Zidovudine-resistant and -sensitive HIV-1 isolates from patients on drug therapy: in vitro studies evaluating level of replication-competent viruses and cytopathogenicity.
OBJECTIVE
To compare biological properties of zidovudine-resistant variants of HIV-1 isolated from subjects on long-term drug therapy with drug-sensitive parental isolates obtained from the same patients before initiation of treatment.


METHODS
Clinical HIV-1 strains were isolated following co-incubation of patient peripheral blood mononuclear cells with mitogen-stimulated umbilical cord blood lymphocytes. Drug resistance was evaluated by infecting MT-4 cells pretreated with zidovudine and maintained under drug pressure.


RESULTS
The drug-resistant phenotype remained stable, following many viral replication cycles in the absence of zidovudine. Drug-resistant variants contained fewer replication-competent viruses but were more cytopathogenic than their corresponding zidovudine-sensitive parental strains.


CONCLUSIONS
These results suggest that drug-resistant strains possess biological properties that may differ from those of drug-sensitive variants of HIV-1.
Tremblay
M
M
Département de Microbiologie, Faculté de Médecine, Université Laval, Ste-Foy, Québec, Canada.
Rooke
R
R
Wainberg
M A
MA
D000163:Acquired Immunodeficiency Syndrome / Q000188:drug therapy / Q000382:microbiology* / Q000503:physiopathology; D002470:Cell Survival; D003588:Cytopathogenic Effect, Viral; D004352:Drug Resistance, Microbial; D014644:Genetic Variation; D016655:HIV Core Protein p24 / Q000032:analysis; D015497:HIV-1 / Q000187:drug effects / Q000254:growth & development*; D006801:Humans; D010641:Phenotype; D012641:Selection, Genetic; D015215:Zidovudine / Q000494:pharmacology*
D016655:HIV Core Protein p24; D015215:Zidovudine