Zidovudine-resistant and -sensitive HIV-1 isolates from patients on drug therapy: in vitro studies evaluating level of replication-competent viruses and cytopathogenicity

• Published in: AIDS (London) Vol. 6; no. 12; p. 1445
• Main Authors: Tremblay, M, Rooke, R, Wainberg, M A
• Format: Journal Article
• Language: English
• Published: England 01.12.1992
• Subjects: Acquired Immunodeficiency Syndrome - drug therapy; Acquired Immunodeficiency Syndrome - microbiology; Acquired Immunodeficiency Syndrome - physiopathology; Cell Survival; Cytopathogenic Effect, Viral; Drug Resistance, Microbial; Genetic Variation; HIV Core Protein p24 - analysis; HIV-1 - drug effects; HIV-1 - growth & development; Humans; Phenotype; Selection, Genetic; Zidovudine - pharmacology
• ISSN: 0269-9370
• DOI: 10.1097/00002030-199212000-00004

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. 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. 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. These results suggest that drug-resistant strains possess biological properties that may differ from those of drug-sensitive variants of HIV-1.