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

Francesca Ceccherini-Silberstein, Alessandro Cozzi-Lepri, Lidia Ruiz, Amanda Mocroft, Andrew N. Phillips, Christian Holkmann Olsen, Jose M. Gatell, Huldrych F. Günthard, Peter Reiss, Carlo Federico Perno, Bonaventura Clotet, Jens D. Lundgren

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Abstract

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 (P = .03). 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.

Original languageEnglish
Pages (from-to)1180-1190
Number of pages11
JournalJournal of Infectious Diseases
Volume196
Issue number8
DOIs
Publication statusPublished - 2007

ASJC Scopus subject areas

  • Public Health, Environmental and Occupational Health
  • Immunology

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    Ceccherini-Silberstein, F., Cozzi-Lepri, A., Ruiz, L., Mocroft, A., Phillips, A. N., Olsen, C. H., Gatell, J. M., Günthard, H. F., Reiss, P., Perno, C. F., Clotet, B., & Lundgren, J. D. (2007). 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. Journal of Infectious Diseases, 196(8), 1180-1190. https://doi.org/10.1086/521678