Dynamics of NRTI resistance mutations during therapy interruption.
Abstract To date, very little information is available regarding the evolution of drug resistance mutations during treatment interruption (TI). Using a survival analysis approach, we investigated the dynamics of mutations associated with resistance to nucleoside analogue reverse transcriptase inhibitors (NRTIs) during TI. Analyzing 132 patients having at least two consecutive genotypes, one at last NRTI-containing regimen failure, and at least one during TI, we observed that the NRTI resistance mutations disappear at different rates during TI and are lost independently of each other in the majority of patients. The disappearance of the K65R and M184I/V mutations occurred in the majority of patients, was rapid, and was associated with the reemergence of wild-type virus, thus showing their negative impact on viral fitness. Overall, it seems that the loss of NRTI drug resistance mutations during TI is not an ordered process, and in the majority of patients occurs without specific interaction among mutations.
Trignetti
Maria
M
Experimental Medicine Department, University of Rome Tor Vergata , 00133, Rome, Italy.
Sing
Tobias
T
Svicher
Valentina
V
Santoro
Maria Mercedes
MM
Forbici
Federica
F
D'arrigo
Roberta
R
Bellocchi
Maria Concetta
MC
Santoro
Mario
M
Marconi
Patrizia
P
Zaccarelli
Mauro
M
Trotta
Maria Paola
MP
Bellagamba
Rita
R
Narciso
Pasquale
P
Antinori
Andrea
A
Lengauer
Thomas
T
Perno
Carlo Federico
CF
Ceccherini-Silberstein
Francesca
F
D000328:Adult; D019943:Amino Acid Substitution / Q000235:genetics; D019380:Anti-HIV Agents / Q000494:pharmacology; D024882:Drug Resistance, Viral; D005260:Female; D006678:HIV / Q000187:drug effects* / Q000235:genetics* / Q000302:isolation & purification; D015658:HIV Infections / Q000188:drug therapy* / Q000821:virology*; D006801:Humans; D008297:Male; D008875:Middle Aged; D020125:Mutation, Missense; D017422:Sequence Analysis, DNA; D028761:Withholding Treatment
D019380:Anti-HIV Agents