Presence of M184I/V in minor HIV-1 populations of patients with lamivudine and/or didanosine treatment failure.
OBJECTIVE
The aim of the study was to investigate the presence of M184I/V in minor HIV-1 populations of patients who failed lamivudine (3TC) and/or didanosine (ddI) treatment.


METHODS
Fourteen 3TC-experienced patients who, after switching therapy to a ddI regimen, had a new failure without M184I/V in the major viral population were included in the study. Ninety plasma samples were analysed by direct sequencing and selective real-time polymerase chain reaction (SPCR), which detects GTG/GTA and ATA mutants down to 1 and 0.2% of the population, respectively.


RESULTS
In five samples, SPCR detected resistant virus when direct sequencing detected wild-type M184. In patients with mixed viral populations at sequencing, the median proportion of mutants detected by SPCR was 30%. SPCRGTG reactivity dominated, while SPCRATA reactivity only was uncommon. M184I/V disappeared in patients in whom 3TC was stopped but ddI continued. Ten patients with ddI failure had no M184I/V.


CONCLUSIONS
Minor HIV-1 strains may harbour M184I/V in patients failing ddI therapy, despite direct sequencing showing wild-type virus. Although M184I/V may reduce the genetic barrier of ddI for mutations such as K65R and L74V, the lack of re-emergence of M184I/V in the minor quasispecies of most patients who failed ddI suggests that M184I/V was not a preferred route to ddI resistance in our patient population.
Svedhem
V
V
Division of Infectious Diseases, Karolinska Institutet, Karolinska University Hospital, Stockholm, Sweden. veronica.svedhem@karolinska.se
Bergroth
T
T
Lidman
K
K
Sönnerborg
A
A
D000328:Adult; D000368:Aged; D016049:Didanosine / Q000494:pharmacology / Q000627:therapeutic use; D024882:Drug Resistance, Viral; D005260:Female; D015658:HIV Infections / Q000188:drug therapy* / Q000821:virology; D015497:HIV-1; D006801:Humans; D019259:Lamivudine / Q000494:pharmacology / Q000627:therapeutic use; D008297:Male; D008875:Middle Aged; D012194:RNA-Directed DNA Polymerase; D017211:Treatment Failure; D019562:Viral Load
D019259:Lamivudine; D012194:RNA-Directed DNA Polymerase; D016049:Didanosine