HIV-1 integrase sequence variability in antiretroviral naïve patients and in triple-class experienced patients subsequently treated with raltegravir.
Viruses were sequenced from 75 antiretroviral therapy (ARV)-naïve and from 75 ARV-treated patients who subsequently received a raltegravir-containing regimen. No major integrase inhibitor (INI)-resistance mutations were present in the 150 integrase (IN) sequences. Four ARV-naïve (5.3%) and two ARV-treated patients (2.7%) had one of the following minor INI-resistance mutations: L74M, E157Q, G163R, and R263K but there was no association between baseline raltegravir genotype and subsequent response to raltegravir treatment. We also combined our sequences with 4170 previously published group M IN sequences from INI-naïve patients to assess IN sequence variability and compared our findings with those of a study we performed in 2008 using data from 1563 patients. The number of polymorphic IN positions increased from 40% to 41% between the two studies. However, none of the major INI-resistance mutations was found to be polymorphic in either study and there were no significant changes in the prevalence of any of the minor INI-resistance mutations.
Department of Medicine, Stanford University School of Medicine, Stanford, California 94305, USA. viciv@stanford.edu
Vici
V
Varghese
Tommy F
TF
Liu
Soo-Yon
SY
Rhee
Paolo
P
Libiran
Christina
C
Trevino
W Jeffrey
WJ
Fessel
Robert W
RW
Shafer
D000595:Amino Acid Sequence; D019943:Amino Acid Substitution / Q000235:genetics; D019380:Anti-HIV Agents / Q000627:therapeutic use*; D014644:Genetic Variation; D015658:HIV Infections / Q000188:drug therapy* / Q000821:virology*; D019427:HIV Integrase / Q000235:genetics*; D015497:HIV-1 / Q000235:genetics* / Q000302:isolation & purification; D006801:Humans; D008969:Molecular Sequence Data; D020125:Mutation, Missense; D011760:Pyrrolidinones / Q000627:therapeutic use*; D000068898:Raltegravir Potassium; D017422:Sequence Analysis, DNA
D019380:Anti-HIV Agents; D011760:Pyrrolidinones; D000068898:Raltegravir Potassium; D019427:HIV Integrase; C514801:p31 integrase protein, Human immunodeficiency virus 1