Lack of persistent drug-resistant mutations evaluated within and between treatment interruptions in chronically HIV-1-infected patients.
OBJECTIVE
To determine the effect of treatment interruptions (TI) on the evolution and persistence of drug-resistant viruses in chronically HIV-1-infected suppressed patients.


METHODS
The emergence of viral resistance to combination antiretroviral therapy was monitored in 11 suppressed chronically HIV-1-infected patients undergoing from one up to four sequential TI (a total of 25 TI), by genotyping of the virus for known mutations in the genes for protease and reverse transcriptase. Resistance assays were performed at the first viral rebound > 100 copies/ml.


RESULTS
All subjects achieved resuppression of HIV-1 under the same antiretroviral therapy, regardless of the number of TI. Five of eleven patients showed no development of resistance. In the remaining six patients, the following patterns of mutations associated with viral resistance were found: one mutation (K70R), which was observed in one patient during the 1st TI and persisted during follow-up; two mutations (L90M, M184V), which were observed in four patients during the 1st TI and were intermittently present or lost following extended TI, treatment reinitiation and/or during subsequent TI; and evolution of two mutations (M184V, K219E) observed in two patients. These two mutations were not present during the 1st TI and were subsequently lost following therapy reinitiation or during the next TI.


CONCLUSIONS
Detection of drug resistance during TI by virus genotyping assays does not predict failure to resuppress after antiretroviral therapy reinitiation nor persistence of a resistant viral population during extended interruptions or subsequent TI.
Wistar Institute and the Philadelphia Field Initiating Group for HIV-1 Trials, Philadelphia, Pennsylvania, USA.
Emmanouil
E
Papasavvas
Robert M
RM
Grant
Junwei
J
Sun
Agnieska
A
Mackiewicz
Maxwell
M
Pistilli
Cecile
C
Gallo
Jay R
JR
Kostman
Karam
K
Mounzer
Jane
J
Shull
Luis J
LJ
Montaner
D000328:Adult; D019380:Anti-HIV Agents / Q000008:administration & dosage*; D018791:CD4 Lymphocyte Count; D002908:Chronic Disease; D004334:Drug Administration Schedule; D024882:Drug Resistance, Viral / Q000235:genetics*; D005260:Female; D005500:Follow-Up Studies; D005838:Genotype; D015658:HIV Infections / Q000188:drug therapy* / Q000821:virology; D015497:HIV-1 / Q000187:drug effects / Q000235:genetics*; D006801:Humans; D008297:Male; D008875:Middle Aged; D009154:Mutation
D019380:Anti-HIV Agents