Generation of drug-resistant variants of human immunodeficiency virus type 1 by in vitro passage in increasing concentrations of 2',3'-dideoxycytidine and 2',3'-dideoxy-3'-thiacytidine. 1993

Q Gao, and Z Gu, and J Hiscott, and G Dionne, and M A Wainberg
Lady Davis Institute-Jewish General Hospital, Montreal, Quebec, Canada.

We selected in vitro human immunodeficiency virus type 1 variants that are resistant to each of 2',3'-dideoxycytidine (ddC) and the racemic mixture of 2',3'-dideoxy-3'-thiacytidine (BCH-189). The median effective concentrations of ddC and BCH-189 obtained for the resistant viruses ranged between 10 and 50 times above those for parental wild-type strains, and extensive cross-resistance was observed against 2',3'-dideoxyinosine (ddI) but not 3'-azido-3'-deoxythymidine (AZT). Two dimer compounds, in which either AZT and ddI or AZT and BCH-189 were linked through phosphodiester linkages, did not permit the emergence of variants resistant to BCH-189, ddI, or AZT but were ineffective at inhibiting the replication of AZT-resistant viruses.

UI MeSH Term Description Entries
D004351 Drug Resistance Diminished or failed response of an organism, disease or tissue to the intended effectiveness of a chemical or drug. It should be differentiated from DRUG TOLERANCE which is the progressive diminution of the susceptibility of a human or animal to the effects of a drug, as a result of continued administration. Resistance, Drug
D006801 Humans Members of the species Homo sapiens. Homo sapiens,Man (Taxonomy),Human,Man, Modern,Modern Man
D000163 Acquired Immunodeficiency Syndrome An acquired defect of cellular immunity associated with infection by the human immunodeficiency virus (HIV), a CD4-positive T-lymphocyte count under 200 cells/microliter or less than 14% of total lymphocytes, and increased susceptibility to opportunistic infections and malignant neoplasms. Clinical manifestations also include emaciation (wasting) and dementia. These elements reflect criteria for AIDS as defined by the CDC in 1993. AIDS,Immunodeficiency Syndrome, Acquired,Immunologic Deficiency Syndrome, Acquired,Acquired Immune Deficiency Syndrome,Acquired Immuno-Deficiency Syndrome,Acquired Immuno Deficiency Syndrome,Acquired Immuno-Deficiency Syndromes,Acquired Immunodeficiency Syndromes,Immuno-Deficiency Syndrome, Acquired,Immuno-Deficiency Syndromes, Acquired,Immunodeficiency Syndromes, Acquired,Syndrome, Acquired Immuno-Deficiency,Syndrome, Acquired Immunodeficiency,Syndromes, Acquired Immuno-Deficiency,Syndromes, Acquired Immunodeficiency
D000998 Antiviral Agents Agents used in the prophylaxis or therapy of VIRUS DISEASES. Some of the ways they may act include preventing viral replication by inhibiting viral DNA polymerase; binding to specific cell-surface receptors and inhibiting viral penetration or uncoating; inhibiting viral protein synthesis; or blocking late stages of virus assembly. Antiviral,Antiviral Agent,Antiviral Drug,Antivirals,Antiviral Drugs,Agent, Antiviral,Agents, Antiviral,Drug, Antiviral,Drugs, Antiviral
D015497 HIV-1 The type species of LENTIVIRUS and the etiologic agent of AIDS. It is characterized by its cytopathic effect and affinity for the T4-lymphocyte. Human immunodeficiency virus 1,HIV-I,Human Immunodeficiency Virus Type 1,Immunodeficiency Virus Type 1, Human
D015658 HIV Infections Includes the spectrum of human immunodeficiency virus infections that range from asymptomatic seropositivity, thru AIDS-related complex (ARC), to acquired immunodeficiency syndrome (AIDS). HTLV-III Infections,HTLV-III-LAV Infections,T-Lymphotropic Virus Type III Infections, Human,HIV Coinfection,Coinfection, HIV,Coinfections, HIV,HIV Coinfections,HIV Infection,HTLV III Infections,HTLV III LAV Infections,HTLV-III Infection,HTLV-III-LAV Infection,Infection, HIV,Infection, HTLV-III,Infection, HTLV-III-LAV,Infections, HIV,Infections, HTLV-III,Infections, HTLV-III-LAV,T Lymphotropic Virus Type III Infections, Human
D016047 Zalcitabine A dideoxynucleoside compound in which the 3'-hydroxy group on the sugar moiety has been replaced by a hydrogen. This modification prevents the formation of phosphodiester linkages which are needed for the completion of nucleic acid chains. The compound is a potent inhibitor of HIV replication at low concentrations, acting as a chain-terminator of viral DNA by binding to reverse transcriptase. Its principal toxic side effect is axonal degeneration resulting in peripheral neuropathy. 2',3'-Dideoxycytidine,Dideoxycytidine,ddC (Antiviral),HIVID Roche,Hivid,NSC-606170,2',3' Dideoxycytidine,NSC 606170,NSC606170
D019259 Lamivudine A reverse transcriptase inhibitor and ZALCITABINE analog in which a sulfur atom replaces the 3' carbon of the pentose ring. It is used to treat HIV disease. 2',3'-Dideoxy-3'-thiacytidine,2(1H)-Pyrimidinone, 4-amino-1-(2-(hydroxymethyl)-1,3-oxathiolan-5-yl)-, (2R-cis)-,3TC Lamivudine,Lamivudine, (+)-cis-,Lamivudine, (+-)-trans-,BCH-189,Epivir,GR-109714X,GR109714X,Lamivudine, (2S-cis)-Isomer,2',3' Dideoxy 3' thiacytidine,BCH 189,BCH189,GR 109714X,Lamivudine, 3TC

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