Quick Search:

uzh logo
Browse by:
bullet
bullet
bullet
bullet

Zurich Open Repository and Archive

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; Colin, C; Kjaer, J; Lundgren, J D; Paredes, R; Pozniak, A; Clotet, B; Phillips, A; Pillay, D; 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. Lancet Infectious Diseases, 11(5):363-371.

Full text not available from this repository.

View at publisher

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.

Citations

104 citations in Web of Science®
113 citations in Scopus®
Google Scholar™

Altmetrics

Additional indexing

Item Type:Journal Article, refereed, original work
Communities & Collections:04 Faculty of Medicine > University Hospital Zurich > Clinic for Infectious Diseases
DDC:610 Medicine & health
Language:English
Date:2011
Deposited On:20 Jan 2012 20:19
Last Modified:27 Nov 2013 22:00
Publisher:Elsevier
ISSN:1473-3099
Publisher DOI:10.1016/S1473-3099(11)70032-9
PubMed ID:21354861

Users (please log in): suggest update or correction for this item

Repository Staff Only: item control page