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

Research output: Contribution to journalArticle

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

Original languageEnglish
Pages (from-to)363-371
Number of pages9
JournalThe Lancet Infectious Diseases
Volume11
Issue number5
DOIs
Publication statusPublished - May 2011

ASJC Scopus subject areas

  • Infectious Diseases

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    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., ... Chêne, G. (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. The Lancet Infectious Diseases, 11(5), 363-371. https://doi.org/10.1016/S1473-3099(11)70032-9