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Y Mouton

Publications and source records attributed to Y Mouton.

At least 37 records · Page 2Linked to original sources
PubMed2003

A novel cellular RNA helicase, RH116, differentially regulates cell growth, programmed cell death and human immunodeficiency virus type 1 replication.

In an effort to define novel cellular factors regulating human immunodeficiency virus type 1 (HIV-1) replication, a differential display analysis has been performed on endogenously infected cells stimulated with the HIV-suppressive immunomodulator Murabutide. In this study, the cloning and identification of a Murabutide-downregulated gene, named RH116, bearing classical motifs that are characteristic of the DExH family of RNA helicases, are reported. The 116 kDa encoded protein shares 99.9 % similarity with MDA-5, an inducible RNA helicase described recently. Ectopic expression of RH116 in HeLa-CD4 cells inhibited cell growth and cell proliferation but had no measurable effect on programmed cell death. RH116 presented steady state cytoplasmic localization and could translocate to the nucleus following HIV-1 infection. Moreover, the endogenous expression of RH116, at both the transcript and protein levels, was found to be considerably upregulated after infection. Overexpression of RH116 in HIV-1-infected HeLa-CD4 cells also resulted in a dramatic increase in the level of secreted viral p24 protein. This enhancement in virus replication did not stem from upregulated proviral DNA levels but correlated with increased unspliced and singly spliced viral mRNA transcripts. These findings implicate RH116 in the regulation of HIV-1 replication and point to an apoptosis-independent role for this novel helicase in inducing cell growth arrest.

Acetylmuramyl-Alanyl-Isoglutamine↗
PubMed2002

Prevention of human immunodeficiency virus-related opportunistic infections in France: a cost-effectiveness analysis.

A simulation model of human immunodeficiency virus (HIV) disease, which incorporated French data on the progression of HIV disease in the absence of antiretroviral therapy and on cost, was used to determine the clinical impact and cost-effectiveness of different strategies for the prevention of opportunistic infections in French patients who receive highly active antiretroviral therapy (HAART). Compared with use of no prophylaxis, use of trimethoprim-sulfamethoxazole (TMP-SMZ) increased per-person lifetime costs from euro 185,600 to euro 187,900 and quality-adjusted life expectancy from 112.2 to 113.7 months, for an incremental cost-effectiveness ratio of euro 18,700 per quality-adjusted life-year (euro/QALY) gained. Compared with use of TMP-SMZ alone, use of TMP-SMZ plus azithromycin cost euro 23,900/QALY gained; adding fluconazole cost an additional euro 54,500/QALY gained. All strategies that included oral ganciclovir had cost-effectiveness ratios that exceeded euro 100,000/QALY gained. In the era of HAART, on the basis of French data, prophylaxis against Pneumocystis carinii pneumonia, toxoplasmic encephalitis, and Mycobacterium avium complex bacteremia is cost-effective. Prophylaxis against fungal and cytomegalovirus infections is less cost-effective than are other therapeutic options for HIV disease and should remain of lower priority.

AIDS-Related Opportunistic Infections↗
PubMed2002

[Are the principles of treatment of chronic osteitis applicable to the diabetic foot?].

OBJECTIVE: The interest of the management of bone infections in the diabetic foot, inspired by the recommendations for the treatment of chronic osteitis, was assessed in this study. METHODS: Twenty bone infections in 17 diabetic patients with moderate to mild infections of the feet were confirmed by the results of X-ray and/or scintigraphic studies and bone surgery biopsy cultures revealing one or more bacteria sensitive to standard osteitis treatment (rifampicine + fluoroquinolone). The patients had received this treatment per os for a median duration of 6 months (3 to 10 months). Clinical follow-up was carried out during a consultation at 1, 3 and 6 months during treatment and then by telephone every six months after the end of treatment. Clinical success was defined as the disappearance of any local sign of infection and by the absence of relapse during the post-treatment follow-up period. The evolution of the bone infection was also assessed by the results of a control conducted 3 to 6 months after initiation of the antibiotic treatment. RESULTS: At the end of the treatment, all signs of infection had disappeared in 15/17 patients (88.2%) and no relapse had occurred in 14 (82.3%) patients at the end of a median post-treatment period of 22 months (12 to 41 months). Resection of necrotic bone was performed at the same time as the bone biopsy in 2 patients. The median duration of hospitalisation was of 14 days (3 to 53 days). During the study, a multi-resistant germ was isolated in 4 patients (1 Pseudomonas aeruginosa, 3 Staphylococcus aureus). During the post-treatment follow-up, 3 patients dies from causes unrelated to the infection treated. No serious adverse event was reported during the study. DISCUSSION: The results of this pilot study support the rationale of applying the treatment regimens of chronic osteitis to diabetic lesions of the feet, but are only applicable to comparable patients presenting with non-severe lesions of the feet. Moreover, the use of antibiotics with potent selection of resistance such as rifampicine and fluoroquinolone, requires that bone biopsies be taken, which is not easy in all the diabetic foot care centres. We are presently conducting a study to identify the sub-populations of diabetic patients who could benefit from such treatment.

Aged↗
PubMed2001

Variations in serum IL-7 and 90K/Mac-2 binding protein (Mac-2 BP) levels analysed in cohorts of HIV-1 patients and correlated with clinical changes following antiretroviral therapy.

Serum levels of interleukin-7 (IL-7), a non-redundant cytokine that plays a crucial role in lymphopoiesis, are known to be elevated in HIV-1-infected subjects. To examine further the association between levels of IL-7, CD4+ cell counts and viraemia, we analysed these parameters in a large cohort of HIV-1 patients along with serum levels of 90K, a marker of disease severity but with no established involvement in lymphopoiesis. While IL-7 levels were only found to correlate with CD4+ cell counts, 90K levels presented strong correlations with both CD4+ cell numbers and with plasma viral loads (VLs). These correlations were maintained in patients naive to treatment with antiretrovirals (n = 38) but were abolished when the analysis was restricted to the group receiving highly active antiretroviral therapy (HAART, n = 82). Moreover, although 90K levels were significantly reduced in patients on HAART, IL-7 levels continued to be elevated despite successful treatment. The influence of HAART on the variations in these serum parameters was further assessed in a longitudinal study on 32 subjects. The HAART-induced decrease in VLs and increase in CD4+ counts were found to correlate with a reduced serum level of 90K and IL-7, respectively. Nevertheless, following a median period of 33 months of immunological and virological successful HAART, serum levels of IL-7 continued to be significantly elevated compared with those detected in healthy controls. These findings suggest that immunotherapy with IL-7, aimed to replenish T-cell stock in HAART-treated subjects, may have a limited impact on the process of immune reconstitution.

Adult↗
PubMed2001

Incidence of primary opportunistic infections in two human immunodeficiency virus-infected French clinical cohorts.

BACKGROUND: Clinical guidelines for the prevention of opportunistic infections in human immunodeficiency virus (HIV)-infected individuals have been developed on the basis of natural history data collected in the USA. The objective of this study was to estimate the incidence of primary opportunistic infections in HIV-infected individuals in geographically distinct cohorts in France. METHODS: We conducted our study on 2664 HIV-infected patients from the Tourcoing AIDS Reference Centre and the hospital-based information system of the Groupe d'Epidémiologie Clinique du SIDA en Aquitaine enrolled from January 1987 to September 1995 and followed through December 1995. We estimated: (1) CD4-adjusted incidence rates of seven primary opportunistic infections in the absence of prophylaxis for that specific infection or any antiretroviral drugs other than zidovudine; and (2) CD4 lymphocyte count decline. RESULTS: The highest incidence rates for all opportunistic infections studied occurred in patients with CD4 counts < 200/microl. With CD4 counts < 50/microl, the most common opportunistic infections were toxoplasmic encephalitis (12.6 per 100 person-years) and Pneumocystis carinii pneumonia (11.4 per 100 person-years). Mycobacterium tuberculosis was the least common opportunistic infection (< 5.0/100 person-years). Even with CD4 counts > 300/microl, cases of Pneumocystis carinii pneumonia and toxoplasmic encephalitis were reported. The mean CD4 lymphocyte decline per month was 4.6 cells/microl. There was a significant association between HIV risk behaviour and the incidence of cytomegalovirus infection, between calendar year and the incidence of Pneumocystis carinii pneumonia, toxoplasmic encephalitis and Candida esophagitis, and between geographical area and the incidence of Pneumocystis carinii pneumonia and cytomegalovirus infection. CONCLUSIONS: Geographical differences exist in the incidence of HIV-related opportunistic infections. These results can be used to define local priorities for prophylaxis of opportunistic infections.

AIDS-Related Opportunistic Infections↗
PubMed2001

Rifampicin-ofloxacin oral regimen for the treatment of mild to moderate diabetic foot osteomyelitis.

Seventeen diabetic patients with moderate to mild foot lesions associated with 20 osteomyelitic bones diagnosed by both bone scan and bone biopsy received rifampicin plus ofloxacin for a median duration of 6 months. Cure was defined as disappearance of all signs and symptoms of infection at the end of the treatment and absence of relapse during follow up. At the end of the treatment period, cure was achieved in 15 patients (88.2%) and was maintained in 13 patients (76.5%) at the end of an average post-treatment follow-up of 22 months. No serious drug-related adverse events were recorded.

Administration, Oral↗
PubMed2001

Selective regulation of human immunodeficiency virus-infected CD4(+) lymphocytes by a synthetic immunomodulator leads to potent virus suppression in vitro and in hu-PBL-SCID mice.

We have previously observed that the synthetic immunomodulator Murabutide inhibits human immunodeficiency virus type 1 (HIV-1) replication at multiple levels in macrophages and dendritic cells. The present study was designed to profile the activity of Murabutide on CD8-depleted phytohemagglutinin-activated lymphocytes from HIV-1-infected subjects and on the outcome of HIV-1 infection in severe combined immunodeficiency mice reconstituted with human peripheral blood leukocytes (hu-PBL-SCID mice). Maintaining cultures of CD8-depleted blasts from 36 patients in the presence of Murabutide produced dramatically reduced levels of viral p24 protein in the supernatants. This activity correlated with reduced viral transcripts and proviral DNA, was evident in cultures harboring R5, X4-R5, or X4 HIV-1 isolates, was not linked to inhibition of cellular DNA synthesis, and did not correlate with beta-chemokine release. Moreover, c-myc mRNA expression was down-regulated in Murabutide-treated cells, suggesting potential interference of the immunomodulator with the nuclear transport of viral preintegration complexes. On the other hand, daily treatment of HIV-1-infected hu-PBL-SCID mice with Murabutide significantly reduced the viral loads in plasma and the proviral DNA content in human peritoneal cells. These results are the first to demonstrate that a clinically acceptable synthetic immunomodulator with an ability to enhance the host's nonspecific immune defense mechanisms against infections can directly regulate cellular factors in infected lymphocytes, leading to controlled HIV-1 replication.

Acetylmuramyl-Alanyl-Isoglutamine↗
PubMed2001

[Availability of antiretroviral agents in the city: a 1-year assessment in the Lille metropolitan area].

OBJECTIVES: Dispensing antiretroviral drugs in private pharmacies has been allowed in France since October 1997. One year after this measure was implemented, we conducted a survey of patients and pharmacists in the Lille metropolitan area to assess its impact. METHOD: Structured interviews with a representative sample of private pharmacists and HIV infected patients in the Lille metropolitan area were carried out. RESULTS: 100 pharmacists were interviewed. Most worked in urban areas and their main clientele were from the neighbourhood. Most felt that HIV infection was a common disease and were interested in dispensing antiretroviral drugs as a public health service despite the marginal income from these sales. Two-thirds had received training on HIV infection and most knew the importance of adhering to the treatment. However, the number of antiretroviral drugs and the classes of these drugs that were available were not well known. Among the 97 patients followed by the Service of Infectious Diseases of the Tourcoing Hospital, 22% received their medications from the local private pharmacy, 62% got them from the hospital pharmacy and 16% got them from both places. However, 39% received at least one drug that was only available from the hospital pharmacy. The patients going to private pharmacies described an improved quality of life and mostly chose their regular pharmacist to get their medications. Most preferred to get their medications openly, as opposed to secretly. Many patients going to the hospital pharmacy made their choice based on better confidentiality. Private pharmacists also expressed the fear of lack of confidentiality. Private pharmacies were seen as friendlier with quicker service, but slightly less competent than the hospital pharmacy. Finally, the topic of adhering to this form of HIV treatment is rarely discussed in private pharmacies. CONCLUSIONS: Both the patients and private pharmacists appreciate the fact that these drugs can be dispensed in private pharmacies, but the impact of this measure is limited by the number of drugs that are only available at the hospital pharmacy. Private pharmacists do not often discuss the importance of adhering to the therapy and progress is needed in this area.

Adult↗
PubMed2000

Symptomatic hyperlactataemia: an emerging complication of antiretroviral therapy.

BACKGROUND: Fatal lactic acidosis is a serious complication of therapy with nucleoside analogues. OBJECTIVE: To examine symptomatic hyperlactataemia in HIV-infected adults treated with antiretroviral drugs. METHODS: In this prospective study, arterial blood lactate levels were measured in patients presenting with unexplained clinical symptoms. When these levels were high, functional respiratory tests (FRT) were carried out. Liver or muscle biopsies were further proposed. Incidences were calculated by comparison with the entire cohort of patients treated in the department. RESULTS: Fourteen HIV-infected adults treated with antiretroviral drugs were identified with symptomatic hyperlactataemia during a 2-year period follow-up study. The incidence of hyperlactataemia was 0.8% per year but reached 1.2% if only patients treated with a regimen including stavudine were considered. Clinical symptoms included abnormal fatigue, tachycardia, abdominal pain, weight loss, peripheral neuropathy, and more specifically exercise-induced dyspnoea occurring despite effective antiretroviral treatment. FRT showed a metabolic deviation towards anaerobiosis with a high lactate/pyruvate ratio. Ultrastructural mitochondrial abnormalities were seen in all four patients for whom this was examined. There was a marked decrease in complex IV activity in muscle biopsies from four of five patients, consistent with a mitochondrial dysfunction. Evolution was favourable in 13 patients, probably because of an early diagnosis. CONCLUSIONS: Potentially fatal adverse events occurring during antiretroviral treatment may be avoided by close monitoring of clinical signs and blood lactate levels. If other studies confirm that the cumulative long-term toxicity of antiretroviral drugs results from mitochondrial dysfunction, the incidence of hyperlactataemia and its clinical consequences may become more important.

Acidosis, Lactic↗
PubMed2000

In HIV-1-infected patients, plasma levels of HIV-1 RNA are inversely correlated with IFN-alpha responsiveness of whole-blood cultures to sendai virus.

BACKGROUND: A diminished or totally blocked IFN-alpha production in cells from HIV-1-infected patients has been reported. OBJECTIVE: To investigate the relationship between the decreased in vitro production of IFN-alpha and the plasma level of HIV-1 RNA. STUDY DESIGN: Whole blood samples of 39 healthy subjects and 44 HIV-1-infected patients were incubated in the presence of Sendai virus for 24 h. IFN-alpha contained in supernatants was assayed by using an immunochemical method (DELFIA) and by using an antiviral assay. Plasma HIV-1 RNA was measured by the Amplicor HIV-1 monitor test. RESULTS: The levels of IFN-alpha obtained were significantly lower in cultures from HIV-1 infected patients than in control subjects (P<0.0001). The antiviral activity in supernatants of Sendai virus-activated whole-blood cultures, assayed by protection of MDBK cells against vesicular stomatitis virus (VSV), was significantly lower in cultures from HIV-1 infected patients than in corresponding controls (P<0.0001). IFN-alpha values determined by DELFIA and those determined by bioassay were significantly correlated. In vitro production of IFN-alpha by whole-blood cultures correlated well with the plasma levels of HIV-1 RNA (P<0.001). CONCLUSIONS: In HIV-infected patients an increased rate of HIV-1 replication is associated with reduced responsiveness to induction of IFN-alpha by indicator virus, suggesting that HIV-1 replication causes impaired production of IFN-alpha by blood cells or vice-versa.

Animals↗
PubMed2000

Cytokine analysis at the single cell level and lymphoproliferative responses to mycobacterial antigens in HIV-1 patients with successful virologic response to potent antiretrovirals.

Immunologic parameters, known to be grossly abnormal in HIV-1-infected subjects, were analyzed in 22 patients with sustained viral load suppression (<200 copies/ml) following long-term highly active antiretroviral therapy (HAART). Responses were compared with those from 18 HIV-seronegative healthy controls. Persistent phenotypic alterations in patients' blood mononuclear cells were minimal, though the percentages of lymphocytes that could be activated to produce interleukin-2 (IL-2) remained severely depressed. Using lymphoproliferative assays, a striking deficit in the capacity of patients to respond to the common mycobacterial antigens and particularly to recombinant heat-shock proteins paralleled the absence of responses to virus p24 antigen. In view of the important immunoregulatory role of stress proteins, these findings reveal profound functional deficiencies and persistent immune dysregulation in HIV-1 patients, despite successful HAART and a considerable recovery of CD4+ lymphocyte numbers. Rational immunotherapeutic approaches should be aimed to correct the characterized immune abnormalities.

Antigens, Bacterial↗
PubMed2000

Hepatitis C virus co-infection is a negative prognostic factor for clinical evolution in human immunodeficiency virus-positive patients.

A longitudinal study of human immunodeficiency virus (HIV)-infected individuals followed-up in 13 centres was performed to assess the influence of hepatitis C virus (HCV) on the clinical and immunological evolution of HIV-infected patients. Eight-hundred and twelve HIV-infected patients with known HIV acquisition date, 89 co-infected with HCV, were included in the cohort. Clinical progression was defined as: 30% decrease of Karnofsky's index; and/or 20% body weight loss; and/or acquired immune deficiency syndrome (AIDS)-defining illness; and/or death (except by accident, suicide, or overdose). Immunological progression was defined as a decrease of initial CD4 count to below 200 mm(-3). If immunological progression was not statistically different between groups (P=0.25), clinical progression was significantly faster in HCV-HIV co-infected patients in univariate (P=0.02) and multivariable survival analysis (hazard ratio=1.63, P=0.03). This argues for active management of hepatitis C chronic infection among HCV-HIV co-infected patients.

Adult↗
PubMed2000

Ex vivo interferon-gamma response to human immunodefiency virus-1 derived peptides in human immunodeficiency virus-1 infected patients.

The pattern of human immunodeficiency virus (HIV)-1 antigen-activated production of interferon (IFN)-gamma by immunocompetent cells of HIV-1 infected patients has been studied using a simplified assay combining a small volume (25 microliter) of whole blood stimulation with various HIV-1 antigens, and cytokine measurement in the same wells of microtitre plates (enzyme-linked immunotrapping assay, ELITA). The levels of IFN-gamma were higher using this assay than in the supernatant from stimulated whole blood cultures, therefore ELITA was used in the rest of the study. Specific immune responses to HIV-1 proteins (gp120, p24) and synthetic peptides derived from these proteins and from gp41 were detected in patients, but not in healthy controls. Decreased levels of IFN-gamma were observed in CDC class B (n = 5) and C (n = 4), compared with CDC class A (n = 5), following HIV-1 antigen-specific challenge. The positive response of cells from different patients to overlapping peptides of p25 (amino acids 329-344 and 335-351) was suggestive of a new epitope of HIV-1 gag recognized by T cells in the overlap region. In conclusion, the difference in in vitro antigen-specific T-cell responses of HIV-1-infected patients was shown using the ELITA method. Our results raise the possibility of using this method in screening specific antigens in HIV-1 infection.

Amino Acid Sequence↗
PubMed2000

The synthetic immunomodulator murabutide controls human immunodeficiency virus type 1 replication at multiple levels in macrophages and dendritic cells.

Macrophages and dendritic cells are known to play an important role in the establishment and persistence of human immunodeficiency virus (HIV) infection. Besides antiretroviral therapy, several immune-based interventions are being evaluated with the aim of achieving better control of virus replication in reservoir cells. Murabutide is a safe synthetic immunomodulator presenting a capacity to enhance nonspecific resistance against viral infections and to target cells of the reticuloendothelial system. In this study, we have examined the ability of Murabutide to control HIV type 1 (HIV-1) replication in acutely infected monocyte-derived macrophages (MDMs) and dendritic cells (MDDCs). Highly significant suppression of viral replication was consistently observed in Murabutide-treated cultures of both cell types. Murabutide did not affect virus entry, reverse transcriptase activity, or early proviral DNA formation in the cytoplasm of infected cells. However, treated MDMs and MDDCs showed a dramatic reduction in nuclear viral two-long terminal repeat circular form and viral mRNA transcripts. This HIV-1-suppressive activity was not mediated by inhibiting cellular DNA synthesis or by activating p38 mitogen-activated protein kinase. Furthermore, Murabutide-stimulated cells expressed reduced CD4 and CCR5 receptors and secreted high levels of beta-chemokines, although neutralization of the released chemokines did not alter the HIV-1-suppressive activity of Murabutide. These results provide evidence that a clinically acceptable immunomodulator can activate multiple effector pathways in macrophages and in dendritic cells, rendering them nonpermissive for HIV-1 replication.

Acetylmuramyl-Alanyl-Isoglutamine↗
PubMed1999

Soluble tumor necrosis factor receptor type II (sTNFRII) in HIV-infected patients: relationship with the plasma level of HIV-1 RNA.

The value of soluble receptor for tumor necrosis factor type II (sTNFRII) as a strong and early predictor of HIV disease progression was suggested. Recently it has been reported that sTNFRII may provide an indication of the HIV load. In this work we focused on the relationship between sTNFRII and HIV burden in 95 HIV-1+ patients without AIDS grouped according to the 1993 classification of the CDC as group A, n = 55, and group B, n = 40. Compared with healthy controls, higher values of sTNFRII were obtained in all groups of HIV-1 infected patients (P < 0.001), but we found no inverse correlation between sTNFRII and CD4+ lymphocyte counts in CDC group A and B of the disease, and no correlation with log RNA copy number in patients with CD4 T-cell counts > 499/microl. A correlation was obtained between sTNFRII and the viral load in patients with CD4 T-cell counts ranging from 200 to 499/microl, but only in CDC group B patients (P < 0.01, n = 26). There was no correlation between the variations of sTNFRII and HIV-1 RNA levels in 19 CDC group A and 15 CDC group B clinically stable patients in the course of a short follow up. The plasma level of sTNFRII do not appear as a valuable surrogate marker of the plasma level of HIV-1 RNA in patients. Further investigations are needed to define the mechanism of the raised level of sTNFRII in HIV-1 infected patients.

Adult↗
PubMed1999

[HIV protease inhibitors: drug interactions].

INTRODUCTION: Management of HIV infection considerably improved over the past few years. Factors that contributed to this improvement are the following: better knowledge of the dynamics of viral replication and immune response, plasma viral load quantitation, use of new combinations with more potent antiretroviral drugs, simultaneous progress in treatment of opportunistic infections. As a result, potential for drug interactions increased. CURRENT KNOWLEDGE AND KEY POINTS: Due to changes in hepatic metabolism, protease inhibitors may interact with concurrent treatment. The most relevant known drug interactions with each of the protease inhibitor (saquinavir, indinavir, ritonavir and nelfinavir) are summarized. Due to toxicity risks, co-administration is contraindicated for various interacting drugs, whereas dosage adjustments may only be required for others. Such interactions have relevant consequences in clinical practice for the choice of the combination that should be prescribed. However, they may have direct therapeutical benefit to the patient, particularly in the case of protease inhibitors. FUTURE PROSPECTS AND PROJECTS: Though potential drug interactions require careful monitoring in clinical practice, they should not limit the use and therefore therapeutical benefit conferred by these highly active drugs. To better define the value of combinations of protease inhibitors and treatment with non-nucleosidic reverse transcriptase inhibitor, further studies are required. As the number of drugs increases, experience and clinical practice in treatment of HIV infection will allow better knowledge of drug interactions and thereby optimal management of HIV-infected individuals.

Anti-HIV Agents↗