Subgroup analyses of maraviroc in previously treated R5 HIV-1 infection
Gerd Fätkenheuer, Mark Nelson, Adriano Lazzarin, Irina Konourina, Andy I M Hoepelman, Harry Lampiris, Bernard Hirschel, Pablo Tebas, François Raffi, Benoit Trottier, Nicholaos Bellos, Michael Saag, David A Cooper, Mike Westby, Margaret Tawadrous, John F Sullivan, Caroline Ridgway, Michael W Dunne, Steve Felstead, Howard Mayer, Elna van der Ryst, MOTIVATE 1 and MOTIVATE 2 Study Teams, Jonathan Angel, Brian Conway, Kevin A Gough, Richard G Lalonde, Francois Laplante, Roger P Leblanc, Julio S G Montaner, Anita R Rachlis, Barbara Romanowski, Stuart J Rosser, Ethan Rubinstein, Stephen David Shafran, Fiona Smaill, Cecile Tremblay, Benoit Trottier, Sylvie Trottier, Christos Tsoukas, Sharon Lynn Walmsley, Alen Voskanian, Bisher Akil, Roberto Claudio Arduino, David Asmuth, George William Beatty, Stephen Lawrence Becker, Nicholaos C Bellos, Sky Robert Blue, Robert Key Bolan, John D Brand, George Ghazaros Burnazian, Alfred F Burnside, Thomas B Campbell, Rafael E Campo, Kathleen King Casey, Paul Joseph Cimoch, Calvin J Cohen, Gregg Oscar Coodley, Roberto B Corales, Edwin DeJesus, Leslie E Diaz, George L Drusano, Jerome A Ernst, Judith E Feinberg, Lawrence Edward Feldman, Steven M Fine, Jason Andrew Flamm, Stephen Eliot Follansbee, Todd Allen Fralich, Emanuel Gallant, Eliot Warren Godofsky, Gary Green, Paula Rosa Greiger-Zanlungo, Barbara Marie Gripshover, Richard K Groger, Roy Gulick, William David Hardy, Shawn K Hassler, Richard Harold Haubrich, Stephen P Hauptman, David Holden Henry, William Keith Henry, Jose Norberto Hernandez, Charles Byron Hicks, Michael Alan Horberg, Joseph G Jemsek, Allan Rowan Kelly, Clifford A Kinder, Daniel Benjamin Klein, Laura Kogelman, Jacob Paul Lalezari, Anthony LaMarca, Harry William Lampiris, Matthew Leibowitz, Jason Mark Leider, Jeffrey Lloyd Lennox, Ralph Liporace, Harold Luther Martin, Lucia M Martinez-Bejar, Claudia Martorell, Joseph P McGowan, Donna Mildvan, Steven Miles, Ronald Takeshi Mitsuyasu, Javier Osvaldo Morales-Ramirez, Anne B Morris, Karam Chucri Mounzer, Robert Anderson Myers, Jeffrey P Nadler, Daniel Pearce, Gerald Pierone, Bruce Stephen Rashbaum, Jayashree Ravishankar, Robert Ray Redfield, Richard Craig Reichman, William Jay Robbins, Stockton Edward Roberts, Jorge E Rodriguez, Michael Saag, Kunthavi Sathasivam, Paul Edward Sax, Lawrence E Schwartz, Sorana Segal-Maurer, Michael Grant Sension, Gladys E Sepulveda-Arzola, Paul Richard Skolnik, Louis Marshall Sloan, Robert P Smith, James Michael Sosman, Jack Thomas Stapleton, Roy Steigbigel, Corklin R Steinhart, Donna Elaine Sweet, Susan Swindells, Pablo Tebas, Melanie Ann Thompson, Silver Sisneros, William James Towner, Peter Gordon, Trevor N Hawkins, David Allen Wheeler, Sally Williams, Dean Wilcox, Steven Williams, Todd Stephen Wills, Michael Bruce Wohlfeiler, David Wright, Angela Xavier, Bienvenido Gamulo Yangco, Barry Stephen Zingman, Carmen D Zorrilla, Anthony M Allworth, Mark T Bloch, Neil J Bodsworth, John Chuah, David Cooper, Nicholas Doong, Dominic Dwyer, Julian Gold, Jennifer Frances Hoy, Richard J Moore, Norman J Roth, Cassy Workman, Nathan Clumeck, Patricia Dellot, Jean Christophe Goffard, Michel Moutschen, Bernard C Vandercam, Dirk Vogelaers, Michele Bentata, Laurent Cotte, Jean-Francois Delfraissy, Jacques Durant, Pierre-Marie Girard, Laurent Hocqueloux, Roland Landman, Alain Lafeuillade, Isabelle Poizot Martin, Jean-Michel Molina, Gilles Pialoux, Christophe Piketty, Francois Raffi, Jacques Reynes, Renaud Verdon, Keikawus Arasteh, Johannes Richard Bogner, Norbert H Brockmeyer, Stefan Esser, Gerd Fätkenheuer, Frank-Detlef Goebel, Thomas Harrer, Peter Kern, Heribert Knechten, Jan van Lunzen, Markus Mueller, Antonius Mutz, Mark Oette, Andreas Plettenberg, Juergen Rockstroh, Jorg-Andres Rump, Reinhold E Schmidt, Lothar Schneider, Dieter Schuster, Schlomo Staszewski, Hans-Juergen Stellbrink, Andreas Trein, Lutwinus Weitner, Fernando Aiuti, Dante Bassetti, Antonio Di Biagio, Pietro Caramello, Giampiero Carosi, Roberto Esposito, Adriano Lazzarin, Francesco Leoncini, Paolo Emilio Manconi, Francesco Mazzotta, Francesco Montella, Enzo Raise, Vicenzo Vullo, Ilja Mohandas Hoepelman, Rosalinde Maria Perenboom, J M Prins, Clemens Richter, Marchina Elisabeth Van der Ende, Marek Beniowski, Anna Boron-Kaczmarska, Robert Flisiak, Waldemar Halota, Andrzej Horban, Tomasz Mach, Tomasz Smiatacz, Fernando Lozano de Leon, Pompeyo Viciana Fernandez, Rafael Rubio Garcia, Jose Josep Gatell Artigas, Juan Julian Gonzalez Garcia, Felix Gutierrez, Juan Gonzalez Lahoz, Jose Iribarren Loyarte, Santiago Moreno, Federico Pulido Ortega, Pere Domingo Pedrol, Antonio Rivero, Bonaventura Clotet, Cristina Sarria, Magnus Gisslen, Leo Flamholc, Anders Karlsson, Manuel Battegay, Enos Bernasconi, Matthias Cavassini, Henning Drechsler, Bernard Hirschel, Milos Opravil, Pietro Vernazza, Philippa Jane Easterbrook, Martin Fisher, Philip Hay, Margaret A Johnson, Clifford L Leen, Mark R Nelson, Edmund Ong, Jonathan N Weber, David J White, Edmund Wilkins, Martin Wiselka, Ana Maria Alvarez-Jacinto, Diana Antoniskis, Barbara A Atkinson, Daniel S Berger, Gary Blick, Robert Owen Brenna, Jeffrey Howard Burack, L W Preston Church, Patrick G Clay, Paul Peniston Cook, Catherine Maria Creticos, Patrick William Daly, Getachew Feleke, Thomas Mc Donald File, Jeffrey Eliot Galpin, Stephen Lloyd Green, Frances Fae Haas, Barbara J Hanna, Chiu-Bin Hsiao, Ricky K Hsu, Robert S Jones, Peter Kadlecik, Robert Charles Kalayjian, Robert H Keller, Shubha Kerkar, Janak Koirala, Leon Liang-Yu Lai, Sujata Lalla-Reddy, Rodger David Macarthur, Gregory John Malanoski, Norman Peter Markowitz, Patrick L McLeroth, Alexander A McMeeking, Goran Miljkovic, John Buscemi Montana, Daniel Edward Nixon, Dorece G Norris, Jesse Pullen Penico, Leonel Perez-Limonte, Lynette H Posorske, David James Prelutsky, James Riddell, Barry Michael Rodwick, Peter Jerome Ruane, James Sampson, Steven Santiago, Amy Seinfeld, Victoria Lee Sharp, Zaher Shebib, Mark Leslie Tanner, Joseph G Timpone, Barbara H Wade, Frances Wallach, Winkler Weinberg, Christine Zurawski, Gerd Fätkenheuer, Mark Nelson, Adriano Lazzarin, Irina Konourina, Andy I M Hoepelman, Harry Lampiris, Bernard Hirschel, Pablo Tebas, François Raffi, Benoit Trottier, Nicholaos Bellos, Michael Saag, David A Cooper, Mike Westby, Margaret Tawadrous, John F Sullivan, Caroline Ridgway, Michael W Dunne, Steve Felstead, Howard Mayer, Elna van der Ryst, MOTIVATE 1 and MOTIVATE 2 Study Teams, Jonathan Angel, Brian Conway, Kevin A Gough, Richard G Lalonde, Francois Laplante, Roger P Leblanc, Julio S G Montaner, Anita R Rachlis, Barbara Romanowski, Stuart J Rosser, Ethan Rubinstein, Stephen David Shafran, Fiona Smaill, Cecile Tremblay, Benoit Trottier, Sylvie Trottier, Christos Tsoukas, Sharon Lynn Walmsley, Alen Voskanian, Bisher Akil, Roberto Claudio Arduino, David Asmuth, George William Beatty, Stephen Lawrence Becker, Nicholaos C Bellos, Sky Robert Blue, Robert Key Bolan, John D Brand, George Ghazaros Burnazian, Alfred F Burnside, Thomas B Campbell, Rafael E Campo, Kathleen King Casey, Paul Joseph Cimoch, Calvin J Cohen, Gregg Oscar Coodley, Roberto B Corales, Edwin DeJesus, Leslie E Diaz, George L Drusano, Jerome A Ernst, Judith E Feinberg, Lawrence Edward Feldman, Steven M Fine, Jason Andrew Flamm, Stephen Eliot Follansbee, Todd Allen Fralich, Emanuel Gallant, Eliot Warren Godofsky, Gary Green, Paula Rosa Greiger-Zanlungo, Barbara Marie Gripshover, Richard K Groger, Roy Gulick, William David Hardy, Shawn K Hassler, Richard Harold Haubrich, Stephen P Hauptman, David Holden Henry, William Keith Henry, Jose Norberto Hernandez, Charles Byron Hicks, Michael Alan Horberg, Joseph G Jemsek, Allan Rowan Kelly, Clifford A Kinder, Daniel Benjamin Klein, Laura Kogelman, Jacob Paul Lalezari, Anthony LaMarca, Harry William Lampiris, Matthew Leibowitz, Jason Mark Leider, Jeffrey Lloyd Lennox, Ralph Liporace, Harold Luther Martin, Lucia M Martinez-Bejar, Claudia Martorell, Joseph P McGowan, Donna Mildvan, Steven Miles, Ronald Takeshi Mitsuyasu, Javier Osvaldo Morales-Ramirez, Anne B Morris, Karam Chucri Mounzer, Robert Anderson Myers, Jeffrey P Nadler, Daniel Pearce, Gerald Pierone, Bruce Stephen Rashbaum, Jayashree Ravishankar, Robert Ray Redfield, Richard Craig Reichman, William Jay Robbins, Stockton Edward Roberts, Jorge E Rodriguez, Michael Saag, Kunthavi Sathasivam, Paul Edward Sax, Lawrence E Schwartz, Sorana Segal-Maurer, Michael Grant Sension, Gladys E Sepulveda-Arzola, Paul Richard Skolnik, Louis Marshall Sloan, Robert P Smith, James Michael Sosman, Jack Thomas Stapleton, Roy Steigbigel, Corklin R Steinhart, Donna Elaine Sweet, Susan Swindells, Pablo Tebas, Melanie Ann Thompson, Silver Sisneros, William James Towner, Peter Gordon, Trevor N Hawkins, David Allen Wheeler, Sally Williams, Dean Wilcox, Steven Williams, Todd Stephen Wills, Michael Bruce Wohlfeiler, David Wright, Angela Xavier, Bienvenido Gamulo Yangco, Barry Stephen Zingman, Carmen D Zorrilla, Anthony M Allworth, Mark T Bloch, Neil J Bodsworth, John Chuah, David Cooper, Nicholas Doong, Dominic Dwyer, Julian Gold, Jennifer Frances Hoy, Richard J Moore, Norman J Roth, Cassy Workman, Nathan Clumeck, Patricia Dellot, Jean Christophe Goffard, Michel Moutschen, Bernard C Vandercam, Dirk Vogelaers, Michele Bentata, Laurent Cotte, Jean-Francois Delfraissy, Jacques Durant, Pierre-Marie Girard, Laurent Hocqueloux, Roland Landman, Alain Lafeuillade, Isabelle Poizot Martin, Jean-Michel Molina, Gilles Pialoux, Christophe Piketty, Francois Raffi, Jacques Reynes, Renaud Verdon, Keikawus Arasteh, Johannes Richard Bogner, Norbert H Brockmeyer, Stefan Esser, Gerd Fätkenheuer, Frank-Detlef Goebel, Thomas Harrer, Peter Kern, Heribert Knechten, Jan van Lunzen, Markus Mueller, Antonius Mutz, Mark Oette, Andreas Plettenberg, Juergen Rockstroh, Jorg-Andres Rump, Reinhold E Schmidt, Lothar Schneider, Dieter Schuster, Schlomo Staszewski, Hans-Juergen Stellbrink, Andreas Trein, Lutwinus Weitner, Fernando Aiuti, Dante Bassetti, Antonio Di Biagio, Pietro Caramello, Giampiero Carosi, Roberto Esposito, Adriano Lazzarin, Francesco Leoncini, Paolo Emilio Manconi, Francesco Mazzotta, Francesco Montella, Enzo Raise, Vicenzo Vullo, Ilja Mohandas Hoepelman, Rosalinde Maria Perenboom, J M Prins, Clemens Richter, Marchina Elisabeth Van der Ende, Marek Beniowski, Anna Boron-Kaczmarska, Robert Flisiak, Waldemar Halota, Andrzej Horban, Tomasz Mach, Tomasz Smiatacz, Fernando Lozano de Leon, Pompeyo Viciana Fernandez, Rafael Rubio Garcia, Jose Josep Gatell Artigas, Juan Julian Gonzalez Garcia, Felix Gutierrez, Juan Gonzalez Lahoz, Jose Iribarren Loyarte, Santiago Moreno, Federico Pulido Ortega, Pere Domingo Pedrol, Antonio Rivero, Bonaventura Clotet, Cristina Sarria, Magnus Gisslen, Leo Flamholc, Anders Karlsson, Manuel Battegay, Enos Bernasconi, Matthias Cavassini, Henning Drechsler, Bernard Hirschel, Milos Opravil, Pietro Vernazza, Philippa Jane Easterbrook, Martin Fisher, Philip Hay, Margaret A Johnson, Clifford L Leen, Mark R Nelson, Edmund Ong, Jonathan N Weber, David J White, Edmund Wilkins, Martin Wiselka, Ana Maria Alvarez-Jacinto, Diana Antoniskis, Barbara A Atkinson, Daniel S Berger, Gary Blick, Robert Owen Brenna, Jeffrey Howard Burack, L W Preston Church, Patrick G Clay, Paul Peniston Cook, Catherine Maria Creticos, Patrick William Daly, Getachew Feleke, Thomas Mc Donald File, Jeffrey Eliot Galpin, Stephen Lloyd Green, Frances Fae Haas, Barbara J Hanna, Chiu-Bin Hsiao, Ricky K Hsu, Robert S Jones, Peter Kadlecik, Robert Charles Kalayjian, Robert H Keller, Shubha Kerkar, Janak Koirala, Leon Liang-Yu Lai, Sujata Lalla-Reddy, Rodger David Macarthur, Gregory John Malanoski, Norman Peter Markowitz, Patrick L McLeroth, Alexander A McMeeking, Goran Miljkovic, John Buscemi Montana, Daniel Edward Nixon, Dorece G Norris, Jesse Pullen Penico, Leonel Perez-Limonte, Lynette H Posorske, David James Prelutsky, James Riddell, Barry Michael Rodwick, Peter Jerome Ruane, James Sampson, Steven Santiago, Amy Seinfeld, Victoria Lee Sharp, Zaher Shebib, Mark Leslie Tanner, Joseph G Timpone, Barbara H Wade, Frances Wallach, Winkler Weinberg, Christine Zurawski
Abstract
Background: We conducted subanalyses of the combined results of the Maraviroc versus Optimized Therapy in Viremic Antiretroviral Treatment-Experienced Patients (MOTIVATE) 1 and MOTIVATE 2 studies to better characterize the efficacy and safety of maraviroc in key subgroups of patients.
Methods: We analyzed pooled data from week 48 from the two studies according to sex, race or ethnic group, clade, CC chemokine receptor 5 (CCR5) delta32 genotype, viral load at the time of screening, the use or nonuse of enfuvirtide in optimized background therapy (OBT), the baseline CD4 cell count, the number of active antiretroviral drugs coadministered, the first use of selected background agents, and tropism at baseline. Changes in viral tropism and the CD4 count at treatment failure were evaluated. Data on aminotransferase levels in patients coinfected with hepatitis B virus (HBV) or hepatitis C virus (HCV) were also analyzed.
Results: A treatment benefit of maraviroc plus OBT over placebo plus OBT was shown in all subgroups, including patients with a low CD4 cell count at baseline, those with a high viral load at screening, and those who had not received active agents in OBT. Analyses of the virologic response according to the first use of selected background drugs showed the additional benefit of adding a potent new drug to maraviroc at the initiation of maraviroc therapy. More patients in whom maraviroc failed had a virus binding to the CXC chemokine receptor 4 (CXCR4) at failure, but there was no evidence of a decrease in the CD4 cell count at failure in such patients as compared with those in whom placebo failed. Subanalyses involving patients coinfected with HBV or HCV revealed no evidence of excess hepatotoxic effects as compared with baseline.
Conclusions: Subanalyses of pooled data from week 48 indicate that maraviroc provides a valuable treatment option for a wide spectrum of patients with R5 HIV-1 infection who have been treated previously. (ClinicalTrials.gov numbers, NCT00098306 and NCT00098722.)
2008 Massachusetts Medical Society
Source: PubMed