Characterization of HIV-1 strains isolated from patients treated with TIBO R82913.
The drug sensitivities of human immunodeficiency virus type 1 (HIV-1) isolates from a group of four untreated and seven TIBO R82913-treated patients were determined in a reverse transcriptase (RT) assay. Five of the treated patients harbored HIV-1 isolates with R82913 sensitivity comparable to that of the isolates of untreated patients, ranging from almost 2-fold higher sensitivity to 13-fold lower sensitivity than that of recombinant p66 RT. From one of the seven treated patients, an HIV-1 strain with a 20-fold reduced sensitivity to R82913 could be isolated; and from another patient, a strain with 100-fold reduced sensitivity (resistance) was isolated. The drug-resistant strain in this patient emerged after 3 weeks of treatment and was due to the Y188L mutation in its RT. On passaging the virus in cord blood lymphocytes, but not in CEM cells, the resistant virus was lost in favor of a different HIV-1 strain harboring the wild-type Y188 with a sensitivity to R82913 comparable to that of wild-type p66 RT. In several HIV-1 isolates (from treated and untreated patients), some HIV-2- and CIVgab-specific amino acids were found. One of these substitutions, that is, I/V179D (from an untreated patient), conferred a sevenfold reduced RT sensitivity to R82913.
Vandamme
A M
AM
Rega Institute for Medical Research, K. U. Leuven, Belgium.
Debyser
Z
Z
Pauwels
R
R
De Vreese
K
K
Goubau
P
P
Youle
M
M
Gazzard
B
B
Stoffels
P A
PA
Cauwenbergh
G F
GF
Anne
J
J
D000163:Acquired Immunodeficiency Syndrome / Q000188:drug therapy* / Q000382:microbiology; D000595:Amino Acid Sequence; D001483:Base Sequence; D001569:Benzodiazepines / Q000627:therapeutic use*; D002478:Cells, Cultured; D017931:DNA Primers; D004352:Drug Resistance, Microbial; D014644:Genetic Variation; D054303:HIV Reverse Transcriptase; D015497:HIV-1 / Q000145:classification / Q000187:drug effects* / Q000302:isolation & purification; D006801:Humans; D007093:Imidazoles / Q000627:therapeutic use*; D008969:Molecular Sequence Data; D012194:RNA-Directed DNA Polymerase / Q000235:genetics; D018894:Reverse Transcriptase Inhibitors; D016415:Sequence Alignment
D017931:DNA Primers; D007093:Imidazoles; D018894:Reverse Transcriptase Inhibitors; C062687:R 82150; D001569:Benzodiazepines; C067413:R-82913; D054303:HIV Reverse Transcriptase; D012194:RNA-Directed DNA Polymerase