Increased detection of HIV-1 drug resistance at time of diagnosis by testing viral DNA with a sensitive assay.
OBJECTIVE
HIV-1 drug resistance has been detected in 8%-24% of recently infected North Americans when assessed by consensus sequencing of plasma. We hypothesized that rates were likely higher but not detected because drug-resistant mutants are transmitted or regressed to levels below the limit of detection by consensus sequencing of HIV-1 RNA.


METHODS
Specimens from antiretroviral-naive individuals recently diagnosed with HIV-1 infection were compared at 15 codons to determine if testing of DNA using a sensitive oligonucleotide ligation assay (OLA) would detect drug resistance mutants not evident by consensus sequencing of serum.


RESULTS
HIV-1 drug resistance at 15 major resistance codons was greater by OLA compared with consensus sequencing: 18 of 104 vs. 12 of 104 individuals (P < or = 0.008) and 33 vs. 18 total mutations (P < or = 0.001); increasing the rate of detection at these 15 codons by 83%. Additional mutations were detected by consensus sequencing at L33, M46, D67, V108, and K219 that were not assessed by OLA.


CONCLUSIONS
The increased detection of drug-resistant HIV-1 by testing peripheral blood cells with a sensitive assay implies that both low and high levels of drug-resistant mutants are transmitted or persist in antiretroviral-naive individuals, suggesting that the clinical relevance of mutants persisting at both levels should be evaluated.
Ellis
Giovanina M
GM
Department of Infections and Prematurity, Seattle Children's Hospital and Research Institute, Seattle, WA, USA.
Page
Libby C
LC
Burman
Blaire E
BE
Buskin
Susan
S
Frenkel
Lisa M
LM
D000328:Adult; D018791:CD4 Lymphocyte Count; D016384:Consensus Sequence; D024882:Drug Resistance, Viral / Q000235:genetics*; D005260:Female; D015658:HIV Infections / Q000175:diagnosis* / Q000188:drug therapy / Q000821:virology*; D015497:HIV-1 / Q000235:genetics* / Q000302:isolation & purification; D006801:Humans; D008297:Male; D008875:Middle Aged; D009154:Mutation; D020411:Oligonucleotide Array Sequence Analysis; D012367:RNA, Viral / Q000097:blood / Q000235:genetics; D019562:Viral Load
D012367:RNA, Viral