Biomaterial Database

Prevalence and incidence of resistance to zidovudine and other antiretroviral drugs. 1997

D L Mayers

Infectious Diseases Department, Naval Medical Research Institute, Bethesda, Maryland, USA.

Drug-resistant human immunodeficiency virus (HIV)-1 has been detected in patients on all of the currently available antiretroviral drug regimens. Continuous, high-level virus replication with an error-prone reverse transcriptase enzyme and potential viral recombination events lead to each patient having numerous viral quasispecies and promote the emergence of drug-resistant strains. Drug resistance is associated with one or more point mutations in the HIV gene of the protein that is targeted by the drug. Factors associated with rapid emergence of drug resistance include host factors, such as advanced HIV disease and low CD4 cell counts; viral factors, such as high plasma HIV RNA, pre-existing drug-resistant virus, and possibly syncytium-inducing (SI) phenotype; and drug-related factors, such as suboptimal drug levels or poor compliance. High-level drug resistance has emerged after weeks to months of therapy for lamivudine (3TC) and nevirapine where drug-resistant quasispecies pre-exist in essentially all patients. Resistance has emerged more slowly for zidovudine (ZDV) and HIV protease inhibitors, which require the sequential accumulation of multiple mutations to develop high-level resistance. Certain drugs, such as didanosine (DDI), dideoxycytidine (DDC), and stavudine (D4T) have only produced viruses with low-level resistance, despite prolonged therapy. Development of drug-resistant HIV-1 has been associated with declining CD4 cell counts and rising plasma viral load. Zidovudine-resistant HIV-1 has been associated with adverse clinical outcomes independent of baseline CD4 cell counts and plasma HIV-1 RNA levels. Combination therapy offers the possibility of delaying or preventing the development of HIV drug resistance via interacting drug resistance mutations or potent antiviral activity. Widespread use of ZDV has been associated with transmission of ZDV-resistant HIV-1 in approximately 10% of adult seroconverters and a significant percentage of infants who fail the AIDS Clinical Trial Group (ACTG) 076 prophylactic regimen.

UI	MeSH Term	Description	Entries
D004352	Drug Resistance, Microbial	The ability of microorganisms, especially bacteria, to resist or to become tolerant to chemotherapeutic agents, antimicrobial agents, or antibiotics. This resistance may be acquired through gene mutation or foreign DNA in transmissible plasmids (R FACTORS).	Antibiotic Resistance,Antibiotic Resistance, Microbial,Antimicrobial Resistance, Drug,Antimicrobial Drug Resistance,Antimicrobial Drug Resistances,Antimicrobial Resistances, Drug,Drug Antimicrobial Resistance,Drug Antimicrobial Resistances,Drug Resistances, Microbial,Resistance, Antibiotic,Resistance, Drug Antimicrobial,Resistances, Drug Antimicrobial
D006801	Humans	Members of the species Homo sapiens.	Homo sapiens,Man (Taxonomy),Human,Man, Modern,Modern Man
D012307	Risk Factors	An aspect of personal behavior or lifestyle, environmental exposure, inborn or inherited characteristic, which, based on epidemiological evidence, is known to be associated with a health-related condition considered important to prevent.	Health Correlates,Risk Factor Scores,Risk Scores,Social Risk Factors,Population at Risk,Populations at Risk,Correlates, Health,Factor, Risk,Factor, Social Risk,Factors, Social Risk,Risk Factor,Risk Factor Score,Risk Factor, Social,Risk Factors, Social,Risk Score,Score, Risk,Score, Risk Factor,Social Risk Factor
D013997	Time Factors	Elements of limited time intervals, contributing to particular results or situations.	Time Series,Factor, Time,Time Factor
D015215	Zidovudine	A dideoxynucleoside compound in which the 3'-hydroxy group on the sugar moiety has been replaced by an azido group. 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, acting as a chain-terminator of viral DNA during reverse transcription. It improves immunologic function, partially reverses the HIV-induced neurological dysfunction, and improves certain other clinical abnormalities associated with AIDS. Its principal toxic effect is dose-dependent suppression of bone marrow, resulting in anemia and leukopenia.	AZT (Antiviral),Azidothymidine,3'-Azido-2',3'-Dideoxythymidine,3'-Azido-3'-deoxythymidine,AZT Antiviral,AZT, Antiviral,BW A509U,BWA-509U,Retrovir,3' Azido 2',3' Dideoxythymidine,3' Azido 3' deoxythymidine,Antiviral AZT,BWA 509U,BWA509U
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
D015994	Incidence	The number of new cases of a given disease during a given period in a specified population. It also is used for the rate at which new events occur in a defined population. It is differentiated from PREVALENCE, which refers to all cases in the population at a given time.	Attack Rate,Cumulative Incidence,Incidence Proportion,Incidence Rate,Person-time Rate,Secondary Attack Rate,Attack Rate, Secondary,Attack Rates,Cumulative Incidences,Incidence Proportions,Incidence Rates,Incidence, Cumulative,Incidences,Person time Rate,Person-time Rates,Proportion, Incidence,Rate, Attack,Rate, Incidence,Rate, Person-time,Rate, Secondary Attack,Secondary Attack Rates
D015995	Prevalence	The total number of cases of a given disease in a specified population at a designated time. It is differentiated from INCIDENCE, which refers to the number of new cases in the population at a given time.	Period Prevalence,Point Prevalence,Period Prevalences,Point Prevalences,Prevalence, Period,Prevalence, Point,Prevalences
D017320	HIV Protease Inhibitors	Inhibitors of HIV PROTEASE, an enzyme required for production of proteins needed for viral assembly.	HIV Protease Inhibitor,Inhibitor, HIV Protease,Inhibitors, HIV Protease,Protease Inhibitor, HIV,Protease Inhibitors, HIV
D018119	Stavudine	A dideoxynucleoside analog that inhibits reverse transcriptase and has in vitro activity against HIV.	2',3'-Didehydro-3'-deoxythymidine,D4T,2',3'-Didehydro-2',3'-dideoxythmidine,BMY-27857,Stavudine, Monosodium Salt,Zerit,2',3' Didehydro 3' deoxythymidine,BMY 27857,BMY27857