Search PubMed⌕ Search

Biomedical subjects

L Belec

Publications and source records attributed to L Belec.

At least 19 recordsLinked to original sources
PubMed2000

Didanosine dosed once daily is equivalent to twice daily dosing for patients on double or triple combination antiretroviral therapy. The AI454-147 Team.

OBJECTIVE: To compare the antiviral activity, effect on CD4 cell count, and tolerability of didanosine (ddI) administered once daily and twice daily in HIV-1-infected patients receiving ddI with stavudine or zidovudine, with or without a protease inhibitor. The study was designed to demonstrate that once-daily dosing of ddI was not inferior to twice-daily dosing. DESIGN: Randomized, open-label, multicenter, two-arm study. PATIENTS AND METHODS: 121 HIV-1-infected adults on a stable regimen including ddI (twice daily) during the previous 3 months with a stable viral load <10,000 copies/ml started therapy. Of these, 62 were randomized to switch to a combination that included ddI once daily and 59 to continue with ddI twice daily. The ddI dose was 400 mg/day (250 mg/day if body weight was <60 kg). The primary efficacy analysis compared the time-averaged difference (TAD) between the two treatment regimens in change from baseline log10 plasma HIV-1 RNA levels over 24 weeks of therapy, with an equivalence margin between the two treatment groups of <0.5 log10 copies/ml. RESULTS: At week 24, the mean plasma HIV-1 RNA level had increased by 0.31 and 0.17 log10 copies/ml in the ddI once-daily and ddI twice-daily groups, respectively. The time-averaged difference between the two groups in change from baseline plasma HIV-1 RNA levels over 24 weeks was (0.05 log10 copies/ml (95% confidence interval, -0.21 to +0.12 log10 copies/ml), indicating that the antiviral activity of ddI once daily is similar to that of ddI twice daily. After 24 weeks of treatment, changes from baseline in CD4 cell counts were similar in the two groups. Both regimens were generally well-tolerated. CONCLUSIONS: Once-daily and twice-daily ddI are equally effective at reducing plasma HIV-1 RNA levels when used in a combination regimen with stavudine or zidovudine, with or without a protease inhibitor.

Adult↗
PubMed2000

Efficacy and safety of combination therapy with interferon-alpha2b and ribavirin for chronic hepatitis C in HIV-infected patients.

OBJECTIVES: To evaluate the efficacy and safety of a combination therapy of interferon-alpha2b (IFN) and ribavirin for the treatment of chronic hepatitis C in HIV-seropositive patients. DESIGN: Open prospective trial. METHODS: Twenty patients co-infected with hepatitis C virus (HCV) and HIV, with a mean CD4 cell count of 350 +/- 153 x 10(6)/l were treated with IFN (3 MU three times per week) in combination with ribavirin (500 mg or 600 mg twice a day) for 6 months. Tolerance and efficacy were monitored at weeks 12 (month 3) and 24 (month 6). The primary endpoint was a complete virological response, as defined by the lack of detectable HCV RNA in serum. RESULTS: Baseline values of alanine aminotransferase (ALT) and aspartate aminotransferase (AST) were 121 +/- 72 IU/l and 75 +/- 67 IU/l, respectively. The total Knodell score was 10.4 +/- 2.4, with nine patients showing histological evidence of active cirrhosis (45%). All patients exhibited circulating HCV RNA. The treatment was well tolerated, with no impact on the course of HIV infection. After 6 months of combination therapy with IFN and ribavirin, 10 patients (50%) exhibited no further detectable HCV RNA viraemia, seven of whom achieved undetectable viraemia at month 3. Levels of ALT and AST decreased after 6 months of treatment from a mean of 121 +/- 72 to 51 +/- 40 IU/l and from a mean of 129 +/- 58 IU/l to 68 +/- 61 IU/l, respectively (P < 0.0002 and P < 0.0001). CONCLUSION: Our results indicate that combination therapy with IFN and ribavirin is effective in 50% of cases in clearing serum HCV RNA and may thus provide effective means of therapy in HIV-HCV-coinfected patients as initial treatment or in patients who have previously failed IFN monotherapy.

Adult↗
PubMed2000

The cumulative occurrence of resistance mutations in the HIV-1 protease gene is associated with failure of salvage therapy with ritonavir and saquinavir in protease inhibitor-experienced patients.

Salvage therapy with ritonavir (RTV) and saquinavir (SQV) failed to achieve virological and immunological improvement in 24 HIV-infected patients who discontinued triple therapy with RTV or indinavir (IDV) because of failure or intolerance to treatment. Changes in the HIV-1 protease gene sequence were analyzed prospectively in 14 patients. No primary protease mutation was found prior to the use of protease inhibitors. After 7 months of treatment with IDV or RTV, primary resistance mutations at codons pol 46 and/or pol 82 were observed in 11 of 13 patients. After 16 weeks on RTV-SQV, novel primary mutations related to SQV emerged in 7 of 13 patients, together with an increase in the number of secondary resistance mutations. Our observations indicate that the cumulative occurrence of resistance mutations in the protease gene was associated with failure of antiretroviral therapy. The presence of mutations to a first protease inhibitor may represent a risk factor for the failure of a subsequent treatment with a second line protease inhibitor.

Adult↗
PubMed2000

Demonstration of an association between Chlamydia pneumoniae infection and venous thromboembolic disease.

Chlamydia pneumoniae infection has been linked to atherosclerosis, but a possible relationship with venous thromboembolism (VTE) has not been sought. We determined circulating anti-C. pneumoniae antibody levels in patients with VTE. We studied 176 case patients with objectively diagnosed VTE and 197 age- and sex-matched healthy controls, in a retrospective study. Acquired risk factors for VTE and frequent predisposing genetic factors (factor V Arg 506 Gln and factor II G 20210 A mutations) were assessed in all the subjects. Anti-C. pneumoniae IgG antibodies were determined by microimmunofluorescence. All positive plasma samples (titer > or =128) were precisely quantified and tested for the presence of specific IgM antibodies. Fifty-four percent of the cases and 15.9% of the controls had specific IgG titers of at least 256 (p <0.0001). The crude odds ratio for VTE was 6.2 (95% CI, 3.8-10.1), and rose to 7.7 (4.5-13.2) after excluding subjects carrying the factor V Arg 506 Gln or factor II G 20210 A mutations. The odds ratio for VTE increased with the IgG titer: the adjusted odds ratios were 2.1 (95% CI, 1.1-4.1), 5.3 (2.7-10.6) and 33.0 (4.4-248.4) for titers of 256, 512 and 1024, respectively. Only one subject (a case patient) with a high IgG titer (> or =256) also had specific IgM. High titers of anti-C. pneumoniae IgG antibodies are frequently found in patients with previous venous thromboembolism. This association deserves to be confirmed in other case-control studies and prospective studies.

Adult↗
PubMed1999

Efficacy of a five-drug combination including ritonavir, saquinavir and efavirenz in patients who failed on a conventional triple-drug regimen: phenotypic resistance to protease inhibitors predicts outcome of therapy.

OBJECTIVE: to assess the safety and efficacy of a combination of ritonavir, efavirenz and two recycled nucleosides in patients who failed on a conventional triple-drug regimen including indinavir or ritonavir. METHODS: An open label study of ritonavir (100 mg twice daily), saquinavir (1000 mg twice daily), efavirenz (600 mg per day) and nucleoside analogues in 32 saquinavir- and efavirenz-naive protease inhibitor-experienced patients. Patients were included on the basis of plasma levels of HIV RNA above 5000 copies/ml while on conventional antiretroviral therapy. Phenotypic resistance and genotypic resistance mutations to saquinavir were assessed at baseline. Peak and trough plasma levels of saquinavir were monitored throughout the study. RESULTS: Median CD4 cell counts and median plasma HIV RNA at baseline were 258 x 10(6)/l and 4.31 log10 copies/ml, respectively. The plasma viral load decreased by a median of 1.20 log10 copies/ml and the CD4 cell count increased by a median 60 x 10(6) cells/l at week 24 of therapy. Seventy-one per cent of the patients achieved a plasma viral load < 500 copies/ml and 45% achieved a viral load < 50 copies/ml. Patients exhibiting phenotypic resistance to saquinavir at baseline experienced a median decrease in HIV RNA of 0.91 log10 copies/ml at week 24 of therapy, as compared with a decrease of 1.52 log10 copies/ml in those exhibiting sensitive viral strains (P = 0.03). Genotypic resistance to saquinavir was not predictive of virologic failure. CONCLUSION: Our results indicate that the combination of ritonavir, saquinavir and efavirenz is safe and effective at 24 weeks in over two-thirds of patients who previously failed on highly active antiretroviral therapy, and that the determination of phenotypic resistance may be of greater value than the detection of resistance mutations to predict the outcome of salvage therapy in this setting.

Adult↗
PubMed1999

Differential expression of the IL-1 system components during in vitro myogenesis: implication of IL-1beta in induction of myogenic cell apoptosis.

We evaluated the expression of IL-1 system by normal human myogenic cells during in vitro myogenesis and the effect of exogenous IL-1beta. Expression of IL-1alpha and beta, IL-1 receptor antagonist (IL-1Ra), IL-1RI and II, IL-1R accessory protein (IL-1RAcP) and IL-1beta converting enzyme (ICE) was studied by immunocytochemistry, immunoblotting, ELISA and RT - PCR. Cell proliferation was evaluated by [3H]thymidine incorporation, cell fusion by flow cytometry and cell death by in situ end-labelling. Human normal myogenic cells constitutively produced IL-1beta and ICE, with a maximum expression at time of cell fusion. IL-1Rs and IL-1RAcP expression reached a peak at time of commitment to fusion. Myogenic cells produced small amounts of IL-1Ra at latest stages of culture, and only the intracellular isoform. Exposure of cultures to exogenous IL-1beta (1-5 ng/ml) induced myogenic cell apoptosis, without effect on cell proliferation or fusion. IL-1beta-induced cell death was associated with morphological changes including spreading appearance of cells and alteration of cell alignment. We conclude that (1) human myogenic cells constitutively produce IL-1beta; (2) IL-1 system components are differentially expressed during in vitro myogenesis; (3) IL-1 system participates to the coordinated regulation of cell density during normal myogenesis, which could serve to control the muscle mass in vivo.

Apoptosis↗
PubMed1999

Reply

Explore the source record for details and available documents.

Journal Article↗
PubMed1999

Increased Ed-B fibronectin plasma levels in spondyloarthropathies: comparison with rheumatoid arthritis patients and a healthy population.

OBJECTIVE: To determine, for the first time, plasma levels of general fibronectin (Fn) and two spliced isoforms, Ed-A and Ed-B, in patients with spondyloarthropathy (SpA) in comparison with rheumatoid arthritis (RA) patients and healthy volunteers (HV). METHODS: Plasmas (EDTA) as well as clinical data, erythrocyte sedimentation rate (ESR) and C-reactive protein (CRP) levels were collected in two groups of 10 patients fulfilling the European Spondylarthropathy Study Group criteria for SpA or the 1987 American College of Rheumatology criteria for RA. Plasmas of 21 blood donors served as controls. Plasma levels of Fns were determined by using an in-house immunocapture ELISA, using monoclonal antibodies (MAbs) against general Fn and its isoforms. RESULTS: Total Fn plasma levels were significantly higher in the SpA group (mean+/-S.D.=1387+/-569 mg/l) than in the RA group (684+/-196 mg/l; P=0.02) and in HV (303+/-211 mg/l; P<0.0001). Ed-A Fn levels appeared higher in SpA (23+/-10.4 mg/l) and RA (32.5+/-16.5 mg/l) groups than in the HV group (2.8+/-0.9 mg/l; P=0.0003 and P<0.0001, respectively), without a significant difference between SpA and RA groups. Ed-B Fn levels were higher in SpA (6.9+/-2.1 mg/l) than in RA (3.2+/-1.9 mg/l; P=0. 02) and HV (1.1+/-0.8 mg/l; P=0.0003) groups. No significant correlation was observed in SpA patients between each Fn level and clinical activity, ESR or CRP levels. CONCLUSIONS: This study showed an increase in plasma levels of Fn and Ed-B Fn in SpA patients compared with RA patients and HV, which could not be attributed solely to systemic inflammation. It may be hypothesized that Ed-A and Ed-B Fn might reflect local turnover in inflamed tissues, and that Ed-B Fn might be particularly involved in the musculoskeletal inflammatory process of SpA.

Adult↗
PubMed1999

[Intrathecal synthesis of anti-Toxoplasma gondii antibodies during cerebral toxoplasmosis associated with African AIDS].

Thirty-four HIV-1-infected in-patients of the Hôpital Central des Forces Armées Congolaises, Brazzaville, Congo, hospitalized for suspected cerebral toxoplasmosis, have been evaluated for integrity of the blood-brain barrier, intrathecal synthesis of total IgG, toxoplasmic serology in blood and cerebrospinal fluid, and for intrathecal synthesis of IgG to Toxoplasma gondii. An empiric scale to gauge the possibility of clinical cerebral toxoplasmosis was used to classify the patients (+, +2, +3). Only an intrathecal synthesis of IgG to Toxoplasma gondii was found to be associated with suspected cerebral toxoplamosis: it was found in about 80% of patients, and more frequently in patients with a higher probability of disease. In contrast, alteration of the blood-brain barrier, intrathecal synthesis of total IgG and toxoplasmic serology in blood as well as in cerebrospinal fluid were not associated with suspected cerebral toxoplamosis. Taken together, these findings confirm that intrathecal synthesis of antitoxoplasmic antibodies of IgG isotype occurs in cerebral toxoplasmosis. Demonstration of intrathecal synthesis of antitoxoplasmic IgG antibodies could be used to confirm clinical diagnosis of cerebral toxoplamosis, especially in an African context, where sophisticated laboratory facilities are often lacking.

Acquired Immunodeficiency Syndrome↗
PubMed1998

Discrepant responses to triple combination antiretroviral therapy in advanced HIV disease.

OBJECTIVES: To determine the clinical, virological and immunological outcome in a cohort of unselected patients receiving triple combination therapy for more than 1 year. METHODS: Prospective follow-up of a cohort of 162 unselected, protease inhibitor-naive, antiretroviral-experienced patients with advanced HIV disease, treated with indinavir combined with two nucleoside analogues. RESULTS: The mean CD4 cell count and plasma HIV RNA level in the study group at baseline were 69+/-5 x 10(6)/l and 4.75+/-0.07 log10 copies/ml, respectively. Five per cent of patients died prematurely or were lost to follow-up. Fifty-seven per cent of patients responded to therapy, as assessed by a sustained increase in CD4 cell counts above 50 x 10(6)/l and a decrease in plasma HIV RNA greater than 1 log10 copies/ml, throughout 12.1 months of follow-up. Seventeen per cent of patients were immunological and virological non-responders. Twenty-one per cent of patients exhibited discrepant virological and immunological responses to treatment, of whom one-half failed to exhibit significant increases in CD4 cells despite a virological response to therapy and one-half exhibited increased CD4 cell counts in the absence of significant decrease in plasma viral load. The incidence of AIDS-defining events in the latter group of patients was similar to that of responder patients, whereas their incidence was higher in patients who failed to exhibit a virological and immunological response and those who failed to increase CD4 cells despite a significant decrease in viral load. CONCLUSION: Our observations of discrepant immunological and virological responses to treatment raise the issue of the significance of persistent elevated levels of plasma HIV RNA and of the relevance of measurements of plasma viral load for assessing the efficacy of antiretroviral therapy in patients whose CD4 cell counts increase despite the absence of significant decrease in plasma HIV viral load.

Adult↗
PubMed1998

The sequential occurrence of pol 215 and pol 41 zidovudine resistance mutations is associated in an additive fashion with low CD4 cell counts and high plasma and cellular HIV viral load.

We report on a cross-sectional study of virological and immunological surrogate markers of HIV infection in 115 patients for whom a determination of the pol 215 and pol 41 zidovudine (ZDV) resistance mutations had been described between January 1995 and February 1996. The patients received ZDV alone or a combination of ZDV and zalcitabine or didanosine. A total of 55, 15 and 45 patients exhibited a wild (W), a mixed (MIX) or a mutant (M) genotype at codon pol 215, respectively; 85, 10 and 20 patients exhibited a W, a MIX or a M genotype at codon pol 41, respectively. Patients exhibiting the pol 215 M genotype had lower CD4 cells, higher plasma viral load and higher proviral burden than patients exhibiting the pol 215 W genotype. Patients who had variants exhibiting both pol 215 M and pol 41 M or MIX genotypes had significantly worsened surrogate marker values than patients having variants only carrying the pol 215 M genotype. These observations demonstrate that the two mutations additively associate with pejorative surrogate markers.

Adult↗
PubMed1998

Intracellular neutralization of HIV transcytosis across tight epithelial barriers by anti-HIV envelope protein dIgA or IgM.

Human immunodeficiency virus, generated during contact between HIV-infected cells and the apical surface of an epithelial cell, can cross a tight epithelial barrier by transcytosis. We show that transcytosis of primary HIV isolates is blocked by dimeric IgA or IgM against HIV envelope proteins. Neutralization occurs intracellularly within the apical recycling endosome, and immune complexes are specifically recycled to the mucosal surface. One epitope involved in neutralization is a conserved sequence of the gp41 HIV envelope protein subunit. Finally, transcytosis also occurs across functional human mucosal tissue in a process inhibited by a serosal internalization of IgM against the HIV envelope protein. These results suggest that induction of mucosal immunity to HIV envelope proteins may impair the transcytotic route of HIV mucosal transmission.

Antigen-Antibody Complex↗
PubMed1998

The specificity patterns of human immunoglobulin G antibodies in serum differ from those in autologous secretions.

The specificity patterns of immunoglobulin G (IgG) antibodies to streptococcal antigens in serum and autologous secretions were compared in order to determine whether IgG found in human secretions is exclusively of serum origin or can also be locally produced irrespective of the systemic immune system. Surface antigens from a type 6 M-protein strain of Streptococcus pyogenes were extracted by cell wall digestion and subjected to sodium lauryl sulfate-polyacrylamide gel electrophoresis under reducing conditions. After being blotted onto nitrocellulose, the antigens were incubated with purified IgG from various body fluids: saliva, cervicovaginal secretions, seminal fluid, and colostrum. Binding was then revealed with labeled antibodies to human Fcgamma fragments. The antibody specificity patterns obtained by computer-assisted analysis were compared with those of paired sera. Major variations were observed between serum and secretions, as well as between different secretions from the same subject. These results are in favor of IgG-associated local immunity within different tissue compartments. This IgG response to mucosal antigens can complement that of secretory IgA in the defense against pathogens and should be taken into account during topical vaccinations.

Antibodies, Bacterial↗
PubMed1997

Peripheral neuropathy in human immunodeficiency virus-infected patients with the diffuse infiltrative lymphocytosis syndrome.

A subset of human immunodeficiency virus (HIV)-infected patients develop persistent CD8 hyperlymphocytosis and a Sjogren's syndrome-like syndrome associated with multivisceral CD8 T-cell infiltration, known as the diffuse infiltrative lymphocytosis syndrome (DILS). Patients with DILS tend to have higher CD4 cell counts, fewer opportunistic infections, and longer survival times than other HIV-infected patients. Peripheral nerve involvement in DILS has been poorly documented. We studied 12 HIV-infected patients with CD8 hyperlymphocytosis, DILS, and clinical signs of peripheral neuropathy. Two of 4 patients who were HLA typed were HLA-DR5 and 1 was HLA-DR6. All patients had the sicca syndrome and multivisceral involvement. The neuropathy was acute or subacute, always painful, and symmetrical in 8 cases. Electrophysiology was consistent with axonal neuropathy in 10 of 12 patients. Nerve biopsy showed marked angiocentric CD8 infiltrates without mural necrosis (12 of 12), and abundant expression of HIV p24 protein in macrophages (12 of 12). The HIV genome was detected by polymerase chain reaction in nerve homogenates. Zidovudine therapy was associated with improvement in 6 of 6 patients and steroid therapy was beneficial in 4 of 5 patients. No T-cell lymphoma was observed during follow-up, but 2 patients developed a primary B-cell lymphoma. We conclude that DILS neuropathy represents HIV-associated neuropathy, characterized by marked CD8 infiltration and abundant HIV in nerve, that improves with zidovudine or steroid therapy, and probably reflects a systemic host-determined and antigen-driven response to HIV.

Acquired Immunodeficiency Syndrome↗