Evolution of human immunodeficiency virus type 1 populations after resumption of therapy following treatment interruption and shift in resistance genotype.
Conventional genotyping of human immunodeficiency virus type 1 often reveals a shift from a drug-resistant genotype to a wild-type genotype after treatment interruption. A real-time polymerase chain reaction-based technique was used to detect minority resistant populations in 13 patients who showed genotype reversion after interruption of treatment for 3 months. Sixty-two percent of patients in whom the V82A and L90M protease mutations were no longer detectable by conventional genotyping still harbored minority resistant variants, in proportions ranging from 0.1% to 21%. None of the patients with these minority resistant variants who received a protease-inhibitor regimen on resumption of therapy had a response to treatment. However, population sequencing and clonal analysis of plasma samples obtained 1-2 months after resumption of treatment revealed the presence of wild-type virus during the initial decline in plasma virus load, which indicates that minority resistant variants were not rapidly selected.
Izopet
Jacques
J
Laboratoire de Virologie, Hôpital Purpan, Centre Hospitalier Universitaire Toulouse, 31059 Toulouse Cédex, France. izopet@cict.fr
Souyris
Corinne
C
Hance
Allan
A
Sandres-Sauné
Karine
K
Alvarez
Muriel
M
Pasquier
Christophe
C
Clavel
François
F
Puel
Jacqueline
J
Massip
Patrice
P
D000595:Amino Acid Sequence; D019380:Anti-HIV Agents / Q000627:therapeutic use; D024882:Drug Resistance, Viral / Q000235:genetics; D016679:Genome, Viral; D005838:Genotype; D015658:HIV Infections / Q000188:drug therapy / Q000821:virology*; D016333:HIV Protease / Q000235:genetics; D015497:HIV-1 / Q000187:drug effects / Q000201:enzymology / Q000235:genetics*; D006801:Humans; D008969:Molecular Sequence Data; D009154:Mutation; D016133:Polymerase Chain Reaction; D012194:RNA-Directed DNA Polymerase / Q000235:genetics; D016079:Refusal to Treat; D016415:Sequence Alignment; D017386:Sequence Homology, Amino Acid
D019380:Anti-HIV Agents; D012194:RNA-Directed DNA Polymerase; D016333:HIV Protease