National survey of the prevalence and conditions of selection of HIV-1 reverse transcriptase K70E mutation.
Tenofovir disoproxil fumarate (TDF) has become an important component of HIV combination therapy because of its potency and once-daily dosing. Key mutation associated with resistance to TDF is a K65R in the reverse transcriptase (RT) gene. According to occurrence of K70E mutation after failure to TDF regimen, this mutation was recently reported as a mutation associated with TDF resistance in most resistance genotypic algorithms. The aim of this study was to analyze, retrospectively, the prevalence and conditions of selection of HIV-1 RT K70E mutation from a national clinical survey. Absence of selection of K70E in 850 HIV-1-infected naive patients suggests its role in NRTI drug resistance. Prevalence of K70E RT was low (99/41601, 0.24%) in patients treated between 1999 and 2005. Conversely with K65R mutation, thymidine analog mutations (TAMs) can be concomitantly observed with K70E mutation but its frequency decreased as the number of TAM increases. Concomitant association of K65R and K70E was possible but infrequent (11%). At the time of K70E selection, 60% of patients had received or received TDF-containing regimen and one-third received exclusive NRTI regimen. In conclusion, the K70E mutation could be an alternative pathway of TDF resistance, but as the K65R mutation, other NRTI as ABC, ddI, and 3TC could be also associated with the K70E selection.
Delaugerre
C
C
CHU Ambroise Pare, Boulogne, France. constance.delaugerre@sls.aphp.fr
Flandre
P
P
Marcelin
A G
AG
Descamps
D
D
Tamalet
C
C
Cottalorda
J
J
Schneider
V
V
Yerly
S
S
LeGoff
J
J
Morand-Joubert
L
L
Chaix
M L
ML
Costagliola
D
D
Calvez
V
V
D019943:Amino Acid Substitution / Q000235:genetics*; D019380:Anti-HIV Agents / Q000627:therapeutic use; D024882:Drug Resistance, Viral; D005602:France; D015658:HIV Infections / Q000188:drug therapy / Q000821:virology*; D054303:HIV Reverse Transcriptase / Q000235:genetics*; D015497:HIV-1 / Q000235:genetics* / Q000302:isolation & purification; D006801:Humans; D020125:Mutation, Missense; D012189:Retrospective Studies; D012641:Selection, Genetic
D019380:Anti-HIV Agents; C514824:reverse transcriptase, Human immunodeficiency virus 1; D054303:HIV Reverse Transcriptase