Update of HIV drug resistance.

Important note: Information in this article was accurate in 1994. The state of the art may have changed since the publication date.

Update of HIV drug resistance.

Annu Conf Australas Soc HIV Med. 1993 Oct 28-30;5:24 (abstract no. SPI-1). Unique Identifier : AIDSLINE ASHM5/94348943
Larder B; Antiviral Therapeutic Research Unit, Wellcome Research; Laboratories, U.K.

Abstract: 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.

Keywords: Acquired Immunodeficiency Syndrome/*DRUG THERAPY/MICROBIOLOGY Antiviral Agents/*THERAPEUTIC USE Drug Resistance/GENETICS Drug Therapy, Combination Human HIV-1/*DRUG EFFECTS/GENETICS Mutation/GENETICS RNA-Directed DNA Polymerase/*ANTAGONISTS & INHIB/GENETICS Zidovudine/THERAPEUTIC USE ABSTRACT
941230
M94C4284

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