Long-term (96-week) follow-up of antiretroviral-naïve HIV-infected patients treated with first-line lopinavir/ritonavir monotherapy in the MONARK trial
Jade Ghosn, P Flandre, I Cohen-Codar, P-M Girard, M-L Chaix, F Raffi, P Dellamonica, P Ngovan, M Norton, J-F Delfraissy, MONARK Study Group, Jean-François Delfraissy, Cecile Goujard, Pascal Robquin, Yann Quertainmont, Olivier Segeral, François Boue, Veronique Chambrin, Gaelle-Anne Estocq, Isabelle Luquet-Besson, Carole Pignon, Pierre Dellamonica, Francine De Salvador, Jacques Durand, Laurence Heripret, Veronique Rahelinirina, Herve Gallais, F Tomei, Herve Tissot Dupont, Isabelle Ravaux, Pierre-Marie Girard, Diane Bollens, Franck Besse, Benedicte Lefebvre, Zineb Ouazene, Alain Lafeuillade, Stephane Chadapaud, Gilles Hittinger, Philippe Morlat, Mojgan Bonarek, Marie-Carmen Pertusa, Caroline Nouts, Fabrice Bonnet, Jean-Luc Pellegrin, Olivier Caubet, Caroline Perlemoine, Jean-François Viallard, François Raffi, Jacques Reynes, Vincent Baillat, Olivier Patey, Sophie Dellion, Manuella Podani, Jacques Gilquin, Pascale Leclercq, Myriam Blanc, Caroline Lascoux, Claire Pintado, Florence Vincent, Olivier Taulera, Thierry May, Christian Rabaud, Laurence Boyer, Thanh Lecompte, Elisabeth Rouveix, Alain Devidas, Pascale Kousignian, Pierre Chevojon, Marie-Aude Khuong, Nacira Khelil, Denis Mechali, Yves Levy, Anne-Sophie Lascaux, Alain Sobel, Fabrice Chaix, Marc Antoine Valantin, Hans Jäger, Andrea Eberhad, Eva Jägel-Guedes, Tim Theobald, Eva Wolf, Dirk Schürmann, Thomas Wünsche, Hans Wesselmann, Mark Oette, Klaus Göbels, Stefanie Koch, Ruth Leidel, Arne Kroidl, Keikawus Arastéh, Adriano Lazzarin, Antonella Castagna, Nicola Gianotti, Mauro Moroni, Antonella D'Arminio Monforte, Teresa Bini, Patrizia Biasi, Giovanni Di Perri, Stefano Bonora, Lorenzo Veronese, Laura Ladetto, Giampiero Carosi, Giusseppe Paraninfo, Paola Nasta, Vincenzo Vullo, Anna Paola Massetti, Claudio Maria Mastroianni, Miriam Lichtner, Azzura Ginevra Miccoli, Andrzej Horban, Piotr Pulik, Anna Ignatowska, Andrzej Gladyzs, Brygida Knysz, Jacek Gasiorowski, Pere Domingo, Montserrat Fuster, Mar Gutierrez, Gracia Mateo, Mercedes Gurgui, Ma Antonia Sambeat, Jose Cadafalch, Bonaventura Clotet, Angel Ballesteros, Jose Miranda, Jordi Puig Pla, Josep Ma Llibre, Silvia Valero, Jade Ghosn, P Flandre, I Cohen-Codar, P-M Girard, M-L Chaix, F Raffi, P Dellamonica, P Ngovan, M Norton, J-F Delfraissy, MONARK Study Group, Jean-François Delfraissy, Cecile Goujard, Pascal Robquin, Yann Quertainmont, Olivier Segeral, François Boue, Veronique Chambrin, Gaelle-Anne Estocq, Isabelle Luquet-Besson, Carole Pignon, Pierre Dellamonica, Francine De Salvador, Jacques Durand, Laurence Heripret, Veronique Rahelinirina, Herve Gallais, F Tomei, Herve Tissot Dupont, Isabelle Ravaux, Pierre-Marie Girard, Diane Bollens, Franck Besse, Benedicte Lefebvre, Zineb Ouazene, Alain Lafeuillade, Stephane Chadapaud, Gilles Hittinger, Philippe Morlat, Mojgan Bonarek, Marie-Carmen Pertusa, Caroline Nouts, Fabrice Bonnet, Jean-Luc Pellegrin, Olivier Caubet, Caroline Perlemoine, Jean-François Viallard, François Raffi, Jacques Reynes, Vincent Baillat, Olivier Patey, Sophie Dellion, Manuella Podani, Jacques Gilquin, Pascale Leclercq, Myriam Blanc, Caroline Lascoux, Claire Pintado, Florence Vincent, Olivier Taulera, Thierry May, Christian Rabaud, Laurence Boyer, Thanh Lecompte, Elisabeth Rouveix, Alain Devidas, Pascale Kousignian, Pierre Chevojon, Marie-Aude Khuong, Nacira Khelil, Denis Mechali, Yves Levy, Anne-Sophie Lascaux, Alain Sobel, Fabrice Chaix, Marc Antoine Valantin, Hans Jäger, Andrea Eberhad, Eva Jägel-Guedes, Tim Theobald, Eva Wolf, Dirk Schürmann, Thomas Wünsche, Hans Wesselmann, Mark Oette, Klaus Göbels, Stefanie Koch, Ruth Leidel, Arne Kroidl, Keikawus Arastéh, Adriano Lazzarin, Antonella Castagna, Nicola Gianotti, Mauro Moroni, Antonella D'Arminio Monforte, Teresa Bini, Patrizia Biasi, Giovanni Di Perri, Stefano Bonora, Lorenzo Veronese, Laura Ladetto, Giampiero Carosi, Giusseppe Paraninfo, Paola Nasta, Vincenzo Vullo, Anna Paola Massetti, Claudio Maria Mastroianni, Miriam Lichtner, Azzura Ginevra Miccoli, Andrzej Horban, Piotr Pulik, Anna Ignatowska, Andrzej Gladyzs, Brygida Knysz, Jacek Gasiorowski, Pere Domingo, Montserrat Fuster, Mar Gutierrez, Gracia Mateo, Mercedes Gurgui, Ma Antonia Sambeat, Jose Cadafalch, Bonaventura Clotet, Angel Ballesteros, Jose Miranda, Jordi Puig Pla, Josep Ma Llibre, Silvia Valero
Abstract
Background: The toxicities, cost and complexity of triple combinations warrant the search for other treatment options, such as boosted protease inhibitor (PI) monotherapy. MONotherapy AntiRetroviral Kaletra (MONARK) is the first randomized trial comparing lopinavir/ritonavir monotherapy to triple combination therapy with zidovudine/lamivudine and lopinavir/ritonavir in antiretroviral-naïve patients.
Methods: A total of 136 antiretroviral-naïve patients, with a CD4 cell count above 100 cells/microL and a plasma HIV RNA below 100,000 HIV-1 RNA copies/mL, were randomized and dosed with either lopinavir/ritonavir monotherapy (n = 83) or lopinavir/ritonavir + zidovudine/lamivudine (n = 53). We focus here on patients in the lopinavir/ritonavir monotherapy arm followed to week 96. The intent-to-treat (ITT) analysis initially involved all patients randomized to lopinavir/ritonavir monotherapy (n = 83), and then focused on patients who had an HIV RNA < 50 copies/mL at week 48 (n = 56).
Results: At week 96, 39 of 83 patients (47%) had HIV RNA < 50 copies/mL, five of 83 had HIV RNA between 50 and 400 copies/mL, and three of 83 had HIV RNA > 400 copies/mL. Focusing on the 56 patients with an HIV RNA < 50 copies/mL at week 48, 38 of 56 patients (68%) had a sustained HIV RNA < 50 copies/mL to week 96. To week 96, a total of 28 patients (34%) had discontinued the study treatment. In addition, the allocated treatment was changed for seven patients. PI-associated resistance mutations were evident in five of 83 patients in the monotherapy arm from baseline to week 96.
Conclusion: By ITT analysis, 39 of the 83 patients initially randomized to lopinavir/ritonavir monotherapy had HIV RNA < 50 copies/mL at week 96. The occurrence in some patients of low-level viraemia (50-500 copies/mL) may increase the risk of drug resistance. First-line lopinavir/ritonavir monotherapy cannot be systematically recommended.
Trial registration: ClinicalTrials.gov NCT00234923.
Source: PubMed