Effect of transmitted drug resistance on virological and immunological response to initial combination antiretroviral therapy for HIV (EuroCoord-CHAIN joint project): a European multicohort study

Linda Wittkop; Huldrych F Günthard; Frank de Wolf; David Dunn; Alessandro Cozzi-Lepri; Andrea de Luca; Claudia Kücherer; Niels Obel; Viktor von Wyl; Bernard Masquelier; Christoph Stephan; Carlo Torti; Andrea Antinori; Federico García; Ali Judd; Kholoud Porter; Rodolphe Thiébaut; Hannah Castro; Ard I van Sighem; Céline Colin; Jesper Kjaer; Jens D Lundgren; Roger Paredes; Anton Pozniak; Bonaventura Clotet; Andrew Phillips; Deenan Pillay; Geneviève Chêne; EuroCoord-CHAIN study group

doi:10.1016/s1473-3099(11)70032-9

Effect of transmitted drug resistance on virological and immunological response to initial combination antiretroviral therapy for HIV (EuroCoord-CHAIN joint project): a European multicohort study

Linda Wittkop, Huldrych F Günthard, Frank de Wolf, David Dunn, Alessandro Cozzi-Lepri, Andrea de Luca, Claudia Kücherer, Niels Obel, Viktor von Wyl, Bernard Masquelier, Christoph Stephan, Carlo Torti, Andrea Antinori, Federico García, Ali Judd, Kholoud Porter, Rodolphe Thiébaut, Hannah Castro, Ard I van Sighem, Céline ColinJesper Kjaer, Jens D Lundgren, Roger Paredes, Anton Pozniak, Bonaventura Clotet, Andrew Phillips, Deenan Pillay, Geneviève Chêne, EuroCoord-CHAIN study group

287 Citations (Scopus)

Abstract

Background: The effect of transmitted drug resistance (TDR) on first-line combination antiretroviral therapy (cART) for HIV-1 needs further study to inform choice of optimum drug regimens. We investigated the effect of TDR on outcome in the first year of cART within a large European collaboration. Methods: HIV-infected patients of any age were included if they started cART (at least three antiretroviral drugs) for the first time after Jan 1, 1998, and were antiretroviral naive and had at least one sample for a genotypic test taken before the start of cART. We used the WHO drug resistance list and the Stanford algorithm to classify patients into three resistance categories: no TDR, at least one mutation and fully-active cART, or at least one mutation and resistant to at least one prescribed drug. Virological failure was defined as time to the first of two consecutive viral load measurements over 500 copies per mL after 6 months of therapy. Findings: Of 10 056 patients from 25 cohorts, 9102 (90·5%) had HIV without TDR, 475 (4·7%) had at least one mutation but received fully-active cART, and 479 (4·8%) had at least one mutation and resistance to at least one drug. Cumulative Kaplan-Meier estimates for virological failure at 12 months were 4·2% (95% CI 3·8-4·7) for patients in the no TDR group, 4·7% (2·9-7·5) for those in the TDR and fully-active cART group, and 15·1% (11·9-19·0) for those in the TDR and resistant group (log-rank p<0·0001). The hazard ratio for the difference in virological failure between patients with TDR and resistance to at least one drug and those without TDR was 3·13 (95% CI 2·33-4·20, p<0·0001). The hazard ratio for the difference between patients with TDR receiving fully-active cART and patients without TDR was 1·47 (95% CI 0·19-2·38, p=0·12). In stratified analysis, the hazard ratio for the risk of virological failure in patients with TDR who received fully-active cART that included a non-nucleoside reverse transcriptase inhibitor (NNRTI) compared with those without TDR was 2·0 (95% CI 0·9-4·7, p=0·093). Interpretation: These findings confirm present treatment guidelines for HIV, which state that the initial treatment choice should be based on resistance testing in treatment-naive patients. Funding: European Community's Seventh Framework Programme FP7/2007-2013 and Gilead.

Original language	English
Journal	Lancet Infectious Diseases
Volume	11
Issue number	5
Pages (from-to)	363-71
Number of pages	9
ISSN	1473-3099
DOIs	https://doi.org/10.1016/s1473-3099(11)70032-9
Publication status	Published - 1 May 2011

Keywords

Adolescent
Adult
Anti-HIV Agents
Child
Child, Preschool
Cohort Studies
Drug Resistance, Viral
Drug Therapy, Combination
Europe
Female
HIV
HIV Infections
Humans
Infant
Male
Middle Aged
Mutation
Viral Load
Young Adult

UN SDGs

This output contributes to the following UN Sustainable Development Goals (SDGs)

Access to Document

10.1016/s1473-3099(11)70032-9

Cite this

Wittkop, L., Günthard, H. F., de Wolf, F., Dunn, D., Cozzi-Lepri, A., de Luca, A., Kücherer, C., Obel, N., von Wyl, V., Masquelier, B., Stephan, C., Torti, C., Antinori, A., García, F., Judd, A., Porter, K., Thiébaut, R., Castro, H., van Sighem, A. I., ... EuroCoord-CHAIN study group (2011). Effect of transmitted drug resistance on virological and immunological response to initial combination antiretroviral therapy for HIV (EuroCoord-CHAIN joint project): a European multicohort study. Lancet Infectious Diseases, 11(5), 363-71. https://doi.org/10.1016/s1473-3099(11)70032-9

Effect of transmitted drug resistance on virological and immunological response to initial combination antiretroviral therapy for HIV (EuroCoord-CHAIN joint project): a European multicohort study. / Wittkop, Linda; Günthard, Huldrych F; de Wolf, Frank et al.

In: Lancet Infectious Diseases, Vol. 11, No. 5, 01.05.2011, p. 363-71.

Research output: Contribution to journal › Journal article › Research › peer-review

Wittkop, L, Günthard, HF, de Wolf, F, Dunn, D, Cozzi-Lepri, A, de Luca, A, Kücherer, C, Obel, N, von Wyl, V, Masquelier, B, Stephan, C, Torti, C, Antinori, A, García, F, Judd, A, Porter, K, Thiébaut, R, Castro, H, van Sighem, AI, Colin, C, Kjaer, J, Lundgren, JD, Paredes, R, Pozniak, A, Clotet, B, Phillips, A, Pillay, D, Chêne, G & EuroCoord-CHAIN study group 2011, 'Effect of transmitted drug resistance on virological and immunological response to initial combination antiretroviral therapy for HIV (EuroCoord-CHAIN joint project): a European multicohort study', Lancet Infectious Diseases, vol. 11, no. 5, pp. 363-71. https://doi.org/10.1016/s1473-3099(11)70032-9

@article{60feb6bed3c64916bafcfabb289c699e,

title = "Effect of transmitted drug resistance on virological and immunological response to initial combination antiretroviral therapy for HIV (EuroCoord-CHAIN joint project): a European multicohort study",

abstract = "Background: The effect of transmitted drug resistance (TDR) on first-line combination antiretroviral therapy (cART) for HIV-1 needs further study to inform choice of optimum drug regimens. We investigated the effect of TDR on outcome in the first year of cART within a large European collaboration. Methods: HIV-infected patients of any age were included if they started cART (at least three antiretroviral drugs) for the first time after Jan 1, 1998, and were antiretroviral naive and had at least one sample for a genotypic test taken before the start of cART. We used the WHO drug resistance list and the Stanford algorithm to classify patients into three resistance categories: no TDR, at least one mutation and fully-active cART, or at least one mutation and resistant to at least one prescribed drug. Virological failure was defined as time to the first of two consecutive viral load measurements over 500 copies per mL after 6 months of therapy. Findings: Of 10 056 patients from 25 cohorts, 9102 (90·5%) had HIV without TDR, 475 (4·7%) had at least one mutation but received fully-active cART, and 479 (4·8%) had at least one mutation and resistance to at least one drug. Cumulative Kaplan-Meier estimates for virological failure at 12 months were 4·2% (95% CI 3·8-4·7) for patients in the no TDR group, 4·7% (2·9-7·5) for those in the TDR and fully-active cART group, and 15·1% (11·9-19·0) for those in the TDR and resistant group (log-rank p<0·0001). The hazard ratio for the difference in virological failure between patients with TDR and resistance to at least one drug and those without TDR was 3·13 (95% CI 2·33-4·20, p<0·0001). The hazard ratio for the difference between patients with TDR receiving fully-active cART and patients without TDR was 1·47 (95% CI 0·19-2·38, p=0·12). In stratified analysis, the hazard ratio for the risk of virological failure in patients with TDR who received fully-active cART that included a non-nucleoside reverse transcriptase inhibitor (NNRTI) compared with those without TDR was 2·0 (95% CI 0·9-4·7, p=0·093). Interpretation: These findings confirm present treatment guidelines for HIV, which state that the initial treatment choice should be based on resistance testing in treatment-naive patients. Funding: European Community's Seventh Framework Programme FP7/2007-2013 and Gilead.",

keywords = "Adolescent, Adult, Anti-HIV Agents, Child, Child, Preschool, Cohort Studies, Drug Resistance, Viral, Drug Therapy, Combination, Europe, Female, HIV, HIV Infections, Humans, Infant, Male, Middle Aged, Mutation, Viral Load, Young Adult",

author = "Linda Wittkop and G{\"u}nthard, {Huldrych F} and {de Wolf}, Frank and David Dunn and Alessandro Cozzi-Lepri and {de Luca}, Andrea and Claudia K{\"u}cherer and Niels Obel and {von Wyl}, Viktor and Bernard Masquelier and Christoph Stephan and Carlo Torti and Andrea Antinori and Federico Garc{\'i}a and Ali Judd and Kholoud Porter and Rodolphe Thi{\'e}baut and Hannah Castro and {van Sighem}, {Ard I} and C{\'e}line Colin and Jesper Kjaer and Lundgren, {Jens D} and Roger Paredes and Anton Pozniak and Bonaventura Clotet and Andrew Phillips and Deenan Pillay and Genevi{\`e}ve Ch{\^e}ne and {EuroCoord-CHAIN study group}",

year = "2011",

month = may,

day = "1",

doi = "10.1016/s1473-3099(11)70032-9",

language = "English",

volume = "11",

pages = "363--71",

journal = "The Lancet Infectious Diseases",

issn = "1473-3099",

publisher = "TheLancet Publishing Group",

number = "5",

}

TY - JOUR

T1 - Effect of transmitted drug resistance on virological and immunological response to initial combination antiretroviral therapy for HIV (EuroCoord-CHAIN joint project): a European multicohort study

AU - Wittkop, Linda

AU - Günthard, Huldrych F

AU - de Wolf, Frank

AU - Dunn, David

AU - Cozzi-Lepri, Alessandro

AU - de Luca, Andrea

AU - Kücherer, Claudia

AU - Obel, Niels

AU - von Wyl, Viktor

AU - Masquelier, Bernard

AU - Stephan, Christoph

AU - Torti, Carlo

AU - Antinori, Andrea

AU - García, Federico

AU - Judd, Ali

AU - Porter, Kholoud

AU - Thiébaut, Rodolphe

AU - Castro, Hannah

AU - van Sighem, Ard I

AU - Colin, Céline

AU - Kjaer, Jesper

AU - Lundgren, Jens D

AU - Paredes, Roger

AU - Pozniak, Anton

AU - Clotet, Bonaventura

AU - Phillips, Andrew

AU - Pillay, Deenan

AU - Chêne, Geneviève

AU - EuroCoord-CHAIN study group

PY - 2011/5/1

Y1 - 2011/5/1

N2 - Background: The effect of transmitted drug resistance (TDR) on first-line combination antiretroviral therapy (cART) for HIV-1 needs further study to inform choice of optimum drug regimens. We investigated the effect of TDR on outcome in the first year of cART within a large European collaboration. Methods: HIV-infected patients of any age were included if they started cART (at least three antiretroviral drugs) for the first time after Jan 1, 1998, and were antiretroviral naive and had at least one sample for a genotypic test taken before the start of cART. We used the WHO drug resistance list and the Stanford algorithm to classify patients into three resistance categories: no TDR, at least one mutation and fully-active cART, or at least one mutation and resistant to at least one prescribed drug. Virological failure was defined as time to the first of two consecutive viral load measurements over 500 copies per mL after 6 months of therapy. Findings: Of 10 056 patients from 25 cohorts, 9102 (90·5%) had HIV without TDR, 475 (4·7%) had at least one mutation but received fully-active cART, and 479 (4·8%) had at least one mutation and resistance to at least one drug. Cumulative Kaplan-Meier estimates for virological failure at 12 months were 4·2% (95% CI 3·8-4·7) for patients in the no TDR group, 4·7% (2·9-7·5) for those in the TDR and fully-active cART group, and 15·1% (11·9-19·0) for those in the TDR and resistant group (log-rank p<0·0001). The hazard ratio for the difference in virological failure between patients with TDR and resistance to at least one drug and those without TDR was 3·13 (95% CI 2·33-4·20, p<0·0001). The hazard ratio for the difference between patients with TDR receiving fully-active cART and patients without TDR was 1·47 (95% CI 0·19-2·38, p=0·12). In stratified analysis, the hazard ratio for the risk of virological failure in patients with TDR who received fully-active cART that included a non-nucleoside reverse transcriptase inhibitor (NNRTI) compared with those without TDR was 2·0 (95% CI 0·9-4·7, p=0·093). Interpretation: These findings confirm present treatment guidelines for HIV, which state that the initial treatment choice should be based on resistance testing in treatment-naive patients. Funding: European Community's Seventh Framework Programme FP7/2007-2013 and Gilead.

AB - Background: The effect of transmitted drug resistance (TDR) on first-line combination antiretroviral therapy (cART) for HIV-1 needs further study to inform choice of optimum drug regimens. We investigated the effect of TDR on outcome in the first year of cART within a large European collaboration. Methods: HIV-infected patients of any age were included if they started cART (at least three antiretroviral drugs) for the first time after Jan 1, 1998, and were antiretroviral naive and had at least one sample for a genotypic test taken before the start of cART. We used the WHO drug resistance list and the Stanford algorithm to classify patients into three resistance categories: no TDR, at least one mutation and fully-active cART, or at least one mutation and resistant to at least one prescribed drug. Virological failure was defined as time to the first of two consecutive viral load measurements over 500 copies per mL after 6 months of therapy. Findings: Of 10 056 patients from 25 cohorts, 9102 (90·5%) had HIV without TDR, 475 (4·7%) had at least one mutation but received fully-active cART, and 479 (4·8%) had at least one mutation and resistance to at least one drug. Cumulative Kaplan-Meier estimates for virological failure at 12 months were 4·2% (95% CI 3·8-4·7) for patients in the no TDR group, 4·7% (2·9-7·5) for those in the TDR and fully-active cART group, and 15·1% (11·9-19·0) for those in the TDR and resistant group (log-rank p<0·0001). The hazard ratio for the difference in virological failure between patients with TDR and resistance to at least one drug and those without TDR was 3·13 (95% CI 2·33-4·20, p<0·0001). The hazard ratio for the difference between patients with TDR receiving fully-active cART and patients without TDR was 1·47 (95% CI 0·19-2·38, p=0·12). In stratified analysis, the hazard ratio for the risk of virological failure in patients with TDR who received fully-active cART that included a non-nucleoside reverse transcriptase inhibitor (NNRTI) compared with those without TDR was 2·0 (95% CI 0·9-4·7, p=0·093). Interpretation: These findings confirm present treatment guidelines for HIV, which state that the initial treatment choice should be based on resistance testing in treatment-naive patients. Funding: European Community's Seventh Framework Programme FP7/2007-2013 and Gilead.

KW - Adolescent

KW - Adult

KW - Anti-HIV Agents

KW - Child

KW - Child, Preschool

KW - Cohort Studies

KW - Drug Resistance, Viral

KW - Drug Therapy, Combination

KW - Europe

KW - Female

KW - HIV

KW - HIV Infections

KW - Humans

KW - Infant

KW - Male

KW - Middle Aged

KW - Mutation

KW - Viral Load

KW - Young Adult

U2 - 10.1016/s1473-3099(11)70032-9

DO - 10.1016/s1473-3099(11)70032-9

M3 - Journal article

SN - 1473-3099

VL - 11

SP - 363

EP - 371

JO - The Lancet Infectious Diseases

JF - The Lancet Infectious Diseases

IS - 5

ER -

Effect of transmitted drug resistance on virological and immunological response to initial combination antiretroviral therapy for HIV (EuroCoord-CHAIN joint project): a European multicohort study

Abstract

Keywords

UN SDGs

Access to Document

Fingerprint

Cite this