title: In vivo dynamics of the K103N mutation following the withdrawal of non-nucleoside reverse transcriptase inhibitors in Human Immunodeficiency Virus-infected patients.
abstract: To investigate the dynamics of the K103N mutation following the withdrawal of non-nucleoside reverse transcriptase inhibitors (NNRTIs), we selected the Human Immunodeficiency Virus (HIV)-infected patients with the mutation at the time or after the failure of an NNRTI-containing regimen from an observational database. Of 62 patients fulfilling the inclusion criteria, 39 continued antiretroviral treatment without NNRTIs (group A), whereas 23 discontinued all antiretrovirals after NNRTI failure (group B). A total of 149 tests were analysed, with a median (IQR) of two (2-3) tests/patient. The overgrowth of wild-type virus at position 103 was observed in 14 subjects in group A (36%) and nine in group B (39%). No significant trend was found in relation to the disappearance of K103N variants in either group, but patients tested while receiving antiretrovirals had a significantly higher probability of retaining the K103N mutation over 24 months than those tested during treatment interruption (P = 0.007). In conclusion, following NNRTI discontinuation, HIV variants carrying the K103N mutation are not overgrown for long by wild-type quasispecies at this position in the majority of patients, although treatment interruption favours their disappearance. This suggests that the K103N mutation per se has little impact on viral fitness in vivo.
authors.affiliation: Clinic of Infectious Diseases, Vita-Salute San Raffaele University, Milan, Italy. nicola.gianotti@hsr.it
authors.forename: Nicola
authors.initials: N
authors.lastname: Gianotti
authors.forename: Laura
authors.initials: L
authors.lastname: Galli
authors.forename: Enzo
authors.initials: E
authors.lastname: Boeri
authors.forename: Myriam
authors.initials: M
authors.lastname: Maillard
authors.forename: Giuseppe
authors.initials: G
authors.lastname: Serra
authors.forename: Deborah
authors.initials: D
authors.lastname: Ratti
authors.forename: Giulia
authors.initials: G
authors.lastname: Gallotta
authors.forename: Daniela
authors.initials: D
authors.lastname: Vacchini
authors.forename: Ylenia
authors.initials: Y
authors.lastname: Tremolada
authors.forename: Adriano
authors.initials: A
authors.lastname: Lazzarin
authors.forename: Massimo
authors.initials: M
authors.lastname: Clementi
authors.forename: Antonella
authors.initials: A
authors.lastname: Castagna
mesh_terms: D019943:Amino Acid Substitution; D019380:Anti-HIV Agents / Q000008:administration & dosage* / Q000627:therapeutic use; D024882:Drug Resistance, Viral / Q000235:genetics*; D005838:Genotype; D015658:HIV Infections / Q000188:drug therapy / Q000821:virology*; D054303:HIV Reverse Transcriptase / Q000235:genetics*; D015497:HIV-1 / Q000187:drug effects* / Q000235:genetics* / Q000502:physiology; D006801:Humans; D009154:Mutation; D012367:RNA, Viral / Q000032:analysis / Q000235:genetics; D018894:Reverse Transcriptase Inhibitors / Q000008:administration & dosage* / Q000627:therapeutic use; D012641:Selection, Genetic; D017422:Sequence Analysis, DNA
chemical_list: D019380:Anti-HIV Agents; D012367:RNA, Viral; D018894:Reverse Transcriptase Inhibitors; D054303:HIV Reverse Transcriptase