부산대학교 도서관

Summary Background In patients co-infected with HIV and tuberculosis, antiretroviral therapy options are limited due to drug--drug interactions with rifampicin. A previous phase 2 trial indicated that raltegravir 400 mg twice a day or efavirenz 600 mg once a day might have similar virological efficacy in patients given rifampicin. In this phase 3 trial, we assessed the non-inferiority of raltegravir to efavirenz. Methods We did a multicentre, open-label, non-inferiority, randomised, phase 3 trial at six sites in Côte d'Ivoire, Brazil, France, Mozambique, and Vietnam. We included antiretroviral therapy (ART)-naive adults (aged [greater than or equal to]18 years) with confirmed HIV-1 infection and bacteriologically confirmed or clinically diagnosed tuberculosis who had initiated rifampicin-containing tuberculosis treatment within the past 8 weeks. Using computerised random numbers, we randomly assigned participants (1:1; stratified by country) to receive raltegravir 400 mg twice daily or efavirenz 600 mg once daily, both in combination with tenofovir and lamivudine. The primary outcome was the proportion of patients with virological suppression at week 48 (defined as plasma HIV RNA concentration Findings Between Sept 28, 2015, and Jan 5, 2018, 460 participants were randomly assigned to raltegravir (n=230) or efavirenz (n=230), of whom 457 patients (230 patients in the raltegravir group; 227 patients in the efavirenz group) were included in the intention-to-treat analysis and 410 (206 patients in the raltegravir group; 204 patients in the efavirenz group) in the on-treatment analysis. At baseline, the median CD4 count was 103 cells per [mu]L and median plasma HIV RNA concentration was 5*5 log.sub.10 copies per mL (IQR 5*0--5*8). 310 (68%) of 457 participants had bacteriologically-confirmed tuberculosis. In the intention-to-treat population, at week 48, 140 (61%) of 230 participants in the raltegravir group and 150 (66%) of 227 patients in the efavirenz had achieved virological suppression (between-group difference -5*2% [95% CI -14*0 to 3*6]), thus raltegravir did not meet the predefined criterion for non-inferiority. The most frequent adverse events were HIV-associated non-AIDS illnesses (eight [3%] of 229 patients in the raltegravir group; 21 [9%] of 230 patients in the efavirenz group) and AIDS-defining illnesses (ten [4%] patients in the raltegravir group; 13 [6%] patients in the efavirenz group). 58 (25%) of 229 patients in raltegravir group and 66 (29%) of 230 patients in the efavirenz group had grade 3 or 4 adverse events. 26 (6%) of 457 patients died during follow-up: 14 in the efavirenz group and 12 in the raltegravir group. Interpretation In patients with HIV given tuberculosis treatment, non-inferiority of raltegravir compared with efavirenz was not shown. Raltegravir was well tolerated and could be considered as an option, but only in selected patients. Funding National French Agency for AIDS Research, Ministry of Health in Brazil, Merck. Translations For the Portuguese and French translations of the abstract see Supplementary Materials section. Author Affiliation: (a) Department of Infectious Diseases, Hôpital Saint-Louis, Assistance Publique Hôpitaux de Paris, Paris, France (b) Department of Virology, Hôpital Saint-Louis, Assistance Publique Hôpitaux de Paris, Paris, France (c) Bordeaux Population Health Research Center, UMR 1219, INSERM, University of Bordeaux, French National Research Institute for Sustainable Development, Bordeaux, France (d) Centre de Prise en charge de Recherche et de Formation, Abidjan, Côte d'Ivoire (e) Programme PACCI/ANRS Research Center, Abidjan, Cote d'Ivoire (f) Département de Dermatologie et d'Infectiologie, Unite de Formation et de Recherche des Sciences Médicales, Université Félix Houphouët Boigny, Abidjan, Cote d'Ivoire (g) Instituto Nacional de Saúde, Marracuene, Mozambique (h) Research Unit 1058 Pathogenesis and Control Chronical Infections, INSERM, French Blood Center, University of Montpellier, Montpellier, France (i) Department of Infectious and Tropical Diseases, Nimes University Hospital, Nimes, France (j) General Planning Department, Pham Ngoc Thach Hospital, Ho Chi Minh City, Vietnam (k) National Agency for Research on AIDS and Viral Hepatitis Research Site, Pham Ngoc Thach Hospital, Ho Chi Minh City, Vietnam (l) National Institute of Infectious Diseases Evandro Chagas, Oswaldo Cruz Foundation, Rio de Janeiro, Brazil (m) INSERM U944, Université de Paris, Paris, France * Correspondence to: Dr Nathalie De Castro, Department of Infectious Diseases, Hôpital Saint-Louis, Assistance Publique Hôpitaux de Paris, 75010 Paris, France (footnote)* Contributed equally (footnote)[Dagger] Members are listed in Byline: Nathalie De Castro, MD [nathalie.de-castro@aphp.fr] (a,c), Olivier Marcy, MD (c), Corine Chazallon, MSc (c), Eugène Messou, MD (d,e,f), Prof Serge Eholié, MD (e,f), Jean-Baptiste N'takpe, MD (e), Nilesh Bhatt, MD (g), Celso Khosa, MD (g), Isabel Timana Massango, MD (g), Didier Laureillard, MD (h,i), Giang Do Chau, MD (j), Anaïs Domergue, MSc (k), Valdilea Veloso, MD (l), Rodrigo Escada, MD (l), Sandra Wagner Cardoso, MD (l), Prof Constance Delaugerre, PhD (b,m), Xavier Anglaret, MD (c,d), Prof Jean-Michel Molina, MD (a,m), Beatriz Grinsztejn, MD (l), Ahyi Irmine, Aka Kakou, Alves Ana cláudia, Amani Jacqueline, Amoakon Bonzou, Anglaret Xavier, Anzian Amani, Azam Khalide, Barreto Débora Faber, Bastos dos Santos Rui, Beuscart Aurélie, Bhatt Nilesh, Bi Antoine, Bonnet Maryline, Bui thi Kim Nhung, Camacho Luiz, Cao Tung khanh, Chazallon Corine, Coelho Lara, Cong thi Mai Luong, Da SILVA Robson Pierre, Dang thi Minh Há, Dano Lehi Florence, De castro Nathalie, De Solère Marie, Delaugerre Constance, Diallo Alpha, Dinh phuong Thanh, Diomandé Donald, Do cha Giang, Do ha thanh Trang, Domergue Anaïs, Dong bui vu hoang Trang Quynh Nhu, Eboumou Fulgence, Eholie Serge, Ello Frederick, Emieme Arlette, Escada Rodrigo, Etilé Etienne, Fanny Salimata, Ferreira Ana cristina, Gbey Robert, Gnokoro Joachim, Gomes Tatiane, Gonzales Maura lassance, Grinsztejn Beatriz, Guiroy Frederique, Ha Thanh Trang Do, Hoagland Brenda, Huynh Anh Phuong, Huynh hoang Khanh thu, Irié Marcelin, Kacou Jean-claude, Kan Samuel, Karcher Sophie, Kassy Mc, Khosa Celso, Konan Lambert, Konan Romuald, Koné Fatoumata, Kouadio Suzanne, Kouamé Martin, Krsitic Tânia, Labibi Georgette, Laureillard Didier, Le Carrou Jérôme, Le Guoc Khanh, Le Thi Ngoc bich, Lessa Flávia, Long Van Duong, Luong Anh Que, Mai Huyen Thi Thu, Mai Thu Huyen Nguyet, Manhiça Emelva, Marcy Olivier, Marins Luana, Matsinhe Lectícia, Menan Hervé, Messou Eugène, Molina Jean-michel, Montoyo Alice, Moreira Ronaldo ismerio, N'takpé Jean-baptiste, Nazer Sandro, Nguyen Cao van thi, Nguyen Nuoi THI, Nguyen duc Bang, Nguyen huu Lân, Nguyen ngoc Lan, Nguyen nhu Viet, Nguyen thi Hong, Nhumaio Dilário, Pham Hang THU, Pham Anh THI QUYNH, Ponscarme Diane, Previllon Miresta, Rabe Cyprien, Rapoud Delphine, Rebelo Daniel, Rekacewicz Claire, Ribeiro Valéria rita, Ribeiro Jorge, Salgado Lucimar, Santana de MOURA Soraia, Santos Desiree, Siloue Yamissa, Siloue Bertine, Sitoe Nádia, Taburet Anne-marie, Tavares Isabel cristina, Tavora dos Santos Filho Ezio, Tchehy Cecile, Timana Isabel, Toni Thomas-d'aquin, Torres Thiago, Tran Thao PHAM PHUONG, Tran Loc HUU, Tran Quy Thi Kim, Tran Tien Thi Thuy, Tran Ton, Tran Thi Hieu Nhi, Tran Thi-Hai Ly, Veloso Valdilea, Vilanculo Arlindo, Vu Xuan Thinh, Vubil Adolfo, Wagner Sandra, Zitha Alcina, Astrid