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

TY - JOUR

T1 - Triple-class virologic failure in HIV-infected patients undergoing antiretroviral therapy for up to 10 years

AU - Lodwick, Rebecca

AU - Costagliola, Dominique

AU - Reiss, Peter

AU - Torti, Carlo

AU - Teira, Ramón

AU - Dorrucci, Maria

AU - Ledergerber, Bruno

AU - Mocroft, Amanda

AU - Podzamczer, Daniel

AU - Cozzi-Lepri, Alessandro

AU - Obel, Niels

AU - Masquelier, Bernard

AU - Staszewski, Schlomo

AU - García, Federico

AU - De Wit, Stephane

AU - Castagna, Antonella

AU - Antinori, Andrea

AU - Judd, Ali

AU - Ghosn, Jade

AU - Touloumi, Giota

AU - Mussini, Cristina

AU - Duval, Xavier

AU - Ramos, José

AU - Meyer, Laurence

AU - Warsawski, Josiane

AU - Thorne, Claire

AU - Masip, Joan

AU - Pérez-Hoyos, Santiago

AU - Pillay, Deenan

AU - van Sighem, Ard

AU - Lo Caputo, Sergio

AU - Günthard, Huldrych

AU - Paredes, Roger

AU - De Luca, Andrea

AU - Paraskevis, Dimitrios

AU - Fabre-Colin, Céline

AU - Kjaer, Jesper

AU - Chêne, Genèvieve

AU - Lundgren, Jens D

AU - Phillips, Andrew N

AU - Pursuing Later Treatment Options II (PLATO II) Project Team for the Collaboration of Observational HIV Epidemiological Research Europe (COHERE)

AU - Kjaer, Jesper

N1 - Keywords: Adolescent; Adult; Anti-HIV Agents; Europe; Female; HIV Infections; HIV Protease Inhibitors; Humans; Kaplan-Meiers Estimate; Life Expectancy; Male; Middle Aged; Proportional Hazards Models; Reverse Transcriptase Inhibitors; Ritonavir; Treatment Failure; Viral Load; Young Adult

PY - 2010/3/8

Y1 - 2010/3/8

N2 - 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 firstline 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 secondline regimens in resource-limited settings.

AB - 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 firstline 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 secondline regimens in resource-limited settings.

U2 - 10.1001/archinternmed.2009.472

DO - 10.1001/archinternmed.2009.472

M3 - Journal article

C2 - 20212176

SN - 2168-6106

VL - 170

SP - 410

EP - 419

JO - JAMA Internal Medicine

JF - JAMA Internal Medicine

IS - 5

ER -