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L Belec

Publications and source records attributed to L Belec.

At least 19 recordsLinked to original sources
PubMed2005

Interactions between human immunodeficiency virus and herpes viruses within the oral mucosa.

There is evidence from clinical case reports and epidemiological studies that human immunodeficiency virus (HIV) can be transmitted through oral sex. Herpes viruses that appear in the oral mucosa might influence the oral replication of HIV. A review of data suggesting that interactions occur between HIV and herpes viruses indicates that such interactions might operate in the oral mucosa. Defining the mechanisms by which herpes viruses interact with HIV in the oral mucosa should permit intervention measures to be targeted more precisely.

CD4 Antigens↗
PubMed2003

Detection of genomic viral RNA in nerve and muscle of patients with HCV neuropathy.

BACKGROUND: Hepatitis C virus (HCV)-associated neuropathy is usually associated with mixed cryoglobulinemia (MC) and vasculitis. MC may contain viral RNA, and tissues showing vasculitis may contain intracellular HCV. Local HCV replication remains to be evidenced. OBJECTIVE: To delineate the spectrum of HCV-associated neuropathy and to assess the presence of HCV in nerve and muscle tissues. METHODS: Thirty consecutive HCV-infected patients with peripheral neuropathy were included. Genomic and replicative strands of HCV RNA were detected in both nerve and muscle biopsy samples using distinctive reverse transcription nested PCR. RESULTS: Neuropathy was consistent with distal axonal polyneuropathy (DPN) in 25 of 30 patients, mononeuropathy multiplex (MM) in 3 of 30, and demyelinating polyneuropathy in 2 of 30. Pain was present in 18 of 30 patients and MC in 16 of 30. Biopsy showed inflammatory vascular lesions in 26 of 30 patients (87%), including necrotizing arteritis (6/30), small-vessel vasculitis (12/30) of either the lymphocytic (9/12) or the leukocytoclastic (3/12) type, and perivascular inflammatory infiltrates (8/30). All patients with necrotizing arteritis had DPN and positive MC detection. Both pain (p < 0.03) and positive MC detection (p < 0.01) were associated with the presence of vasculitis. Positive-strand genomic HCV RNA was detected in tissues of 10 of 30 patients (muscle 9, nerve 3). In contrast, negative-strand replicative RNA was never detected. Genomic RNA was found in nerve tissue samples showing vasculitis (necrotizing arteritis 2, small-vessel lymphocytic vasculitis 1). CONCLUSION: Painful DPN associated with MC and neuromuscular vasculitis is the most frequent type of HCV neuropathy. The usual detection of MC and the lack of local HCV replication indicate that HCV neuropathy results from virus-triggered immune-mediated mechanisms rather than direct nerve infection and in situ replication.

Action Potentials↗
PubMed2003

Herpes simplex virus type 2 and heterosexual spread of human immunodeficiency virus infection in developing countries: hypotheses and research priorities.

Herpes simplex virus type 2 (HSV-2) infection is almost always sexually transmitted, and causes genital ulceration. Significant progress in our understanding of HSV infection has occurred over the last decade, in part related to the development of accurate and sensitive laboratory tests to study HSV-2. The application of PCR and type-specific serology to individual cases and in population-based studies has enabled the identification of a potentially important role for HSV-2 infection as a cofactor in the sexual transmission of HIV. This is a particular issue in developing countries. This review describes the epidemiology of HSV-2 infection in the HIV era, the hypotheses regarding HSV-HIV interactions, and research priorities for the developing world.

Developing Countries↗
PubMed2001

Long-term efficacy of combination therapy with interferon-alpha 2b and ribavirin for severe chronic hepatitis C in HIV-infected patients.

BACKGROUND: We have assessed the long-term efficacy and safety of a combination therapy of interferon alpha-2b (IFN) and ribavirin (RBV) for the treatment of severe chronic hepatitis C in co-infected HIV-seropositive patients in an open prospective study. METHODS: Fifty-one patients were treated for 12 months. Mean baseline CD4 cell count, alanine aminotransferase and aspartate aminotransferase were 412 +/- 232 x 106/l, 113 +/- 75 IU/l and 111 +/- 84 IU/l respectively. The mean Knodell score was 11.5 +/- 2.1 with 28 patients (55%) exhibiting histological evidence of active cirrhosis. RESULTS: Fifteen (29%) patients discontinued the treatment prematurely because of adverse events. An end of treatment response (ETR) as defined by the lack of detectable hepatitis C virus (HCV) RNA in plasma at the end of treatment was achieved in 15 patients (29%). A sustained virological response (SVR), defined by the lack of detectable HCV RNA in plasma 6 months after completion of combination therapy, was achieved in 11 patients (21%). The HCV genotype 3a was associated with ETR and SVR (P = 0.002 and P = 0.003, respectively). HCV viraemia at baseline was lower in patients who achieved SVR and ETR than in those who did not (6.7 +/- 7.8 versus 24 +/- 26.7 x 10(6) genome equivalents/ml, P = 0.03 and 14.3 +/- 28.7 versus 22.5 +/- 23, P = 0.05, respectively). CONCLUSION: Our results indicate that combination therapy with IFN and RBV is effective in approximately 20% of co-infected patients with severe liver disease.

Adult↗
PubMed2001

Long-term clinical outcome of human immunodeficiency virus-infected patients with discordant immunologic and virologic responses to a protease inhibitor-containing regimen.

Within a prospective cohort of 150 human immunodeficiency virus (HIV)-infected patients who began first-line protease inhibitor therapy in 1996, the outcome of 42 patients with discrepant virologic and immunologic responses to antiretroviral treatment at 12 months was analyzed at 30 months of treatment. The incidence of AIDS-defining events and deaths (14%) in the group of patients with immunologic responses in the absence of a virologic response was higher than that in full-responder patients (2%); yet, the incidence in this group was lower than that in patients with no immunologic response, despite a virologic response (21%), and was lower than that in patients without an immunologic or virologic response (67%; P<.0001, log-rank test). Differences in outcome were significant (relative risk, 6.9; 95% confidence interval, 1.9-39.3) when factors for progression were compared with those of responder patients. The results support the relevance of the CD4 cell marker over plasma HIV load for predicting clinical outcome in patients who do not achieve full immunologic and virologic responses.

Adult↗
PubMed2001

Macrophagic myofasciitis lesions assess long-term persistence of vaccine-derived aluminium hydroxide in muscle.

Macrophagic myofasciitis (MMF) is an emerging condition of unknown cause, detected in patients with diffuse arthromyalgias and fatigue, and characterized by muscle infiltration by granular periodic acid-Schiff's reagent-positive macrophages and lymphocytes. Intracytoplasmic inclusions have been observed in macrophages of some patients. To assess their significance, electron microscopy was performed in 40 consecutive cases and chemical analysis was done by microanalysis and atomic absorption spectrometry. Inclusions were constantly detected and corresponded to aluminium hydroxide, an immunostimulatory compound frequently used as a vaccine adjuvant. A lymphocytic component was constantly observed in MMF lesions. Serological tests were compatible with exposure to aluminium hydroxide-containing vaccines. History analysis revealed that 50 out of 50 patients had received vaccines against hepatitis B virus (86%), hepatitis A virus (19%) or tetanus toxoid (58%), 3-96 months (median 36 months) before biopsy. Diffuse myalgias were more frequent in patients with than without an MMF lesion at deltoid muscle biopsy (P < 0.0001). Myalgia onset was subsequent to the vaccination (median 11 months) in 94% of patients. MMF lesion was experimentally reproduced in rats. We conclude that the MMF lesion is secondary to intramuscular injection of aluminium hydroxide-containing vaccines, shows both long-term persistence of aluminium hydroxide and an ongoing local immune reaction, and is detected in patients with systemic symptoms which appeared subsequently to vaccination.

Adjuvants, Immunologic↗
PubMed2001

Quantitation of human immunodeficiency virus type 1 (HIV-1) RNA in cell-free cervicovaginal secretions: comparison of reverse transcription-PCR amplification (AMPLICOR HIV-A MONITOR 1.5) with enhanced-sensitivity branched-DNA assay (Quantiplex 3.0).

Two commercially available hypersensitive assays for human immunodeficiency virus type 1 (HIV-1) RNA quantitation, AMPLICOR HIV-1 Monitor Test 1.5 and Quantiplex HIV RNA 3.0, were compared to detect and quantify HIV-1 RNA in the cell-free fraction of cervicovaginal secretions collected by vaginal washing. Three panel specimens were used: pooled cervicovaginal secretions spiked with HIV-1 subtype A or HIV-1 subtype B and cervicovaginal lavages from HIV-positive and HIV-negative women. Compared to the AMPLICOR HIV-1 Monitor Test 1.5 assay, the Quantiplex HIV-1 3.0 assay yielded higher estimates of HIV-1 RNA concentrations in several tested samples spiked with HIV-1 RNA subtype A, as well as subtype B, particularly samples containing low amounts of HIV-1 RNA. The sensitivity and specificity of the AMPLICOR HIV-1 Monitor Test 1.5 assay were 93 and 100%, respectively; the sensitivity and specificity of the Quantiplex HIV RNA 3.0 assay were 97 and 50%, respectively. In conclusion, in quantifying HIV-1 RNA in cervicovaginal secretions, the Quantiplex HIV RNA 3.0 may lack specificity, and the AMPLICOR HIV-1 Monitor Test 1.5 assay, although highly specific, may lack sensitivity.

Branched DNA Signal Amplification Assay↗
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

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