1st National Conference Human Retroviruses and Related Infections Washington, DC - December 12-16, 1993

Natl Conf Hum Retrovir Relat Infect 1993 Dec 12-16;1: (abstract no. 5)

Chatis PA^1,2, Japour AJ¹, Mayers DL³, McCutcheon FE⁴, Kim L¹, Page C³, Crumpacker CS^1
1Beth Israel Hospital and Harvard Medical School, Boston, MA; ²DuPont Medical Products, Boston, MA; ³Walter Reed Army Institute of Research and Naval Medical Research Institute, Rockville, MD; ⁴Henry M. Jackson Foundation Research Laboratories, Rockville, MD

The genetic basis for ddI resistance in human immunodeficiency virus (HIV-1) has previously been shown to be associated with a Leu to Val change at codon 74 in the HIV-1 reverse transcriptase (RT) gene. Sequential viral isolates were analyzed from five patients with prior zidovudine (ZDV) use who received six to sixteen months of didanosine (ddI) therapy. Following ddI therapy, viral isolates exhibited an increased ZDV susceptibility and decreased ddI susceptibility. Sequence and nested PCR analysis of the HIV-RT gene revealed that only two of the five viral isolates analyzed contained the Leu to Val change at codon 74. Three viral isolates with reduced susceptibility to ddI each contained changes near to codon 74, namely, at codons 65, 70, and 72. Therefore, a clustering of mutations in the amino terminal end of the HIV-1 RT between codons 65 and 74, a region that corresponds to the β3- β4 connecting loop, appears to be associated with decreased susceptibility to ddI.

Keywords: Acquired Immunodeficiency Syndrome, Anti-HIV Agents, Base Sequence, Codon, Didanosine, HIV, HIV Core Protein p24, HIV Infections, HIV Seropositivity, HIV-1, HIV-1 Reverse Transcriptase, Humans, Mutation, Polymerase Chain Reaction, Zidovudine, genetics, immunology, therapy

Download abstract

1993-12-12
5

Copyright © 1993 - The American Society for Microbiology. Reproduction of this abstract (other than one copy for personal reference) must be cleared through the American Society for Microbiology.