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Vincent Baillat

Publications and source records attributed to Vincent Baillat.

18 recordsLinked to original sources
PubMed2005

Is tenofovir involved in hypophosphatemia and decrease of tubular phosphate reabsorption in HIV-positive adults?

OBJECTIVES: Tubulopathy with hypophosphatemia have been observed in HIV-positive patients receiving a tenofovir-containing regimen. However, the real incidence and prevalence of hypophosphatemia and their relation to tubular reabsorption disorders in tenofovir-treated patients remain uncertain. The aim of our study was to explore the effect of tenofovir on phosphatemia and on tubular phosphate reabsorption. METHODS: In a first transversal study, 145 HIV-positive adults (44+/-9 years) receiving tenofovir 300 mg daily with a mean exposure of 11+/-9 months were included. In a second prospective study, 29 HIV-positive antiretroviral experienced adults (44+/-10 years) were evaluated before introduction of tenofovir 300 mg daily (M0) and at 3 months (M3) and 6 months (M6), thereafter. Phosphate, creatinine, glucose and protein levels were determined in plasma and urine. The ratio of maximal reabsorption capacity (TmPO4)/glomerular filtration rate (GFR) was determined by using the normogramm of Walton and Bijvoet. RESULTS: In the transversal study, 26% of patients had hypophosphatemia (<0.84 mmol/l) while 47% of patients had a decreased TmPO4/GFR (<0.8 mmol/l). In the prospective study, baseline prevalence of hypophosphatemia (<0.84 mmol/l) and decreased TmPO4/GFR (<0.8mmol/l) was 31 and 41%, respectively. Three and 6 months after starting tenofovir, there is no significant change in mean phosphate levels (M0:0.91 mmol/l, M3:0.97 mmol/l, M6:0.98 mmol/l) and mean TmPO4/GFR (M0:0.80 mmol/l, M3:0.88 mmol/l, M6:0.84 mmol/l). Moreover, prevalence of hypophosphatemia (M3:28%, M6:28%) and decreased TmPO4/GFR (M3:41%, M6:45%) remained stable. CONCLUSION: Hypophosphatemia linked to a decreased proximal tubular reabsorption was frequently observed in HIV-positive adults independently of the use of tenofovir. In this preliminary study, no worsening effect on phosphatemia and tubular phosphate reabsorption was observed 6 months after introduction of tenofovir in treatment experienced patients.

Adenine↗
PubMed2005

CXCR4 overexpression during the course of HIV-1 infection correlates with the emergence of X4 strains.

The factors that determine the emergence of X4 isolates in some HIV-1-infected subjects are unknown. As the level of expression of CXCR4 could favor an R5 to X4 switch, quantitative flow cytometry was used to measure CXCR4 density on CD4 T cells in 200 HIV-1-positive adults, and this was compared with CD4 counts, interleukin-7 (IL-7), and RANTES (regulated on activation, normal T expressed and secreted) plasma levels and the R5/X4 virus phenotype. CD4 T-cell surface CXCR4 densities were increased in infected subjects and inversely correlated with CD4 T-cell count (r=-0.548, P<0.001). Yet, in vitro infection with either R5 or X4 strains and in vivo increases in viral load following interruption of antiretroviral treatment did not induce CXCR4 overexpression. The plasma levels of IL-7 and RANTES, 2 cytokines able to induce CXCR4 expression, did not correlate with CXCR4 density. Finally, higher CXCR4 densities were observed in patients harboring X4 strains (3300, 95% CI 2431-4169 CXCR4 molecules per cell) than in patients harboring only R5 strains (2406, 95% CI 2135-2677, P=0.027). These data suggest that CXCR4 overexpression during the course of the disease in some patients could favor the emergence of X4 strains.

Adolescent↗
PubMed2005

T-Cell surface CCR5 density is not correlated with hepatitis severity in hepatitis C virus/HIV-coinfected individuals: implications for the therapeutic use of CCR5 antagonists.

CCR5 antagonists represent promising anti-HIV agents. Yet, if the CCR5 chemokine receptor plays a positive role in hepatitis C virus (HCV) infection, CCR5 antagonists might be contraindicated in HCV/HIV-coinfected subjects. Therefore, we tested the hypothesis that the level of T-cell surface CCR5 expression, which might determine the intensity of HCV-specific T-cell recruitment into the liver, and thereby the efficiency of the anti-HCV response, could determine HCV disease evolution. For this purpose, we compared CCR5 density, measured by quantitative flow cytometry at the surface of nonactivated (human leukocyte antigen-D-related [HLA-DR]-) T cells of 51 HCV/HIV patients, with HCV load, serum aminotransferase levels, and liver histology (inflammatory activity, fibrosis, and rate of fibrosis progression). DR-CD4+ T-cell surface CCR5 density, which correlated with DR-CD8+ T-cell surface CCR5 density and was stable over time in HCV/HIV-coinfected individuals, did not correlate with any of the biologic parameters of HCV infection analyzed and was not linked to the capacity to clear the virus. In conclusion, we failed to demonstrate any impact of interindividual variability in T-cell surface CCR5 density on HCV infection, which would have argued against the use of CCR5 antagonists in HIV/HCV-coinfected subjects.

Adult↗
PubMed2004

Detection and enumeration of circulating HIV-1-specific memory B cells in HIV-1-infected patients.

Memory B cells are long-living cells that circulate throughout the body and differentiate into plasma cells after stimulation by antigens, cytokines, and direct cell-to-cell interaction in lymphoid tissues. For HIV-1-infected patients, we assessed whether in vitro polyclonal B cell activation that induces immunoglobulin secreting cells (SCs) also generates HIV-1-specific resting B cells to synthesize antibodies specific to HIV-1. To this end, highly purified B cells from 10 HIV-1-untreated patients were cultured with or without mouse fibroblastic cells expressing the CD40 ligand in the presence of IL-2 and IL-10. The percentage of immunoglobulin SCs we obtained by using the B cell-CD40L stimulation system was equal to 55% to 98% of the circulating memory B cells. Moreover, the anti-HIV-1 IgG, IgA, or IgM antibody SCs represented 1 x 10-2 to 1 x 10-3 of the total immunoglobulin SCs. The anti-HIV-1-specific antibodies detected in cell culture supernatants were directed to gag-, pol-, and env-encoded viral proteins. We found that in AIDS patients, HIV-1-specific resting memory B cells circulate in the blood and can be quantified by their anti-HIV-1 antibody secretion after strong B cell polyclonal stimulation.

Acquired Immunodeficiency Syndrome↗
PubMed2004

Fenofibrate improves the atherogenic lipid profile and enhances LDL resistance to oxidation in HIV-positive adults.

BACKGROUND: Low HDL-cholesterol, hypertriglyceridemia (HTG) and occurrence of small dense LDL could be involved in increased cardiovascular risk in HIV-infected patients. This study evaluates the effects of fenofibrate and/or Vitamin E on lipoprotein profile. DESIGN: Thirty-six HIV-positive adults with fasting triglycerides (TGs) > or =2 mmol/l and stable antiretroviral therapy (ART) were randomly assigned to receive either micronised fenofibrate (200 mg/day) or Vitamin E (500 mg/day) for a first period of 3 months and the association of both for an additional 3-month period. METHODS AND RESULTS: Total cholesterol, HDL-C, LDL-C, triglycerides, apoA1, apoB, apoCIII, lipoprotein composition, LDL size and LDL resistance to copper-induced oxidation were determined before initiation of fenofibrate or Vitamin E, and 3 and 6 months thereafter. Three months of fenofibrate treatment results in a significant decrease in triglycerides (-40%), apoCIII (-21%), total cholesterol (-14%), apoB (-17%) levels, non-HDL-C (-17%), TG/apoA1 ratio in HDL (-27%) associated with an increase in HDL-C (+15%) and apoA1 (+11%) levels. Moreover, fenofibrate increases LDL size and enhances LDL resistance to oxidation. Three months of Vitamin E supplementation only improves LDL resistance to oxidation and addition to fenofibrate results in a slightly greater effect. CONCLUSION: Fenofibrate therapy improves the atherogenic lipid profile in HIV-positive adults with hypertriglyceridemia.

Adult↗
PubMed2004

Enumeration of latently infected CD4+ T cells from HIV-1-infected patients using an HIV-1 antigen ELISPOT assay.

BACKGROUND: Latently infected resting CD4(+) T cells carrying replication-competent HIV-1 are present in naive, chronically infected individuals as well as in those who are receiving highly active antiretroviral therapy (HAART). These cells serve as a potential source of reactivation of viral replication and remain a major obstacle for the eradication of HIV-1. OBJECTIVES: The enzyme-linked immunospot (ELISPOT) assay was adapted to the detection and the enumeration of HIV-1 antigen-secreting cells at the single cell level. We applied this test to count latently HIV-1-infected CD4(+) T cells. STUDY DESIGN: Latently infected CD4(+) T cells were assessed in an in vitro model of HIV-1-infected resting CD4(+) T cells as well as in eighteen HAART-treated and in four HIV-1-infected untreated patients. Enriched CD4(+) T cells were cultured with or without antibodies against CD3 and CD28 T cell receptors and with irradiated peripheral blood mononuclear cells from HIV-1 seronegative individuals. At the term of the cell culture, CD4(+) T lymphocytes were tested using the HIV-1 antigen ELISPOT assay. RESULTS: In the experimental HIV-1 infection model, 5579+/-4190 CD4(+) T cells secreting HIV-1 antigen were enumerated after polyclonal activation. In contrast, only 15+/-6 HIV-1 immunospots were obtained from unstimulated T cells. In all patients tested, induced HIV-1 antigen-secreting cells were measured at a frequency of 55+/-108/10(6) CD4(+) T cells. CONCLUSION: As each immunospot represents one HIV-1 antigen-secreting cell, the HIV-1 ELISPOT assay is a powerful to enumerate circulating CD4(+) T lymphocytes latently infected with HIV-1.

CD4 Lymphocyte Count↗
PubMed2004

Human immunodeficiency virus type 1 (HIV-1) antigen secretion by latently infected resting CD4+ T lymphocytes from HIV-1-infected individuals.

In resting CD4(+) T lymphocytes harboring human immunodeficiency virus type 1 (HIV-1), replication-competent virus persists in patients responding to highly active antiretroviral therapy (HAART). This small latent reservoir represents between 10(3) and 10(7) cells per patient. However, the efficiency of HIV-1 DNA-positive resting CD4(+) T cells in converting to HIV-1-antigen-secreting cells (HIV-1-Ag-SCs) after in vitro CD4(+)-T-cell polyclonal stimulation has not been satisfactorily evaluated. By using an HIV-1-antigen enzyme-linked immunospot assay, 8 HIV-1-Ag-SCs per 10(6) CD4(+) resting T cells were quantified in 25 patients with a plasma viral load of <20 copies/ml, whereas 379 were enumerated in 10 viremic patients. In parallel, 369 and 1,238 copies of HIV-1 DNA per 10(6) CD4(+) T cells were enumerated in the two groups of patients, respectively. Only a minority of latently HIV-1 DNA-infected CD4(+) T cells could be stimulated in vitro to become HIV-1-Ag-SCs, particularly in aviremic patients. The difference between the number of HIV-1 immunospots in viremic versus aviremic patients could be explained by HIV-1 unintegrated viral DNA that gave additional HIV-1-Ag-SCs after in vitro CD4(+)-T-cell polyclonal stimulation. The ELISPOT approach to targeting the HIV-1-Ag-SCs could be a useful method for identifying latently HIV-1-infected CD4(+) T cells carrying replication-competent HIV-1 in patients responding to HAART.

Antiretroviral Therapy, Highly Active↗
PubMed2003

Detection of peripheral HIV-1-specific memory B cells in patients untreated or receiving highly active antiretroviral therapy.

OBJECTIVES: To examine whether polyclonal activation of circulating B cells, in a process that involves CD40-CD40 ligand and cytokine interactions, could induced HIV-1-specific memory B cells to synthesize HIV-1-specific antibodies. METHODS: B cells from 26 HIV-1-infected patients were cultured with a CD40L-transfected cell line plus interleukins 2 and 10 and tested for their secretion of HIV-1- and Toxoplasma gondii-specific antibodies. RESULTS: In vitro activated B lymphocytes from HIV-1-infected patients secreted anti-HIV-1-specific antibodies. B cells from HIV-1-infected patients as well as those from controls chronically infected by T. gondii synthesized T. gondii-specific antibodies. HIV-1-specific IgG-, IgA- or IgM-secreting B cells represented approximately 1 x 10(-4) to 1 x 10(-5) of total circulating B cells and 1 x 10(-2) to 1 x 10(-3) of immunoglobulin-secreting cells. HIV-1-specific memory B cells were found in 9/9 untreated patients and in 8/17 patients receiving highly active antiretroviral therapy (HAART). The other nine patients showed a normal CD40-CD40L B cell response and six of them produced T. gondii-specific antibody B cells. The follow-up of seven patients indicated that HIV-1-specific memory B cells became undetectable after 8 to 46 months of HAART, whereas T. gondii-specific memory B cells persisted in parasite coinfected patients. CONCLUSIONS: Circulating memory HIV-1-specific B cells were detected in untreated patients and in about half of the patients taking HAART, suggesting that persistent low-level ongoing viral replication is not sufficient to maintain HIV-1-specific memory B cells.

Anti-HIV Agents↗
PubMed2003

Interferon-alpha restores HIV-induced alteration of natural killer cell perforin expression in vivo.

OBJECTIVE: The percentage and the activity of natural killer (NK) cells are known to be decreased in HIV-infected patients. However, the mechanisms responsible for this NK deficiency are poorly understood. Because of the role of NK cells in the host defence against microbial infections, this defect contributes to the virus-induced immune deficiency. The aim of the present study was to better understand this defect in order to be able to restore NK function in HIV infection. DESIGN AND METHODS: The expression of the cytolytic mediators perforin and granzyme A was analysed by flow cytometry, the lytic activity of peripheral blood NK cells of HIV-infected patients was analysed by cytotoxic assay, and the expression of perforin was followed during administration of interferon (IFN)alpha attached to polyethylene glycol (PEG)-IFNalpha. RESULTS: The lytic activity and the expression of perforin and granzyme A was low in NK cells of infected individuals in comparison with normal control volunteers. In both groups NK cytotoxic capacity was linked to perforin expression. The low perforin expression in HIV-infected subjects negatively correlated with HIV RNA plasma level. administration of PEG-IFNalpha restored perforin expression even in patients whose viral load was not reduced by this treatment. CONCLUSIONS: These results suggest that HIV-induced NK deficiency could be partly mediated by a defect in perforin and granzyme A expression, and that PEG-IFNalpha could be used in infected subjects to directly improve their natural immunity in addition to eventually reducing their viraemia.

Adult↗
PubMed2003

Perforin expression in T cells and virological response to PEG-interferon alpha2b in HIV-1 infection.

OBJECTIVE AND DESIGN: Interferon alpha (IFNalpha), which is known to directly inhibit the HIV-1 replicative cycle and to increase the activity of cytotoxic T lymphocytes (CTL), is being tested as an anti-HIV agent. As CTL play a major role in immune defence against HIV, we wanted to further characterize CTL activity and the effect of IFNalpha on it. METHODS: We followed by flow cytometry the intracellular expression of the key mediator of cytotoxicity, perforin, in peripheral blood T cells of patients treated with IFNalpha. RESULTS: We observed that the percentage of T cells harbouring perforin was higher in infected subjects than in non-infected controls. Administration of IFNalpha2b attached to polyethylene glycol increased this perforin expression further and reduced viral load (P = 0.010). The increase in the percentage of T cells expressing perforin correlated with IFNalpha-induced decrease in viral load (r, 0.753; P = 0.003). In addition, the level of perforin expression before IFNalpha administration was inversely correlated with viral load remaining after IFNalpha administration (r, -0.647; P= 0.017). CONCLUSION: The pre-therapeutic percentage of perforin-positive T cells might be a predictive marker of the virological response to IFNalpha in HIV-1-infected patients.

Adult↗
PubMed2003

Reasons for early abacavir discontinuation in HIV-infected patients.

OBJECTIVE: To determine incidence of and reasons for discontinuation of abacavir within the first 6 months of therapy. METHODS: Retrospective study performed in the cohort of HIV-infected adults who started abacavir in a medical unit between 1997 and December 2000. All adverse drug reactions (ADRs) (especially hypersensitivity) observed in this cohort were reported. The association between drugs and complications were evaluated, using the French method to assess unexpected and toxic drug reactions. According to the variables studied, statistical analysis was performed using the chi2 test, Fisher's exact test, Mann-Whitney, Wilcoxon, or Kruskal-Wallis tests. RESULTS: All 331 patients treated with abacavir during this time period were included in this study. Early discontinuation of abacavir was observed in 34.1% of patients, the main reasons being adverse effects (20.8%), virologic failure (3.3%), drug holidays (2.7%), poor adherence (2.7%), and death (1.8%). Adverse effects were mostly represented by hypersensitivity reactions. After retrospective analysis, abacavir was stopped for likely hypersensitivity in 8.5% of patients, for doubtful hypersensitivity in 4.2%, and for other adverse effects in 8.1% of patients. CONCLUSIONS: This study shows that abacavir is mainly stopped during the first 6 months of therapy for ADRs. The rate of likely hypersensitivity reaction observed in this study (8.5%) is higher than that observed in clinical trials (5%). After retrospective evaluation, the causality assessment of abacavir is not always certain.

Adult↗
PubMed2002

Dynamics of spontaneous HIV-1 specific and non-specific B-cell responses in patients receiving antiretroviral therapy.

OBJECTIVES: As spontaneous anti-HIV-1 antibody and IgG secretion by peripheral blood mononuclear cells (PBMC) reflect immune system activation by HIV-1 antigens, we evaluated the impact of antiretroviral therapies on HIV-1 specific and non-specific B cell responses. METHODS: Anti-HIV-1 antibody and non-specific IgG were measured by ELISA in supernatants of PBMC cultured during 7 day from 30 patients initiating an antiretroviral therapy at baseline, 8, 16, 24, 36 and 48 weeks. RESULTS: An early and sustained fall in plasma viral load to below the detection limit (20 copies/ml) was observed in 17 sustained responder patients (SR), whereas HIV-1 RNA remained detectable in 13 others incomplete responders. In both groups, HIV-1 specific antibody secretion decreased significantly in parallel with plasma viral load and polyclonal immunoglobulin production became similar to that of PBMC controls. However, HIV-1 specific antibody production became negative in only six SR, exhibiting a greater increase of CD4 T-cell counts and higher levels of the spontaneous HIV-1 specific IgA secretion at baseline than the other SR. CONCLUSIONS: Antiretroviral therapy induced a rapid and dramatic decrease of spontaneous HIV-1 specific and non-specific B cell responses. These results pointed out that HIV-1 specific antibody secretion persisted in 11 out of 17 SR patients, suggesting persistent immune system activation by residual HIV-1 antigens.

Adult↗
PubMed2002

Spontaneous secretion of immunoglobulins and anti-HIV-1 antibodies by in vivo activated B lymphocytes from HIV-1-infected subjects: monocyte and natural killer cell requirement for in vitro terminal differentiation into plasma cells.

Peripheral blood mononuclear cells from HIV-1-infected subjects secrete spontaneously in vitro immunoglobulins (Ig) and anti-HIV-1 antibodies (Ab). Purified B lymphocytes secrete only minute amounts of Ig and anti-HIV-1 Ab compared with unfractionated cells. Monocytes and natural killer cells enhanced both secretions by cell-to-cell contacts, involving adhesion and CD27, CD80 costimulatory molecules and IL-6. Cell interactions prolonged the survival and allowed the terminal maturation of in vivo activated B cells. The secreting cell precursors were highly differentiated B cells expressing a broad diversity of maturation markers (CD27(+), CD38(+), CD20(+/-), CD37(+/-), CD71(+/-), HLA-DQ(+/-), sIg(+/-)) but not sIgD, CD28, or CD40. This phenotype and the cytologic aspect of purified B cells suggest that these cells are early plasma cells originated from germinal center. Ex vivo secreting peripheral B cells had probably gone beyond the CD40/CD40 ligand interaction; then following CD28/CD80 and CD27/CD27 ligand (CD70) interactions in the presence of IL-6, they achieved in vitro their differentiation into plasma cells.

Acquired Immunodeficiency Syndrome↗