Publications (22)98.09 Total impact
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Article: Consistent high concentration of the viral microRNA BART17 in plasma samples from nasopharyngeal carcinoma patients - evidence of non-exosomal transport.
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ABSTRACT: BACKGROUND: Because latent Epstein Barr (EBV)-infection is a specific characteristic of malignant nasopharyngeal carcinoma (NPC), various molecules of viral origin are obvious candidate biomarkers in this disease. In a previous study, we could show in a few clinical samples that it was possible to detect a category of EBV microRNAs called miR-BARTs in the plasma of at least a fraction of NPC patients. The first aim of the present study was to investigate the status of circulating miR-BART17-5p (one of the miR-BARTs hereafter called miR-BART17) and EBV DNA in a larger series of NPC plasma samples. The second aim was to determine whether or not circulating miR-BART17 was carried by plasma exosomes. Patients and methods: Plasma samples were collected from 26 NPC patients and 10 control donors, including 9 patients with non-NPC Head and Neck squamous cell carcinoma and one healthy EBV carrier. Concentrations of miR-BART17 and two cellular microRNAs (hsa-miR-16 and -146a) were assessed by real-time quantitative PCR with spike-in normalization and absolute quantification. In addition, for 2 patients, exosome distributions of miR-BART17 and miR-16 were investigated following plasma lipoprotein fractionation by isopycnic density gradient ultrcentrifugation. RESULTS: The miR-BART17 was significantly more abundant in plasma samples from NPC patients compared to non-NPC donors. Above a threshold of 506 copies/mL, detection of miR-BART17 was highly specific for NPC patients (ROC curve analysis: AUC=0.87 with true positive rate = 0.77, false positive rate = 0.10). In this relatively small series, the concentration of plasma miR-BART17 and the plasma EBV DNA load were not correlated. When plasma samples were fractionated, miR-BART17 co-purified with a protein-rich fraction but not with exosomes. CONCLUSIONS: Detection of high concentrations of plasma miR-BART17 is consistent in NPC patients. This parameter is, at least in part, independent of the viral DNA load. Circulating miR-BART17 does not co-purify with exosomes.Virology Journal 04/2013; 10(1):119. · 2.34 Impact Factor -
Article: A cohort study of treatment-experienced HIV-1-infected patients treated with raltegravir: factors associated with virological response and mutations selected at failure.
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ABSTRACT: This study aimed to identify factors associated with virological response (VR) to raltegravir (RAL)-containing regimens in 468 treatment-experienced but integrase inhibitor-naive HIV-1 patients receiving a RAL-containing regimen. VR was defined at Month 6 (M6) as HIV-1 RNA viral load (VL) <50copies/mL. The impacts on VR of baseline integrase mutations, VL, CD4 count, genotypic sensitivity score for nucleoside reverse transcriptase inhibitors, non-nucleoside reverse transcriptase inhibitors and protease inhibitors, and the number of new antiretrovirals used for the first time associated with RAL were investigated. For patients with VL >50copies/mL at M6, integrase mutations selected were characterised. Median baseline VL was 4.2log10copies/mL (IQR 3.3-4.9log10copies/mL) and CD4 count was 219 cells/mm(3) (IQR 96-368 cells/mm(3)). At M6, 71% of patients were responders. In multivariate analysis, baseline VL and CD4 count and ≥2 new antiretrovirals among darunavir, etravirine, maraviroc and enfuvirtide were associated with VR to RAL. Neither HIV-1 subtype nor baseline integrase polymorphisms were associated with VR to RAL. Among 63 failing patients at M6, selection of ≥1 change in the integrase gene was observed in 49 (77.8%), and 27/63 (42.9%) were considered as RAL-associated resistance mutations. Factors independently associated with the occurrence of ≥1 RAL-associated resistance mutation were VL at failure >3log10 and having no new drugs associated with RAL. RAL showed great potency in treatment-experienced patients. The number of new drugs associated with RAL was an important factor associated with VR. HIV-1 subtype and baseline integrase polymorphisms do not influence the RAL VR.International journal of antimicrobial agents 04/2013; · 3.03 Impact Factor -
Article: CD8 Encephalitis in HIV-Infected Patients Receiving cART: A Treatable Entity.
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ABSTRACT: Background. Despite its overall efficacy, combined antiretroviral therapy has failed to control HIV infection of the central nervous system (CNS). New acute and chronic neurological complications are still being reported. Methods. We made a retrospective study of 14 HIV-infected patients with documented encephalitis, initially attributed to an undetermined origin, and brain MRIs uniformly revealing unusual, multiple linear gadolinium-enhanced perivascular lesions. Results. All the patients had manifested acute or subacute neurological symptoms, the brain MRIs indicating diffuse brain damage. The mean duration of HIV infection was about 10 years, and eight patients were immunovirologically stable. Cerebrospinal fluid abnormalities with mildly elevated protein, and pleocytosis with >90% lymphocytes, predominantly CD8, were found in all patients but one. The mean CSF HIV viral load was 5,949 copies/mL. Six patients reported a trivial infection a few days prior to neurological symptoms, two patients presented criteria for the immune reconstitution inflammatory syndrome of the CNS, two were in virological escape, and one developed encephalitis after interruption of cART. Brain biopsies revealed inflammatory encephalitis associated with astrocytic and microglial activation and massive perivascular infiltration by polyclonal CD8+ lymphocytes. All patients had been treated with glucocorticosteroids. The long term therapeutic response varied from excellent, with no sequalae (n=5), to moderate, with cognitive disorders (n=4). The mean survival time was 8 years; however, five of the patients died within 13 months of the initiation of treatment. Conclusion. CD8 encephalitis in HIV-infected patients receiving cART is a clinical entity that should be added to the list of HIV complications.Clinical Infectious Diseases 03/2013; · 9.15 Impact Factor -
Article: Changes in blood B cell phenotypes and Epstein-Barr virus load in chronically human immunodeficiency virus–infected patients before and after antiretroviral therapy.
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ABSTRACT: Switched and nonswitched memory B cells, which usually constitute the main reservoirs of Epstein‐Barr virus (EBV), are rapidly depleted in patients with chronic human immunodeficiency virus (HIV) infection. Because the EBV load is frequently increased in these patients, other B cell reservoirs might participate in EBV persistence. We examined the combined expression of CD27, SIgD/G/M, CD38, CD10, CD5, CXCR5, CD62L, CD44, and CXCR3 on B cells from healthy donors (n = 30) and from HIV type 1-infected patients (n = 23) at diagnosis and after highly active antiretroviral therapy. The plasma HIV load and the DNA EBV load in peripheral blood mononuclear cells were assessed. Increased frequencies of CD38+SIgD+CD10+ B cells were found in patients with an EBV load >10(3)copies per 10(6)peripheral blood mononuclear cells and a strong depletion of memory B cells. This phenotype resembles that of transitional B cell subsets. Elevated percentages of these B cells were still found in 2 patients showing no decrease in EBV load after highly active antiretroviral therapy. Because transitional-like B cells persist concomitantly with high EBV load after highly active antiretroviral therapy, we suggest that this population might be an alternative EBV reservoir in patients with chronic HIV infection who have strongly reduced numbers of memory B cells. The consequences of EBV infection of immature B cells are discussed with regard to B cell maturation and a higher prevalence of B cell lymphoma in HIV‐infected patients.The Journal of Infectious Diseases 11/2010; 202(9):1424-34. · 6.41 Impact Factor -
Article: Extra-cellular release and blood diffusion of BART viral micro-RNAs produced by EBV-infected nasopharyngeal carcinoma cells.
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ABSTRACT: Nasopharyngeal carcinoma (NPC) is a human epithelial malignancy consistently associated with the Epstein-Barr virus. The viral genome is contained in the nuclei of all malignant cells with abundant transcription of a family of viral microRNAs called BART miRNAs. MicroRNAs are well known intra-cellular regulatory elements of gene expression. In addition, they are often exported in the extra-cellular space and sometimes transferred in recipient cells distinct from the producer cells. Extra-cellular transport of the microRNAs is facilitated by various processes including association with protective proteins and packaging in secreted nanovesicles called exosomes. Presence of microRNAS produced by malignant cells has been reported in the blood and saliva of tumor-bearing patients, especially patients diagnosed with glioblastoma or ovarian carcinoma. In this context, it was decided to investigate extra-cellular release of BART miRNAs by NPC cells and their possible detection in the blood of NPC patients. To address this question, we investigated by quantitative RT-PCR the status of 5 microRNAs from the BART family in exosomes released by NPC cells in vitro as well as in plasma samples from NPC xenografted nude mice and NPC patients. We report that the BART miRNAs are released in the extra-cellular space by NPC cells being associated, at least to a large extent, with secreted exosomes. They are detected with a good selectivity in plasma samples from NPC xenografted nude mice as well as NPC patients. Viral BART miRNAs are secreted by NPC cells in vitro and in vivo. They have enough stability to diffuse from the tumor site to the peripheral blood. This study provides a basis to explore their potential as a source of novel tumor biomarkers and their possible role in communications between malignant and non-malignant cells.Virology Journal 10/2010; 7:271. · 2.34 Impact Factor -
Article: Factors predictive of virological failure on atazanavir in 310 HIV-infected patients.
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ABSTRACT: We examined factors associated with virological failure in 310 HIV-infected patients receiving atazanavir (ATV). Independent links were identified with virological failure under ATV: virological failure previous history (P = 0.006) and ATV underdosing (P = 0.04). A maintenance therapy was protective (P = 0.01). The optimal therapeutic ranges of ATV concentration were found to be from 300 ng/ml (or 180 for patients treated with maintenance therapy) to 650 ng/ml for C24 and from 1000 ng/ml (or 500 for patients treated with maintenance therapy) to 2000 ng/ml for C12.AIDS (London, England) 06/2010; 24(10):1593-5. · 4.91 Impact Factor -
Article: Discordance between cerebral spinal fluid and plasma HIV replication in patients with neurological symptoms who are receiving suppressive antiretroviral therapy.
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ABSTRACT: We report data on 11 patients with neurological symptoms and human immunodeficiency virus (HIV) cerebrospinal fluid (CSF) viremia contrasting with suppressed plasma HIV RNA during receipt of combined antiretroviral therapy. We retrospectively identified instances of central nervous system (CNS) symptoms in patients who had been receiving stable combination antiretroviral therapy. Discordance between plasma and CSF HIV RNA levels was defined by any detectable CSF HIV RNA level >200 copies/mL while plasma levels were <50 copies/mL or by a CSF HIV RNA level that was 1 log greater than the plasma HIV RNA level. Eleven patients had experienced acute or subacute neurological symptoms. All but one patient had CSF pleocytosis and/or elevated protein levels. The median CSF HIV RNA level was 880 copies/mL (range, 558-12,885 copies/mL). Patients had been receiving stable combination antiretroviral therapy for a median of 13 months (range, 10-32 months). Eight of 11 patients had a plasma HIV RNA level <50 copies/mL, and 3 had plasma HIV RNA blips with their CSF HIV RNA level >1 log higher than their plasma HIV RNA level. Resistance-associated mutations were detected in 7 of 8 CSF HIV RNA genotypic strains. The median number of resistance-associated mutations was 6 (range, 2-8) to nucleoside reverse-transcriptase inhibitors and 3 (range, 1-9) to protease inhibitors. One patient had a virus harboring nonnucleoside reverse-transcriptase inhibitor mutations. The median central nervous system penetration-effectiveness (CPE) rank was 2 (range, 1-3), and 5 patients had a CPE 1.5. After antiretroviral therapy optimization based on genotypes and CPE, all patients clinically improved, with normalization of CSF. Despite successful suppression of plasma viremia with antiretroviral therapy, HIV may replicate in CSF, with development of CSF HIV resistance resulting in acute or subacute neurological manifestations.Clinical Infectious Diseases 03/2010; 50(5):773-8. · 9.15 Impact Factor -
Article: Strong correlations of anti-viral capsid antigen antibody levels in first-degree relatives from families with Epstein-Barr virus-related lymphomas.
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ABSTRACT: Markers of Epstein-Barr virus (EBV) infection include anti-viral capsid antigen (VCA) immunoglobulin (Ig) G. High anti-VCA titers are associated with EBV-related lymphoproliferation, such as Burkitt lymphoma (BL) and Hodgkin lymphoma (HL). Intrafamilial correlations of anti-VCA IgG levels were studied in 3 settings: 127 families recruited through patients with HL in France (population A), 31 families recruited through patients with BL in Uganda (population B), and 74 large families from a general population in Cameroon (population C). Titers were determined by enzyme-linked immunosorbent assay (populations A and C) or by immunofluorescence analysis (population B). In populations A and B, the anti-VCA IgG titers of the relatives of patients with HL or BL increased significantly (P = .01 and P < .001, respectively) with those of the index case patient. In all 3 populations, anti-VCA IgG titers were significantly correlated (P < .001 for A, P = .002 for B, and P < .001 for C) between genetically related individuals (father-offspring, mother-offspring, and sibling-sibling) but not between spouses. Similar results were obtained for population A after adjustment for total IgG levels. In all cases, the pattern of correlations was consistent with a polygenic model, with heritability ranging from 0.32 to 0.48. These results provide evidence for the genetic control of anti-VCA IgG titers and pave the way for identification of the loci involved.The Journal of Infectious Diseases 05/2009; 199(8):1121-7. · 6.41 Impact Factor -
Article: Epstein-Barr virus load in whole blood correlates with HIV surrogate markers and lymphoma: a French national cross-sectional study.
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ABSTRACT: An abstract is unavailable. This article is available as HTML full text and PDF.JAIDS Journal of Acquired Immune Deficiency Syndromes 05/2009; 50(4):427-9. · 4.43 Impact Factor -
Article: Tipranavir-ritonavir genotypic resistance score in protease inhibitor-experienced patients.
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ABSTRACT: To identify mutations associated with the virological response (VR) to a tipranavir-ritonavir (TPV/r)-based regimen, 143 patients previously treated with protease inhibitor (PI) were studied. VR was defined by a decrease of at least 1 log(10) in, or undetectable, human immunodeficiency virus (HIV) RNA at month 3. The effect of each mutation in the protease, considering all variants at a residue as a single variable, on the VR to TPV/r was investigated. Mutations at six residues were associated with a lower VR (E35D/G/K/N, M36I/L/V, Q58E, Q61D/E/G/H/N/R, H69I/K/N/Q/R/Y, and L89I/M/R/T/V), and one mutation was associated with a higher VR (F53L/W/Y). The genotypic score M36I/L/V-53L/W/Y + Q58E + H69I/K/N/Q/R/Y + L89I/M/R/T/V was selected as providing a strong association with VR. For the seven patients with a genotypic score of -1 (viruses with only mutation at codon 53), the percentage of responders was 100% and the percentages were 79%, 56%, 33%, 21%, and 0% for those with scores of 0, 1, 2, 3, and 4, respectively. The percentage of patients showing a response to TPV/r was lower for patients infected with non-clade B viruses (n = 16, all non-B subtypes considered together) than for those infected with clade B viruses (n = 127) (25% and 59%, respectively; P = 0.015). Most mutations associated with VR to TPV/r had not previously been associated with PI resistance. This is consistent with phenotypic analysis showing that TPV has a unique resistance profile. Mutations at five positions (35, 36, 61, 69, and 89) were observed significantly more frequently in patients infected with a non-B subtype than in those infected with the B subtype, probably explaining the lower VR observed in these patients.Antimicrobial Agents and Chemotherapy 08/2008; 52(9):3237-43. · 4.84 Impact Factor -
Article: Hepatitis B escape mutant reactivation in a renal transplant patient.
Journal of Clinical Virology 10/2007; 40(1):74-6. · 3.97 Impact Factor -
Article: Association of killer cell immunoglobulin-like receptor genes with Hodgkin's lymphoma in a familial study.
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ABSTRACT: Epstein-Barr virus (EBV) is the major environmental factor associated with Hodgkin's lymphoma (HL), a common lymphoma in young adults. Natural killer (NK) cells are key actors of the innate immune response against viruses. The regulation of NK cell function involves activating and inhibitory Killer cell Immunoglobulin-like receptors (KIRs), which are expressed in variable numbers on NK cells. Various viral and virus-related malignant disorders have been associated with the presence/absence of certain KIR genes in case/control studies. We investigated the role of the KIR cluster in HL in a family-based association study. We included 90 families with 90 HL index cases (age 16-35 years) and 255 first-degree relatives (parents and siblings). We developed a procedure for reconstructing full genotypic information (number of gene copies) at each KIR locus from the standard KIR gene content. Out of the 90 collected families, 84 were informative and suitable for further analysis. An association study was then carried out with specific family-based analysis methods on these 84 families. Five KIR genes in strong linkage disequilibrium were found significantly associated with HL. Refined haplotype analysis showed that the association was supported by a dominant protective effect of KIR3DS1 and/or KIR2DS1, both of which are activating receptors. The odds ratios for developing HL in subjects with at least one copy of KIR3DS1 or KIR2DS1 with respect to subjects with neither of these genes were 0.44[95% confidence interval 0.23-0.85] and 0.42[0.21-0.85], respectively. No significant association was found in a tentative replication case/control study of 68 HL cases (age 18-71 years). In the familial study, the protective effect of KIR3DS1/KIR2DS1 tended to be stronger in HL patients with detectable EBV in blood or tumour cells. This work defines a template for family-based association studies based on full genotypic information for the KIR cluster, and provides the first evidence that activating KIRs can have a protective role in HL.PLoS ONE 02/2007; 2(5):e406. · 4.09 Impact Factor -
Article: Virologic and immunologic efficacy of the tenofovir/didanosine/lamivudine regimen.
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ABSTRACT: An abstract is unavailable. This article is available as HTML full text and PDF.JAIDS Journal of Acquired Immune Deficiency Syndromes 08/2006; 42(3):389-90. · 4.43 Impact Factor -
Article: Positive correlation between Epstein-Barr virus viral load and anti-viral capsid immunoglobulin G titers determined for Hodgkin's lymphoma patients and their relatives.
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ABSTRACT: Markers of Epstein-Barr virus (EBV) infection include measures of specific serological titers and of viral load (VLo) in peripheral blood mononuclear cells. Few studies have investigated the correlation between these two phenotypes. Here, we found that there was no correlation between VLo and either anti-EBV nuclear antigen type 1 or anti-early antigen immunoglobulin G (IgG) titer but that anti-viral capsid antigen (VCA) IgG titer increased with VLo in peripheral blood mononuclear cells in patients with Hodgkin's lymphoma (P = 3.10(-3)). A similar pattern was observed in healthy first-degree relatives (parents and siblings) of patients (P = 6.10(-4)). Our results indicate that anti-VCA IgG titers and EBV VLo are specifically correlated EBV phenotypes.Journal of Clinical Microbiology 02/2006; 44(1):47-50. · 4.15 Impact Factor -
Article: A new insertion in the HIV-1 reverse transcriptase gene inducing major resistance to non-nucleoside reverse transcriptase inhibitors.
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ABSTRACT: We identified an HIV-1 isolate with a 3 base pairs insertion in the 100-105 region of the reverse transcriptase gene (RT) along with a G190E and a V75A mutation. Virus carrying the insertion alone or in association with G190A was not infectious. The association of G190E and the 100-105 insertion displayed a high level of resistance to non-nucleoside reverse transcriptase inhibitors; the addition of the insertion to G190E may increase the activity of RT.AIDS 12/2005; 19(16):1922-4. · 6.24 Impact Factor -
Article: Early impairment of CD8+ T cells immune response against Epstein-Barr virus (EBV) antigens associated with high level of circulating mononuclear EBV DNA load in HIV infection.
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ABSTRACT: Immunodeficiency related to HIV may increase the incidence of EBV-associated lymphomas, by altering EBV-specific immune control and consequently favoring EBV reactivation. The aim of the present study was to assess the relationship between the decrease of EBV-specific cellular immunity and the increase of EBV reactivation in a prospective cohort of 72 unselected HIV-infected individuals. EBV-specific immunity was evaluated by a highly sensitive IFN-gamma ELISPOT assay using 22 peptides mimicking latent and lytic antigens, and circulating mononuclear (PBMC) EBV DNA load was quantified by real-time quantitative PCR. The mean circulating cell-associated EBV DNA load was higher in HIV-infected patients (639 copies/10(6) PBMC) than in healthy controls (21, n = 14) ( P = 0.005) and was higher in patients with CD4(+) T-cell count below 350/microL than that in patients harboring higher CD4(+) T-cell count (1112 vs. 389, P = 0.003). The mean intensity of EBV-specific cellular responses was lower in HIV-infected patients than in controls ( P = 0.001), even in patients with CD4(+) T-cell count above 350/-microL ( P = 0.007). The number of EBV peptides recognized was lower in HIV-infected patients than in controls (frequency: 0.44 vs. 0.67; P = 0.02), indicating reduced polyclonality in HIV-infected patients. The polyclonality was 1.5-fold lower in HIV-infected patients with CD4(+) T-cell count below 350/-microL ( P =0.007). For EBV load >1000 copies/10(6) PBMC, the levels of cell-associated EBV DNA and those of EBV-specific cellular immunity, either in intensity or in polyclonality, or both, were inversely correlated. These findings demonstrate early impairment of the EBV-specific cellular immune control with progressive increase of EBV reactivation in the course of HIV infection. These observations likely provide a basis for appreciating the risk to develop non-Hodgkin's lymphomas in HIV-infected individuals.Journal of Clinical Immunology 03/2004; 24(2):125-34. · 3.08 Impact Factor -
Article: A phase I study of a six-week cycle of immunotherapy with Murabutide in HIV-1 patients naive to antiretrovirals.
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ABSTRACT: Limitations in the use of antiretroviral therapy suggest the need for additional approaches to enhance immune restoration and the control of HIV-1 replication. Therefore, we evaluated the clinical tolerance and biological effects of immunotherapy with the synthetic immunomodulator Murabutide in 9 treatment-naive HIV-1 patients presenting with CD4+ lymphocyte counts >500 cells/mm3 and plasma viral loads <30.000 copies/ml. Murabutide was administered at a daily dose of 7 mg on 5 consecutive days per week, for a period of 6 weeks. The study duration extended over 22 weeks, and clinical, virological, and immunological evaluations were carried out on 2 occasions before, during, and after immunotherapy. With acceptable clinical tolerance and only 2 reversible grade III adverse events, clinical and virological parameters remained highly stable throughout the study period. However, maintained or improved lymphoproliferative responses to several recall and HIV-1 antigens, as well as modest but significant increases in the percentages of naive cells were noted during or/and after immunotherapy. These changes could not be demonstrated in an observation group of 9 additional patients who were identically followed for a 22-week period. Our results suggest that non-specific immunotherapy targeting dysfunctions in innate immunity could bring about restoration of immune responses in HIV disease.Medical science monitor: international medical journal of experimental and clinical research 06/2003; 9(6):PI43-50. · 1.70 Impact Factor -
Article: Clinical and immunological effects of a 6 week immunotherapy cycle with murabutide in HIV-1 patients with unsuccessful long-term antiretroviral treatment.
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ABSTRACT: In an effort to evaluate the potential of non-specific immunotherapy in restoring global immunity, we have examined the clinical tolerance and biological effects of a 6 week administration of the immunomodulator, murabutide, in chronically infected HIV-1 patients. Forty-two subjects, presenting weak immune reconstitution and ineffective virus suppression following long-term highly active antiretroviral therapy (HAART), were randomized to receive, or not, murabutide 7 mg/day on five consecutive days/week. Clinical and immunological parameters were monitored before and after the immunotherapy period. Administration of murabutide was generally well tolerated, although some grade III adverse events, reversible on treatment cessation, were observed. Interestingly, in comparison with pre-inclusion levels, at 1 week after the immunotherapy cycle, only murabutide recipients presented a significant increase in CD4 cells, platelet counts, and in the percentage of patients with undetectable viral loads (<50 copies/mL). Statistical significance between the two groups was only evident with the latter parameter. Some of these clinical changes were maintained even up to 12 weeks after murabutide administration, and were accompanied by an increased ability to mount cellular responses to active immunization with a recall antigen, and by a significant increase in the percentage of patients presenting positive lymphoproliferative responses to the viral antigen gp160. These results warrant further evaluation of extended periods or cycles of murabutide immunotherapy as adjunct to HAART.Journal of Antimicrobial Chemotherapy 06/2003; 51(6):1377-88. · 5.07 Impact Factor -
Article: High variability of plasma drug concentrations in dual protease inhibitor regimens.
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ABSTRACT: Ritonavir (RTV) strongly increases the concentrations of protease inhibitors (PIs) in plasma in patients given a combination of RTV and another PI. This pharmacological interaction is complex and poorly characterized and shows marked inter- and intraindividual variations. In addition, RTV interacts differently with saquinavir (SQV), indinavir (IDV), amprenavir (APV), and lopinavir (LPV). In this retrospective study on 542 human immunodeficiency virus-infected patients, we compared inter- and intraindividual variability of plasma PI concentrations and correlations between the C(min) (minimum concentration of drug in plasma) values for RTV and the coadministered PI C(min) values. Mean RTV C(min)s are significantly lower in patients receiving combinations containing APV or LPV than in combinations with SQV or IDV. With the most common PI dose regimens (600 mg of IDV twice a day [BID], 800 mg of SQV BID, and 400 mg of LPV BID), the interindividual C(min) variability of patients treated with a PI and RTV seemed to be lower with APV and LPV than with IDV and SQV. As regards intraindividual variability, APV also differed from the other PIs, exhibiting lower C(min) variability than with the other combinations. Significant positive correlations between RTV C(min) and boosted PI C(min) were observed with IDV, SQV, and LPV, but not with APV. Individual dose adjustments must take into account the specificity the pharmacological interaction of each RTV/PI combination and the large inter- and intraindividual variability of plasma PI levels to avoid suboptimal plasma drug concentrations which may lead to treatment failure and too high concentrations which may induce toxicity and therefore reduce patient compliance.Antimicrobial Agents and Chemotherapy 04/2003; 47(3):986-90. · 4.84 Impact Factor -
Article: Clinical tolerance and immunologic effects after single or repeated administrations of the synthetic immunomodulator murabutide in HIV-1-infected patients.
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ABSTRACT: Correction of the virus-induced deficits in innate immunity of HIV-infected subjects could well contribute to enhanced immune recovery and efficacious control of viral replication. The safe synthetic immunomodulator Murabutide (ISTAC Biotechnology, Lille, France) has been found to regulate the function of antigen-presenting cells and to selectively activate CD4 lymphocytes leading to dramatic suppression of HIV replication, in vitro. Therefore, as a first step toward the evaluation of the immunotherapeutic potential of Murabutide in HIV disease, we have conducted two phase 1/2 clinical trials to address the safety and the immunologic effects of Murabutide administration into HIV-infected subjects receiving antiretroviral therapy. The first study revealed that single administration of 5, 7, or 9 mg of Murabutide, to 6 patients per dose, was well tolerated. This was accompanied by a selective induction of cytokines and chemokines detectable in the serum, and the levels appeared to plateau at the 7-mg dose. The second study then evaluated the safety and biological effects of repeated administrations of 7 mg Murabutide, on 5 consecutive days, in 12 HIV-1-infected patients. A good clinical tolerance was noted throughout the study. Moreover, changes in several immune parameters, including downregulation of coreceptor expression on lymphocytes and improved lymphoproliferative responses, were detected during or/and up to 3 weeks after Murabutide administration. These encouraging results warrant further evaluation of longer periods or cycles of immunotherapy with Murabutide in HIV-infected subjects.JAIDS Journal of Acquired Immune Deficiency Syndromes 08/2002; 30(3):294-305. · 4.43 Impact Factor
Top co-authors
Top Journals
Institutions
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2006
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Université René Descartes - Paris 5
- Génétique Humaine des Maladies Infectieuses (UMR_S 980)
Paris, Ile-de-France, France
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2004
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Hôpital européen Georges-Pompidou – Hôpitaux universitaires Paris-Ouest
Paris, Ile-de-France, France
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