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1. Rapid decrease in IL-1Ra and IP-10 plasma levels following tuberculosis treatment initiation

Author

Polidy Pean, Roseline Affi, Corine Chazalon, Ben Cheick Soumahoro, Delphine Gabillard, Bunnet Dim, Laurence Borand, Raoul Moh, Xavier Anglaret, François-Xavier Blanc, Pierre-Marie Girard, Guislaine Carcelain, Didier Laureillard, and Laurence Weiss

Subjects
Tuberculosis, HIV, Biomarkers, Treatment response, Infectious and parasitic diseases, RC109-216
Abstract

Objectives: Monitoring tools that could provide quick predictions of tuberculosis (TB) treatment outcomes are urgently needed. Here, we assessed whether the evolution of selected biomarkers of innate immunity may help monitoring TB treatment response within 2 weeks of treatment initiation. Methods: ANRS12394-LILAC-TB was a proof-of-concept prospective study: adults with a rifampicin-susceptible TB who are HIV-negative and HIV-infected documented by a positive Xpert MTB/RIF test were enrolled in Cambodia and Côte d'Ivoire. Plasma concentrations of interleukin-1 receptor antagonist (IL-1Ra), interferon-γ–induced protein-10 and clusters of differentiation (CD) (scavenging CD163) were measured by commercial enzyme-linked immunosorbent assay kits. A Wilcoxon test for paired data was used for longitudinal comparisons. Results: A total of 55 patients were enrolled (women: 31%, median age: 37 years; median CD4 count in the 10 of 13 participants with HIV: 53 cells/mm3). Overall, 83% were considered in TB treatment success. Compared with baseline, the IL-1Ra plasma levels significantly decreased as soon as week (W) 1, independent of HIV status (−71% in HIV-positive vs −33% in HIV-negative; P

Published
2024
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2. Simplified Criteria to Assess Long-Term Antiviral Treatment Indication in Chronic HBV-Infected Pregnant Women in Cambodia

Author

Jee-Seon Yang, Saren Sovann, Yusuke Shimakawa, Sovann Nhoueng, Bunnet Dim, Chanlina Vong, Channa Sann, Julia Guillebaud, Darapolin Vann, Bunrith Touch, Hyna Chea, Wathanak Pisey Choupoan Phirum, Eric Rosenthal, Christelle Paul, Leangchhun Khun, Chantana Yay, Denis Laurent, Samsorphea Chhun, Laurence Borand, and Olivier Segeral

Subjects
hepatitis B, pregnancy, postpartum, long-term treatment, public health, international guidelines, Microbiology, QR1-502
Abstract

Pregnant women identified to carry hepatitis B surface antigen (HBsAg) should be linked to care for the determination of the need for long-term antiviral therapy (LTT). We assessed the performance of simplified criteria, free from HBV DNA quantification, to select women eligible for LTT using different international guidelines as a reference. A retrospective analysis of HBV-infected pregnant women enrolled in the phase 4 ANRS TA-PROHM study was conducted in Cambodia. Sensitivity, specificity, and AUROC were computed to compare three simplified criteria (TREAT-B, HBcrAg/ALT, and TA-PROHM) with the American (AASLD) and European (EASL) guidelines as a reference. An additional assessment was performed at 6 months postpartum. Of 651 HBsAg-positive women, 209 (32%) received peripartum antiviral prophylaxis using tenofovir disoproxil fumarate (TDF). During pregnancy, 9% and 12% of women were eligible for LTT according to AASLD and EASL guidelines, respectively; 21% and 24% of women were eligible for prophylactic TDF and 2% and 5% in those ineligible (p < 0.001). Using the AASLD guidelines, the AUROC of TREAT-B, HBcrAg/ALT, and TA-PROHM scores were 0.88 (95%CI, 0.85–0.90), 0.90 (95%CI, 0.87–0.92), and 0.76 (95%CI, 0.73–0.80), respectively. Using the EASL guidelines, the AUROCs were lower: 0.73 (95%CI, 0.69–0.76), 0.76 (95%CI, 0.73–0.80), and 0.71 (95%CI, 0.67–0.74), respectively. Among those ineligible for prophylactic TDF, only 2% to 6% present an indication for LTT at 24 weeks postpartum. Few pregnant women are eligible for LTT, and the use of simplified criteria could represent an efficient triage option in decentralized areas to identify those negative for whom there is no urgent indication for LTT and focus on those positive for whom other exams must be conducted to confirm LTT indication.

Published
2024
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3. Circulation of Bordetella pertussis in vaccinated Cambodian children: A transversal serological study

Author

Gaelle Noel, Laurence Borand, Chanthy Leng, Chanthy Keang, Chhunly Botr, Bunnet Dim, Alexandra Kerleguer, Yik S. Peng, Navin Sreng, Vichit Ork, Mohand Ait-Ahmed, Nicole Guiso, and Fabien Taieb

Subjects
Pertussis, Cambodia, Whole-cell vaccine, Sero-prevalence, Timeliness, Infectious and parasitic diseases, RC109-216
Abstract

Background: The Cambodia pertussis immunization schedule includes three doses given at age 6, 10 and 14 weeks using a whole-pertussis vaccine. No booster doses are included. Pertussis biological diagnosis is unavailable in Cambodia and its burden remains unclear. This study aimed to provide accurate data on pertussis serological status of Cambodian children and adolescents, and to evaluate vaccination timeliness. Methods: Fully vaccinated children aged 3–15 years were recruited at the Rabies Prevention Center, Institut Pasteur in Cambodia, Phnom Penh. Capillary blood samples and information on pertussis vaccination history were collected. Anti-pertussis toxin (PT) IgG titers were quantified by ELISA. Results: Compliance with the national immunization schedule was 95.1%. Initiation of vaccination after 8 weeks of age was observed for 29.0% of the children, but was less frequent in the youngest children (13.0%) compared with the oldest ones (46.4%). Rate of children exhibiting anti-PT IgG varied across age groups, and increased from 35.7% to 55.0% in 3–5 and 12–15 years age groups, respectively. Conclusion: Pertussis circulates among vaccinated Cambodian children and adolescents. These data support the need for public health authorities to strengthen pertussis surveillance and use local epidemiological data to make evidence-based decision for the establishment of an optimal vaccination strategy.

Published
2021
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4. Diagnostic Advances in Childhood Tuberculosis—Improving Specimen Collection and Yield of Microbiological Diagnosis for Intrathoracic Tuberculosis

Author

Eric Wobudeya, Maryline Bonnet, Elisabetta Ghimenton Walters, Pamela Nabeta, Rinn Song, Wilfred Murithi, Walter Mchembere, Bunnet Dim, Jean-Voisin Taguebue, Joanna Orne-Gliemann, Mark P. Nicol, and Olivier Marcy

Subjects
tuberculosis, children, diagnosis, microbiological tests, sample collection methods, Medicine
Abstract

There is no microbiological gold standard for childhood tuberculosis (TB) diagnosis. The paucibacillary nature of the disease, challenges in sample collection in young children, and the limitations of currently available microbiological tests restrict microbiological confirmation of intrathoracic TB to the minority of children. Recent WHO guidelines recommend the use of novel rapid molecular assays as initial diagnostic tests for TB and endorse alternative sample collection methods for children. However, the uptake of these tools in high-endemic settings remains low. In this review, we appraise historic and new microbiological tests and sample collection techniques that can be used for the diagnosis of intrathoracic TB in children. We explore challenges and possible ways to improve diagnostic yield despite limitations, and identify research gaps to address in order to improve the microbiological diagnosis of intrathoracic TB in children.

Published
2022
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5. Plasma concentrations, efficacy and safety of efavirenz in HIV-infected adults treated for tuberculosis in Cambodia (ANRS 1295-CIPRA KH001 CAMELIA trial).

Author

Laurence Borand, Yoann Madec, Didier Laureillard, Monidarin Chou, Olivier Marcy, Phearavin Pheng, Narom Prak, Chindamony Kim, Khemarin Kim Lak, Chanroeun Hak, Bunnet Dim, Eric Nerrienet, Arnaud Fontanet, Thim Sok, Anne E Goldfeld, François-Xavier Blanc, and Anne-Marie Taburet

Subjects
Medicine, Science
Abstract

ObjectiveTo assess efavirenz plasma concentrations and their association with treatment efficacy and tolerance of efavirenz 600 mg daily in HIV-tuberculosis co-infected patients.MethodsHIV-infected adults with CD4+ T cell count ≤ 200/mm(3) received standard 6-month tuberculosis treatment and antiretroviral therapy including a daily-dose of 600 mg of efavirenz, irrespective of their body weight. Mid-dose blood samples were drawn both on tuberculosis treatment (week +2 and week +6 after antiretroviral therapy initiation, and week 22 of follow-up) and off tuberculosis treatment (week 50 of follow-up). Considered therapeutic range was 1,000 to 4,000 ng/mL. Multivariate analysis was performed to evaluate the association between efavirenz concentration below 1,000 ng/mL and virological failure. Linear regression was used to test the association between efavirenz exposure and CD4+ T cell gain. Severe side effects potentially related to efavirenz were described and their association with efavirenz exposure was tested by multivariate analysis.ResultsEfavirenz plasma concentrations were available in 540 patients. Median [interquartile range] efavirenz concentrations were 2,674 ng/mL [1,690-4,533], 2,667 ng/mL [1,753-4,494] and 2,799 ng/mL [1,804-4,744] at week +2, week +6, week 22, respectively, and 2,766 ng/mL [1,941-3,976] at week 50. Efavirenz concentrations were lower at week 50 (off rifampicin) compared to week 22 (on rifampicin) (pConclusionBody weight and tuberculosis treatment were not associated with low efavirenz concentrations or treatment failure, supporting the 600 mg daily-dose of efavirenz in HIV-tuberculosis co-infected patients. High efavirenz concentrations were related to a higher risk of central nervous system side effects and hepatotoxicity.Trial registrationClinicalTrials.gov NCT01300481.

Published
2014
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6. Effect of decentralising childhood tuberculosis diagnosis to primary health centre versus district hospital levels on disease detection in children from six high tuberculosis incidence countries: an operational research, pre-post intervention study

Author

Laurence, Borand, Agathe, de Lauzanne, Bunnet, Dim, Seyla, Heang, Sanary, Kaing, Chanty, Keang, Socheat, L.Y., Pichpiseth, Meas, Sovann, Nhoueng, Long, Pring, Vouchleang, Sreng, Song, Yin, Saren, Sovan, Chanvirak, Phan, Chanra, Chreng, Ratha, Khoun, Monicando, Rin, Sophea, Pal, Boraneath, Nang, Rathakrun, Pom, Tan Eang, Mao, Simoy, Chhim, Huot, Touch, Kosal, Suon, Saronn, Chum, Kimhong, Tok, Kimchorn, Pring, Satya, Krouch, Chean, Chok, Sunleng, Seun, Savtey, Phon, Mai, Nang, Kimda, Hun, Vanny, Hong, Dara, Sok, Kosal, Chea, Bunthoeun, Chheang, Rino, Sem, Lam, Lay, Haysan, Say, Pholly, Kem, Sreyphal, Meng, Sokheng, Phorn, Sreyvann, Him, Peakdey, Pheach, Dalai, Kive, Moeur, Sar, Sreydy, Kong, Seyha, Kong, Sreytouch, Yorn, Soam, Tes, Sophal, Kep, Seroeung HENG Thy, Leng, Savorn, Neak, Sim, Seng, Pheakna, Pay, Sithan, Suon, Sophanna, Chan, Dyna, Um, Savuth, Sin, Sam, Phan, Sarim, Kum, Sokheng, Khath, Pong, Phem, Seyha, Sok, Chanty, Ny, Van, Leim, Sereyvuth, Pich, Sengkry, Chheang, Nhin, Eang, Vannareth, Sao, Vannak, Sim, Sopheak, Som, Ney, Pong, Sokha, Van, Sreyleap, Seng, Vanna, Yoeurng, Kakada, Toem, Thida, Keo, Vuochny, Sem, Sophal, Veng, Chanthol, Rin, Vanny, Seang, Kiri, Lok, Khemra, Mao, Keovanna, Ouk, Maiya, Min, Suomun, Morm, Rattana, Koy, Sreypov, Chhann, Sreytouch, Set, Audrey, Amboua Schouame, Clifford, Babey, Masama, Eden Ngu, Etienne, Guenou, Sylvie, Kwedi Nolna, Douglas, Mbang Massom, Bernard Fortune, Melingui, Nadia, Nga Elomo, Moïse, Mvetumbo, Angeline, Nkembe, Krystel, Ebo, Albert, Kuate Kuate, Michelline, Choupa, Maggi, Mbede, Valerie, Donkeng, Nelly, Kamgaing, Jean-Voisin, Taguebue, Achille, Touha Yannick, Estelle, Abomo Zang, Rosette, Bakoa, Esperance, Mimbouombela Leger, Sabine, Eleme, Gabrielle, Eteme Marie, Thierry, Elouna Nkoa, Dieudonné, Ndzana, Christophe, Bitti, Olivier, Fotsing, Charlotte, Lani Boko, Mathieu, Mbonga, Ghislain Ulrich, Njakou Sagang, Innocent, Onomo, Charlotte, Essaga Hortense, Daniel Desiré, Mboudi Kouang, Léon, Eloundou, Helene, Kengne, Felix, Mbassi, Juliette, Bidjeme, Hortense, Toua Eteme, Nadege, Essama, Roger, Belinga Balla, Norbert, Tassi, Roline, Nguiko Elsa, Leonard, Mekongo, Fabien, Eyebe Ayissi, Francine Christelle, Biloa Anaba, Philomène, Nsom, Celestin Géraud, Yam Essola, Edwige Léa, Mame Moo, Noé, Makon, Arllette Rita, Nounkep Yanghu, Frank, Ebanga, Antoinette, Assiga Ntsama, Carlyle Sorelle, Kamguia Djuimsop, Diane, Mbabou, Marie, Maguip Abanda, Rosine Berthe, Nguemafouo Doummene, Amos, Mekone, Ngwankfu, Konfor Blessing, Jérome, Mimboe, Virginie, Tiona, Roland, Beleck, Sairou, Zam, Nicole, Adibone, Claude, Biaback Jean, Denis, Bessong, Gilbert, Aminou, Jeremie Pagnol, Bille Bonga, Aubin, Fotso Monkap, Epse NGON Annie, Hitekelek, Vitrice, Sebe, Leo, Makon, Marie, Ennah, Mpie, Paul Boyolo, Diane Viviane, Metchoum, Celin, Nzambe, Arnaud, Dado, Milobert, Mbengang, Marceline, Eyebi, Vanessa, Ngah, Alice, Mballa Batonga, Solange, Ayouba, Pierrette, Ebode, Majino, Mamou, Marguerite, Botomogne Bomba, Salametou, Ngnet, Augustine Florence, Essengue Ngono, Rolland, Odionoloba Charles, Bernice, Bisso, Suzy, Balemaken Ingrid, Marie Louise, Mandoki a Bilong, Gertrude, Ndeng Ayouba, Josue, Ngon, Roger, Aka Bony, Kacou Michel, Bah, Dro, Bakayoko, Rolande, Baki Aimee, Marie-France Larissa, Banga, Olivier, Bouzié, Kan, Brou, Pan, Coulibaly, Serge, Danho, Flavien, Deli, Alphonse, Dion, Bi, Do, Armand, Dohoun, William, Edjeme, Cathérine, Falé, Melissa, Gogoua Saulé, Constant, Kesse, Eric, Komena Auguste, Christian, Kouadio, Arkason, Kouame Abel, Raoul, Moh, Sandrine, Nguessan Marcelle, Bertine, Siloué, Nina, Soua, Cyrille Prisca, Yao Yapi, Timothée, Ouassa, Jacquemin, Kouakou, Eric, Balestre, Aurélie, Beuscart, Aurélie, Charpin, Marc, D'elbee, Hélène, Font, Basant, Joshi, Nicolas, Koskas, Olivier, Marcy, Estelle, Occelli, Joanna, Orne-Gliemann, Julien, Poublan, Elodie, Vernoux, Maryline, Bonnet, Savine, Chauvet, Manon, Lounnas, Guillaume, Breton, Pierre-Yves, Norval, Sheyla, Cassy, Verna, Chambal, Valter, Chiúle, Supinho, Chimbanje, Saniata, Cumbe, Mércia, Matsinhe, Celso, Khosa, Nairo, Mabote, Salvador, Machava, Emelva, Machonisse, Verónica, Macuácua, Denise, Milice, Jorge, Ribeiro, Elcídio, Tivane, Dorlim, Uetela, Yara, Voss de Lima, Américo, Zandamela, Alcina, Zita, Ivan, Manhiça, Benedita, José, Dalila, Rego, Chris, Buck W., Kapoli, Kasembe, Atália, Massangaie, Assa, Sitoe, Ambostique, Argola, Césio, Miambo, Presequila, Nhatsave, Gilda, Sitoe, Charifito, Vesta, Salvador, Dimande, Lázaro, Mazembe, Nilza, Amade, Manuela, Chavela, Nomsa, Macheque, Salomão, Comé, Eulália, Machava, Narciso, Mucavele, Jacinto, Nhabanga, Marlene, Nicolau, Natércia, Simbine, Lina, Uendela, Micaela, Juaio, Abiba, Saíde, Naira, Macie, Fernando, Mondlane, Stélio, Simango, Prince, Beyan, Benjamin M, Flomo, Abubakarr, Jalloh Joseph, Ishmael, Kamara, Monica G, Koroma, Mohamed, Lamin, Lena, Matata, Ross, Mugisha Jacob, Christiana M, Senesie, Sheriff, S.E.S.A.Y., Egerton, Tamba Kamara, Ayeshatu, Mustapha, Lynda, Foray, Sandra, Agondeze, Agnes, Kobusingye, Mastula, Nanfuka, Faith, Namulinda, Eric, Wobudeya, Rinah, Arinaitwe, Rodney, Kaitano, Martin, Kasujja, Juliet, Mwanga-Amumpaire, Evans, Mwesigwa, Naome, Natukunda, Simpson, Nuwamanya, Miria, Nyangoma, Patrick, Orikiriza, Johnbosco, Tumwijukye, Esther, Turyashemererwa, Nyehangane, Dan, Mugisha, Ivan, Winnie, Biryeri, George, Naika, Robert, Ongwara O., Allen, Najjuko, Augustine, Kayiira, Samuel, Yairo, Immaculate, Tumwebaze, Goreth, Nalwoga, Paul, Nsiyaleta, Annet, Agaba, Martin, Mpimbaza M., Norbert, Akampurira, Agatha, Tugumisirize, Evans, Ariyo, Julius, Agaba, Yovita, Natukunda, Nelson, Musazi, Edmund, Musinguzi, Brown, Baluku Julius, Moorine, Sekadde, Stavia, Turyahabwe, Chishala, Chabala, Luis, Cuevas, Christophe, Delacourt, Steve, Graham, Malgorzata, Grzemska, Sabine, Verkuijl, Anneke, Hesseling, Elizabeth, Maleche-Obimbo, Mark, Nicol, Wobudeya, Eric, Nanfuka, Mastula, Ton Nu Nguyet, Minh Huyen, Taguebue, Jean-Voisin, Moh, Raoul, Breton, Guillaume, Khosa, Celso, Borand, Laurence, Mwanga-Amumpaire, Juliet, Mustapha, Ayeshatu, Nolna, Sylvie Kwedi, Komena, Eric, Mugisha, Jacob Ross, Natukunda, Naome, Dim, Bunnet, de Lauzanne, Agathe, Cumbe, Saniata, Balestre, Eric, Poublan, Julien, Lounnas, Manon, Ngu, Eden, Joshi, Basant, Norval, Pierre-Yves, Terquiem, Etienne Leroy, Turyahabwe, Stavia, Foray, Lynda, Sidibé, Souleymane, Manhiça, Ivan, Sekadde, Moorine, Detjen, Anne, Verkuijl, Sabine, Mao, Tan Eang, Orne-Gliemann, Joanna, Bonnet, Maryline, and Marcy, Olivier

Published
2024
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7. Cost-effectiveness and budget impact of decentralising childhood tuberculosis diagnosis in six high tuberculosis incidence countries: a mathematical modelling study

Author

Arlt-Hilares, Doris, Balestre, Eric, Banga, Marie-France, Bénard, Antoine, Bernard, Tanguy, Bonnet, Maryline, Borand, Laurence, Breton, Guillaume, Bunnet, Dim, Chateau, Paul-Damien, Cumbe, Saniata, d’Elbée, Marc, de Lauzanne, Agathe, Dodd, Peter James, Harker, Martin, Huyen Ton Nu Nguyet, Minh, Kaing, Sanary, Khosa, Celso, Komena, Eric, Koroma, Monica, Kwedi Nolna, Sylvie, Mafirakureva, Nyashadzaishe, Mao, Tan Eang, Marcy, Olivier, Mbang Masson, Douglas, Moh, Raoul, Mugisha, Jacob, Mustapha, Ayeshatu, Mwanga-Amumpere, Juliet, Nanfuka, Mastula, Natukunda, Naome, Orne-Gliemann, Joanna, Ouattara, Eric, Poublan, Julien, Sohn, Hojoon, Taguebue, Jean-Voisin, Tulinawe, Immaculate, Voss de Lima, Yara, Wittwer, Jérôme, Wobudeya, Eric, Nolna, Sylvie Kwedi, and Dodd, Peter J.

Published
2024
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8. High Performance of Systematic Combined Urine Liboarabinomannan Test and Sputum Xpert MTB/RIF for Tuberculosis Screening in Severely Immunosuppressed Ambulatory Adults With Human Immunodeficiency Virus.

Author

Bonnet, Maryline, Gabillard, Delphine, Domoua, Serge, Muzoora, Conrad, Messou, Eugène, Sovannarith, Samreth, Nguyen, Duc Bang, Badje, Anani, Juchet, Sylvain, Bunnet, Dim, Borand, Laurence, Natukunda, Naome, Tran, Thị Hong, Anglaret, Xavier, Laureillard, Didier, and Blanc, François-Xavier

Subjects
TUBERCULOSIS diagnosis, SPUTUM microbiology, LIPOPOLYSACCHARIDES, HIV-positive persons, CHEST X rays, IMMUNOCOMPROMISED patients, MEDICAL screening, IMMUNOSUPPRESSION, RAPID diagnostic tests, ANTIRETROVIRAL agents, CD4 lymphocyte count, DESCRIPTIVE statistics, WALKING, RESEARCH funding, DIAGNOSTIC errors, SECONDARY analysis
Abstract

Background In people with human immunodeficiency virus (PWH), the World Health Organization–recommended tuberculosis (TB) 4-symptom screen (W4SS) targeting those who need molecular rapid testing may be suboptimal. We assessed the performance of different TB screening approaches in severely immunosuppressed PWH enrolled in the guided-treatment group of the STATIS trial (NCT02057796). Methods Ambulatory PWH with no overt evidence of TB and CD4 count <100 cells/µL were screened for TB prior to antiretroviral therapy (ART) initiation with W4SS, chest radiograph (CXR), urine lipoarabinomannan (LAM) test, and sputum Xpert MTB/RIF (Xpert). Correctly and wrongly identified cases by screening approaches were assessed overall and by CD4 count threshold (≤50 and 51–99 cells/µL). Results Of 525 enrolled participants (median CD4 count, 28 cells/µL), 48 (9.9%) were diagnosed with TB at enrollment. Among participants with a negative W4SS, 16% had either a positive Xpert, a CXR suggestive of TB, or a positive urine LAM test. The combination of sputum Xpert and urine LAM test was associated with the highest proportion of participants correctly identified as TB (95.8%) and non-TB cases (95.4%), with proportions equally high among participants with CD4 counts above or below 50 cells/µL. Restricting the use of sputum Xpert, urine LAM test, or CXR to participants with a positive W4SS reduced the proportion of wrongly and correctly identified cases. Conclusions There is a clear benefit to perform both sputum Xpert and urine LAM tests as TB screening in all severely immunosuppressed PWH prior to ART initiation, not only in those with a positive W4SS. Clinical Trials Registration. NCT02057796. [ABSTRACT FROM AUTHOR]

Published
2023
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10. Isolation of Nontuberculous Mycobacteria in Southeast Asian and African Human Immunodeficiency Virus-infected Children With Suspected Tuberculosis

Author

Christophe Delacourt, Ngoc Lan Nguyen, Sokleaph Cheng, Laurence Borand, Agathe de Lauzanne, Boubacar Nacro, Sylvain Godreuil, Philippe Msellati, Thu Hang Pham, Malin Inghammar, Abdoul-Salam Ouédraogo, Sara Eyangoh, Stéphane Blanche, Olivier Marcy, Vibol Ung, Bunnet Dim, Mathurin Cyrille Tejiokem, Recherches Translationnelles sur le VIH et les maladies infectieuses endémiques er émergentes (TransVIHMI), Université Cheikh Anta Diop [Dakar, Sénégal] (UCAD)-Institut de Recherche pour le Développement (IRD)-Université de Yaoundé I-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Montpellier (UM)-Université Montpellier 1 (UM1), CHU Montpellier, Centre Hospitalier Régional Universitaire [Montpellier] (CHRU Montpellier), Bordeaux population health (BPH), Université de Bordeaux (UB)-Institut de Santé Publique, d'Épidémiologie et de Développement (ISPED)-Institut National de la Santé et de la Recherche Médicale (INSERM), Recherches Translationnelles sur le VIH et les maladies infectieuses endémiques et émergentes (TransVIHMI), and Institut de Recherche pour le Développement (IRD)-Université de Yaoundé I-Université Cheikh Anta Diop [Dakar, Sénégal] (UCAD)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Montpellier (UM)

Subjects
0301 basic medicine, Microbiology (medical), nontuberculous mycobacteria, Tuberculosis, Isolation (health care), [SDV]Life Sciences [q-bio], 030106 microbiology, Human immunodeficiency virus (HIV), Mycobacterium Infections, Nontuberculous, HIV Infections, medicine.disease_cause, Southeast asian, 03 medical and health sciences, 0302 clinical medicine, children, parasitic diseases, medicine, Humans, Mycobacterium avium complex, 030212 general & internal medicine, Prospective Studies, Child, Immunodeficiency, Asia, Southeastern, biology, business.industry, Clinical Laboratory Techniques, Immunologic Deficiency Syndromes, virus diseases, HIV, biology.organism_classification, medicine.disease, Mycobacterium avium Complex, Virology, 3. Good health, Infectious Diseases, tuberculosis, Child, Preschool, Africa, Nontuberculous mycobacteria, Brief Reports, business, [SDV.MHEP]Life Sciences [q-bio]/Human health and pathology
Abstract

We enrolled 427 human immunodeficiency virus–infected children (median age, 7.3 years), 59.2% severely immunodeficient, with suspected tuberculosis in Southeast Asian and African settings. Nontuberculous mycobacteria were isolated in 46 children (10.8%); 45.7% of isolates were Mycobacterium avium complex. Southeast Asian origin, age 5–9 years, and severe immunodeficiency were independently associated with nontuberculous mycobacteria isolation. Clinical Trials Registration NCT01331811.

Published
2019

11. A treatment-decision score for HIV-infected children with suspected tuberculosis

Author

Francis Ateba-Ndongo, Mathurin Cyrille Tejiokem, Bunnet Dim, Philippe Msellati, Duong Ngoc Tran, Laureline Berteloot, Bintou Sanogo, Isabelle Fournier, Stéphane Blanche, Catherine Quillet, Guislaine Carcelain, Laurence Borand, Sylvain Godreuil, Vibol Ung, Viet Do Chau, Khanh Truong Huu, Polidy Pean, Leakhena Neou, Suzie Tetang-Ndiang, Olivier Marcy, Christophe Delacourt, Boubacar Nacro, Sophie Goyet, Unité d'Épidémiologie et de Santé Publique [Phnom Penh], Institut Pasteur du Cambodge, Réseau International des Instituts Pasteur (RIIP)-Réseau International des Instituts Pasteur (RIIP), Bordeaux population health (BPH), Université de Bordeaux (UB)-Institut de Santé Publique, d'Épidémiologie et de Développement (ISPED)-Institut National de la Santé et de la Recherche Médicale (INSERM), University of Health Sciences [Phnom-Penh, Cambodia] (UHS), Tuberculosis and HIV Department [Phnom Penh, Cambodia], National pediatric hospital [Phnom Penh, Cambodge] (NPH), Recherches Translationnelles sur le VIH et les maladies infectieuses endémiques er émergentes (TransVIHMI), Université Cheikh Anta Diop [Dakar, Sénégal] (UCAD)-Institut de Recherche pour le Développement (IRD)-Université de Yaoundé I-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Montpellier (UM)-Université Montpellier 1 (UM1), Laboratoire d'Epidémiologie et de Santé Publique, Centre Pasteur du Cameroun, Benh Vien Nhi Dong 1 Children's Hospital [Vietnam], Pham Ngoc Thach Hospital, Centre Mère et Enfant de la Fondation Chantal Biya, Centre international de référence Chantal Biya pour la recherche sur la prévention et la prise en charge du VIH/SIDA (CIRCB), Fondation Chantal Biya (FCB)-Fondation Chantal Biya (FCB), Centre Hospitalier Essos [Yaoundé, Cameroun], Centre Hospitalier Universitaire Souro Sanou [Bobo-Dioulasso] (CHUSS), Unité d'Immunologie Hématologie et Rhumatologie Pédiatrique [Necker, Paris], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-CHU Necker - Enfants Malades [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP), Angkor Hospital for Children (AHC), Immunologie [Phnom Penh], ANRS Research Site [Ho Chi Minh City, Vietnam], Essais Thérapeutiques et Maladies Infectieuses, Université Paris-Sud - Paris 11 (UP11)-Institut National de la Santé et de la Recherche Médicale (INSERM), Service de radiologie pédiatrique [CHU Necker], Service Immunologie Biologique [Paris], AP-HP Hôpital universitaire Robert-Debré [Paris], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP), Service de Bactériologie-Virologie [Montpellier], Hôpital Arnaud de Villeneuve-Centre Hospitalier Régional Universitaire [Montpellier] (CHRU Montpellier)-Université Montpellier 1 (UM1), Service de Pneumologie et d'Allergologie Pédiatriques, Funded by the ANRS (ANRS 12229) and Fondation Total., and We thank all children and their parents and caregivers for their participation in the study, national tuberculosis and HIV programs from participating countries for their support, Françoise Barré-Sinoussi and Jean-François Delfraissy for their continuous support, Xavier Anglaret for general guidance, Julien Asselineau and Paul Perez for methodologic advice, and Corine Chazallon and Vincent Bouteloup for statistical support.

Subjects
Male, Pediatrics, medicine.medical_specialty, Miliary tuberculosis, Tuberculosis, Antitubercular Agents, Infectious Disease, HIV Infections, Sensitivity and Specificity, QuantiFERON, 03 medical and health sciences, 0302 clinical medicine, Tuberculosis diagnosis, [SDV.MHEP.MI]Life Sciences [q-bio]/Human health and pathology/Infectious diseases, 030225 pediatrics, Clinical Decision Rules, Abdomen, medicine, Humans, 030212 general & internal medicine, Child, Lung, Receptors, Interferon, Ultrasonography, Bacteriological Techniques, Microscopy, medicine.diagnostic_test, Receiver operating characteristic, AIDS-Related Opportunistic Infections, business.industry, Reproducibility of Results, medicine.disease, 3. Good health, Radiography, Abdominal ultrasonography, Child, Preschool, Pediatrics, Perinatology and Child Health, Commentary, HIV/AIDS, Female, Sample collection, business, Chest radiograph
Abstract

BACKGROUND: Diagnosis of tuberculosis should be improved in children infected with HIV to reduce mortality. We developed prediction scores to guide antituberculosis treatment decision in HIV-infected children with suspected tuberculosis. METHODS: HIV-infected children with suspected tuberculosis enrolled in Burkina Faso, Cambodia, Cameroon, and Vietnam (ANRS 12229 PAANTHER 01 Study), underwent clinical assessment, chest radiography, Quantiferon Gold In-Tube (QFT), abdominal ultrasonography, and sample collection for microbiology, including Xpert MTB/RIF (Xpert). We developed 4 tuberculosis diagnostic models using logistic regression: (1) all predictors included, (2) QFT excluded, (3) ultrasonography excluded, and (4) QFT and ultrasonography excluded. We internally validated the models using resampling. We built a score on the basis of the model with the best area under the receiver operating characteristic curve and parsimony. RESULTS: A total of 438 children were enrolled in the study; 251 (57.3%) had tuberculosis, including 55 (12.6%) with culture- or Xpert-confirmed tuberculosis. The final 4 models included Xpert, fever lasting >2 weeks, unremitting cough, hemoptysis and weight loss in the past 4 weeks, contact with a patient with smear-positive tuberculosis, tachycardia, miliary tuberculosis, alveolar opacities, and lymph nodes on the chest radiograph, together with abdominal lymph nodes on the ultrasound and QFT results. The areas under the receiver operating characteristic curves were 0.866, 0.861, 0.850, and 0.846, for models 1, 2, 3, and 4, respectively. The score developed on model 2 had a sensitivity of 88.6% and a specificity of 61.2% for a tuberculosis diagnosis. CONCLUSIONS: Our score had a good diagnostic performance. Used in an algorithm, it should enable prompt treatment decision in children with suspected tuberculosis and a high mortality risk, thus contributing to significant public health benefits.

Published
2019

12. Mortality and its determinants in antiretroviral treatment-naive HIV-infected children with suspected tuberculosis: an observational cohort study

Author

Olivier Marcy, Mathurin Tejiokem, Philippe Msellati, Khanh Truong Huu, Viet Do Chau, Duong Tran Ngoc, Boubacar Nacro, Francis Ateba-Ndongo, Suzie Tetang-Ndiang, Vibol Ung, Bunnet Dim, Leakhena Neou, Laureline Berteloot, Laurence Borand, Christophe Delacourt, Stéphane Blanche, Sao Sarady Ay, Malen Chan, Phalla Chea, Sophie Goyet, Nimul Roat Men, Phearavin Pheng, Susan Ramsay, Sophea Suom, Arnaud Tarantola, Naisim Te, Sreymom Than, Sovannary Ung, Chorn Chhuk, Chantheany Huot, Sang Han Kath, Sokoeun Khin, Peou Kim, Kim Eng Lim, Phary Lim, Vannareth Lim, Yany Nav, Boren Pich, Sotharin Tuy, Phal Chea, Sengtray Chhraing, Bophal Chuop, Ramy Hem, Phanoeurn Heng, Seng Hap Huon, Sokhorn Khum, Thear Liv, Vichea Ly, Makara Moch, Leakheana Neou, Phanith Rey, Vina Sath, Nopheavann Sun, Pheron Chat, Viso Srey, Sitha Chheang, Putchhat Hor, Manory Oum, Monorea Keo, Sokchea Kou, Sokleaph Cheng, Alexandra Kerleguer, Michel Gomgnimbou, Antoinette Kabore, Anselme Millogo, Zakari Nikiema, Abdul Salam Ouedraogo, Sawadogo Saidou, Moumini Nouctara, Diane Ursule Sangare/Ouattara, Bintou Sanogo, Edgard Sib Sié, Dézémon Zingué, Roger Ngoya Abiguide, Patrice Assene Ngo'o, Francis Ateba Ndongo, Suzanne Balla, Verlaine Bolyse Mbouchong, Jean Marie Ehongo Amanya, Sara Eyangoh, Afi Leslie Kaiyven, Paul Koki Ndombo, Samuel Walter Kokola Bayanak, Marie Josée Mapah Kampaing, Elizabeth Mangoya, Minkala Mvogo, Jean Pierre Ndongo, Laurence Ngassam, Francine Nanda, Sylviane Ndjantou, Jean Audrey Ndongo, Marcelle Njind Nkoum, Anne Esther Njom Lend, Angeline Nkembe, Marie Flore Oyanche, Jean-Voisin Taguebue, Suzy Tetang-Moyo, Sylvie Georgette Zebaze, Thi Oanh Nguyen, Thi Ngoc Lan Nguyen, Catherine Quillet, Khanh Lê Quoc, My Huong To, Thi Kim Phung Tran, Chau Giang Do, Duc Bang Nguyen, Ngo Vi Vi Nguyen, Thi Hieu Nguyen, Thi Thanh Thanh Nguyen, Ngoc Duong Tran, Duy An Vo, Thi Xuan Lan Dang, Thi Kim Phuong Do, Thi Thanh Tuyen Dang, Hoang Chau Nguyen, Ngoc Tuong Vy Pham, Huu Khanh Truong, Chau Viet Do, Bich Ngoc Huynh, Thi Thanh Thuy Le, Thi Thu Hiep Nguyen, Ngoc Luu Tran, Thien An Vu, Huu Loc Tran, Manh Hoang Nguyen, Ngoc Lan Nguyen, Thi Cao Van Nguyen, Thu Hang Pham, Dinh Quyen Phan, Thi Ha Vo, Xuan Lien Truong, Xuan Thinh Vu, Guislaine Carcelain, Sylvain Godreuil, Isabelle Fournier-Nicolle, Institut Pasteur du Cambodge, Institut Pasteur du Cambodge-Réseau International des Instituts Pasteur ( RIIP ), Bordeaux population health ( BPH ), Université de Bordeaux ( UB ) -Institut de Santé Publique, d'Épidémiologie et de Développement (ISPED)-Institut National de la Santé et de la Recherche Médicale ( INSERM ), Centre Pasteur du Cameroun, Centre Pasteur du Cameroun-Réseau International des Instituts Pasteur ( RIIP ), Recherches Translationnelles sur le VIH et les maladies infectieuses ( TransVIHMI ), Université Montpellier 1 ( UM1 ) -Université Cheikh Anta Diop ( UCAD ) -Universtié Yaoundé 1 (Cameroun)-Université de Montpellier ( UM ), Service de radiologie pédiatrique [CHU Necker], Assistance publique - Hôpitaux de Paris (AP-HP)-CHU Necker - Enfants Malades [AP-HP], Service de Pneumologie Allergologie [CHU Necker], Service d'immunologie, hématologie et rhumatologie pédiatriques [CHU Necker], Réseau International des Instituts Pasteur (RIIP), Bordeaux population health (BPH), Université de Bordeaux (UB)-Institut de Santé Publique, d'Épidémiologie et de Développement (ISPED)-Institut National de la Santé et de la Recherche Médicale (INSERM), Recherches Translationnelles sur le VIH et les maladies infectieuses endémiques er émergentes (TransVIHMI), Université Cheikh Anta Diop [Dakar, Sénégal] (UCAD)-Institut de Recherche pour le Développement (IRD)-Université de Yaoundé I-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Montpellier (UM)-Université Montpellier 1 (UM1), Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-CHU Necker - Enfants Malades [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP), and Service d'immuno-hématologie pédiatrique [CHU Necker]

Subjects
Male, 0301 basic medicine, Pediatrics, medicine.medical_specialty, Tuberculosis, Adolescent, Anti-HIV Agents, Epidemiology, 030106 microbiology, Immunology, Antitubercular Agents, HIV Infections, Kaplan-Meier Estimate, Cohort Studies, 03 medical and health sciences, 0302 clinical medicine, [SDV.MHEP.MI]Life Sciences [q-bio]/Human health and pathology/Infectious diseases, Virology, Hiv infected, Burkina Faso, medicine, Antiretroviral treatment, Humans, [ SDV.IMM ] Life Sciences [q-bio]/Immunology, Cameroon, 030212 general & internal medicine, Mortality, Child, Coinfection, business.industry, medicine.disease, 3. Good health, Clinical trial, [ SDV.MHEP.MI ] Life Sciences [q-bio]/Human health and pathology/Infectious diseases, Infectious Diseases, Vietnam, Child, Preschool, Cohort, [SDV.IMM]Life Sciences [q-bio]/Immunology, Female, Observational study, Cambodia, business, Cohort study
Abstract

International audience; BACKGROUND:Tuberculosis is a major cause of morbidity and mortality in HIV-infected children, but is difficult to diagnose. We studied mortality and its determinants in antiretroviral treatment (ART)-naive HIV-infected children presenting with suspected tuberculosis.METHODS:In this observational cohort study, HIV-infected children aged 13 years or younger with suspected tuberculosis were followed up for 6 months as part of the ANRS 12229 PAANTHER 01 cohort in eight hospitals in four countries (Burkina Faso, Cambodia, Cameroon, and Vietnam). Children started ART and antituberculosis treatment at the clinician's discretion and were retrospectively classified into one of three groups by tuberculosis documentation: confirmed by culture or Xpert MTB/RIF, unconfirmed, and unlikely. We assessed mortality and associated factors using Kaplan-Meier methods and Cox proportional hazard models. The ANRS 12229 PAANTHER 01 study is registered at ClinicalTrials.gov, number NCT01331811.FINDINGS:266 (61%) of 438 children enrolled in the study between April 27, 2011, and May 31, 2014, were ART-naive and included in the analysis (40 had confirmed tuberculosis, 119 unconfirmed tuberculosis, and 107 unlikely tuberculosis). 112·5 person-years of follow-up were available. 154 children (58%) started antituberculosis treatment and 212 (80%) started ART. 50 children (19%) died. Mortality by 6 months was higher in children with confirmed tuberculosis (14 deaths; 2 month survival probability 65·0% [95% CI 50·2-79·8]) compared with unconfirmed tuberculosis (19 deaths; 83·5% [76·8-90·3]) and unlikely tuberculosis (17 deaths; 83·5% [76·3-90·7]; log-rank p=0·0141) and was lower in children with confirmed or unconfirmed tuberculosis who started antituberculosis treatment (p

Published
2018

13. A Treatment-Decision Score for HIV-Infected Children With Suspected Tuberculosis.

Author

Marcy, Olivier, Borand, Laurence, Ung, Vibol, Msellati, Philippe, Tejiokem, Mathurin, Khanh Truong Huu, Viet Do Chau, Duong Ngoc Tran, Ateba-Ndongo, Francis, Tetang-Ndiang, Suzie, Nacro, Boubacar, Sanogo, Bintou, Neou, Leakhena, Goyet, Sophie, Bunnet Dim, Pean, Polidy, Quillet, Catherine, Fournier, Isabelle, Berteloot, Laureline, and Carcelain, Guislaine

Published
2019
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14. Plasma Concentrations, Efficacy and Safety of Efavirenz in HIV-Infected Adults Treated for Tuberculosis in Cambodia (ANRS 1295-CIPRA KH001 CAMELIA Trial)

Author

Narom Prak, Arnaud Fontanet, Monidarin Chou, Chanroeun Hak, Olivier Marcy, Anne-Marie Taburet, Chindamony Kim, Laurence Borand, François-Xavier Blanc, Eric Nerrienet, Bunnet Dim, Khemarin Kim Lak, Anne E. Goldfeld, Thim Sok, Yoann Madec, Didier Laureillard, Phearavin Pheng, Unité d'Épidémiologie et de Santé Publique [Phnom Penh], Institut Pasteur du Cambodge, Réseau International des Instituts Pasteur (RIIP)-Réseau International des Instituts Pasteur (RIIP), Epidémiologie des Maladies Emergentes - Emerging Diseases Epidemiology, Pasteur-Cnam Risques infectieux et émergents (PACRI), Institut Pasteur [Paris] (IP)-Conservatoire National des Arts et Métiers [CNAM] (CNAM), HESAM Université - Communauté d'universités et d'établissements Hautes écoles Sorbonne Arts et métiers université (HESAM)-HESAM Université - Communauté d'universités et d'établissements Hautes écoles Sorbonne Arts et métiers université (HESAM)-Institut Pasteur [Paris] (IP)-Conservatoire National des Arts et Métiers [CNAM] (CNAM), HESAM Université - Communauté d'universités et d'établissements Hautes écoles Sorbonne Arts et métiers université (HESAM)-HESAM Université - Communauté d'universités et d'établissements Hautes écoles Sorbonne Arts et métiers université (HESAM), ANRS Research Site [Ho Chi Minh City, Vietnam], Pham Ngoc Thach Hospital, University of Health Sciences [Phnom-Penh, Cambodia] (UHS), Khmero-Sovietic Friendship Hospital, Donkeo Provincial Hospital [Phnom Penh], Médecins Sans Frontières [Phnom Penh, Cambodge], Cambodian Health Committee, Svay Rieng Provincial [Svay Rieng, Cambodge], Calmette Hospital [Phnom Penh], Siem Reap Referral Hospital [Siem Reap, Cambodge], Réseau International des Instituts Pasteur (RIIP), Conservatoire National des Arts et Métiers [CNAM] (CNAM), HESAM Université - Communauté d'universités et d'établissements Hautes écoles Sorbonne Arts et métiers université (HESAM), Harvard Medical School [Boston] (HMS), Hôpital Bicêtre, Université Paris-Sud - Paris 11 (UP11)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Hôpital Bicêtre, Unité de recherche de l'institut du thorax (ITX-lab), Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-Université de Nantes - UFR de Médecine et des Techniques Médicales (UFR MEDECINE), Université de Nantes (UN)-Université de Nantes (UN), Boutin, Marion, Institut Pasteur [Paris]-Conservatoire National des Arts et Métiers [CNAM] (CNAM)-Institut Pasteur [Paris]-Conservatoire National des Arts et Métiers [CNAM] (CNAM), and unité de recherche de l'institut du thorax UMR1087 UMR6291 (ITX)

Subjects
CD4-Positive T-Lymphocytes, Cyclopropanes, Male, Viral Diseases, HIV Infections, Pharmacology, chemistry.chemical_compound, 0302 clinical medicine, Interquartile range, immune system diseases, [SDV.MHEP.MI]Life Sciences [q-bio]/Human health and pathology/Infectious diseases, Blood plasma, Drug Interactions, 030212 general & internal medicine, 0303 health sciences, Multidisciplinary, Coinfection, Clinical Pharmacology, virus diseases, Antivirals, 3. Good health, AIDS, Infectious Diseases, Alkynes, [SDV.SP.PHARMA] Life Sciences [q-bio]/Pharmaceutical sciences/Pharmacology, [SDV.MHEP.MI] Life Sciences [q-bio]/Human health and pathology/Infectious diseases, Reverse Transcriptase Inhibitors, Medicine, Female, Cambodia, Research Article, medicine.drug, Adult, Drugs and Devices, Tuberculosis, Efavirenz, Clinical Research Design, Science, Sexually Transmitted Diseases, Microbiology, 03 medical and health sciences, Adverse Reactions, Virology, medicine, Humans, Clinical Trials, Adverse effect, Biology, 030306 microbiology, business.industry, Body Weight, HIV, medicine.disease, Benzoxazines, Pharmacodynamics, chemistry, [SDV.SP.PHARMA]Life Sciences [q-bio]/Pharmaceutical sciences/Pharmacology, Hemoglobinemia, business, Rifampicin
Abstract

ObjectiveTo assess efavirenz plasma concentrations and their association with treatment efficacy and tolerance of efavirenz 600 mg daily in HIV-tuberculosis co-infected patients.MethodsHIV-infected adults with CD4+ T cell count ≤ 200/mm(3) received standard 6-month tuberculosis treatment and antiretroviral therapy including a daily-dose of 600 mg of efavirenz, irrespective of their body weight. Mid-dose blood samples were drawn both on tuberculosis treatment (week +2 and week +6 after antiretroviral therapy initiation, and week 22 of follow-up) and off tuberculosis treatment (week 50 of follow-up). Considered therapeutic range was 1,000 to 4,000 ng/mL. Multivariate analysis was performed to evaluate the association between efavirenz concentration below 1,000 ng/mL and virological failure. Linear regression was used to test the association between efavirenz exposure and CD4+ T cell gain. Severe side effects potentially related to efavirenz were described and their association with efavirenz exposure was tested by multivariate analysis.ResultsEfavirenz plasma concentrations were available in 540 patients. Median [interquartile range] efavirenz concentrations were 2,674 ng/mL [1,690-4,533], 2,667 ng/mL [1,753-4,494] and 2,799 ng/mL [1,804-4,744] at week +2, week +6, week 22, respectively, and 2,766 ng/mL [1,941-3,976] at week 50. Efavirenz concentrations were lower at week 50 (off rifampicin) compared to week 22 (on rifampicin) (pConclusionBody weight and tuberculosis treatment were not associated with low efavirenz concentrations or treatment failure, supporting the 600 mg daily-dose of efavirenz in HIV-tuberculosis co-infected patients. High efavirenz concentrations were related to a higher risk of central nervous system side effects and hepatotoxicity.Trial registrationClinicalTrials.gov NCT01300481.

Published
2014

15. Paradoxical tuberculosis-associated immune reconstitution inflammatory syndrome after early initiation of antiretroviral therapy in a randomized clinical trial

Author

Laurence Borand, Didier Laureillard, Sarin Chan, Marcelo Fernandez, Narom Prak, Chindamony Kim, François-Xavier Blanc, Anne E. Goldfeld, Bunnet Dim, Thim Sok, Olivier Marcy, Yoann Madec, Sokeo Chea, Eric Nerrienet, Jean-François Delfraissy, Agence Nationale de Recherches sur le Sida et les Hépatites Virales (ANRS), Institut Pasteur du Cambodge, Réseau International des Instituts Pasteur (RIIP), Epidémiologie des Maladies Emergentes - Emerging Diseases Epidemiology, Pasteur-Cnam Risques infectieux et émergents (PACRI), Institut Pasteur [Paris]-Conservatoire National des Arts et Métiers [CNAM] (CNAM)-Institut Pasteur [Paris]-Conservatoire National des Arts et Métiers [CNAM] (CNAM), Cambodian Health Committee, Khmero-Sovietic Friendship Hospital, Donkeo Provincial Hospital, Hôpital Bicêtre, Université Paris-Sud - Paris 11 (UP11)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Hôpital Bicêtre, and Harvard Medical School [Boston] (HMS)

Subjects
Adult, Male, medicine.medical_specialty, Tuberculosis, Immunology, Antitubercular Agents, HIV Infections, Risk Assessment, law.invention, 03 medical and health sciences, 0302 clinical medicine, Pharmacotherapy, Randomized controlled trial, Immune reconstitution inflammatory syndrome, Acquired immunodeficiency syndrome (AIDS), law, Immune Reconstitution Inflammatory Syndrome, Internal medicine, Antiretroviral Therapy, Highly Active, medicine, Immunology and Allergy, Humans, 030212 general & internal medicine, Immunodeficiency, ComputingMilieux_MISCELLANEOUS, 0303 health sciences, 030306 microbiology, Proportional hazards model, business.industry, medicine.disease, 3. Good health, Infectious Diseases, Female, [SDV.SPEE]Life Sciences [q-bio]/Santé publique et épidémiologie, business, Cambodia, Viral load
Abstract

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/μl 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/μl 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.

Published
2013

16. Early (2 weeks) vs. late (8 weeks) initiation of highly active antiretroviral treatment (HAART) significantly enhance survival of severely immunosuppressed HIV-infected adults with newly diagnosed tuberculosis: results of the CAMELIA clinical trial

Author

Yoann Madec, Olivier Marcy, Eric Nerrienet, Sarin Chan, Chhun Im Sin, Didier Laureillard, Chanroeurn Hak, Narom Prak, Borann Sar, Anne E. Goldfeld, Claire Rekacewicz, Sath Sun, Lawrence Fox, Chindamony Kim, Marcelo Fernandez, Bunnet Dim, François-Xavier Blanc, Jean-François Delfraissy, Thim Sok, Khemarin Kim Lak, Sirenda Vong, Laurence Borand, and Bertrand Guillard

Subjects
Pediatrics, medicine.medical_specialty, Tuberculosis, Efavirenz, business.industry, lcsh:R, Stavudine, lcsh:Medicine, Lamivudine, General Medicine, Newly diagnosed, medicine.disease, General Biochemistry, Genetics and Molecular Biology, Clinical trial, chemistry.chemical_compound, chemistry, Hiv infected, medicine, Antiretroviral treatment, Oral Presentation, lcsh:Q, lcsh:Science, business, medicine.drug
Abstract

Early (2 weeks) vs. late (8 weeks) initiation of highly active antiretroviral treatment (HAART) significantly enhance survival of severely immunosuppressed HIV-infected adults with newly diagnosed tuberculosis: results of the CAMELIA clinical trial Francois-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-Francois Delfraissy, Anne E Goldfeld

Published
2011

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