Rare selection of the K65R mutation in antiretroviral-naive patients failing a first-line abacavir/ lamivudine-containing HAART regimen.
OBJECTIVE
Previous studies have described the presence of the L74V reverse transcriptase (RT) mutation in highly experienced individuals as a risk factor for reduced response to tenofovir and selection of the K65R mutation. This study examined whether, in the context of a first-line abacavir/lamivudine highly active antiretroviral therapy (HAART) regimen, K65R might occur as a minority population where L74V was detected at virological failure.


METHODS
Four previously ART-naive individuals undergoing virological failure were selected, all receiving abacavir and lamivudine with either protease inhibitors or efavirenz and with virus displaying L74V and M184V or M184V alone following transient L74V emergence. Clonal analyses from plasma viral RNA were performed on samples taken at baseline and after virological failure. Clones were screened for the presence of K65R by real time K65R-selective PCR (K65R-sPCR). RT genes from clones displaying K65R were sequenced.


RESULTS
At baseline, all clones were wild type at codon 65 by K65R-sPCR, except in one patient in which one of 720 clones exhibited K65R. At failure with M184V and L74V present by bulk sequencing, this K65R was retained in one of 855 clones assessed. One additional patient (M 184V alone by bulk sequencing) displayed K65R in one of 466 failure clones. Virological failure samples from the remaining two patients were wild type at codon 65 in all of 524 and 270 clones, respectively.


CONCLUSIONS
Minority species harbouring K65R are uncommon and occur at very low population densities in patients experiencing virological failure on first-line abacavir/lamivudine-containing HAART.
Descamps
Diane
D
Laboratoire de Virologie, Hôpital Bichat-Claude Bernard, Paris, France. diane.descamps@bch.aphp.fr
Ait-Khaled
Mounir
M
Craig
Charles
C
Delarue
Séverine
S
Damond
Florence
F
Collin
Gilles
G
Brun-Vézinet
Françoise
F
D019380:Anti-HIV Agents / Q000008:administration & dosage / Q000627:therapeutic use; D023241:Antiretroviral Therapy, Highly Active; D015224:Dideoxynucleosides / Q000008:administration & dosage / Q000627:therapeutic use*; D024882:Drug Resistance, Viral; D004359:Drug Therapy, Combination; D015658:HIV Infections / Q000188:drug therapy / Q000821:virology; D054303:HIV Reverse Transcriptase / Q000187:drug effects / Q000235:genetics*; D015497:HIV-1 / Q000187:drug effects / Q000201:enzymology / Q000235:genetics; D006801:Humans; D019259:Lamivudine / Q000008:administration & dosage / Q000627:therapeutic use*; D009154:Mutation; D012367:RNA, Viral / Q000097:blood; D018894:Reverse Transcriptase Inhibitors / Q000008:administration & dosage / Q000627:therapeutic use; D017211:Treatment Failure; D019562:Viral Load; D000099227:Abacavir
D019380:Anti-HIV Agents; D015224:Dideoxynucleosides; D054303:HIV Reverse Transcriptase; D019259:Lamivudine; D012367:RNA, Viral; D018894:Reverse Transcriptase Inhibitors; D000099227:Abacavir