Triple-class virologic failure in HIV-infected patients undergoing antiretroviral therapy for up to 10 years

Pursuing Later Treatment Options II (PLATO II) Project Team for the Collaboration of Observational HIV Epidemiological Research Europe (COHERE), Rebecca Lodwick, Dominique Costagliola, Peter Reiss, Carlo Torti, Ramón Teira, Maria Dorrucci, Bruno Ledergerber, Amanda Mocroft, Daniel Podzamczer, Alessandro Cozzi-Lepri, Niels Obel, Bernard Masquelier, Schlomo Staszewski, Federico García, Stephane De Wit, Antonella Castagna, Andrea Antinori, Ali Judd, Jade Ghosn, Giota Touloumi, Cristina Mussini, Xavier Duval, José Ramos, Laurence Meyer, Josiane Warsawski, Claire Thorne, Joan Masip, Santiago Pérez-Hoyos, Deenan Pillay, Ard van Sighem, Sergio Lo Caputo, Huldrych Günthard, Roger Paredes, Andrea De Luca, Dimitrios Paraskevis, Céline Fabre-Colin, Jesper Kjaer, Genèvieve Chêne, Jens D Lundgren, Andrew N Phillips, Ian Weller, Dominique Costagliola, Bruno Ledergerber, Jens Lundgren, Genèvieve Chêne, Giota Touloumi, Josiane Warszawski, Laurence Meyer, François Dabis, Murielle Mary Kraus, Catherine Leport, Frank de Wolf, Peter Reiss, Maria Dorrucci, Caroline Sabin, Diana Gibb, Gerd Fätkenheuer, Julia Del Amo, Niels Obel, Claire Thorne, Amanda Mocroft, Ole Kirk, Scholomo Staszewski, Santiago Pérez-Hoyos, Jesus Almeda, Andrea Antinori, Antonella Monforte d'Arminio, Annalisa Ridolfo, Pier-Angelo Tovo, Maurizio de Martino, Norbert H Brockmeyer, José Ramos, Manuel Battegay, Cristina Mussini, Pat Tookey, Jordi Casabona, Jose M Miró, Antonella Castagna, Stephane De Wit, Carlo Torti, Ramon Teira, Myrian Garrido, François Dabis, Matthias Egger, Hansjakob Furrer, Ole Kirk, Charlotte Lewden, Marie-Louise Newell, Andrew Phillips, Caroline Sabin, Jonathan Sterne, Amalio Telenti, Fidéline Collin-Filleul, Michelle Ellefson, Céline Fabre-Colin, Jesper Kjaer, Nikos Dedes, Pursuing Later Treatment Options II (PLATO II) Project Team for the Collaboration of Observational HIV Epidemiological Research Europe (COHERE), Rebecca Lodwick, Dominique Costagliola, Peter Reiss, Carlo Torti, Ramón Teira, Maria Dorrucci, Bruno Ledergerber, Amanda Mocroft, Daniel Podzamczer, Alessandro Cozzi-Lepri, Niels Obel, Bernard Masquelier, Schlomo Staszewski, Federico García, Stephane De Wit, Antonella Castagna, Andrea Antinori, Ali Judd, Jade Ghosn, Giota Touloumi, Cristina Mussini, Xavier Duval, José Ramos, Laurence Meyer, Josiane Warsawski, Claire Thorne, Joan Masip, Santiago Pérez-Hoyos, Deenan Pillay, Ard van Sighem, Sergio Lo Caputo, Huldrych Günthard, Roger Paredes, Andrea De Luca, Dimitrios Paraskevis, Céline Fabre-Colin, Jesper Kjaer, Genèvieve Chêne, Jens D Lundgren, Andrew N Phillips, Ian Weller, Dominique Costagliola, Bruno Ledergerber, Jens Lundgren, Genèvieve Chêne, Giota Touloumi, Josiane Warszawski, Laurence Meyer, François Dabis, Murielle Mary Kraus, Catherine Leport, Frank de Wolf, Peter Reiss, Maria Dorrucci, Caroline Sabin, Diana Gibb, Gerd Fätkenheuer, Julia Del Amo, Niels Obel, Claire Thorne, Amanda Mocroft, Ole Kirk, Scholomo Staszewski, Santiago Pérez-Hoyos, Jesus Almeda, Andrea Antinori, Antonella Monforte d'Arminio, Annalisa Ridolfo, Pier-Angelo Tovo, Maurizio de Martino, Norbert H Brockmeyer, José Ramos, Manuel Battegay, Cristina Mussini, Pat Tookey, Jordi Casabona, Jose M Miró, Antonella Castagna, Stephane De Wit, Carlo Torti, Ramon Teira, Myrian Garrido, François Dabis, Matthias Egger, Hansjakob Furrer, Ole Kirk, Charlotte Lewden, Marie-Louise Newell, Andrew Phillips, Caroline Sabin, Jonathan Sterne, Amalio Telenti, Fidéline Collin-Filleul, Michelle Ellefson, Céline Fabre-Colin, Jesper Kjaer, Nikos Dedes

Abstract

Background: Life expectancy of people with human immunodeficiency virus (HIV) is now estimated to approach that of the general population in some successfully treated subgroups. However, to attain these life expectancies, viral suppression must be maintained for decades.

Methods: We studied the rate of triple-class virologic failure (TCVF) in patients within the Collaboration of Observational HIV Epidemiological Research Europe (COHERE) who started antiretroviral therapy (ART) that included a nonnucleoside reverse-transcriptase inhibitor (NNRTI) or a ritonavir-boosted protease inhibitor (PI/r) from 1998 onwards. We also focused on TCVF in patients who started a PI/r-containing regimen after a first-line NNRTI-containing regimen failed.

Results: Of 45 937 patients followed up for a median (interquartile range) of 3.0 (1.5-5.0) years, 980 developed TCVF (2.1%). By 5 and 9 years after starting ART, an estimated 3.4% (95% confidence interval [CI], 3.1%-3.6%) and 8.6% (95% CI, 7.5%-9.8%) of patients, respectively, had developed TCVF. The incidence of TCVF rose during the first 3 to 4 years on ART but plateaued thereafter. There was no significant difference in the risk of TCVF according to whether the initial regimen was NNRTI or PI/r based (P = .11). By 5 years after starting a PI/r regimen as second-line therapy, 46% of patients had developed TCVF.

Conclusions: The rate of virologic failure of the 3 original drug classes is low, but not negligible, and does not appear to diminish over time from starting ART. If this trend continues, many patients are likely to need newer drugs to maintain viral suppression. The rate of TCVF from the start of a PI/r regimen after NNRTI failure provides a comparator for studies of response to second-line regimens in resource-limited settings.

Figures

Figure 1
Figure 1
Incidence (with 95% confidence interval) of triple class virologic failure (TCVF) during each year after the start of antiretroviral therapy.

Source: PubMed

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