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Biomedical subjects

H J Fleury

Publications and source records attributed to H J Fleury.

At least 19 recordsLinked to original sources
PubMed2001

Mechanism of virologic failure after substitution of a protease inhibitor by nevirapine in patients with suppressed plasma HIV-1 RNA.

A prospective study was set up to evaluate the emergence of HIV-1 resistance after a switch from an effective protease inhibitor (PI)-containing regimen to a multitherapy regimen including nevirapine (NVP). After 6 months with an undetectable viral load under a PI-containing regimen, the patients were switched to NVP with conservation of the associated nucleoside reverse transcriptase inhibitors (NRTIs). Patients were followed-up at 1 month and then every 3 months after switching therapy. Nucleotide sequence analysis of the pol gene was performed at the first points of virologic failure. Thirty-four patients were included. The NRTI-naive group (22 patients) had begun antiretroviral therapy with a PI-containing regimen, whereas 12 patients (experienced group) had been previously treated by nucleoside mono-and/or dual therapy. After a median follow-up of 40 weeks, no patient of the naive group, versus 41% of the experienced group, developed a virologic failure after the change toward NVP ( p =.003). The virologic failures were associated with the appearance of NNRTI-resistant mutations. All rebound mutants also presented NRTI-resistance mutations. These results are consistent with a higher risk of virologic failure after a switch to an NNRTI in patients with prior suboptimal treatment and suggest the hypothesis that archived resistant viruses may facilitate the emergence of NNRTI resistance.

Anti-HIV Agents↗
PubMed2001

Sequence analysis of env C2/V3, gag p17/p24, and pol protease regions of 25 HIV type 1 isolates from Ho Chi Minh City, Vietnam.

Env C2/V3, gag p17/p24, pol protease, and RT regions of HIV-1 isolates recently obtained from 25 HIV-1 seropositive individuals from Ho Chi Minh City (Vietnam) were studied, and genes subtypes were determined by DNA sequence analyses. Twenty-three isolates out of 25 were identified as belonging to subtype E, now recognized as circulating recombinant form 1 (CRF01_AE). The motif at the top of the V3 loop (generally GPGQ) was then preceded by an isoleucine or a methionine (M) residue; the M residue might be a local signature of Vietnamese E isolates compared to Thai E viruses. Two isolates (8%) were shown to be intersubtype recombinants: one E/B and one CRF02_AG(IBNG)/D. The polymorphism of pol protease was considered only for CRF01_AE isolates and is clearly different from that recorded for B viruses with substitutions at positions 13, 35, 36, 41, 69, and 89.

Adolescent↗
PubMed2001

Qualitative and quantitative molecular detection of enteroviruses in water from bathing areas and from a sewage treatment plant.

Pathogenic enteric viruses can be introduced into the environment as a result of human activities. Enteroviruses are regularly detected in environmental waters or shellfish and can provoke potentially serious diseases. Some authors believe that enteroviruses could represent an interesting indicator of viral contamination in the environment. Since molecular approaches seem to be promising for the detection of these viruses, we developed a simple qualitative RT-PCR procedure for enteroviruses, together with a quantitative RT-PCR assay using RNA internal standard. After one-tube-RT-PCR, this standard and wild enterovirus RNA were detected by differential hybridization with specific probes and a fluorimetric reaction. The quantification of enteroviruses, conducted in a sewage treatment plant, showed a decreasing number of genomic copies from the entrance to the exit (from 3.8 x 10(5) to 5.4 x 10(4) RNA copies/mL) but indicated the presence of enterovirus RNA in the neighboring river (2.2 x 10(3) RNA copies/mL). In bathing areas, enterovirus RNA was detected in 16 out of 226 samples, with copies numbers ranging from 3.7 x 10(2) RNA copies/mL to 7 x 10(4) RNA copies/mL.

Bathing Beaches↗
PubMed2001

Pharmacokinetics and resistance mutations affect virologic response to ritonavir/saquinavir-containing regimens.

The authors assessed the impact of protease and reverse transcription (RT) mutations and individual pharmacokinetic parameters on virologic response to a four-drug regimen including ritonavir/saquinavir. Treatment was given at the start of the study (M0) to 22 HIV-1 protease inhibitor-naive or pretreated patients. Protease and RT genes were sequenced at M0, at the time of virologic failure, or at the end of the follow-up. Plasma ritonavir and saquinavir peak C(max), C(min), and area under the curve (AUC) were determined based on samples taken 0, 1, 2, 3, 4, 6, 8, and 12 hours after administration. HIV-1 RNA decreased to less than 50 copies/mL in 11 patients (group 1). At M0, five of them had no RT mutation and 10 had three or fewer secondary protease mutations with no new mutation during follow-up. Ritonavir and saquinavir pharmacokinetics showed wide interindividual variability. Treatment failed in 11 patients (group 2): 9 had three to eight protease mutations and a mean of 5.8 RT mutations at M0, with emergence of new mutations during follow-up. Pharmacokinetics was similar to those of group 1. The other two patients with virologic failure showed no baseline primary mutation but were the only patients with insufficient saquinavir and ritonavir AUC. The authors showed the complementarity between drug-resistance genotype and individual pharmacokinetics and the potential utility of AUC and Cmax to manage treatment.

CD4 Lymphocyte Count↗
PubMed2001

Hepatitis C virus genotyping based on 5' noncoding sequence analysis (Trugene).

Hepatitis C virus (HCV) genotyping of samples from 184 patients with chronic HCV infection by the Trugene 5'NC genotyping kit, based on sequence analysis of the 5' noncoding region (5' NCR), and the InnoLiPA assay was evaluated. In addition to these methods, the 184 samples were also analyzed by sequencing of part of the NS5B of the HCV genome after in-house PCR amplification, as a means of validating results obtained with the 5' NCR. The distribution of the genotypes typed by NS5B sequence analysis was as follows: 1a, 41 samples; 1b, 58 samples; 1d, 1 sample; 2a, 5 samples; 2b, 2 samples; 2c, 7 samples; 3a, 46 samples; 4a, 7 samples; 4c, 1 samples; 4e, 9 samples; 5a, 6 samples; 6a, 1 sample. The Trugene and InnoLiPA assays gave concordant results within HCV types in 100% of cases. The ability to discriminate at the subtype level was 76 and 74% for the Trugene and the InnoLiPA assays, respectively.

5' Untranslated Regions↗
PubMed2000

PCR detection of human enteric viruses in bathing areas, waste waters and human stools in Southwestern France.

Detection of human pathogenic viruses by molecular techniques might be suitable for identifying viral pollution in environmental waters and for improving diagnosis in patients. Environmental samples were taken from bathing areas and sewage treatment plants in southwestern France. Small volume samples (50 microL) were tested. Five groups of enteric pathogenic viruses were studied: enteroviruses, Norwalk-like viruses (NLVs), hepatitis A virus, rotaviruses and adenoviruses. Moreover, human samples were tested for NLV. After extraction of viral nucleic acids (Boom's procedure), a nested polymerase chain reaction was conducted before hybridization. Five bathing waters out of 26 were positive for one viral group, without systematic association with bacterial contamination. Eight sewage plant samples out of 13 were positive for at least one viral group. Seven patients out of 45 were NLV-positive. Molecular techniques allow efficient screening of viral contamination in environmental waters and the study of NLV molecular epidemiology.

Adenoviridae↗
PubMed2000

Hepatitis B exacerbation with a precore mutant virus following withdrawal of lamivudine in a human immunodeficiency virus-infected patient.

Chronic active hepatitis B exacerbations have been reported following development of resistance to or withdrawal of lamivudine in HIV-infected patients. A 38-year-old woman with HIV and chronic HBV infections was hospitalized because of acute hepatitis. The occurrence of cytolysis with replication of HBV 2 months after withdrawing lamivudine suggests that our patient experienced a severe reactivation of HBV infection due to the modification of her treatment. Sequencing of the HBV precore region showed the strain to be a mutant. We conclude that lamivudine should not be stopped in HIV- and HBV-infected patients, but could be continued at the dose of 100mg/day as used in isolated HBV infection.

Adult↗
PubMed1999

Human polyomavirus JC latency and reactivation status in blood of HIV-1-positive immunocompromised patients with and without progressive multifocal leukoencephalopathy.

BACKGROUND: Human polyomavirus JC (JCV) induces human progressive multifocal leukoencephalopathy (PML) in patients with AIDS. Peripheral blood mononuclear cells (PBMC) of HIV-1-positive immunocompetent and immunocompromised patients can harbour JCV genome, but their precise role in JCV latency or reactivation status before the onset of PML remains hypothetical. OBJECTIVES: To assess JCV latency or reactivation status in PBMC of HIV-1-positive immunocompromised patients without PML. DESIGN: A group of 82 HIV-1-positive immunocompromised patients who did not have PML were compared with 10 patients with AIDS and PML and with 69 HIV-1-positive immunocompetent patients without PML. METHODS: DNA and total RNA were extracted from PBMC. The presence of JCV DNA was demonstrated by a semi-nested polymerase chain reaction (PCR). By using primer pairs specific for an early gene,T, and a late gene, VP1, the expression of both early and late gene mRNA in PBMC could be identified using reverse transcriptase (RT) PCR. RESULTS: JCV DNA was detected by PCR in 17.4% of 69 HIV-1-positive immunocompetent patients, in 23.2% of 82 HIV-1-positive immunocompromised patients, and in 60% of 10 patients with AIDS and PML. No correlation could be drawn between the detection of JCV DNA in the PBMC and the clinical or biological status of the HIV-1-positive patients. By using RT-PCR procedures, no expression of JCV early and late mRNA in PBMC was found in any patients. CONCLUSIONS: JCV DNA is detectable in the PBMC of 20.5% of 151 HIV-1-infected patients independently of the CDC (Centers for Disease Control and Prevention) stages of the infection. Moreover, our results suggest that active replication of JCV in PBMC appears to be absent or at least a very rare event in HIV-1-positive immunocompromised patients with and without PML.

Acquired Immunodeficiency Syndrome↗
PubMed1999

Effect of nucleoside analogs and non-nucleoside inhibitors of HIV-1 reverse transcriptase on cell-free virions.

Reverse transcription takes place in the cytoplasm of infected cells, although it has been demonstrated that retroviruses can also initiate reverse transcription prior to infection of target cells. In addition to partial reverse transcripts, full-length proviral molecules have been detected in the plasma and seminal fluid of HIV-1 seropositive patients. Intravirion endogenous reverse transcription appears to be directly correlated with an increased level of infectivity. Therefore, the ability of an inhibitor to reach and inhibit the replication complex in the core of the free-virion may constitute an important part of its capacity to suppress viral infection. In this work we tested the ability of some reverse transcriptase inhibitors to decrease viral infectivity in pretreated highly purified virions. Our results showed that Curie pyridinone [Dollé et al. (1995), J Med Chem 38: 4,679-4,686], a non nucleoside RT inhibitor, strongly inhibited the infectivity of extracellular HIV-1 particles. Other non nucleoside inhibitors (TIBO R82913, HEPT, nevirapine) tested in these conditions were unable to do so. Our data indicate that the effect of Curie pyridinone on intact virions may be related to its capacity to tightly bind the target RT. This approach may lead to the design and synthesis of new drugs able to interact with the retroviral enzyme inside the viral core.

Anti-HIV Agents↗
PubMed1999

A hospital outbreak of gastroenteritis possibly related to the contamination of tap water by a small round structured virus.

Small round structured viruses (SRSVs) are a major cause of gastroenteritis in institutions and sensitive new molecular techniques allow rapid diagnosis and the establishment of control measures. In January 1999, a 10 day-long outbreak of gastroenteritis in a re-education ward, was reported by a hospital hygiene department. A potential common source of contamination was tap water. The stools of six patients with gastroenteritis and seven tap water samples from the hospital ward, were tested for SRSV by reverse transcription and polymerase chain reaction (RT-PCR): three stools and four water samples, all bacteriologically negative, were SRSV-positive. Nucleotide sequencing of a fragment of the SRSV polymerase gene showed that the sequences of the positive samples (two patients and four water samples) were identical (genogroup II). We cannot exclude interhuman transmission of SRSV together with viral soiling of some taps in the ward, but this hospital infection was more likely due to the transient contamination of the ward supply of drinking water with a SRSV strain.

Caliciviridae Infections↗
PubMed1999

Clinical and biological characteristics of human immunodeficiency virus-infected and uninfected intravascular drug users in Ho Chi Minh City, Vietnam.

To define the medical characteristics of intravascular drug users in Ho Chi Minh City, Vietnam, we examined 280 men, of whom 235 were infected with human immunodeficiency virus (HIV), being treated in a rehabilitation center. The patients used mainly opium, often in shooting galleries (50%). The prevalence of oral candidiasis (58%) and zoster infection (20%) was high in HIV-seropositive patients, whereas oral hairy leukoplasia and Kaposi's sarcoma were absent. The prevalence of acquired immunodeficiency syndrome was 24%. More than 80% of the patients had infections with hepatitis C virus, hepatitis B virus, cytomegalovirus, or human T cell lymphotropic virus type-1. The CD4+ cell counts correlated well with viral load. Only HIV-1 subtype E was detected in the 30 patients tested. A cohort study of HIV-infected subjects in this population seems feasible, and would permit introduction of anti-retroviral therapy The large number of HIV-seronegative subjects sharing the same at-risk practices as the HIV-infected subjects raises the possibility of natural protection in this population.

AIDS-Related Opportunistic Infections↗
PubMed1999

Zidovudine resensitization and dual HIV-1 resistance to zidovudine and lamivudine in the delta lamivudine roll-over study.

OBJECTIVE: To study zidovudine resensitization and dual resistance to zidovudine/lamivudine in HIV-1 isolates from nucleoside reverse transcriptase (RT) inhibitor-experienced patients during selective pressure exerted by zidovudine/lamivudine combination therapy. DESIGN AND METHODS: HIV-1 isolates from 29 patients receiving zidovudine/lamivudine combination therapy in the Delta roll-over study were analysed at entry and during a 1 year follow-up period for phenotypic susceptibility to zidovudine and lamivudine in the ANRS PBMC assay. The RT gene from codon 20 to 230 and at codon 333 was analysed by nucleotide sequencing of the corresponding isolates. RESULTS: HIV-1 isolates from 23 of the 29 patients were phenotypically resistant to zidovudine at baseline; 61% of these patients showed significant zidovudine resensitization during follow-up. The zidovudine IC50 value correlated positively with log10 plasma HIV-1 RNA (P = 0.02) and negatively with the CD4 cell count (P = 0.004). Zidovudine resensitization (related to acquisition of the M184V mutation) was transient, with evolution towards dual resistance to zidovudine and lamivudine in 20 of the 29 patients. The phenotype of certain dually resistant isolates coincided with the emergence of multiple mutations in the 5' part of the RT gene. CONCLUSIONS: M184V-mediated zidovudine resensitization of HIV-1 is transient in most patients who are given zidovudine/lamivudine combination therapy when zidovudine resistance has already emerged. The subsequent evolution towards dual phenotypic resistance to zidovudine/lamivudine corresponds to complex genotypic profiles.

Anti-HIV Agents↗
PubMed1998

Foscarnet decreases HIV-1 plasma load.

OBJECTIVE: To evaluate the effect of foscarnet on HIV-1 replication in vivo. PATIENTS AND METHODS: Seventeen AIDS patients with cytomegalovirus (CMV), herpes simplex virus (HSV), varicella-zoster virus (VZV) infection, Kaposi's sarcoma (KS), or a combination of these were treated with foscarnet. HIV RNA quantification (bDNA 2.0, Chiron, Emeryville, CA, U.S.A.), CMV pp65 antigenemia (Argene Biosoft, Varilhes, France), and CMV viremia were determined before and during therapy. RESULTS: Four patients had CMV retinitis (1 with KS), 2 patients had CMV pneumonia (1 with KS), 1 patient had CMV cholecystitis, 2 patients had VZV infection (1 with KS), 1 patient had HSV-2 infection, and 7 patients had KS alone. The decrease in HIV-1 load was -0.73 +/- 0.39 log copies/ml (p = 2.10(-6)) after 3 days of treatment and -1.15 +/- 0.49 log copies/ml (p < 10(-7)) after 10 days of treatment, compared with day 0. Furthermore, reduction of HIV-1 plasma load during foscarnet therapy did not depend on the presence or absence of CMV disease or on a positive pp65 antigenemia at day 0. CONCLUSION: We observed decreased HIV-1 plasma load in all patients treated with foscarnet, regardless of presence or absence of clinical or biologic CMV infection. This decrease supports the proposition that foscarnet anti-HIV-1 activity may be of clinical importance.

Acquired Immunodeficiency Syndrome↗
PubMed1998

JC virus remains latent in peripheral blood B lymphocytes but replicates actively in urine from AIDS patients.

JC virus (JCV) is thought to reach the central nervous system by a vascular route. To determine whether JCV is conveyed in peripheral blood as latent or reactivated virus, blood leukocytes, plasma, and urine from 50 AIDS patients and plasma and B lymphocytes from 60 AIDS patients were investigated. Peripheral blood from 88 human immunodeficiency virus-negative blood donors was studied. Nested polymerase chain reaction assays allowed the identification of JCV T DNA and VP1 mRNAs. The latter indicate viral replication. Blood harbored JCV DNA in 31.8% of AIDS patients (only 2.3% of blood donors; P > .001) and urine in 56%. VP1 mRNAs were detected in blood of 1 AIDS patient. Notably, 38% of DNA-positive urine samples and 10 cerebrospinal fluid samples (CSF) from AIDS patients with progressive multifocal leukoencephalopathy contained JCV mRNAs. Thus, JCV was significantly more frequent in blood from AIDS patients than from controls, but, in most instances, it was latent, whereas active replication was detected in urine and CSF.

Acquired Immunodeficiency Syndrome↗