Yoann Madec
Pasteur Institute
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Featured researches published by Yoann Madec.
The New England Journal of Medicine | 2011
François-Xavier Blanc; Thim Sok; Didier Laureillard; Laurence Borand; Claire Rekacewicz; Eric Nerrienet; Yoann Madec; Olivier Marcy; Sarin Chan; Narom Prak; Chindamony Kim; Khemarin Kim Lak; Chanroeurn Hak; Bunnet Dim; Chhun Im Sin; Sath Sun; Bertrand Guillard; Borann Sar; Sirenda Vong; Marcelo Fernandez; Lawrence Fox; Jean-François Delfraissy; Anne E. Goldfeld
BACKGROUND Tuberculosis remains an important cause of death among patients infected with the human immunodeficiency virus (HIV). Robust data are lacking with regard to the timing for the initiation of antiretroviral therapy (ART) in relation to the start of antituberculosis therapy. METHODS We tested the hypothesis that the timing of ART initiation would significantly affect mortality among adults not previously exposed to antiretroviral drugs who had newly diagnosed tuberculosis and CD4+ T-cell counts of 200 per cubic millimeter or lower. After beginning the standard, 6-month treatment for tuberculosis, patients were randomly assigned to either earlier treatment (2 weeks after beginning tuberculosis treatment) or later treatment (8 weeks after) with stavudine, lamivudine, and efavirenz. The primary end point was survival. RESULTS A total of 661 patients were enrolled and were followed for a median of 25 months. The median CD4+ T-cell count was 25 per cubic millimeter, and the median viral load was 5.64 log(10) copies per milliliter. The risk of death was significantly reduced in the group that received ART earlier, with 59 deaths among 332 patients (18%), as compared with 90 deaths among 329 patients (27%) in the later-ART group (hazard ratio, 0.62; 95% confidence interval [CI]; 0.44 to 0.86; P=0.006). The risk of tuberculosis-associated immune reconstitution inflammatory syndrome was significantly increased in the earlier-ART group (hazard ratio, 2.51; 95% CI, 1.78 to 3.59; P<0.001). Irrespective of the study group, the median gain in the CD4+ T-cell count was 114 per cubic millimeter, and the viral load was undetectable at week 50 in 96.5% of the patients. CONCLUSIONS Initiating ART 2 weeks after the start of tuberculosis treatment significantly improved survival among HIV-infected adults with CD4+ T-cell counts of 200 per cubic millimeter or lower. (Funded by the French National Agency for Research on AIDS and Viral Hepatitis and the National Institutes of Health; CAMELIA ClinicalTrials.gov number, NCT01300481.).
PLOS Neglected Tropical Diseases | 2013
Clémentine Schilte; Frédérik Staikovsky; Thérèse Couderc; Yoann Madec; Florence Carpentier; Somar Kassab; Matthew L. Albert; Marc Lecuit; Alain Michault
Background Arthritogenic alphaviruses, including Chikungunya virus (CHIKV), are responsible for acute fever and arthralgia, but can also lead to chronic symptoms. In 2006, a Chikungunya outbreak occurred in La Réunion Island, during which we constituted a prospective cohort of viremic patients (n = 180) and defined the clinical and biological features of acute infection. Individuals were followed as part of a longitudinal study to investigate in details the long-term outcome of Chikungunya. Methodology/Principal Findings Patients were submitted to clinical investigations 4, 6, 14 and 36 months after presentation with acute CHIKV infection. At 36 months, 22 patients with arthralgia and 20 patients without arthralgia were randomly selected from the cohort and consented for blood sampling. During the 3 years following acute infection, 60% of patients had experienced symptoms of arthralgia, with most reporting episodic relapse and recovery periods. Long-term arthralgias were typically polyarthralgia (70%), that were usually symmetrical (90%) and highly incapacitating (77%). They were often associated with local swelling (63%), asthenia (77%) or depression (56%). The age over 35 years and the presence of arthralgia 4 months after the disease onset are risk factors of long-term arthralgia. Patients with long-term arthralgia did not display biological markers typically found in autoimmune or rheumatoid diseases. These data helped define the features of CHIKV-associated chronic arthralgia and permitted an estimation of the economic burden associated with arthralgia. Conclusions/Significance This study demonstrates that chronic arthralgia is a frequent complication of acute Chikungunya disease and suggests that it results from a local rather than systemic inflammation.
Blood | 2009
Bénédicte Neven; Sandrine Leroy; Hélène Decaluwe; Françoise Le Deist; Capucine Picard; Despina Moshous; Nizar Mahlaoui; Marianne Debré; Jean-Laurent Casanova; Liliane Dal Cortivo; Yoann Madec; Salima Hacein-Bey-Abina; Geneviève de Saint Basile; Jean-Pierre de Villartay; Stéphane Blanche; Marina Cavazzana-Calvo; Alain Fischer
Allogeneic hematopoietic stem cell transplantation (HSCT) is a curative treatment for severe combined immunodeficiency (SCID). Detailed assessment of the long-term outcome of HSCT, ie, the occurrence of clinical events and the quality and stability of immune reconstitution, is now required. We performed a single-center retrospective analysis of the long-term outcome of HSCT in 90-patient cohort followed for between 2 and 34 years (median, 14 years). Clinical events and immune reconstitution data were collected. Almost half the patients have experienced one or more significant clinical events, including persistent chronic graft-versus-host disease (GVHD), autoimmune and inflammatory manifestations, opportunistic and nonopportunistic infections, chronic human papilloma virus (HPV) infections, and a requirement for nutritional support. With the notable exception of severe HPV infection, these complications tend to become less common 15 years later after HSCT. A multivariate analysis showed that the occurrence of these events correlated with non-genoidentical donors, diagnosis of Artemis SCID, and quality of immune reconstitution. In most cases, HSCT enables long-term survival with infrequent sequelae. However, the occurrence of relatively late-onset complications is a concern that requires specific means of prevention and justifies careful patient follow-up.
AIDS | 2005
Yoann Madec; Faroudy Boufassa; Kholoud Porter; Laurence Meyer
Objectives:To identify factors associated with sustained undetectable viraemia after HIV-1 seroconversion in treatment-naive patients, and to describe concomitant CD4 cell count progression. Methods:Seroconverters enrolled in CASCADE were assumed to control viraemia if at least two consecutive viral load measurements were < 400/500 copies/ml without treatment. Factors associated with undetectable viraemia were identified through a logistic regression. A joint model was used to describe simultaneously the CD4 cell count progression during and after that period and to identify factors associated with sustained undetectable viraemia. Results:Of 2176 seroconverters, 145 (6.7%) spontaneously controlled viraemia. Women were more likely than men to achieve undetectable viraemia [adjusted odds ratio (OR), 2.12; 95% confidence interval (CI), 1.49–3.12] unlike patients who reported a symptomatic primary infection (adjusted OR, 0.58; 95% CI, 0.36–0.94). AIDS and death rates were significantly lower in patients achieving undetectable viraemia than in the others. The median period of undetectable viraemia was 11.2 months; on average, CD4 cell counts remained stable during that period, and decreased with a mean rate of 5 cells/μl per month thereafter. High CD4 cell count at the beginning of undetectable viraemia and non-symptomatic primary infection favoured the preservation of undetectable viraemia. Conclusion:A small proportion of seroconverters appeared to be able to control HIV viraemia spontaneously, mostly those without seroconversion illness and within a few years following seroconversion; this is associated with the benefits of slower CD4 cell count decline and improved long-term prognosis. Such persons should be targeted for in depth investigation.
Molecular Ecology | 2010
Laurence Mousson; Estelle Martin; Karima Zouache; Yoann Madec; Patrick Mavingui; Anna-Bella Failloux
The Aedes albopictus mosquito has been involved as the principal vector of recent major outbreaks due to the chikungunya virus (CHIKV). The species is naturally infected by two strains of Wolbachia (wAlbA and wAlbB). Wolbachia infections are thought to have spread by manipulating the reproduction of their hosts; cytoplasmic incompatibility is the mechanism used by Wolbachia to invade natural populations of many insects including Ae. albopictus. Here, we report a study on the effects of removing Wolbachia from Ae. albopictus on CHIKV replication and examine the consequences of CHIKV infection on some life‐history traits (survival and reproduction) of Wolbachia‐free Ae. albopictus. We found that Wolbachia‐free mosquitoes maintained a highly heterogeneous CHIKV replication compared to Wolbachia‐infected individuals. In Wolbachia‐infected Ae. albopictus, the regular increase of CHIKV followed by a steady viral load from day 4 post‐infection onwards was concomitant with a decline in Wolbachia density. This profile was also detected when examining the two key organs for viral transmission, the midgut and the salivary glands. Moreover, Wolbachia‐free Ae. albopictus was not altered in life‐history traits such as survival, oviposition and hatching characteristics whether infected or not with CHIKV. We found that Wolbachia is not essential for viral replication, its presence could lead to optimize replication from day 4 post‐infection onwards, coinciding with a decrease in Wolbachia density. Wolbachia may regulate viral replication in Ae. albopictus, with consequences on survival and reproduction.
AIDS | 2007
Yoann Madec; Didier Laureillard; Loretxu Pinoges; Marcelo Fernandez; Narom Prak; Chanchhaya Ngeth; Sumanak Moeung; Sovannara Song; Suna Balkan; Laurent Ferradini; Catherine Quillet; Arnaud Fontanet
Background:HAART efficacy was evaluated in a real-life setting in Phnom Penh (Médecins Sans Frontières programme) among severely immuno-compromised patients. Methods:Factors associated with mortality and immune reconstitution were identified using Cox proportional hazards and logistic regression models, respectively. Results:From July 2001 to April 2005, 1735 patients initiated HAART, with median CD4 cell count of 20 (inter-quartile range, 6–78) cells/μl. Mortality at 2 years increased as the CD4 cell count at HAART initiation decreased, (4.4, 4.5, 7.5 and 24.7% in patients with CD4 cell count > 100, 51–100, 21–50 and ≤ 20 cells/μl, respectively; P < 10−4). Cotrimoxazole and fluconazole prophylaxis were protective against mortality as long as CD4 cell counts remained ≤ 200 and ≤ 100 cells/μl, respectively. The proportion of patients with successful immune reconstitution (CD4 cell gain > 100 cells/μl at 6 months) was 46.3%; it was lower in patients with previous ART exposure [odds ratio (OR), 0.16; 95% confidence interval (CI), 0.05–0.45] and patients developing a new opportunistic infection/immune reconstitution infection syndromes (OR, 0.71; 95% CI, 0.52–0.98). Similar efficacy was found between the stavudine–lamivudine–nevirapine fixed dose combination and the combination stavudine–lamivudine–efavirenz in terms of mortality and successful immune reconstitution. No surrogate markers for CD4 cell change could be identified among total lymphocyte count, haemoglobin, weight and body mass index. Conclusion:Although CD4 cell count-stratified mortality rates were similar to those observed in industrialized countries for patients with CD4 cell count > 50 cells/μl, patients with CD4 cell count ≤ 20 cells/μl posed a real challenge to clinicians. Widespread voluntary HIV testing and counselling should be encouraged to allow HAART initiation before the development of severe immuno-suppression.
AIDS | 2009
Yoann Madec; Elisabeth Szumilin; Christine Genevier; Laurent Ferradini; Suna Balkan; Mar Pujades; Arnaud Fontanet
BACKGROUND In developing countries, access to laboratory tests remains limited, and the use of simple tools such as weight to monitor HIV-infected patients treated with antiretroviral therapy should be evaluated. METHODS Cohort study of 2451 Cambodian and 2618 Kenyan adults who initiated antiretroviral therapy between 2001 and 2007. The prognostic value of weight gain at 3 months of antiretroviral therapy on 3-6 months mortality, and at 6 months on 6-12 months mortality, was investigated using Poisson regression. RESULTS Mortality rates [95% confidence interval (CI)] between 3 and 6 months of antiretroviral therapy were 9.9 (7.6-12.7) and 13.5 (11.0-16.7) per 100 person-years in Cambodia and Kenya, respectively. At 3 months, among patients with initial body mass index less than or equal to 18.5 kg/m (43% of the study population), mortality rate ratios (95% CI) were 6.3 (3.0-13.1) and 3.4 (1.4-8.3) for those with weight gain less than or equal to 5 and 5-10%, respectively, compared with those with weight gain of more than 10%. At 6 months, weight gain was also predictive of subsequent mortality: mortality rate ratio (95% CI) was 7.3 (4.0-13.3) for those with weight gain less than or equal to 5% compared with those with weight gain of more than 10%. CONCLUSION Weight gain at 3 months is strongly associated with survival. Poor compliance or undiagnosed opportunistic infections should be investigated in patients with initial body mass index less than or equal to 18.5 and achieving weight gain less than or equal to 10%.
Journal of Antimicrobial Chemotherapy | 2010
David Germanaud; Anne Derache; Mamadou Traore; Yoann Madec; Safiatou Toure; Fatoumata Dicko; Hadizatou Coulibaly; Malick Traore; Mariam Sylla; Vincent Calvez; Anne-Geneviève Marcelin
OBJECTIVES To evaluate the virological response and to describe the resistance profiles in the case of failure after 6 months of first-line highly active antiretroviral therapy (HAART) in HIV-1-infected children living in resource-limited settings. PATIENTS AND METHODS Ninety-seven HIV-1-infected children who started two nucleoside reverse transcriptase inhibitors (NRTIs) and one non-nucleoside reverse transcriptase inhibitor (NNRTI) (mainly zidovudine/lamivudine/nevirapine) in Mali were prospectively studied. Virological failure (VF) was defined as loss to follow-up, death or HIV-1 RNA viral load (VL) of >400 copies/mL at 6 months. When VL was >50 copies/mL, a genotypic resistance test was performed. RESULTS Among the 97 children, median age at antiretroviral initiation was 31 months and the majority were in WHO clinical (77.3%) and immunological (70.1%) stage III or IV. At month 6, 44% of children had VL > 400 copies/mL (61% VF). Among the children with detectable VL, 30/37 genotypic resistance tests were available, 8 with wild-type viruses and 22 with resistance mutations (73%): 19 M184V/I, 21 NNRTI mutations and only 3 thymidine analogue mutations (TAMs) (K70R, D67N and L210W in three distinct viruses). At failure, 6/8 children with wild-type viruses had a VL of <1000 copies/mL whereas 21/22 with resistant viruses had a VL of >1000 copies/mL. CONCLUSIONS Under NNRTI-based regimens, early detection of VF could allow the reinforcement of adherence when VL was <1000 copies/mL, because in most of these cases no resistance mutations were detected, or a change to a protease inhibitor-based regimen if VL was >1000 copies/mL. The low frequency of TAMs suggests that most NRTIs can be used in a second-line regimen after early failure.
AIDS | 2013
Didier Laureillard; Olivier Marcy; Yoann Madec; Sokeo Chea; Sarin Chan; Laurence Borand; Marcelo Fernandez; Narom Prak; Chindamony Kim; Bunnet Dim; Eric Nerrienet; Thim Sok; Jean-François Delfraissy; Anne E. Goldfeld; François-Xavier Blanc
Objective:To analyze cases of paradoxical tuberculosis-associated immune reconstitution inflammatory syndrome (TB-IRIS) in the CAMbodian Early versus Late Introduction of Antiretrovirals (CAMELIA) randomized trial designed to compare early (2 weeks) versus late (8 weeks) antiretroviral therapy (ART) initiation after tuberculosis treatment onset in Cambodia (NCT00226434). Methods:ART-naive adults with CD4+ cell count of 200 cells/&mgr;l or less, newly diagnosed tuberculosis, and at least one follow-up visit after ART initiation were included in this analysis. Each case of suspected TB-IRIS was systematically validated by two physicians not involved in patients’ management. Factors associated with occurrence of TB-IRIS were identified using the Cox proportional hazard model. Results:Among 597 patients, 26% experienced TB-IRIS with an incidence rate of 37.9 cases per 100 person-years [95% confidence interval (CI) 32.4–44.4]. Main clinical manifestations included new or worsening lymphadenopathy (77.4%) and fever (68.4%). Chest radiograph revealed new or worsening abnormalities in 53.4%. Symptoms resolved in 95.5% of patients. Six deaths were directly related to TB-IRIS. Initiating ART early increased the risk of TB-IRIS by 2.61 (95% CI 1.84–3.70). Extrapulmonary or disseminated tuberculosis, CD4+ cell count of 100 cells/&mgr;l or less, and HIV RNA concentration more than 6 log10 copies/ml were also significantly associated with higher risk of TB-IRIS. Conclusion:Shortening the delay between tuberculosis treatment onset and ART initiation to 2 weeks was associated with an increased risk of developing TB-IRIS. However, TB-IRIS was generally easily manageable. Given the marked reported survival advantage of early ART initiation after tuberculosis treatment onset, these data indicate that fear of TB-IRIS should not be an impediment to early ART in adults with advanced immunodeficiency in resource-limited, high burden settings.
Blood | 2012
Polidy Pean; Eric Nerrienet; Yoann Madec; Laurence Borand; Didier Laureillard; Marcelo Fernández; Olivier Marcy; Chan Sarin; Kerya Phon; Sylvia Taylor; Gianfranco Pancino; Françoise Barré-Sinoussi; Daniel Scott-Algara
Immune reconstitution inflammatory syndrome (IRIS) is a common and potentially serious complication occurring in HIV-infected patients being treated for tuberculosis (TB) using combined antiretroviral treatment. A role of adaptive immunity has been suggested in the onset of IRIS, whereas the role of natural killer (NK) cells has not yet been explored. The present study sought to examine the involvement of NK cells in the onset of IRIS in HIV-infected patients with TB and to identify predictive markers of IRIS. A total of 128 HIV-infected patients with TB from the Cambodian Early versus Late Introduction of Antiretroviral Drugs (CAMELIA) trial were enrolled in Cambodia. Thirty-seven of the 128 patients developed IRIS. At inclusion, patients had low CD4 cell counts (27 cells/mm(3)) and high plasma viral load (5.76 and 5.50 log/mL in IRIS and non-IRIS patients, respectively). At baseline, NK-cell degranulation capacity was significantly higher in IRIS patients than in non-IRIS patients (9.6% vs 6.38%, P < .005). At IRIS onset, degranulation capacity did not differ between patients, whereas activating receptor expression was lower in IRIS patients. Patients with degranulation levels > 10.84% had a higher risk of IRIS (P = .002 by log-rank test). Degranulation level at baseline was the most important IRIS predictor (hazard ratio = 4.41; 95% confidence interval, 1.60-12.16). We conclude that NK-degranulation levels identify higher IRIS risk in HIV-infected patients with TB.