Ultra-deep sequencing of HIV-1 reverse transcriptase before start of an NNRTI-based regimen in treatment-naive patients.
There are conflicting data on the impact of low frequency HIV-1 drug-resistant mutants on the response of first-line highly active antiretroviral therapy (HAART), more specifically containing a NNRTI. As population sequencing does not detect resistant viruses representing less than 15-25% of the viral population, more sensitive techniques have been developed but still need clinical validation. We evaluated ultra-deep sequencing (UDPS), recently more available and affordable, as a tool for the detection of HIV-1 minority species carrying drug resistant mutation (DRM) in a clinical setting. A retrospective analysis of the reverse transcriptase (RT) gene of plasma HIV-1 from 70 patients starting a NNRTI based regimen was performed. Minority populations were defined as representing > 1% and < 20% of the total viral population. Using UDPS, we could not confirm an association between the presence of low minority variants harbouring RT mutations at the start of therapy and primary or secondary therapeutic failure.
AIDS Reference Laboratory, Ghent University, De Pintelaan 185-9000 Gent, Belgium.
Peter
P
Messiaen
Chris
C
Verhofstede
Ina
I
Vandenbroucke
Sylvie
S
Dinakis
Veerle
V
Van Eygen
Kim
K
Thys
Bart
B
Winters
Jeroen
J
Aerssens
Dirk
D
Vogelaers
Lieven J
LJ
Stuyver
Linos
L
Vandekerckhove
D000328:Adult; D019380:Anti-HIV Agents / Q000627:therapeutic use*; D023241:Antiretroviral Therapy, Highly Active; D024882:Drug Resistance, Viral; D005260:Female; D015658:HIV Infections / Q000188:drug therapy* / Q000821:virology; D054303:HIV Reverse Transcriptase / Q000037:antagonists & inhibitors / Q000235:genetics*; D015497:HIV-1 / Q000145:classification / Q000201:enzymology* / Q000235:genetics / Q000302:isolation & purification*; D059014:High-Throughput Nucleotide Sequencing / Q000379:methods*; D006801:Humans; D008297:Male; D008875:Middle Aged; D009154:Mutation; D012189:Retrospective Studies; D018894:Reverse Transcriptase Inhibitors / Q000627:therapeutic use*
D019380:Anti-HIV Agents; D018894:Reverse Transcriptase Inhibitors; C514824:reverse transcriptase, Human immunodeficiency virus 1; D054303:HIV Reverse Transcriptase