Genotypic analysis of HIV-1 drug resistance at the limit of detection: virus production without evolution in treated adults with undetectable HIV loads.
Human immunodeficiency virus (HIV) production continues in patients receiving highly active antiretroviral therapy (HAART) with undetectable (<50 copies/mL) virus loads. Our initial cross-sectional study showed that this viremia is composed of viruses that lack new resistance mutations to the HAART regimen. Here we describe a longitudinal, clonal genotypic analysis of plasma virus loads in treated adults who had undetectable virus loads. We document a continuous production of virus in 8 HIV-1-infected adults who maintained suppression of viremia for up to 15 months. Using analytical approaches for distinguishing selected resistance mutations from nonselected mutations and polymerase chain reaction errors, we detected no evolution of resistance in the reverse-transcriptase and protease genes. Sporadic resistance mutations were detected in some viral clones that were not selected for subsequently. Thus, in some patients, HAART suppresses replication to a level that does not allow the evolution of drug resistance over a time frame of years.
Kieffer
Tara L
TL
Department of Medicine, Johns Hopkins University School of Medicine, Baltimore, Maryland 21025, USA.
Finucane
Mariel M
MM
Nettles
Richard E
RE
Quinn
Thomas C
TC
Broman
Karl W
KW
Ray
Stuart C
SC
Persaud
Deborah
D
Siliciano
Robert F
RF
D000328:Adult; D023241:Antiretroviral Therapy, Highly Active; D001483:Base Sequence; D024882:Drug Resistance, Viral / Q000235:genetics*; D019143:Evolution, Molecular; D015684:Gene Products, pol / Q000235:genetics; D015658:HIV Infections / Q000188:drug therapy* / Q000821:virology*; D016333:HIV Protease / Q000235:genetics; D054303:HIV Reverse Transcriptase / Q000235:genetics; D015497:HIV-1 / Q000201:enzymology / Q000235:genetics*; D006801:Humans; D008137:Longitudinal Studies; D008297:Male; D008875:Middle Aged; D008969:Molecular Sequence Data; D010802:Phylogeny; D017354:Point Mutation; D012367:RNA, Viral / Q000097:blood / Q000737:chemistry / Q000235:genetics; D020133:Reverse Transcriptase Polymerase Chain Reaction; D014766:Viremia / Q000188:drug therapy / Q000821:virology
D015684:Gene Products, pol; D012367:RNA, Viral; D054303:HIV Reverse Transcriptase; D016333:HIV Protease