Kinetics of disappearance of resistance mutations and reappearance of wild-type during structured treatment interruptions.
OBJECTIVE
To monitor the disappearance of resistance-associated mutations and reappearance of wild-type (WT) virus during structured treatment interruptions (STI) using DNA sequencing and line probe assay.


METHODS
Eleven HIV-1-infected patients participating in the MUTAVIR study undergoing a 3-month STI after multi-HAART failure were monitored biweekly. Genotypes were assessed by sequencing and VERSANT HIV-1 Resistance Assays (LiPA).


RESULTS
At treatment interruption, 54 mutations in total were identified with both methods among the patients. LiPA provided a result for 93.3% of the codons at baseline. For 37 mutations, a complete reversion of mutant to WT was observed with one of the two methods. Among these, LiPA detected mutations in 23 codons for 7 to 52 days longer, in 10 codons for the same period, and in four codons for a shorter time than sequencing. Similarly, LiPA detected 35 WT codons 8 to 86 days earlier, and 15 at the same time point as sequencing. A sharp reduction in the number of mutations was observed at the time of viral load increase in five of the 11 patients. Taking only the codons detected by LiPA into consideration, two patients showed a complete reversion to WT according to both genotyping assays at the end of the STI period.


CONCLUSIONS
The determination of the timepoint at which a virus population of an HIV-1 patient undergoing STI reverts to WT is dependent on the assay used. The viral load increase in most patients is compatible with the outgrowth of virus with fewer or no mutations.
Halfon
Philippe
P
Laboratoire Alphabio, Marseilles, Belgium.
Durant
Jacques
J
Clevenbergh
Philippe
P
Carsenti
Hélène
H
Celis
Linda
L
Khiri
Hacene
H
De Smet
Koen
K
De Brauwer
Annelies
A
Hulstaert
Frank
F
Dellamonica
Pierre
P
D023241:Antiretroviral Therapy, Highly Active; D003062:Codon; D004252:DNA Mutational Analysis; D024921:Drug Resistance, Multiple, Viral / Q000235:genetics*; D016679:Genome, Viral; D015658:HIV Infections / Q000188:drug therapy* / Q000821:virology*; D015497:HIV-1 / Q000235:genetics*; D006801:Humans; D009154:Mutation; D020133:Reverse Transcriptase Polymerase Chain Reaction; D017211:Treatment Failure; D019562:Viral Load
D003062:Codon