Detection of HIV drug resistance during antiretroviral treatment and clinical progression in a large European cohort study

Alessandro Cozzi-Lepri; Andrew N Phillips; Bonaventura Clotet; Amanda Mocroft; Lidia Ruiz; Ole Kirk; Adriano Lazzarin; Alicja Wiercinska-Drapalo; Anders Karlsson; Jens Lundgren; Eurosida Study Group

doi:10.1097/QAD.0b013e328310e04f

Detection of HIV drug resistance during antiretroviral treatment and clinical progression in a large European cohort study

Alessandro Cozzi-Lepri, Andrew N Phillips, Bonaventura Clotet, Amanda Mocroft, Lidia Ruiz, Ole Kirk, Adriano Lazzarin, Alicja Wiercinska-Drapalo, Anders Karlsson, Jens Lundgren, Eurosida Study Group

39 Citations (Scopus)

Abstract

OBJECTIVE(S): To investigate the relationship between detection of HIV drug resistance by 2 years from starting antiretroviral therapy and the subsequent risk of progression to AIDS and death. DESIGN: Virological failure was defined as experiencing two consecutive viral loads of more than 400 copies/ml in the time window between 0.5 and 2 years from starting antiretroviral therapy (baseline). Patients were grouped according to evidence of virological failure and whether there was detection of the International AIDS Society resistance mutations to one, two or three drug classes in the time window. METHODS: Standard survival analysis using Kaplan-Meier curves and Cox proportional hazards regression model with time-fixed covariates defined at baseline was employed. RESULTS: We studied 8229 patients in EuroSIDA who started antiretroviral therapy and who had at least 2 years of clinical follow-up. We observed 829 AIDS events and 571 deaths during 38,814 person-years of follow-up resulting in an overall incidence of new AIDS and death of 3.6 per 100 person-years of follow-up [95% confidence interval (CI):3.4-3.8]. By 96 months from baseline, the proportion of patients with a new AIDS diagnosis or death was 20.3% (95% CI:17.7-22.9) in patients with no evidence of virological failure and 53% (39.3-66.7) in those with virological failure and mutations to three drug classes (P = 0.0001). An almost two-fold difference in risk was confirmed in the multivariable analysis (adjusted relative hazard = 1.8, 95% CI:1.2-2.7, P = 0.005). CONCLUSION: Although this study shows an association between the detection of resistance at failure and risk of clinical progression, further research is needed to clarify whether resistance reflects poor adherence or directly increases the risk of clinical events via exhaustion of drug options.

Original language	English
Journal	AIDS
Volume	22
Issue number	16
Pages (from-to)	2187-98
Number of pages	11
ISSN	0269-9370
DOIs	https://doi.org/10.1097/QAD.0b013e328310e04f
Publication status	Published - 2008

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@article{bcf84310ff3111ddb219000ea68e967b,

title = "Detection of HIV drug resistance during antiretroviral treatment and clinical progression in a large European cohort study",

abstract = "OBJECTIVE(S): To investigate the relationship between detection of HIV drug resistance by 2 years from starting antiretroviral therapy and the subsequent risk of progression to AIDS and death. DESIGN: Virological failure was defined as experiencing two consecutive viral loads of more than 400 copies/ml in the time window between 0.5 and 2 years from starting antiretroviral therapy (baseline). Patients were grouped according to evidence of virological failure and whether there was detection of the International AIDS Society resistance mutations to one, two or three drug classes in the time window. METHODS: Standard survival analysis using Kaplan-Meier curves and Cox proportional hazards regression model with time-fixed covariates defined at baseline was employed. RESULTS: We studied 8229 patients in EuroSIDA who started antiretroviral therapy and who had at least 2 years of clinical follow-up. We observed 829 AIDS events and 571 deaths during 38,814 person-years of follow-up resulting in an overall incidence of new AIDS and death of 3.6 per 100 person-years of follow-up [95% confidence interval (CI):3.4-3.8]. By 96 months from baseline, the proportion of patients with a new AIDS diagnosis or death was 20.3% (95% CI:17.7-22.9) in patients with no evidence of virological failure and 53% (39.3-66.7) in those with virological failure and mutations to three drug classes (P = 0.0001). An almost two-fold difference in risk was confirmed in the multivariable analysis (adjusted relative hazard = 1.8, 95% CI:1.2-2.7, P = 0.005). CONCLUSION: Although this study shows an association between the detection of resistance at failure and risk of clinical progression, further research is needed to clarify whether resistance reflects poor adherence or directly increases the risk of clinical events via exhaustion of drug options.",

author = "Alessandro Cozzi-Lepri and Phillips, {Andrew N} and Bonaventura Clotet and Amanda Mocroft and Lidia Ruiz and Ole Kirk and Adriano Lazzarin and Alicja Wiercinska-Drapalo and Anders Karlsson and Jens Lundgren and {Eurosida Study Group}",

year = "2008",

doi = "10.1097/QAD.0b013e328310e04f",

language = "English",

volume = "22",

pages = "2187--98",

journal = "AIDS, Supplement",

issn = "1350-2840",

publisher = "Lippincott Williams & Wilkins",

number = "16",

}

TY - JOUR

T1 - Detection of HIV drug resistance during antiretroviral treatment and clinical progression in a large European cohort study

AU - Cozzi-Lepri, Alessandro

AU - Phillips, Andrew N

AU - Clotet, Bonaventura

AU - Mocroft, Amanda

AU - Ruiz, Lidia

AU - Kirk, Ole

AU - Lazzarin, Adriano

AU - Wiercinska-Drapalo, Alicja

AU - Karlsson, Anders

AU - Lundgren, Jens

AU - Eurosida Study Group

PY - 2008

Y1 - 2008

N2 - OBJECTIVE(S): To investigate the relationship between detection of HIV drug resistance by 2 years from starting antiretroviral therapy and the subsequent risk of progression to AIDS and death. DESIGN: Virological failure was defined as experiencing two consecutive viral loads of more than 400 copies/ml in the time window between 0.5 and 2 years from starting antiretroviral therapy (baseline). Patients were grouped according to evidence of virological failure and whether there was detection of the International AIDS Society resistance mutations to one, two or three drug classes in the time window. METHODS: Standard survival analysis using Kaplan-Meier curves and Cox proportional hazards regression model with time-fixed covariates defined at baseline was employed. RESULTS: We studied 8229 patients in EuroSIDA who started antiretroviral therapy and who had at least 2 years of clinical follow-up. We observed 829 AIDS events and 571 deaths during 38,814 person-years of follow-up resulting in an overall incidence of new AIDS and death of 3.6 per 100 person-years of follow-up [95% confidence interval (CI):3.4-3.8]. By 96 months from baseline, the proportion of patients with a new AIDS diagnosis or death was 20.3% (95% CI:17.7-22.9) in patients with no evidence of virological failure and 53% (39.3-66.7) in those with virological failure and mutations to three drug classes (P = 0.0001). An almost two-fold difference in risk was confirmed in the multivariable analysis (adjusted relative hazard = 1.8, 95% CI:1.2-2.7, P = 0.005). CONCLUSION: Although this study shows an association between the detection of resistance at failure and risk of clinical progression, further research is needed to clarify whether resistance reflects poor adherence or directly increases the risk of clinical events via exhaustion of drug options.

AB - OBJECTIVE(S): To investigate the relationship between detection of HIV drug resistance by 2 years from starting antiretroviral therapy and the subsequent risk of progression to AIDS and death. DESIGN: Virological failure was defined as experiencing two consecutive viral loads of more than 400 copies/ml in the time window between 0.5 and 2 years from starting antiretroviral therapy (baseline). Patients were grouped according to evidence of virological failure and whether there was detection of the International AIDS Society resistance mutations to one, two or three drug classes in the time window. METHODS: Standard survival analysis using Kaplan-Meier curves and Cox proportional hazards regression model with time-fixed covariates defined at baseline was employed. RESULTS: We studied 8229 patients in EuroSIDA who started antiretroviral therapy and who had at least 2 years of clinical follow-up. We observed 829 AIDS events and 571 deaths during 38,814 person-years of follow-up resulting in an overall incidence of new AIDS and death of 3.6 per 100 person-years of follow-up [95% confidence interval (CI):3.4-3.8]. By 96 months from baseline, the proportion of patients with a new AIDS diagnosis or death was 20.3% (95% CI:17.7-22.9) in patients with no evidence of virological failure and 53% (39.3-66.7) in those with virological failure and mutations to three drug classes (P = 0.0001). An almost two-fold difference in risk was confirmed in the multivariable analysis (adjusted relative hazard = 1.8, 95% CI:1.2-2.7, P = 0.005). CONCLUSION: Although this study shows an association between the detection of resistance at failure and risk of clinical progression, further research is needed to clarify whether resistance reflects poor adherence or directly increases the risk of clinical events via exhaustion of drug options.

U2 - 10.1097/QAD.0b013e328310e04f

DO - 10.1097/QAD.0b013e328310e04f

M3 - Journal article

C2 - 18832882

SN - 1350-2840

VL - 22

SP - 2187

EP - 2198

JO - AIDS, Supplement

JF - AIDS, Supplement

IS - 16

ER -

Detection of HIV drug resistance during antiretroviral treatment and clinical progression in a large European cohort study

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