Document 0712
 DOCN  M94A0712
 TI    Update of HIV drug resistance.
 DT    9412
 AU    Larder B; Antiviral Therapeutic Research Unit, Wellcome Research;
       Laboratories, U.K.
 SO    Annu Conf Australas Soc HIV Med. 1993 Oct 28-30;5:24 (abstract no.
       SPI-1). Unique Identifier : AIDSLINE ASHM5/94348943
 AB    Initial reports that human immunodeficiency virus (HIV) isolates from
       individuals with advanced disease can become resistant to AZT after
       prolonged therapy precipitated considerable interest in the study of HIV
       drug resistance. Genetic analysis of these variants has allowed us to
       identify mutations at 5 codons of the HIV-1 reverse transcriptase (RT)
       that confer AZT resistance (codons: 41, 67, 70, 215 and 219). A detailed
       picture has been obtained of the specific order these mutations appear
       in RT during treatment of asymptomatic individuals. The study of
       resistance to other HIV inhibitors including nucleoside analogues and
       non-nucleoside RT inhibitors (NNRTI) has revealed a number of
       interesting interactions between different mutations in RT. A common
       observation is the suppression of AZT resistance by other drug
       resistance mutations that appear at codons 74, 181 and 184 of RT. This
       masking effect of AZT resistance occurs in the continued presence of AZT
       resistance mutations. However, co-resistance can occur with AZT, ddl and
       NNRTIs (e.g. nevirapine) when a specific combination of mutations is
       present. Thus, it is clear that under certain circumstances multiple
       drug resistant HIV mutants may occur. Studies of this nature should
       provide insight and guidance as to which specific combinations of
       inhibitors might be valuable in the clinic to combat drug resistance.
 DE    Acquired Immunodeficiency Syndrome/*DRUG THERAPY/MICROBIOLOGY  Antiviral
       Agents/*THERAPEUTIC USE  Drug Resistance/GENETICS  Drug Therapy,
       Combination  Human  HIV-1/*DRUG EFFECTS/GENETICS  Mutation/GENETICS
       Reverse Transcriptase/*ANTAGONISTS & INHIB/GENETICS
       Zidovudine/THERAPEUTIC USE  MEETING ABSTRACT

       SOURCE: National Library of Medicine.  NOTICE: This material may be
       protected by Copyright Law (Title 17, U.S.Code).