Multiple drug resistance to nucleoside analogues and nonnucleoside reverse transcriptase inhibitors in an efficiently replicating human immunodeficiency virus type 1 patient strain.
A human immunodeficiency virus type 1 (HIV-1)-seropositive patient was treated sequentially with the dideoxynucleoside (ddN) analogues zidovudine, didanosine, zalcitabine, stavudine, and lamivudine and the nonnucleoside HIV-1-specific reverse transcriptase inhibitor (NNRTI) loviride (alpha-APA). Accumulation of drug resistance mutations (mainly V75I, F77L, K103N, F116Y, Q151M, and M184V) eventually resulted in a strain that was genotypically and phenotypically resistant to all tested ddNs and the majority of NNRTIs. However, the multidrug-resistant virus retained wild type sensitivities to drugs such as foscarnet, phosphonomethoxyethyl adenine, dextran sulfate, JM3100, saquinavir, and NNRTI TSAO-m3T. Drug-resistant isolates showed replication kinetics and infectivity in an in vitro peripheral blood mononuclear cell system similar to those of the wild type isolate from the same patient. The multi-ddN-resistant isolate was not eliminated in a competition culture with the wild type isolate. Sequential therapy did not prevent the appearance of multidrug-resistant virus with a conserved replication rate.
Rega Institute for Medical Research, Katholieke Universiteit Leuven, Belgium.
J C
JC
Schmit
J
J
Cogniaux
P
P
Hermans
C
C
Van Vaeck
S
S
Sprecher
B
B
Van Remoortel
M
M
Witvrouw
J
J
Balzarini
J
J
Desmyter
E
E
De Clercq
A M
AM
Vandamme
D000998:Antiviral Agents / Q000494:pharmacology*; D001483:Base Sequence; D018432:Drug Resistance, Multiple; D054303:HIV Reverse Transcriptase / Q000235:genetics; D015497:HIV-1 / Q000187:drug effects* / Q000502:physiology; D006801:Humans; D008875:Middle Aged; D008969:Molecular Sequence Data; D009154:Mutation; D010641:Phenotype; D018894:Reverse Transcriptase Inhibitors / Q000494:pharmacology*; D014779:Virus Replication
D000998:Antiviral Agents; D018894:Reverse Transcriptase Inhibitors; D054303:HIV Reverse Transcriptase