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Le Kremlin-Bicêtre, France

Seng R.,University Paris - Sud | Rolland M.,University Paris - Sud | Beck-Wirth G.,Mulhouse Hospital | Souala F.,Rennes Hospital | And 4 more authors.
AIDS | Year: 2011

Background: In the current context of increasing unsafe sex, HIV incidence may have evolved, depending on HIV prevalence in sexual networks and, among HIV-infected persons who practice unsafe sex, on their infectivity and partners HIV serostatus. We examined calendar trends in sexual behaviours at risk of HIV-1 transmission (SBR) among 967 adults followed since primary HIV infection (ANRS PRIMO cohort) and relationship with current treatments and viral load. Methods: Patients completed since 2000 self-administered questionnaires on sexual practices every 6 months. SBR with HIV-negative/unknown partners were analyzed among 155 heterosexual women, 142 heterosexual men and 670 MSM by using logistic generalized estimating equation models (6656 visits). Results: During 2000-2009, the frequency of SBR did not increase significantly among women with steady partners; risk factors were a low education level and alcohol/smoking use. Among heterosexual men with steady partners, the frequency of SBR doubled since 2006; during this period, the only associated factor was combined antiretroviral treatment for at least 6 months or viral load less than 400 copies/ml. Among MSM, SBR increased gradually over time; SBR with steady partners was associated with a low education level and alcohol use. SBR was more frequent among MSM with casual partners; no association with viral load was found. Conclusion: In France, recent trends and risk factors in unprotected sex with HIV-negative/unknown partners differ according to sex/sexual preference. The recent increase in SBR among heterosexual men with low viral load may be related to increasing awareness of the 'treatment-as-prevention' concept. The lack of association between SBR and viral load among MSM supports use of treatment-as-prevention as part of diversified prevention strategies. © 2011 Wolters Kluwer Health | Lippincott Williams & Wilkins.

Rostaing L.,Toulouse University Hospital Center | Charpentier B.,Bicetre Hospital | Glyda M.,Province Hospital | Rigotti P.,University of Padua | And 5 more authors.
American Journal of Transplantation | Year: 2013

Memory T cells play a central role in mediating allograft rejection and are a rational target for immunosuppressive therapy. Alefacept is a recombinant LFA3/IgG1 fusion protein that reduces the number of memory T cells in both psoriatic lesions and the peripheral circulation of psoriasis patients. This study evaluated the efficacy and safety of alefacept compared with placebo when combined with tacrolimus, mycophenolate mofetil and corticosteroids in de novo renal transplant recipients. Between December 2007 and March 2009 patients were randomized in a double-blind fashion to receive alefacept (n = 105) or placebo (n = 107) for 3 months and were then followed for a further 3 months. The primary efficacy endpoint was the incidence of biopsy-confirmed acute T cell mediated rejection (Banff grade ≥1) through Month 6. Memory T cell counts were significantly reduced in the alefacept group from Week 3 to study end compared with placebo. However, there was no significant difference between the alefacept and placebo groups for the primary efficacy endpoint (alefacept, 11.0% vs. placebo, 7.0%, p = 0.3). Patient and graft survival as well as renal function was similar between treatment groups. Safety and tolerability were generally similar between the treatment arms. Malignancy was higher in the alefacept treatment arm. © Copyright 2013 The American Society of Transplantation and the American Society of Transplant Surgeons.

Geri G.,Laboratory I3 Immunology | Terrier B.,Laboratory I3 Immunology | Rosenzwajg M.,Laboratory I3 Immunology | Wechsler B.,University Pierre and Marie Curie | And 11 more authors.
Journal of Allergy and Clinical Immunology | Year: 2011

Background: Behet disease (BD) is a chronic systemic inflammatory disorder of unknown etiology. Objective: To determine the nature of T cells driving inflammatory lesions in BD. Methods: T cell homeostasis and cytokines production were analyzed in peripheral blood and brain inflammatory lesions from 45 adult patients with BD (active and untreated BD [n = 25] and patients in remission [n = 20]) and 20 healthy donors, using Luminex, flow cytometry, immunohistochemistry, and immunofluorescence analysis. Results: We found a marked increase in TH17 cells and a decrease in the frequency of CD4+ forkhead box P3+ regulatory T cells (Tregs) in peripheral blood that were induced by IL-21 production and that correlate with BD activity. The addition of serum from patients with active BD in a sorted CD4+ T cells culture of healthy donors induced a significant and dose-dependent production of IL-17A and a decrease in forkhead box P3 expression. We demonstrated the presence of IL-21- and IL-17A-producing T cells within the cerebrospinal fluid, brain parenchyma inflammatory infiltrates, and intracerebral blood vessels from patients with active BD and central nervous system involvement. The stimulation of CD4+ T cells with IL-21 increased TH17 and TH1 differentiation and decreased the frequency of Treg cells. Conversely, IL-21 blockade with an IL-21R-Fc restored the TH17 and Treg homeostasis in patients with BD. Conclusion: We provided here the first evidence of the critical role of IL-21 in driving inflammatory lesions in BD by promoting TH17 effectors and suppressing Treg cells. IL-21 represents a promising target for novel therapy in BD. © 2011 American Academy of Allergy, Asthma & Immunology.

Mazouz S.,Antoine Beclere Hospital | Lee J.K.,Korea University | Fernandez H.,Bicetre Hospital | Fernandez H.,French Institute of Health and Medical Research
Fertility and Sterility | Year: 2011

Objective: To evaluate the performance of a one-step test detecting intact hCG and free β-hCG isoforms in the urine of pregnant women to diagnose an abnormal pregnancy. Design: Prospective study. Setting: Emergency gynecology departments in teaching hospitals. Patient(s): Five hundred twenty-six patients were enrolled, 272 who were not pregnant and 254 who were pregnant. Intervention(s) and Main Outcome Measure(s): Semiquantitative determination of intact urinary hCG of supposedly not pregnant and pregnant women with vaginal bleeding and/or vaginal pain between 5 and 8 weeks of amenorrhea. Result(s): The sensitivity and specificity of the urine test for diagnosing nonpregnancy were, respectively, 100% (252/252) and 100% (272/272). The sensitivity and specificity of the urine test for diagnosing ectopic pregnancy (EP) were, respectively, 97% (32/33) and 83% (142/171). The negative predictive value is 99.3% (142/143). The sensitivity and specificity or the urine test for diagnosing miscarriage were, respectively, 89.6% (43/48) and 83% (142/171). The negative predictive value is 96.6% (142/147). Conclusion(s): Abnormal pregnancy, such as an EP or a miscarriage, can be rapidly detected with the one-step test for intact hCG and free β-hCG isoforms. If ultrasound cannot confirm the localization and/or evolution of a pregnancy, using this test reduces medical supervision and repeated quantification of hCG. © 2011 American Society for Reproductive Medicine, Published by Elsevier Inc.

Vincenti F.,University of California at San Francisco | Larsen C.P.,Emory University | Alberu J.,Instituto Nacional Of Ciencias Medicas Y Nutricion Salvador Zubiran | Bresnahan B.,Medical College of Wisconsin | And 14 more authors.
American Journal of Transplantation | Year: 2012

The clinical profile of belatacept in kidney transplant recipients was evaluated to determine if earlier results in the BENEFIT study were sustained at 3 years. BENEFIT is a randomized 3 year, phase III study in adults receiving a kidney transplant from a living or standard criteria deceased donor. Patients were randomized to a more (MI) or less intensive (LI) regimen of belatacept, or cyclosporine. 471/666 patients completed ≥3 years of therapy. A total of 92% (MI), 92% (LI), and 89% (cyclosporine) of patients survived with a functioning graft. The mean calculated GFR (cGFR) was ∼21 mL/min/1.73 m 2 higher in the belatacept groups versus cyclosporine at year 3. From month 3 to month 36, the mean cGFR increased in the belatacept groups by +1.0 mL/min/1.73 m 2/year (MI) and +1.2 mL/min/1.73 m 2/year (LI) versus a decline of -2.0 mL/min/1.73 m 2/year (cyclosporine). One cyclosporine-treated patient experienced acute rejection between year 2 and year 3. There were no new safety signals and no new posttransplant lymphoproliferative disorder (PTLD) cases after month 18. Belatacept-treated patients maintained a high rate of patient and graft survival that was comparable to cyclosporine-treated patients, despite an early increased occurrence of acute rejection and PTLD. © Copyright 2011 The American Society of Transplantation and the American Society of Transplant Surgeons.

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