Document 1096
 DOCN  M94A1096
 TI    HIV-1 resistance genotypes in the plasma RNA and PBMC DNA during ZDV/DDI
       combination therapy.
 DT    9412
 AU    Eastman PS; Boyer E; Urdea M; Kolberg J; Mole L; Holodniy M; Chiron
       Corporation, Emeryville, CA 94608.
 SO    Int Conf AIDS. 1994 Aug 7-12;10(2):21 (abstract no. 375A). Unique
       Identifier : AIDSLINE ICA10/94371479
 AB    OBJECTIVE: Evaluation of Zidovudine (ZDV) and Didanosine (ddI)
       resistance mutations in the reverse transcriptase gene (RT) of plasma
       HIV RNA and peripheral blood mononuclear cell (PBMC) proviral DNA with
       respect to viral and proviral load and CD4 counts after the addition of
       ddI in subjects who have received longterm ZDV therapy. METHODS: Ten
       patients with longterm ZDV experience (mean 27 months) had ddI (400
       mg/day) added to their regimen. Plasma and PBMCs were collected at
       baseline and serially for up to 12 months after addition of ddI. Plasma
       virus RNA and PBMC proviral DNA were PCR amplified and changes in the
       codon 215, 74 and 135 mutant (MUT) and wild-type (WT) populations were
       determined by differential hybridization using either a nonisotopic
       ELISA type format or an isotopic dot blot format. Plasma virus RNA was
       quantitated by the branched DNA (bDNA) Chiron Quantiplex HIV RNA assay.
       Proviral DNA was quantitated by a PCR-ELISA assay. RESULTS: While ZDV
       genotypic resistance at codon 215 was observed in both the plasma RNA
       and PBMC proviral DNA of all subjects at baseline, a decrease in plasma
       virus RNA was observed only in those patients with significant levels of
       WT RNA. No changes in proviral DNA levels were observed. After addition
       of ddI, relative levels of codon 215 WT RNA declined to undetectable
       levels, however, no significant change in the relative levels of codon
       215 MUT and WT proviral DNA was observed. By 12 months of ddI therapy
       viral load again increased and CD4 counts declined in the responding
       patients. Genotypic resistance to ddI at codon 74 was not observed.
       Mutations at codon 135 were present prior to addition of ddI in both
       responders and nonresponders. DISCUSSION AND CONCLUSIONS: The addition
       of ddI results in a decline of HIV RNA levels and codon 215 WT RNA in
       the plasma of some patients. Proviral load and codon 215 MUT and WT
       proviral populations appear not to be affected. Furthermore, mutation at
       sites other than codons 74 and 135 must be responsible for the observed
       resistance to ZDV/ddI combination therapy.
 DE    *Codon  Didanosine/*PHARMACOLOGY/THERAPEUTIC USE  Drug Resistance,
       Microbial/GENETICS  DNA, Viral/*BLOOD  Enzyme-Linked Immunosorbent Assay
       Genotype  Human  HIV Infections/*DRUG THERAPY/MICROBIOLOGY  HIV-1/*DRUG
       EFFECTS/GENETICS/ISOLATION & PURIF  Leukocytes,
       Mononuclear/*MICROBIOLOGY  Polymerase Chain Reaction
       Proviruses/ISOLATION & PURIF  RNA, Viral/*BLOOD  Viremia/*MICROBIOLOGY
       Zidovudine/*PHARMACOLOGY/THERAPEUTIC USE  MEETING ABSTRACT

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