High frequency of selection of K65R and Q151M mutations in HIV-2 infected patients receiving nucleoside reverse transcriptase inhibitors containing regimen.
The objective of the study was to determine retrospectively which substitutions in the reverse transcriptase (RT) gene are selected in vivo during nucleoside RT inhibitors (NRTI) containing regimen in HIV-2 infected subjects. Thirty-four HIV-2 patients having received NRTI-containing regimen with available specimens and amplifiable RT gene were studied. Analyses of RT gene were undertaken after a median NRTI exposure of 51 months (range: 5-128). Mutations at positions known to be involved in HIV-1 resistance were observed in 26/34 patients. Selection of Q151M mutation was observed in nine out of 34 isolates (26%) after a median NRTIs exposure of 41 months (range: 12-77). In 8/9 cases, Q151M mutation was associated with other substitutions at positions known to be involved in HIV-1 resistance: K65R (n = 6), D67N (n = 1), N69S or T (n = 2), K70R (n = 3), M184V (n = 4), S215Y (n = 1). Compared with HIV-1 infection, there is a high frequency of selection of Q151M mutation in HIV-2 infected patients receiving various combinations of NRTIs. In these highly thymidine analogue pretreated patients, the selection of thymidine analogue mutations was low suggesting that the pathway to resistance is very different between these two viruses.
Descamps
Diane
D
Hôpital Bichat-Claude Bernard, Paris, France. descamps@bch.ap-hop-paris.fr
Damond
Florence
F
Matheron
Sophie
S
Collin
Gilles
G
Campa
Pauline
P
Delarue
Severine
S
Pueyo
Sophie
S
Chêne
Genevieve
G
Brun-Vézinet
Francoise
F
D019380:Anti-HIV Agents / Q000494:pharmacology / Q000627:therapeutic use*; D024882:Drug Resistance, Viral; D004359:Drug Therapy, Combination; D015658:HIV Infections / Q000188:drug therapy* / Q000821:virology; D054303:HIV Reverse Transcriptase / Q000235:genetics*; D015498:HIV-2 / Q000187:drug effects* / Q000201:enzymology / Q000235:genetics; D006801:Humans; D009154:Mutation; D012367:RNA, Viral / Q000097:blood; D012189:Retrospective Studies; D018894:Reverse Transcriptase Inhibitors / Q000494:pharmacology / Q000627:therapeutic use*
D019380:Anti-HIV Agents; D012367:RNA, Viral; D018894:Reverse Transcriptase Inhibitors; D054303:HIV Reverse Transcriptase