. Resistance to 3TC could develop in the absence of specific mutations. Low-level resistance to ddI was noticed in 40% of the patients. The deletions of codon 67 seemed to have little effect on NRTI sensitivity. Most of the rearrangements were shown to contribute to cross-resistance to NRTI. The results regarding susceptibility to ddI raise the question of the interpretation of the phenotypic data concerning this drug.

Drug Resistance, Microbial↗
PubMed2000

Cell-associated HIV-1-DNA quantitation after highly active antiretroviral therapy-treated primary infection in patients with persistently undetectable plasma HIV-1 RNA.

OBJECTIVE: To determine the usefulness of cell-associated HIV-1-DNA quantification during the follow-up of highly active antiretroviral therapy (HAART)-treated primary-infected patients with persistently undetectable plasma RNA loads. PATIENTS AND METHODS: In 27 patients given HAART within a median of 24 days after symptomatic primary HIV infection, plasma and peripheral blood mononuclear cell (PBMC) HIV-1 RNA were less than 50 copies/ml and less than 50 copies/10(6) cells after 18 months of treatment. HIV-1 RNA and DNA were quantified every 6 months in PBMC in these 27 patients, 14 of whom accepted excision lymph node biopsy after month 18 for HIV-1-RNA and -DNA quantification in lymph node mononuclear cells (LNMC). RESULTS: The median decreases in plasma HIV-1 RNA, PBMC HIV-1 RNA and DNA over the 18 months of follow-up were 3.6 log (P< 0.005), 1.1 log (P< 0.05), and 1.0 log (P<0.001), respectively. HIV-1 DNA was detected in 92.3% of PBMC samples at baseline and at month 18. In LNMC, 100% of samples were detectable for HIV-1 DNA. CONCLUSION: In this highly selected population of patients with excellent plasma virological response under HAART, HIV-1 DNA showed a progressive decrease but was still detectable in 92.3% of samples at month 18, whereas all LNMC samples tested scored positive for HIV-1 DNA. The utility of proviral HIV-1-DNA monitoring was not clearly demonstrated in this 18-month follow-up of HAART-treated primary-infected patients. However, this finding could be reconsidered when using other therapeutic strategies such as structured treatment interruptions, reinforced treatment or additive immunotherapy.

Adult↗
PubMed2000

New molecular assays to predict occurrence of cytomegalovirus disease in renal transplant recipients.

Thirty renal transplant recipients, after transplantation, were tested weekly with the following assays: cytomegalovirus (CMV) antigenemia (pp65 Ag), plasma qualitative Amplicor CMV (P-AMP), plasma and peripheral blood leukocyte quantitative Amplicor CMV monitor (P- and PBL-CMM), peripheral blood leukocyte (PBL) quantitative Quantiplex bDNA CMV, version 2.0 (bDNA), and whole-blood Nuclisens pp67 CMV (pp67). Eleven patients developed symptomatic CMV disease, and 7 developed asymptomatic CMV infection. For prediction of CMV disease, the sensitivity, specificity, and positive and negative predictive values, respectively, were as follows: 100%, 63%, 61%, and 100% for pp65 Ag; 100%, 42%, 50%, and 100% for bDNA; 91%, 47%, 50%, and 90% for PBL-CMM; 55%, 74%, 55%, and 74% for P-AMP; 55%, 74%, 55%, and 74% for P-CMM; and 64%, 79%, 64%, and 79% for pp67. First positive results in PBL were obtained 9-10 days before symptoms of CMV disease, compared with 5-6 days in plasma and 0 days in whole blood. PBL assays appear to be more appropriate than plasma assays when pre-emptive therapy is required to prevent the rapid progression from the first detection of the virus to CMV disease.

Adult↗
PubMed2000

HIV-1 diversity in France, 1996-1998. The AC 11 laboratory network.

OBJECTIVE: To study the distribution of HIV-1 subtypes in France and to describe the characteristics of patients infected with non-B subtypes. METHODS: All adults who tested HIV-1 positive on Western blot for the first time in one of the participating laboratories between September 1996 and March 1998 were eligible, whether or not they had been diagnosed previously elsewhere. Data on age, sex, country of birth, HIV-transmission group, dates of the last negative and first positive HIV test and clinical stage were collected. Serotyping was performed with a peptide subtype-specific enzyme immunoassay on each plasma sample and genotyping with heteroduplex mobility assay on each non-B serotype-infected patient. Patients characteristics were compared in B and non-B subtypes. RESULTS: Of the 2168 HIV-positive patients included by 32 laboratories, subtype,results were available for 2042. Among those, 73.4% were men, 12.2% born in sub-Saharan Africa, 41.5% infected through heterosexual contact and 67.6% in CDC stage A. Among the 2042 patients, 1 725 (84.5%) were infected with B subtype. Among the 317 non-B subtypes, subtype A was predominant (66.9%); all other subtypes (C, D, E, F, G, H, O) were present. Factors independently associated with a non-B subtype were to be included in the Paris area [adjusted odds ratio (aOR), 1.6; 95% confidence interval (CI), 1.1-2.3], to be born in sub-Saharan Africa (aOR, 26.0; 95% CI, 17.5-37.8) and to be infected through heterosexual contact (aOR, 4.2; 95% CI, 2.8-6.4). CONCLUSIONS: In France, although B subtype is still predominant, all non-B subtypes are now present. The diversity of HIV strains may affect diagnostic tests and clinical practice, especially viral load measurements. Moreover, the decreased susceptibility of non-B subtypes to antiretroviral drugs emphasizes the importance of surveillance of HIV diversity.

Adult↗
PubMed2000

Quantitation of hepatitis C virus RNA in plasma and peripheral blood mononuclear cells of patients with chronic hepatitis treated with interferon-alpha.

We quantified hepatitis C virus (HCV) RNA at different times in plasma and peripheral blood mononuclear cells (PBMC) in 51 patients with chronic hepatitis C undergoing interferon-alpha2a (IFN-alpha2a) therapy. HCV RNA loads in plasma correlated with those in PBMC before and during the treatment (P<0.001). After treatment, a sustained response was observed in 19 patients (SR), a response followed by relapse in 9 (RR), and non response in 23 (NR). By univariate analysis PBMC HCV RNA load before treatment was lower in SR than in RR and NR (P = 0.003). In the 9 RR, HCV RNA disappeared in PBMC before or at the same time as in plasma and again became detectable in plasma and PBMC simultaneously or earlier in plasma. These results indicate that quantitation of HCV RNA in PBMC is not a useful parameter for the follow-up of treated patients.

Adult↗
PubMed2000

TT virus infection during chronic hepatitis C.

OBJECTIVE: The pathogenic role of TT virus (TTV) is not well known, especially during chronic hepatitis C virus (HCV) infection. We retrospectively investigated the presence of TTV DNA in the plasma of patients with chronic HCV infection and compared the characteristics of TTV-DNA-positive and -negative groups. METHODS: Between November 1996 and November 1998, 234 patients were included. Inclusion criteria were persistently elevated serum alanine aminotransferase (ALT) levels, anti-HCV and HCV-RNA positivity, and seronegativity for hepatitis B virus and human immunodeficiency virus markers. TTV DNA was amplified in nested polymerase chain reaction with TTV-specific primers, and products were analyzed by agarose-gel electrophoresis. Data were analyzed using the chi2, Fisher's exact test, or Mann-Whitney test, as appropriate. RESULTS: TTV DNA was detected in 19 (8.1%; 95% confidence interval: 4.6-11.6%) patients. TTV-DNA-positive and TTV-DNA-negative patients did not differ statistically for age, gender ratio, source of HCV infection, HCV disease duration, biological parameters, histological grade, HCV-RNA load, or HCV genotype. Although nonsignificant (p = 0.21), there was a trend for a higher prevalence of TTV DNA in patients with an unknown cause of HCV infection (4/22, 18.2%) than in intravenous drug users (4/84; 4.8%), in those exposed to potential risk factors (4/49; 8.2%), or in those having received blood transfusion (7/79; 8.9%). CONCLUSIONS: Because the rates of HCV replication and the severity of liver lesions in TTV-DNA-negative and -positive patients were similar, the hepatic pathogenicity of TTV in chronic hepatitis C patients is questionable.

Adult↗