BIOMAT Database Logo BIOMAT Database Logo

Emergence of zidovudine and multidrug-resistance mutations in the HIV-1 reverse transcriptase gene in therapy-naive patients receiving stavudine plus didanosine combination therapy. STADI Group. 1999

I Pellegrin, and J Izopet, and J Reynes, and M Denayrolles, and B Montes, and J L Pellegrin, and P Massip, and J Puel, and H Fleury, and M Segondy
Department of Virology, Bordeaux University Hospital, France.

OBJECTIVE Assessment of genotypic changes in the reverse transcriptase gene of HIV-1 occurring in antiretroviral naive patients treated by stavudine plus didanosine combination therapy. METHODS Sequence analysis (codons 1-230) was performed after amplification of the reverse transcriptase gene from plasma samples collected at baseline and at the end of treatment from 39 previously treatment-naive patients treated for 24-48 weeks. RESULTS At baseline, mutations associated with zidovudine resistance were detected in plasma from two patients: Asp67Asn/Lys219Gln and Leu210Trp. Among the 39 subjects, 18 (46%) developed mutations: one developed the Val75Thr/Ala mutation, four (10%) developed a Gln151Met multidrug-resistance mutation (MDR), associated in one of them with the Phe77Leu and the Phe116Tyr MDR mutations and 14 (36%) developed one or more zidovudine-specific mutations (Met41Leu, Asp67Asn, Lys70Arg, Leu210Trp, Thr215Tyr/Phe). The development of a Met41Leu zidovudine-specific mutation was associated with the development of a Gln151Met mutation in one patient. Other reverse transcriptase mutations known to confer resistance to nucleoside analogues were not detected. At inclusion, there was no statistical difference in HIV-1 load between patients who developed resistance mutations and those who did not. RNA HIV-1 load decrease was higher (P = 0.05) in patients who maintained a wild-type reverse transcriptase genotype (-2.22 log10 copies/ml) than in patients who developed resistance mutations (-1.14 log10 copies/ml). CONCLUSIONS Stavudine/didanosine combination therapy is associated with emergence of zidovudine-related resistance or MDR mutations in naive patients. These findings should be considered when optimizing salvage therapy for patients who have received a treatment including stavudine/didanosine combination.

UI MeSH Term Description Entries
D009154 Mutation Any detectable and heritable change in the genetic material that causes a change in the GENOTYPE and which is transmitted to daughter cells and to succeeding generations. Mutations
D004359 Drug Therapy, Combination Therapy with two or more separate preparations given for a combined effect. Combination Chemotherapy,Polychemotherapy,Chemotherapy, Combination,Combination Drug Therapy,Drug Polytherapy,Therapy, Combination Drug,Chemotherapies, Combination,Combination Chemotherapies,Combination Drug Therapies,Drug Polytherapies,Drug Therapies, Combination,Polychemotherapies,Polytherapies, Drug,Polytherapy, Drug,Therapies, Combination Drug
D006801 Humans Members of the species Homo sapiens. Homo sapiens,Man (Taxonomy),Human,Man, Modern,Modern Man
D000328 Adult A person having attained full growth or maturity. Adults are of 19 through 44 years of age. For a person between 19 and 24 years of age, YOUNG ADULT is available. Adults
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
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
D016049 Didanosine 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. Didanosine is a potent inhibitor of HIV replication, acting as a chain-terminator of viral DNA by binding to reverse transcriptase; ddI is then metabolized to dideoxyadenosine triphosphate, its putative active metabolite. 2',3'-Dideoxyinosine,Dideoxyinosine,ddI (Antiviral),NSC-612049,Videx,2',3' Dideoxyinosine,NSC 612049,NSC612049
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
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
D018432 Drug Resistance, Multiple Simultaneous resistance to several structurally and functionally distinct drugs. Drug Resistance, Extensively,Extensively Drug Resistance,Extensively-Drug Resistance,Multidrug Resistance,Multi-Drug Resistance,Extensively Drug Resistances,Extensively-Drug Resistances,Multiple Drug Resistance,Resistance, Extensively Drug,Resistance, Extensively-Drug,Resistance, Multiple Drug

Related Publications

I Pellegrin, and J Izopet, and J Reynes, and M Denayrolles, and B Montes, and J L Pellegrin, and P Massip, and J Puel, and H Fleury, and M Segondy
Low-rate emergence of thymidine analogue mutations and multi-drug resistance mutations in the HIV-1 reverse transcriptase gene in therapy-naive patients receiving stavudine plus lamivudine combination therapy.
September 2001, Antiviral therapy,
I Pellegrin, and J Izopet, and J Reynes, and M Denayrolles, and B Montes, and J L Pellegrin, and P Massip, and J Puel, and H Fleury, and M Segondy
HIV-1 drug susceptibilities and reverse transcriptase mutations in patients receiving combination therapy with didanosine and delavirdine.
February 1997, Journal of acquired immune deficiency syndromes and human retrovirology : official publication of the International Retrovirology Association,
I Pellegrin, and J Izopet, and J Reynes, and M Denayrolles, and B Montes, and J L Pellegrin, and P Massip, and J Puel, and H Fleury, and M Segondy
Mutations in the reverse transcriptase gene of HIV type 1 from subjects after stavudine-didanosine dual therapy.
May 2000, AIDS research and human retroviruses,
I Pellegrin, and J Izopet, and J Reynes, and M Denayrolles, and B Montes, and J L Pellegrin, and P Massip, and J Puel, and H Fleury, and M Segondy
Zidovudine resistance reverse transcriptase mutations during didanosine monotherapy.
August 1996, The Journal of infectious diseases,
I Pellegrin, and J Izopet, and J Reynes, and M Denayrolles, and B Montes, and J L Pellegrin, and P Massip, and J Puel, and H Fleury, and M Segondy
Emergence of zidovudine resistance in HIV-infected patients receiving stavudine.
March 2000, Journal of acquired immune deficiency syndromes (1999),
I Pellegrin, and J Izopet, and J Reynes, and M Denayrolles, and B Montes, and J L Pellegrin, and P Massip, and J Puel, and H Fleury, and M Segondy
Mutations conferring resistance to zidovudine diminish the antiviral effect of stavudine plus didanosine.
December 1999, Journal of medical virology,
I Pellegrin, and J Izopet, and J Reynes, and M Denayrolles, and B Montes, and J L Pellegrin, and P Massip, and J Puel, and H Fleury, and M Segondy
The VIRGO study: nevirapine, didanosine and stavudine combination therapy in antiretroviral-naive HIV-1-infected adults.
December 2000, Antiviral therapy,
I Pellegrin, and J Izopet, and J Reynes, and M Denayrolles, and B Montes, and J L Pellegrin, and P Massip, and J Puel, and H Fleury, and M Segondy
Failure of stavudine-lamivudine combination therapy in antiretroviral-naive patients with AZT-like HIV-1 resistance mutations.
December 2001, Journal of medical virology,
I Pellegrin, and J Izopet, and J Reynes, and M Denayrolles, and B Montes, and J L Pellegrin, and P Massip, and J Puel, and H Fleury, and M Segondy
Stavudine, didanosine and nevirapine in antiretroviral-naive HIV-1-infected patients.
January 1999, Antiviral therapy,
I Pellegrin, and J Izopet, and J Reynes, and M Denayrolles, and B Montes, and J L Pellegrin, and P Massip, and J Puel, and H Fleury, and M Segondy
Zidovudine therapy and HIV type 1 mutations in children with symptomatic HIV type 1 infection: effect of switching to didanosine or zidovudine plus didanosine therapy. Italian Multicenter Study Group on HIV Mutations in Children.
December 1998, AIDS research and human retroviruses,
Copied contents to your clipboard!