1. Dolutegravir-based and low-dose efavirenz-based regimen for the initial treatment of HIV-1 infection (NAMSAL): week 96 results from a two-group, multicentre, randomised, open label, phase 3 non-inferiority trial in Cameroon
- Author
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Alexandra Calmy, Tamara Tovar Sanchez, Charles Kouanfack, Mireille Mpoudi-Etame, Sandrine Leroy, Ségolène Perrineau, Martial Lantche Wandji, Darius Tetsa Tata, Pierette Omgba Bassega, Thérèse Abong Bwenda, Marie Varloteaux, Marcel Tongo, Eitel Mpoudi-Ngolé, Alice Montoyo, Noémie Mercier, Vincent LeMoing, Martine Peeters, Jacques Reynes, Eric Delaporte, A Calmy, T Tovar Sanchez, C Kouanfack, M Mpoudi-Etame, S Leroy, S Perrineau, M Lantche-Wandji, D Tetsa-Tata, P Omgba-Bassega, T Abong-Bwenda, M Varloteaux, M Tongo, E Mpoudi-Ngolé, A Montoyo, N Mercier, V LeMoing, M Peeters, J Reynes, E Delaporte, A Ayouba, A Agholeng, C Butel, A Cournil, S Eymard-Duvernay, B Granouillac, S Izard, A Lacroix, L Serrano, N Vidal, PJ Fouda, R Mougnoutou, J Olinga, V Omgba, SC Tchokonte-Ngandé, B Ymele, CD Epoupa-Mpacko, M Fotso, R Moukoko, T Nké, A Akamba, S Lekelem, SB Tongo-Fotack, S Ngono, M Tanga, E Ebong, G Edoul-Mbesse, L Ciaffi, S Koulla-Shiro, G Manirakiza, ED Mimbé, S Boyer, M Bousmah, G Maradan, ML Nishimwe, B Spire, MP Lê, G Peytavin, A Diallo, I Fournier, C Rekacewicz, C Perez Casas, Hôpitaux Universitaires de Genève (HUG), 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), Université de Dschang, Hôpital Central de Yaoundé [Yaoundé], Hôpital Militaire de Yaoundé, Partenaires INRAE, Hôpital de la Cité Verte [Yaoundé], Institut de Recherches Médicales et d'Etudes des Plantes Médicinales (IMPM), Agence Nationale de Recherches sur le Sida et les Hépatites Virales (ANRS), and Centre Hospitalier Régional Universitaire [Montpellier] (CHRU Montpellier)
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Cyclopropanes ,0301 basic medicine ,MESH: CD4 Lymphocyte Count ,Epidemiology ,MESH: Piperazines ,HIV Infections ,Piperazines ,MESH: Antiretroviral Therapy, Highly Active ,law.invention ,MESH: HIV-1 ,chemistry.chemical_compound ,0302 clinical medicine ,MESH: Cyclopropanes ,Randomized controlled trial ,law ,[SDV.MHEP.MI]Life Sciences [q-bio]/Human health and pathology/Infectious diseases ,Antiretroviral Therapy, Highly Active ,Clinical endpoint ,MESH: Duration of Therapy ,030212 general & internal medicine ,MESH: Anti-HIV Agents ,MESH: Treatment Outcome ,MESH: Middle Aged ,Lamivudine ,virus diseases ,MESH: HIV Infections ,Middle Aged ,Viral Load ,3. Good health ,Treatment Outcome ,Infectious Diseases ,MESH: Young Adult ,Alkynes ,MESH: Benzoxazines ,Dolutegravir ,[SDV.IMM]Life Sciences [q-bio]/Immunology ,Female ,MESH: Viral Load ,Heterocyclic Compounds, 3-Ring ,Viral load ,medicine.drug ,Adult ,medicine.medical_specialty ,Efavirenz ,Anti-HIV Agents ,Pyridones ,Immunology ,Young Adult ,03 medical and health sciences ,Acquired immunodeficiency syndrome (AIDS) ,Virology ,Internal medicine ,MESH: Pyridones ,Oxazines ,medicine ,Humans ,MESH: Heterocyclic Compounds, 3-Ring ,Duration of Therapy ,MESH: Humans ,business.industry ,MESH: Adult ,medicine.disease ,030112 virology ,Benzoxazines ,CD4 Lymphocyte Count ,Regimen ,chemistry ,HIV-1 ,business ,MESH: Alkynes ,MESH: Oxazines ,MESH: Female - Abstract
International audience; Background: Updated WHO guidelines recommend a dolutegravir-based regimen as the preferred first-line treatment for HIV infection and low-dose efavirenz (400 mg) as an alternative. We aimed to report the non-inferior efficacy of dolutegravir compared with efavirenz 400 mg at week 96.Methods: We did a multicentre, randomised, open label, phase 3 trial in in three hospitals in Yaoundé, Cameroon, in HIV-1 infected antiretroviral-naive adults with an HIV RNA viral load of greater than 1000 copies per mL to compare dolutegravir 50 mg with efavirenz 400 mg (reference treatment), both combined with lamivudine and tenofovir disoproxil fumarate. The primary endpoint was the proportion with a viral load of less than 50 copies per mL at week 48 (10% non-inferiority margin). The study is registered with ClinicalTrials.gov, NCT02777229 and is ongoing.Findings: Between July, 2016, and August, 2019, of 820 patients assessed, 613 were randomly assigned to receive at least one dose of study medication, with 310 in the dolutegravir group and 303 in the efavirenz 400 mg group. At week 96 in the intention-to-treat analysis, 229 (74%) of 310 patients receiving dolutegravir and 219 (72%) of 303 patients receiving efavirenz, achieved plasma HIV-1 RNA less than 50 copies per mL (difference 1·6%, 95% CI -5·4 to 8·6; p=0.66). Viral load suppression was reached significantly more rapidly in the dolutegravir group (p1000 copies per mL) was observed in 27 patients (eight in the dolutegravir group, among which, three women switched to efavirenz 600 mg because of the dolutegravir teratogeneicity signal, and 19 in the efavirenz 400 mg group). No acquired resistance mutations to dolutegravir were observed against 17 mutations to efavirenz with or without mutations to lamivudine and tenofovir disoproxil fumarate among the 19 efavirenz 400 mg participants with virological failure. Weight gain was greater in the dolutegravir group (median weight gain, 5·0 kg in the dolutegravir group and 3·0 kg in the efavirenz 400 mg group, p
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- 2020