Lack of resistance to integrase inhibitors among antiretroviral-naive subjects with primary HIV-1 infection, 2007-2013.
BACKGROUND
US guidelines recommend genotyping for persons newly diagnosed with HIV infection to identify transmitted drug resistance mutations associated with decreased susceptibility to nucleoside reverse transcriptase inhibitors, non-nucleoside reverse transcriptase inhibitors and protease inhibitors. To date, testing for integrase strand transfer inhibitor (INSTI) mutations has not been routinely recommended. We aimed to evaluate the prevalence of transmitted INSTI mutations among persons with primary HIV-1 infection in Seattle, WA, USA.


METHODS
Persons with primary HIV-1 infection have enrolled in an observational cohort at the University of Washington Primary Infection Clinic since 1992. We performed a retrospective analysis of plasma specimens collected prospectively from the 82 antiretroviral-naive subjects who were enrolled from 2007-2013, after FDA-approval of the first INSTI. Resistance testing was performed by consensus sequencing.


RESULTS
Specimens for analysis had been obtained a median of 24 (IQR 18-41, range 8-108) days after the estimated date of HIV-1 infection. All subjects were infected with HIV-1 subtype B except for one subject infected with subtype C. Consensus sequencing identified no subjects with major INSTI mutations (T66I, E92Q, G140S, Y143C/H/R, S147G, Q148H/K/R, N155H). Using exact binomial CIs, the upper bound of the 95% CI was 4.4%.


CONCLUSIONS
Although our sample size was small, this study does not support the need at this time to evaluate integrase mutations as part of routine consensus sequencing among persons newly diagnosed with HIV-1 infection. However, it is likely that the prevalence of transmitted INSTI mutations may increase with the recent commercial introduction of additional INSTIs and presumably greater INSTI use among persons living with HIV-1.
Departments of Medicine and Epidemiology, University of Washington, Seattle, WA, USA. jstekler@uw.edu.
Joanne D
JD
Stekler
Jennifer
J
McKernan
Ross
R
Milne
Kenneth A
KA
Tapia
Kateryna
K
Mykhalchenko
Sarah
S
Holte
Janine
J
Maenza
Claire E
CE
Stevens
Susan E
SE
Buskin
James I
JI
Mullins
Lisa M
LM
Frenkel
Ann C
AC
Collier
D000328:Adult; D024882:Drug Resistance, Viral; D005838:Genotype; D015658:HIV Infections / Q000188:drug therapy* / Q000821:virology; D019427:HIV Integrase / Q000235:genetics* / Q000378:metabolism; D019428:HIV Integrase Inhibitors / Q000627:therapeutic use*; D015497:HIV-1 / Q000187:drug effects* / Q000201:enzymology / Q000235:genetics; D006801:Humans; D008297:Male; D009154:Mutation; D015363:Quinolones / Q000627:therapeutic use; D000068898:Raltegravir Potassium / Q000627:therapeutic use; D012189:Retrospective Studies; D017423:Sequence Analysis, RNA
D019428:HIV Integrase Inhibitors; D015363:Quinolones; D000068898:Raltegravir Potassium; C509700:elvitegravir; D019427:HIV Integrase