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M94A0712.TXT
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1994-10-21
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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).