Resistance mutations before and after tenofovir regimen failure in HIV-1 infected patients.
So far, no study has examined the real impact of tenofovir (TDF)-regimen failure taking into account all patients in a current clinical practice. The aim of this study was to compare the nucleoside reverse transcriptase inhibitors (NRTIs) mutation profiles observed before TDF initiation and after TDF-regimen failure. All patients with genotypic resistance tests performed in this context were selected from the database of the department of virology. The patients were categorized in two groups according to the presence (group I) or absence (group II) of thymidine analogue mutations (TAMs) documented before starting TDF. The proportions of the two groups were compared using Chi-squared tests. Odds-ratios were analyzed with a regression logistic test. Ninety-six patients met the criteria. The median number of TAMs before TDF initiation did not change at failure. The K65R mutation, absent from all baseline genotypes, developed in 19 of the 96 patients, with an incidence significantly higher in group II than in group I. In addition, five genotypes harboring K65R with TAMs or L74V mutation were observed at failure. The changes regarding the other NRTI-associated mutations concern mostly the codons 74, 75, 115, and 118. The selection of K65R was closely linked to the absence of TAMs at baseline and to the regimens sparing both protease inhibitors (PIs) and non-NRTIs. The K65R mutation can emerge even with TAMs or L74V. No obvious impact was shown on the TAMs or other NRTI mutations, although a trend towards emergence of some particular mutations was observed.
Wirden
Marc
M
Department of Virology, Pitié-Salpêtrière Hospital, Paris, France. marc.wirden@psl.ap-hop-paris.fr
Marcelin
Anne Genevieve
AG
Simon
Anne
A
Kirstetter
Myriam
M
Tubiana
Roland
R
Valantin
Marc-Antoine
MA
Paris
Luc
L
Bonmarchand
Manuela
M
Conan
Francoise
F
Kalkias
Laurence
L
Katlama
Christine
C
Calvez
Vincent
V
D000225:Adenine / Q000008:administration & dosage / Q000031:analogs & derivatives* / Q000627:therapeutic use; D019943:Amino Acid Substitution; D019380:Anti-HIV Agents / Q000008:administration & dosage / Q000627:therapeutic use*; D024882:Drug Resistance, Viral / Q000235:genetics*; D005602:France; D015658:HIV Infections / Q000188:drug therapy / Q000821:virology*; D015497:HIV-1 / Q000187:drug effects* / Q000235:genetics* / Q000302:isolation & purification; D006801:Humans; D009154:Mutation; D063065:Organophosphonates / Q000008:administration & dosage / Q000627:therapeutic use*; D018894:Reverse Transcriptase Inhibitors / Q000008:administration & dosage / Q000627:therapeutic use; D000068698:Tenofovir; D017211:Treatment Failure
D019380:Anti-HIV Agents; D063065:Organophosphonates; D018894:Reverse Transcriptase Inhibitors; D000068698:Tenofovir; D000225:Adenine