BIOMAT Database Logo BIOMAT Database Logo

Broad nucleoside reverse-transcriptase inhibitor cross-resistance in human immunodeficiency virus type 1 clinical isolates. 2003

Jeannette M Whitcomb, and Neil T Parkin, and Colombe Chappey, and Nicholas S Hellmann, and Christos J Petropoulos
ViroLogic, South San Francisco, California 94080, USA.

Nucleoside reverse-transcriptase inhibitors (NRTIs) are important components of most antiretroviral combination treatment regimens. Using a large collection of clinical isolates, we characterized patterns of cross-resistance among all NRTIs. Drugs were grouped by the effect of the M184V mutation: susceptibility to group 1 drugs (zidovudine, stavudine, tenofovir, and adefovir) increased when M184V was present, whereas susceptibility to group 2 drugs (didanosine, zalcitabine, abacavir, and lamivudine) decreased. Significant cross-resistance was observed among all NRTIs and was most notable when samples with or without M184V were analyzed separately. An increasing number of thymidine-analogue mutations (TAMs) was associated with a progressive reduction in drug susceptibility for all NRTIs. The modulating effect of M184I/V on drug susceptibility was present regardless of the number of TAMs. The broad range of susceptibility observed for viruses containing the same number of TAMs indicates that the genetic correlates of NRTI resistance remain to be fully elucidated.

UI MeSH Term Description Entries
D006801 Humans Members of the species Homo sapiens. Homo sapiens,Man (Taxonomy),Human,Man, Modern,Modern Man
D012367 RNA, Viral Ribonucleic acid that makes up the genetic material of viruses. Viral RNA
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
D017354 Point Mutation A mutation caused by the substitution of one nucleotide for another. This results in the DNA molecule having a change in a single base pair. Mutation, Point,Mutations, Point,Point Mutations
D017422 Sequence Analysis, DNA A multistage process that includes cloning, physical mapping, subcloning, determination of the DNA SEQUENCE, and information analysis. DNA Sequence Analysis,Sequence Determination, DNA,Analysis, DNA Sequence,DNA Sequence Determination,DNA Sequence Determinations,DNA Sequencing,Determination, DNA Sequence,Determinations, DNA Sequence,Sequence Determinations, DNA,Analyses, DNA Sequence,DNA Sequence Analyses,Sequence Analyses, DNA,Sequencing, DNA
D054303 HIV Reverse Transcriptase A reverse transcriptase encoded by the POL GENE of HIV. It is a heterodimer of 66 kDa and 51 kDa subunits that are derived from a common precursor protein. The heterodimer also includes an RNAse H activity (RIBONUCLEASE H, HUMAN IMMUNODEFICIENCY VIRUS) that plays an essential role the viral replication process. Reverse Transcriptase, HIV,Reverse Transcriptase, Human Immunodeficiency Virus,Transcriptase, HIV Reverse
D018894 Reverse Transcriptase Inhibitors Inhibitors of reverse transcriptase (RNA-DIRECTED DNA POLYMERASE), an enzyme that synthesizes DNA on an RNA template. Reverse Transcriptase Inhibitor,Inhibitors, Reverse Transcriptase,Inhibitor, Reverse Transcriptase,Transcriptase Inhibitor, Reverse
D019380 Anti-HIV Agents Agents used to treat AIDS and/or stop the spread of the HIV infection. These do not include drugs used to treat symptoms or opportunistic infections associated with AIDS. AIDS Drug,AIDS Drugs,Anti-AIDS Agents,Anti-AIDS Drug,Anti-HIV Agent,Anti-HIV Drug,Anti-AIDS Drugs,Anti-HIV Drugs,Agent, Anti-HIV,Agents, Anti-AIDS,Agents, Anti-HIV,Anti AIDS Agents,Anti AIDS Drug,Anti AIDS Drugs,Anti HIV Agent,Anti HIV Agents,Anti HIV Drug,Anti HIV Drugs,Drug, AIDS,Drug, Anti-AIDS,Drug, Anti-HIV,Drugs, AIDS,Drugs, Anti-AIDS,Drugs, Anti-HIV
D020133 Reverse Transcriptase Polymerase Chain Reaction A variation of the PCR technique in which cDNA is made from RNA via reverse transcription. The resultant cDNA is then amplified using standard PCR protocols. Polymerase Chain Reaction, Reverse Transcriptase,Reverse Transcriptase PCR,PCR, Reverse Transcriptase,Transcriptase PCR, Reverse

Related Publications

Jeannette M Whitcomb, and Neil T Parkin, and Colombe Chappey, and Nicholas S Hellmann, and Christos J Petropoulos
Nucleoside reverse transcriptase inhibitors and resistance of human immunodeficiency virus type 1.
March 1995, The Journal of infectious diseases,
Jeannette M Whitcomb, and Neil T Parkin, and Colombe Chappey, and Nicholas S Hellmann, and Christos J Petropoulos
Novel nonnucleoside inhibitors that select nucleoside inhibitor resistance mutations in human immunodeficiency virus type 1 reverse transcriptase.
August 2006, Antimicrobial agents and chemotherapy,
Jeannette M Whitcomb, and Neil T Parkin, and Colombe Chappey, and Nicholas S Hellmann, and Christos J Petropoulos
Nucleoside inhibitors of human immunodeficiency virus type 1 reverse transcriptase.
January 2004, Current topics in medicinal chemistry,
Jeannette M Whitcomb, and Neil T Parkin, and Colombe Chappey, and Nicholas S Hellmann, and Christos J Petropoulos
Broad nucleoside-analogue resistance implications for human immunodeficiency virus type 1 reverse-transcriptase mutations at codons 44 and 118.
April 2002, The Journal of infectious diseases,
Jeannette M Whitcomb, and Neil T Parkin, and Colombe Chappey, and Nicholas S Hellmann, and Christos J Petropoulos
The human immunodeficiency virus type 1 nonnucleoside reverse transcriptase inhibitor resistance mutation I132M confers hypersensitivity to nucleoside analogs.
April 2009, Journal of virology,
Jeannette M Whitcomb, and Neil T Parkin, and Colombe Chappey, and Nicholas S Hellmann, and Christos J Petropoulos
The non-nucleoside reverse transcriptase inhibitor efavirenz stimulates replication of human immunodeficiency virus type 1 harboring certain non-nucleoside resistance mutations.
July 2010, Virology,
Jeannette M Whitcomb, and Neil T Parkin, and Colombe Chappey, and Nicholas S Hellmann, and Christos J Petropoulos
ATP-dependent removal of nucleoside reverse transcriptase inhibitors by human immunodeficiency virus type 1 reverse transcriptase.
July 2002, Antimicrobial agents and chemotherapy,
Jeannette M Whitcomb, and Neil T Parkin, and Colombe Chappey, and Nicholas S Hellmann, and Christos J Petropoulos
Human immunodeficiency virus type 1 isolates with the reverse transcriptase (RT) mutation Q145M retain nucleoside and nonnucleoside RT inhibitor susceptibility.
May 2009, Antimicrobial agents and chemotherapy,
Jeannette M Whitcomb, and Neil T Parkin, and Colombe Chappey, and Nicholas S Hellmann, and Christos J Petropoulos
Identification of a Non-Nucleoside Reverse Transcriptase Inhibitor against Human Immunodeficiency Virus-1.
August 2023, ACS infectious diseases,
Jeannette M Whitcomb, and Neil T Parkin, and Colombe Chappey, and Nicholas S Hellmann, and Christos J Petropoulos
Kinetic studies with the non-nucleoside human immunodeficiency virus type-1 reverse transcriptase inhibitor U-90152E.
June 1994, Biochemical pharmacology,
Copied contents to your clipboard!