Beatriz Grinsztejn1, Nathalie De Castro2, Vincent Arnold3, Valdiléa G Veloso4, Mariza Morgado5, José Henrique Pilotto6, Carlos Brites7, José Valdez Madruga8, Nêmora Tregnago Barcellos9, Breno Riegel Santos10, Carla Vorsatz4, Catherine Fagard3, Marilia Santini-Oliveira4, Olivier Patey11, Constance Delaugerre12, Geneviève Chêne13, Jean-Michel Molina2. 1. STD/AIDS Clinical Research Laboratory-Evandro Chagas Clinical Research Institute-Fiocruz, Hôpital Saint-Louis, Assistance Publique Hôpitaux de Paris, France. Electronic address: gbeatriz@ipec.fiocruz.br. 2. University of Paris Diderot Paris 7, Sorbonne Paris Cité, INSERM U941, Department of Infectious Diseases, Hôpital Saint-Louis, Assistance Publique Hôpitaux de Paris, France. 3. INSERM U897, University of Bordeaux, ISPED, Epidemiologie- Biostatistique, Bordeaux, France. 4. STD/AIDS Clinical Research Laboratory-Evandro Chagas Clinical Research Institute-Fiocruz, Hôpital Saint-Louis, Assistance Publique Hôpitaux de Paris, France. 5. Laboratory of AIDS and Molecular Immunology, Oswaldo Cruz Institute-Fiocruz, Rio de Janeiro, Brazil. 6. Departamento de DST/AIDS, Hospital Geral de Nova Iguaçu, Rio de Janeiro, Brazil. 7. Laboratório de Pesquisa em Doenças Infecciosas, Hospital Universitário Prof Edgar Santos, Bahia, Brazil. 8. Centro de Referência e Treinamento DST/AIDS, São Paulo, Brazil. 9. Hospital Sanatório Partenon, Health State Secretariat/RS, Brazil. 10. Serviço de Infectologia, Hospital Nossa Senhora da Conceição, Porto Alegre Brazil. 11. Department of Internal and Tropical Medicine, Villeneuve St George, France. 12. Department of Virology, Hôpital Saint-Louis, Assistance Publique Hôpitaux de Paris, France. 13. INSERM U897, University of Bordeaux, ISPED, Epidemiologie- Biostatistique, Bordeaux, France; CHU de Bordeaux, Pôle de Santé Publique, Service d'information médicale, Bordeaux, France.
Abstract
BACKGROUND: Concurrent treatment of HIV and tuberculosis is complicated by drug interactions. We explored the safety and efficacy of raltegravir as an alternative to efavirenz for patients co-infected with HIV and tuberculosis. METHODS: We did a multicentre, phase 2, non-comparative, open-label, randomised trial at eight sites in Brazil and France. Using a computer-generated randomisation sequence, we randomly allocated antiretroviral-naive adult patients with HIV-1 and tuberculosis (aged ≥18 years with a plasma HIV RNA concentration of >1000 copies per mL) to receive raltegravir 400 mg twice a day, raltegravir 800 mg twice daily, or efavirenz 600 mg once daily plus tenofovir and lamivudine (1:1:1; stratified by country). Patients began study treatment after the start of tuberculosis treatment. The primary endpoint was virological suppression at 24 weeks (HIV RNA <50 copies per mL) in all patients who received at least one dose of study drug (modified intention-to-treat analysis). We recorded death, study drug discontinuation, and loss to follow-up as failures to achieve the primary endpoint. We assessed safety in all patients who received study drugs. This study is registered in ClinicalTrials.gov, number NCT00822315. FINDINGS:Between July 3, 2009, and June 6, 2011, we enrolled and randomly assigned treatment to 155 individuals; 153 (51 in each group) received at least one dose of the study drug and were included in the primary analysis. 133 patients (87%) completed follow-up at week 48. At week 24, virological suppression was achieved in 39 patients (76%, 95% CI 65-88) in the raltegravir 400 mg group, 40 patients (78%, 67-90) in the raltegravir 800 mg group, and 32 patients (63%, 49-76) in the efavirenz group. The adverse-event profile was much the same across the three groups. Three (6%) patients allocated to efavirenz and three (6%) patients allocated to raltegravir 800 mg twice daily discontinued the study drugs due to adverse events. Seven patients died during the study (one in the raltegravir 400 mg group, four in the raltegravir 800 mg group, and two in the efavirenz group): none of the deaths was deemed related to study treatment. INTERPRETATION:Raltegravir 400 mg twice daily might be an alternative to efavirenz for the treatment of patients co-infected with HIV and tuberculosis. FUNDING: French National Agency for Research on AIDS and Viral Hepatitis (ANRS), Brazilian National STD/AIDS Program-Ministry of Health.
RCT Entities:
BACKGROUND: Concurrent treatment of HIV and tuberculosis is complicated by drug interactions. We explored the safety and efficacy of raltegravir as an alternative to efavirenz for patients co-infected with HIV and tuberculosis. METHODS: We did a multicentre, phase 2, non-comparative, open-label, randomised trial at eight sites in Brazil and France. Using a computer-generated randomisation sequence, we randomly allocated antiretroviral-naive adult patients with HIV-1 and tuberculosis (aged ≥18 years with a plasma HIV RNA concentration of >1000 copies per mL) to receive raltegravir 400 mg twice a day, raltegravir 800 mg twice daily, or efavirenz 600 mg once daily plus tenofovir and lamivudine (1:1:1; stratified by country). Patients began study treatment after the start of tuberculosis treatment. The primary endpoint was virological suppression at 24 weeks (HIV RNA <50 copies per mL) in all patients who received at least one dose of study drug (modified intention-to-treat analysis). We recorded death, study drug discontinuation, and loss to follow-up as failures to achieve the primary endpoint. We assessed safety in all patients who received study drugs. This study is registered in ClinicalTrials.gov, number NCT00822315. FINDINGS: Between July 3, 2009, and June 6, 2011, we enrolled and randomly assigned treatment to 155 individuals; 153 (51 in each group) received at least one dose of the study drug and were included in the primary analysis. 133 patients (87%) completed follow-up at week 48. At week 24, virological suppression was achieved in 39 patients (76%, 95% CI 65-88) in the raltegravir 400 mg group, 40 patients (78%, 67-90) in the raltegravir 800 mg group, and 32 patients (63%, 49-76) in the efavirenz group. The adverse-event profile was much the same across the three groups. Three (6%) patients allocated to efavirenz and three (6%) patients allocated to raltegravir 800 mg twice daily discontinued the study drugs due to adverse events. Seven patients died during the study (one in the raltegravir 400 mg group, four in the raltegravir 800 mg group, and two in the efavirenz group): none of the deaths was deemed related to study treatment. INTERPRETATION:Raltegravir 400 mg twice daily might be an alternative to efavirenz for the treatment of patients co-infected with HIV and tuberculosis. FUNDING: French National Agency for Research on AIDS and Viral Hepatitis (ANRS), Brazilian National STD/AIDS Program-Ministry of Health.
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