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.

Links

Publisher Full Text

Authors

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

Institution

INSERM U897 Centre of Epidemiology and Biostatistics, ISPED Bordeaux School of Public Health, University Bordeaux Segalen, Bordeaux, France. linda.wittkop@isped.u-bordeaux2.fr

Source

The Lancet infectious diseases 11:5 2011 May pg 363-71

MeSH

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

Pub Type(s)

Clinical Trial
Journal Article
Multicenter Study
Research Support, Non-U.S. Gov't

Language

eng

PubMed ID

21354861