{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,8,20]],"date-time":"2026-08-20T16:28:23Z","timestamp":1787243303229,"version":"build-2736575974"},"reference-count":47,"publisher":"Frontiers Media SA","license":[{"start":{"date-parts":[[2019,6,28]],"date-time":"2019-06-28T00:00:00Z","timestamp":1561680000000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100006507","name":"Funda\u00e7\u00e3o Oswaldo Cruz","doi-asserted-by":"publisher","id":[{"id":"10.13039\/501100006507","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100003593","name":"Conselho Nacional de Desenvolvimento Cient\u00edfico e Tecnol\u00f3gico","doi-asserted-by":"publisher","award":["303919\/2018-3"],"award-info":[{"award-number":["303919\/2018-3"]}],"id":[{"id":"10.13039\/501100003593","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100003593","name":"Conselho Nacional de Desenvolvimento Cient\u00edfico e Tecnol\u00f3gico","doi-asserted-by":"publisher","award":["407632\/2012-3"],"award-info":[{"award-number":["407632\/2012-3"]}],"id":[{"id":"10.13039\/501100003593","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100002322","name":"Coordena\u00e7\u00e3o de Aperfeii\u00e7oamento de Pessoal de N\u00edvel Superior","doi-asserted-by":"publisher","award":["88881.169912\/2018-01"],"award-info":[{"award-number":["88881.169912\/2018-01"]}],"id":[{"id":"10.13039\/501100002322","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100004586","name":"Funda\u00e7\u00e3o Carlos Chagas Filho de Amparo \u00e0 Pesquisa do Estado do Rio de Janeiro","doi-asserted-by":"publisher","award":["E-26\/202.764\/2016"],"award-info":[{"award-number":["E-26\/202.764\/2016"]}],"id":[{"id":"10.13039\/501100004586","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100004586","name":"Funda\u00e7\u00e3o Carlos Chagas Filho de Amparo \u00e0 Pesquisa do Estado do Rio de Janeiro","doi-asserted-by":"publisher","award":["E-26\/202.347\/2017"],"award-info":[{"award-number":["E-26\/202.347\/2017"]}],"id":[{"id":"10.13039\/501100004586","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100004586","name":"Funda\u00e7\u00e3o Carlos Chagas Filho de Amparo \u00e0 Pesquisa do Estado do Rio de Janeiro","doi-asserted-by":"publisher","award":["E-26\/202.764\/2016"],"award-info":[{"award-number":["E-26\/202.764\/2016"]}],"id":[{"id":"10.13039\/501100004586","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100004586","name":"Funda\u00e7\u00e3o Carlos Chagas Filho de Amparo \u00e0 Pesquisa do Estado do Rio de Janeiro","doi-asserted-by":"publisher","award":["E-26\/202.807\/2018"],"award-info":[{"award-number":["E-26\/202.807\/2018"]}],"id":[{"id":"10.13039\/501100004586","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100004586","name":"Funda\u00e7\u00e3o Carlos Chagas Filho de Amparo \u00e0 Pesquisa do Estado do Rio de Janeiro","doi-asserted-by":"publisher","award":["E-26\/010.001675\/2016"],"award-info":[{"award-number":["E-26\/010.001675\/2016"]}],"id":[{"id":"10.13039\/501100004586","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100004586","name":"Funda\u00e7\u00e3o Carlos Chagas Filho de Amparo \u00e0 Pesquisa do Estado do Rio de Janeiro","doi-asserted-by":"publisher","award":["E-26\/010.001904\/2015"],"award-info":[{"award-number":["E-26\/010.001904\/2015"]}],"id":[{"id":"10.13039\/501100004586","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100004586","name":"Funda\u00e7\u00e3o Carlos Chagas Filho de Amparo \u00e0 Pesquisa do Estado do Rio de Janeiro","doi-asserted-by":"publisher","award":["E-26\/202.918\/2018"],"award-info":[{"award-number":["E-26\/202.918\/2018"]}],"id":[{"id":"10.13039\/501100004586","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["frontiersin.org"],"crossmark-restriction":true},"short-container-title":["Front. Cell. Infect. Microbiol."],"DOI":"10.3389\/fcimb.2019.00229","type":"journal-article","created":{"date-parts":[[2019,6,28]],"date-time":"2019-06-28T08:50:47Z","timestamp":1561711847000},"update-policy":"https:\/\/doi.org\/10.3389\/crossmark-policy","source":"Crossref","is-referenced-by-count":29,"title":["Miltefosine-Lopinavir Combination Therapy Against Leishmania infantum Infection: In vitro and in vivo Approaches"],"prefix":"10.3389","volume":"9","author":[{"given":"Karina M.","family":"Rebello","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Valter V.","family":"Andrade-Neto","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Claudia Regina B.","family":"Gomes","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Marcos Vin\u00edcius N.","family":"de Souza","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Marta H.","family":"Branquinha","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Andr\u00e9 L. S.","family":"Santos","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Eduardo Caio","family":"Torres-Santos","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Claudia M.","family":"d'Avila-Levy","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1965","published-online":{"date-parts":[[2019,6,28]]},"reference":[{"key":"B1","doi-asserted-by":"publisher","first-page":"1943","DOI":"10.3389\/fimmu.2017.01943","article-title":"Immunomodulatory therapy of visceral leishmaniasis in human immunodeficiency virus-coinfected patients","volume":"8","author":"Adriaensen","year":"2017","journal-title":"Front. Immunol."},{"key":"B2","doi-asserted-by":"publisher","first-page":"93","DOI":"10.1007\/BF02767767","article-title":"Mediterranean leishmaniasis in HIV-infected patients: epidemiological, clinical, and diagnostic features of 22 cases","volume":"26","author":"Agostoni","year":"1998","journal-title":"Infection"},{"key":"B3","doi-asserted-by":"publisher","first-page":"334","DOI":"10.1128\/CMR.00061-07","article-title":"The relationship between leishmaniasis and AIDS: the second 10 years","volume":"21","author":"Alvar","year":"2008","journal-title":"Clin. Microbiol. Rev."},{"key":"B4","doi-asserted-by":"publisher","first-page":"183","DOI":"10.1186\/s13071-016-1467-8","article-title":"Imipramine alters the sterol profile in Leishmania amazonensis and increases its sensitivity to miconazole","volume":"9","author":"Andrade-Neto","year":"2016","journal-title":"Parasit. Vectors"},{"key":"B5","doi-asserted-by":"publisher","first-page":"e02095","DOI":"10.1128\/AAC.02095-17","article-title":"Complex interplay between sphingolipid and sterol metabolism revealed by perturbations to the leishmania metabolome caused by miltefosine","volume":"62","author":"Armitage","year":"2018","journal-title":"Antimicrob. Agents Chemother."},{"key":"B6","doi-asserted-by":"publisher","first-page":"2167","DOI":"10.1128\/AAC.39.9.2167","article-title":"Culture microtitration: a sensitive method for quantifying Leishmania infantum in tissues of infected mice","volume":"39","author":"Buffet","year":"1995","journal-title":"Antimicrob. Agents Chemother."},{"key":"B7","doi-asserted-by":"publisher","first-page":"951","DOI":"10.1016\/S0140-6736(18)31204-2","article-title":"Leishmaniasis","volume":"392","author":"Burza","year":"2018","journal-title":"Lancet"},{"key":"B8","doi-asserted-by":"publisher","first-page":"e3053","DOI":"10.1371\/journal.pntd.0003053","article-title":"Visceral leishmaniasis and HIV co-infection in Bihar, India: long-term effectiveness and treatment outcomes with liposomal amphotericin B (AmBisome)","volume":"8","author":"Burza","year":"2014","journal-title":"PLoS Negl. Trop. Dis."},{"key":"B9","doi-asserted-by":"publisher","first-page":"825","DOI":"10.1186\/s13104-018-3927-z","article-title":"Docking simulation between HIV peptidase inhibitors and Trypanosoma cruzi aspartyl peptidase","volume":"11","author":"Castilho","year":"2018","journal-title":"BMC Res. Notes"},{"key":"B10","doi-asserted-by":"publisher","first-page":"e0153921","DOI":"10.1371\/journal.pone.0153921","article-title":"Time to HAART initiation after diagnosis and treatment of opportunistic infections in patients with AIDS in Latin America","volume":"11","author":"Crabtree-Ram\u00edrez","year":"2016","journal-title":"PLoS ONE"},{"key":"B11","doi-asserted-by":"publisher","first-page":"e0005281","DOI":"10.1371\/journal.pntd.0005281","article-title":"Cyclobenzaprine raises ROS levels in Leishmania infantum and reduces parasite burden in infected mice","volume":"11","author":"Cunha-J\u00fanior","year":"2017","journal-title":"PLoS Negl. Trop. Dis."},{"key":"B12","doi-asserted-by":"publisher","first-page":"3794","DOI":"10.1128\/AAC.01787-15","article-title":"Preclinical studies evaluating subacute toxicity and therapeutic efficacy of LQB-118 in experimental visceral leishmaniasis","volume":"60","author":"Cunha-J\u00fanior","year":"2016","journal-title":"Antimicrob. Agents Chemother."},{"key":"B13","doi-asserted-by":"publisher","first-page":"2576","DOI":"10.1093\/jac\/dks275","article-title":"Miltefosine: a review of its pharmacology and therapeutic efficacy in the treatment of leishmaniasis","volume":"67","author":"Dorlo","year":"2012","journal-title":"J. Antimicrob. Chemother."},{"key":"B14","doi-asserted-by":"publisher","first-page":"248","DOI":"10.4103\/0974-777X.68528","article-title":"Human immunodeficiency virus and leishmaniasis","volume":"2","author":"Ezra","year":"2010","journal-title":"J. Glob. Infect. Dis."},{"key":"B15","doi-asserted-by":"publisher","first-page":"161","DOI":"10.1016\/0166-6851(84)90004-5","article-title":"Sterols of Leishmania species. implications for biosynthesis","volume":"10","author":"Goad","year":"1984","journal-title":"Mol. Biochem. Parasitol."},{"key":"B16","doi-asserted-by":"publisher","first-page":"1795","DOI":"10.1056\/NEJM199912093412403","article-title":"Miltefosine, an oral agent, for the treatment of Indian visceral leishmaniasis","volume":"341","author":"Jha","year":"1999","journal-title":"N. Engl. J. Med."},{"key":"B17","doi-asserted-by":"publisher","first-page":"751","DOI":"10.1038\/nrd4683","article-title":"Hit and lead criteria in drug discovery for infectious diseases of the developing world","volume":"14","author":"Katsuno","year":"2015","journal-title":"Nat. Rev. Drug Discov."},{"key":"B18","doi-asserted-by":"publisher","first-page":"825","DOI":"10.1007\/s00436-012-3212-3","article-title":"Validation of a simple resazurin-based promastigote assay for the routine monitoring of miltefosine susceptibility in clinical isolates of Leishmania donovani","volume":"112","author":"Kulshrestha","year":"2013","journal-title":"Parasitol. Res."},{"key":"B19","doi-asserted-by":"publisher","first-page":"e0006164","DOI":"10.1371\/journal.pntd.0006164","article-title":"Changing demographics of visceral leishmaniasis in northeast Brazil: lessons for the future","volume":"12","author":"Lima","year":"2018","journal-title":"PLoS Negl. Trop. Dis."},{"key":"B20","doi-asserted-by":"publisher","first-page":"147","DOI":"10.2147\/HIV.S93789","article-title":"Leishmaniasis-HIV coinfection: current challenges","volume":"8","author":"Lindoso","year":"2016","journal-title":"HIV AIDS"},{"key":"B21","doi-asserted-by":"publisher","first-page":"9375","DOI":"10.1073\/pnas.0703678104","article-title":"Evolutionary and geographical history of the Leishmania donovani complex with a revision of current taxonomy","volume":"104","author":"Lukes","year":"2007","journal-title":"Proc. Natl. Acad. Sci. U.S.A."},{"key":"B22","doi-asserted-by":"publisher","first-page":"e0003588","DOI":"10.1371\/journal.pntd.0003588","article-title":"Targeting ergosterol biosynthesis in Leishmania donovani: essentiality of sterol 14 alpha-demethylase","volume":"9","author":"McCall","year":"2015","journal-title":"PLoS Negl. Trop. Dis."},{"key":"B23","doi-asserted-by":"publisher","first-page":"e3021","DOI":"10.1371\/journal.pntd.0003021","article-title":"Visceral leishmaniasis and HIV coinfection in the Mediterranean region","volume":"8","author":"Monge-Maillo","year":"2014","journal-title":"PLoS Negl. Trop. Dis."},{"key":"B24","doi-asserted-by":"publisher","first-page":"298","DOI":"10.1016\/j.trstmh.2011.01.006","article-title":"The emergence of concurrent HIV-1\/AIDS and visceral leishmaniasis in Northeast Brazil","volume":"105","author":"Nascimento","year":"2011","journal-title":"Trans. R. Soc. Trop. Med. Hyg."},{"key":"B25","doi-asserted-by":"publisher","first-page":"1","DOI":"10.1093\/jac\/dkg301","article-title":"Synergy, antagonism, and what the chequerboard puts between them","volume":"52","author":"Odds","year":"2003","journal-title":"J. Antimicrob. Chemother."},{"key":"B26","doi-asserted-by":"publisher","first-page":"6137","DOI":"10.1128\/AEM.01078-12","article-title":"Multidrug therapy and evolution of antibiotic resistance: when order matters","volume":"78","author":"Perron","year":"2012","journal-title":"Appl. Environ. Microbiol."},{"key":"B27","doi-asserted-by":"publisher","first-page":"58","DOI":"10.1016\/j.pt.2004.11.003","article-title":"The impact of HIV-protease inhibitors on opportunistic parasites","volume":"21","author":"Pozio","year":"2005","journal-title":"Trends Parasitol."},{"key":"B28","doi-asserted-by":"publisher","first-page":"147","DOI":"10.2147\/CLEP.S44267","article-title":"Epidemiology of visceral leishmaniasis","volume":"6","author":"Ready","year":"2014","journal-title":"Clin. Epidemiol."},{"key":"B29","doi-asserted-by":"publisher","first-page":"1304","DOI":"10.1017\/S0031182018000823","article-title":"Lopinavir, an HIV-1 peptidase inhibitor, induces alteration on the lipid metabolism of Leishmania amazonensis promastigotes","volume":"145","author":"Rebello","year":"2018","journal-title":"Parasitology"},{"key":"B30","doi-asserted-by":"publisher","first-page":"e152","DOI":"10.1093\/cid\/cir674","article-title":"Limited effectiveness of high-dose liposomal amphotericin B (AmBisome) for treatment of visceral leishmaniasis in an Ethiopian population with high HIV prevalence","volume":"53","author":"Ritmeijer","year":"2011","journal-title":"Clin. Infect. Dis."},{"key":"B31","doi-asserted-by":"publisher","first-page":"129","DOI":"10.1016\/S0166-6851(02)00280-3","article-title":"Fatty acid and sterol metabolism: potential antimicrobial targets in apicomplexan and trypanosomatid parasitic protozoa","volume":"126","author":"Roberts","year":"2003","journal-title":"Mol. Biochem. Parasitol."},{"key":"B32","doi-asserted-by":"publisher","first-page":"21","DOI":"10.4331\/wjbc.v1.i2.21","article-title":"HIV aspartyl protease inhibitors as promising compounds against Candida albicans Andr\u00e9 Luis Souza dos Santos","volume":"1","author":"Santos","year":"2010","journal-title":"World J. Biol. Chem."},{"key":"B33","doi-asserted-by":"publisher","first-page":"e4918","DOI":"10.1371\/journal.pone.0004918","article-title":"HIV aspartyl peptidase inhibitors interfere with cellular proliferation, ultrastructure and macrophage infection of Leishmania amazonensis","volume":"4","author":"Santos","year":"2009","journal-title":"PLoS ONE"},{"key":"B34","doi-asserted-by":"publisher","first-page":"348","DOI":"10.1093\/jac\/dks410","article-title":"Nelfinavir is effective in inhibiting the multiplication and aspartic peptidase activity of Leishmania species, including strains obtained from HIV-positive patients","volume":"68","author":"Santos","year":"2013","journal-title":"J. Antimicrob. Chemother."},{"key":"B35","doi-asserted-by":"publisher","first-page":"103","DOI":"10.1016\/j.ijid.2014.07.011","article-title":"Changing trends in the epidemiology, clinical presentation, and diagnosis of Leishmania-HIV co-infection in India","volume":"29","author":"Singh","year":"2014","journal-title":"Int. J. Infect. Dis."},{"key":"B36","doi-asserted-by":"publisher","first-page":"e91","DOI":"10.1093\/cid\/cir521","article-title":"Liposomal amphotericin B for visceral leishmaniasis in human immunodeficiency virus-coinfected patients: 2-year treatment outcomes in Bihar, India","volume":"53","author":"Sinha","year":"2011","journal-title":"Clin. Infect. Dis."},{"key":"B37","doi-asserted-by":"publisher","first-page":"e109903","DOI":"10.1371\/journal.pone.0109903","article-title":"Morphine and clonidine combination therapy improves therapeutic window in mice: synergy in antinociceptive but not in sedative or cardiovascular effects","volume":"9","author":"Stone","year":"2014","journal-title":"PLoS ONE"},{"key":"B38","doi-asserted-by":"publisher","first-page":"1189","DOI":"10.1016\/j.drudis.2016.05.015","article-title":"Drug combination therapy increases successful drug repositioning","volume":"21","author":"Sun","year":"2016","journal-title":"Drug Discov. Today"},{"key":"B39","doi-asserted-by":"publisher","first-page":"2608","DOI":"10.1128\/AAC.01315-13","article-title":"Combination therapy with tamoxifen and amphotericin B in experimental cutaneous leishmaniasis","volume":"58","author":"Trinconi","year":"2014","journal-title":"Antimicrob. Agents Chemother."},{"key":"B40","doi-asserted-by":"publisher","first-page":"1292","DOI":"10.1086\/592280","article-title":"Intracellular survival of Leishmania species that cause visceral leishmaniasis is significantly reduced by HIV-1 protease inhibitors","volume":"198","author":"Trudel","year":"2008","journal-title":"J. Infect. Dis."},{"key":"B41","doi-asserted-by":"publisher","first-page":"682","DOI":"10.1016\/j.ijantimicag.2018.06.016","article-title":"Potentiation of the leishmanicidal activity of nelfinavir in combination with miltefosine or amphotericin B","volume":"52","author":"Valdivieso","year":"2018","journal-title":"Int. J. Antimicrob. Agents"},{"key":"B42","doi-asserted-by":"publisher","first-page":"556","DOI":"10.1093\/cid\/ciu334","article-title":"Visceral leishmaniasis and HIV coinfection in Bihar, India: a wake-up call?","volume":"59","author":"Van Griensven","year":"2014","journal-title":"Clin. Infect. Dis."},{"key":"B43","doi-asserted-by":"publisher","first-page":"286","DOI":"10.1111\/1469-0691.12556","article-title":"Leishmaniasis in immunosuppressed individuals","volume":"20","author":"Van Griensven","year":"","journal-title":"Clin. Microbiol. Infect."},{"key":"B44","doi-asserted-by":"publisher","first-page":"e3011","DOI":"10.1371\/journal.pntd.0003011","article-title":"A screen-and-treat strategy targeting visceral leishmaniasis in HIV-infected individuals in endemic East African countries: the way forward?","volume":"8","author":"Van Griensven","year":"","journal-title":"PLoS Negl. Trop. Dis."},{"key":"B45","doi-asserted-by":"publisher","first-page":"e3023","DOI":"10.1371\/journal.pntd.0003023","article-title":"Visceral leishmaniasis and HIV coinfection: time for concerted action","volume":"8","author":"Van Griensven","year":"","journal-title":"PLoS Negl. Trop. Dis."},{"key":"B46","doi-asserted-by":"publisher","first-page":"e1741","DOI":"10.1371\/journal.pntd.0001741","article-title":"Leishmania major infection in humanized mice induces systemic infection and provokes a nonprotective human immune response","volume":"6","author":"Wege","year":"2012","journal-title":"PLoS Negl. Trop. Dis."},{"key":"B47","doi-asserted-by":"publisher","first-page":"1","DOI":"10.11648\/j.ajbls.20140201.11","article-title":"Proportion of visceral leishmaniasis and human immune deficiency virus co-infection among clinically confirmed visceral leishmaniasis patients at the endemic foci of the Amhara National Regional State, North-West Ethiopia","volume":"2","author":"Yimer","year":"2014","journal-title":"Am. J. Biomed. Life Sci."}],"container-title":["Frontiers in Cellular and Infection Microbiology"],"original-title":[],"link":[{"URL":"https:\/\/www.frontiersin.org\/article\/10.3389\/fcimb.2019.00229\/full","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2019,9,19]],"date-time":"2019-09-19T21:42:03Z","timestamp":1568929323000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.frontiersin.org\/article\/10.3389\/fcimb.2019.00229\/full"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2019,6,28]]},"references-count":47,"alternative-id":["10.3389\/fcimb.2019.00229"],"URL":"https:\/\/doi.org\/10.3389\/fcimb.2019.00229","relation":{},"ISSN":["2235-2988"],"issn-type":[{"value":"2235-2988","type":"electronic"}],"subject":[],"published":{"date-parts":[[2019,6,28]]},"article-number":"229"}}