title: Dynamics of NRTI resistance mutations during therapy interruption.
abstract: 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.
authors.affiliation: Experimental Medicine Department, University of Rome Tor Vergata , 00133, Rome, Italy.
authors.forename: Maria
authors.initials: M
authors.lastname: Trignetti
authors.forename: Tobias
authors.initials: T
authors.lastname: Sing
authors.forename: Valentina
authors.initials: V
authors.lastname: Svicher
authors.forename: Maria Mercedes
authors.initials: MM
authors.lastname: Santoro
authors.forename: Federica
authors.initials: F
authors.lastname: Forbici
authors.forename: Roberta
authors.initials: R
authors.lastname: D'arrigo
authors.forename: Maria Concetta
authors.initials: MC
authors.lastname: Bellocchi
authors.forename: Mario
authors.initials: M
authors.lastname: Santoro
authors.forename: Patrizia
authors.initials: P
authors.lastname: Marconi
authors.forename: Mauro
authors.initials: M
authors.lastname: Zaccarelli
authors.forename: Maria Paola
authors.initials: MP
authors.lastname: Trotta
authors.forename: Rita
authors.initials: R
authors.lastname: Bellagamba
authors.forename: Pasquale
authors.initials: P
authors.lastname: Narciso
authors.forename: Andrea
authors.initials: A
authors.lastname: Antinori
authors.forename: Thomas
authors.initials: T
authors.lastname: Lengauer
authors.forename: Carlo Federico
authors.initials: CF
authors.lastname: Perno
authors.forename: Francesca
authors.initials: F
authors.lastname: Ceccherini-Silberstein
mesh_terms: 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
chemical_list: D019380:Anti-HIV Agents