In vivo dynamics of the K103N mutation following the withdrawal of non-nucleoside reverse transcriptase inhibitors in Human Immunodeficiency Virus-infected patients.
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.
Gianotti
Nicola
N
Clinic of Infectious Diseases, Vita-Salute San Raffaele University, Milan, Italy. nicola.gianotti@hsr.it
Galli
Laura
L
Boeri
Enzo
E
Maillard
Myriam
M
Serra
Giuseppe
G
Ratti
Deborah
D
Gallotta
Giulia
G
Vacchini
Daniela
D
Tremolada
Ylenia
Y
Lazzarin
Adriano
A
Clementi
Massimo
M
Castagna
Antonella
A
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
D019380:Anti-HIV Agents; D012367:RNA, Viral; D018894:Reverse Transcriptase Inhibitors; D054303:HIV Reverse Transcriptase