Impact of HIV‐1 Reverse Transcriptase Polymorphism F214L on Virological Response to Thymidine Analogue–Based Regimens in Antiretroviral Therapy (ART)–Naive and ART‐Experienced Patients
1University of Rome “Tor Vergata,” Rome, Italy; 2Royal Free and University College Medical School, London, United Kingdom; 3IrsiCaixa Foundation and Lluita contra la SIDA Foundation, Badalona, and 4Division of Infectious Diseases, Faculty of Medicine, University of Barcelona, Barcelona, Spain; 5Copenhagen HIV Programme, Hvidovre Hospital, Hvidovre, Denmark; 6Division of Infectious Diseases and Hospital Epidemiology, University Hospital Zürich, Zürich, Switzerland; 7Academisch Medisch Centrum bij de Universiteit van Amsterdam, Amsterdam, The Netherlands
Background.
A negative association between the polymorphism F214L and type 1 thymidine analogue (TA) mutations (TAMs) has been observed. However, the virological response to TAs according to the detection of F214L has not been evaluated.
Methods.We studied 590 patients from EuroSIDA who started TA therapy for the first time as part of potent combination antiretroviral therapy (cART) and who were tested for genotypic resistance within the past 6 months. End points were median reduction in the week 24 viral load and time to virological failure (2 consecutive VL measurements >400 copies/mL after at least 6 months of the TA‐containing cART).
Results.In ART‐naive patients, the prevalence of F214L was 17%. By 48 months after starting TA‐based cART, the proportion of patients who experienced virological failure was 16% in patients with 214L and 36% in those with 214F (
). In a multivariable Cox regression model, the relative hazard of virological failure for patients with 214L compared with those with 214F was 0.22 (95% confidence interval, 0.07–0.72). In ART‐experienced patients, results were similar, and larger differences in virological response associated with the detection of 214L versus F were observed in patients with M41L/T215Y and mixed TAM profiles detected before the initiation of cART.
Conclusions.This study provides evidence that the detection of polymorphism F214L is associated with a favorable virological response to TA‐based cART.
Received 29 December 2006; accepted 14 May 2007; electronically published 19 September 2007.
Cited by
Online publication date: 15-Apr-2008.
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Financial support: European Commission BIOMED 1 (grant CT94‐1637), BIOMED 2 (grant CT97‐2713), and 5th Framework (QLK2‐2000‐00773) programs (primary sponsorship of the study); Bristol‐Myers Squibb, GlaxoSmithKline, Roche, and Boehringer‐Ingelheim (unrestricted grants); Swiss Federal Office for Education and Science (grant to support the participation of centers from Switzerland in EuroSIDA).
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F.C.‐S. and A.C.‐L. contributed equally to this work.
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Study group members are listed after the text.
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Presented in part: 13th Conference on Retroviruses and Opportunistic Infections, Denver, 5–8 February 2006 (abstract 604); European HIV Drug Resistance Workshop—From Basic Science to Clinical Implications, Cascais, Portugal, 28–30 March 2007 (abstract 46).
Potential conflicts of interest: Some authors have received reimbursement, fees, and/or funding for attending symposiums, speaking, advisory board membership, organizing educational activities, consulting, and/or research from Abbott (B.C., A.N.P., C.F.P., and H.F.G.), Boeringher Ingelheim (B.C., A.N.P., J.D.L., and H.F.G.), Bristol‐Myers Squibb (B.C., A.N.P., C.F.P., F.C.‐S., and H.F.G.), Gilead Sciences (B.C., A.N.P., C.F.P., and F.C.‐S.), GlaxoSmithKline (B.C., A.C.‐L., A.N.P., C.F.P., F.C.‐S., and H.F.G.), Merck (B.C., C.F.P., and H.F.G.), Pfizer Pharmaceutical (B.C. and A.N.P.), Roche (B.C., A.C.‐L., A.N.P., C.F.P., F.C.‐S., and H.F.G.), and Tibotec (B.C., A.N.P., and C.F.P.).