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.
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.
Ceccherini-Silberstein
Francesca
F
Department of Experimental Medicine, University of Rome Tor Vergata, Rome, Italy. ceccherini@med.uniroma2.it
Cozzi-Lepri
Alessandro
A
Ruiz
Lidia
L
Mocroft
Amanda
A
Phillips
Andrew N
AN
Olsen
Christian Holkmann
CH
Gatell
Jose M
JM
Gunthard
Huldrych F
HF
Reiss
Peter
P
Perno
Carlo Federico
CF
Clotet
Bonaventura
B
Lundgren
Jens D
JD
D005060:Europe; D015658:HIV Infections / Q000235:genetics*; D054303:HIV Reverse Transcriptase / Q000187:drug effects* / Q000235:genetics; D015497:HIV-1 / Q000187:drug effects / Q000235:genetics; D006801:Humans; D009154:Mutation; D020641:Polymorphism, Single Nucleotide / Q000187:drug effects* / Q000235:genetics; D012189:Retrospective Studies; D018894:Reverse Transcriptase Inhibitors / Q000494:pharmacology*; D013936:Thymidine / Q000031:analogs & derivatives*
D018894:Reverse Transcriptase Inhibitors; D054303:HIV Reverse Transcriptase; D013936:Thymidine