Trends in virological and clinical outcomes in individuals with HIV-1 infection and virological failure of drugs from three antiretroviral drug classes: a cohort study
Pursuing Later Treatment Option II (PLATO II) project team, Observational HIV Epidemiological Research Europe (COHERE) Group, Dominique Costagliola, Rebecca Lodwick, Bruno Ledergerber, Carlo Torti, Ard van Sighem, Daniel Podzamczer, Amanda Mocroft, Maria Dorrucci, Bernard Masquelier, Andrea de Luca, Klaus Jansen, Stephane De Wit, Niels Obel, Gerd Fätkenheuer, Giota Touoloumi, Cristina Mussini, Antonella Castagna, Cristoph Stephan, Federico García, Robert Zangerle, Xavier Duval, Santiago Pérez-Hoyos, Laurence Meyer, Jade Ghosn, Céline Fabre-Colin, Jesper Kjaer, Genevieve Chene, Jesper Grarup, Andrew Phillips, Antonella Castagna, Dominique Costagliola, Alessandro Cozzi-Lepri, Andrea De Luca, Stephane De Wit, Frank de Wolf, Maria Dorrucci, Xavier Duval, Gerd Fätkenheuer, Federico García, Jade Ghosn, Huldrych Günthard, Klaus Jansen, Louise Jørgensen, Ali Judd, Bruno Ledergerber, Sergio Lo Caputo, Rebecca Lodwick, Bernard Masquelier, Laurence Meyer, Amanda Mocroft, Cristina Mussini, Antoni Noguera-Julian, Niels Obel, Dimitrios Paraskevis, Roger Paredes, Santiago Pérez-Hoyos, Andrew Phillips, Deenan Pillay, Daniel Podzamczer, José T Ramos, Christoph Stephan, Pat A Tookey, Carlo Torti, Giota Touloumi, Ard van Sighem, Josiane Warszawski, Robert Zangerle, Laurence Meyer, François Dabis, Murielle Mary Krause, Jade Ghosn, Catherine Leport, Frank de Wolf, Peter Reiss, Maria Prins, Heiner Bücher, Caroline Sabin, Diana Gibb, Gerd Fätkenheuer, Julia Del Amo, Niels Obel, Claire Thorne, Amanda Mocroft, Ole Kirk, Christoph Stephan, Santiago Pérez-Hoyos, Antoni Noguera-Julian, Andrea Antinori, Antonella d'Arminio Monforte, Norbert Brockmeyer, José Ramos, Manuel Battegay, Andri Rauch, Cristina Mussini, Pat Tookey, Jordi Casabona, Jose M Miró, Antonella Castagna, Stephane de Wit, Tessa Goethebuer, Carlo Torti, Ramon Teira, Myriam Garrido, David Haerry, Dominque Costagliola, Antonella d'Arminio-Monforte, Manuel Battegay, Maria Prins, Frank de Wolf, Jesper Grarup, Genevieve Chene, Céline Colin, Christine Schwimmer, Guillaume Touzeau, Jesper Kjaer, Maria Paulsen, Julia Bohlius, Vincent Bouteloup, Heiner Bücher, Alessandro Cozzi-Lepri, François Dabis, Antonella d'Arminio Monforte, Frank de Wolf, Maria Dorrucci, Matthias Egger, Frederik Engsig, Hansjakob Furrer, Ole Kirk, Olivier Lambotte, Charlotte Lewden, Rebecca Lodwick, Sophie Matheron, Laurence Meyer, Jose M Miró, Amanda Mocroft, Niels Obel, Roger Paredes, Andrew Phillips, Massimo Puoti, Joanne Reekie, Caroline Sabin, Alexandra Scherrer, Colette Smit, Joanthan Sterne, Rodolphe Thiebaut, Claire Thorne, Carlo Torti, Viktor von Wyl, Linda Wittkop, Jim Young, Pursuing Later Treatment Option II (PLATO II) project team, Observational HIV Epidemiological Research Europe (COHERE) Group, Dominique Costagliola, Rebecca Lodwick, Bruno Ledergerber, Carlo Torti, Ard van Sighem, Daniel Podzamczer, Amanda Mocroft, Maria Dorrucci, Bernard Masquelier, Andrea de Luca, Klaus Jansen, Stephane De Wit, Niels Obel, Gerd Fätkenheuer, Giota Touoloumi, Cristina Mussini, Antonella Castagna, Cristoph Stephan, Federico García, Robert Zangerle, Xavier Duval, Santiago Pérez-Hoyos, Laurence Meyer, Jade Ghosn, Céline Fabre-Colin, Jesper Kjaer, Genevieve Chene, Jesper Grarup, Andrew Phillips, Antonella Castagna, Dominique Costagliola, Alessandro Cozzi-Lepri, Andrea De Luca, Stephane De Wit, Frank de Wolf, Maria Dorrucci, Xavier Duval, Gerd Fätkenheuer, Federico García, Jade Ghosn, Huldrych Günthard, Klaus Jansen, Louise Jørgensen, Ali Judd, Bruno Ledergerber, Sergio Lo Caputo, Rebecca Lodwick, Bernard Masquelier, Laurence Meyer, Amanda Mocroft, Cristina Mussini, Antoni Noguera-Julian, Niels Obel, Dimitrios Paraskevis, Roger Paredes, Santiago Pérez-Hoyos, Andrew Phillips, Deenan Pillay, Daniel Podzamczer, José T Ramos, Christoph Stephan, Pat A Tookey, Carlo Torti, Giota Touloumi, Ard van Sighem, Josiane Warszawski, Robert Zangerle, Laurence Meyer, François Dabis, Murielle Mary Krause, Jade Ghosn, Catherine Leport, Frank de Wolf, Peter Reiss, Maria Prins, Heiner Bücher, Caroline Sabin, Diana Gibb, Gerd Fätkenheuer, Julia Del Amo, Niels Obel, Claire Thorne, Amanda Mocroft, Ole Kirk, Christoph Stephan, Santiago Pérez-Hoyos, Antoni Noguera-Julian, Andrea Antinori, Antonella d'Arminio Monforte, Norbert Brockmeyer, José Ramos, Manuel Battegay, Andri Rauch, Cristina Mussini, Pat Tookey, Jordi Casabona, Jose M Miró, Antonella Castagna, Stephane de Wit, Tessa Goethebuer, Carlo Torti, Ramon Teira, Myriam Garrido, David Haerry, Dominque Costagliola, Antonella d'Arminio-Monforte, Manuel Battegay, Maria Prins, Frank de Wolf, Jesper Grarup, Genevieve Chene, Céline Colin, Christine Schwimmer, Guillaume Touzeau, Jesper Kjaer, Maria Paulsen, Julia Bohlius, Vincent Bouteloup, Heiner Bücher, Alessandro Cozzi-Lepri, François Dabis, Antonella d'Arminio Monforte, Frank de Wolf, Maria Dorrucci, Matthias Egger, Frederik Engsig, Hansjakob Furrer, Ole Kirk, Olivier Lambotte, Charlotte Lewden, Rebecca Lodwick, Sophie Matheron, Laurence Meyer, Jose M Miró, Amanda Mocroft, Niels Obel, Roger Paredes, Andrew Phillips, Massimo Puoti, Joanne Reekie, Caroline Sabin, Alexandra Scherrer, Colette Smit, Joanthan Sterne, Rodolphe Thiebaut, Claire Thorne, Carlo Torti, Viktor von Wyl, Linda Wittkop, Jim Young
Abstract
Background: Limited treatment options have been available for people with HIV who have had virological failure of the three original classes of HIV antiretroviral drugs-so-called triple-class virological failure (TCVF). However, introduction of new drugs and drug classes might have improved outcomes. We aimed to assess trends in virological and clinical outcomes for individuals with TCVF in 2000-09.
Methods: In our cohort study, we analysed data for adults starting antiretroviral therapy from 1998 in cohorts participating in the PLATO II project, which is part of COHERE, a collaboration of European cohorts. TCVF was defined as virological failure to at least two nucleoside reverse transcriptase inhibitors, one non-nucleoside reverse-transcriptase inhibitor, and one ritonavir-boosted protease inhibitor, with virological failure of a drug defined as one viral-load measurement of greater than 500 copies per mL after at least 4 months of continuous use. We used multivariable generalised estimating equation logistic models and Poisson regression models to study trends in virological suppression and incidence of AIDS or death after TCVF. We adjusted for sex, transmission group, age, AIDS status, CD4 cell count, plasma viral loads at TCVF, achievement of virological response (<50 copies per mL), and number of drug failures before TCVF.
Findings: 28 of 33 cohorts in COHERE contributed data to the PLATO II project, of which four had no participants eligible for inclusion in this study. 2476 (3%) of 91 764 participants from the remaining 24 cohorts had TCVF and at least one viral load measurement in 2000-09. The proportion of patients with virological response after TCVF increased from 19·5% in 2000 to 57·9% in 2009 (adjusted p<0·0001). Incidence of AIDS decreased from 7·7 per 100 person-years in 2000-02 to 2·3 in 2008 and 1·2 in 2009 (adjusted p<0·0001). Mortality decreased from 4·0 per 100 person-years between 2000 and 2002 to 1·9 in 2007 and 1·4 in 2008 (unadjusted p=0·023), but the trend was not significant after adjustment (p=0·22).
Interpretation: A substantial improvement in viral load suppression and accompanying decrease in the rates of AIDS in people after extensive failure to drugs from the three original antiretroviral classes during 2000-09 was probably mainly driven by availability of newer drugs with better tolerability and ease of use and small cross-resistance profiles, suggesting the public health benefit of the introduction of new drugs.
Copyright © 2012 Elsevier Ltd. All rights reserved.
Source: PubMed