Document 1125
 DOCN  M94A1125
 TI    In vivo effects of zidovudine on HIV-1 proviral load and 2-LTR circular
       HIV-1 DNA.
 DT    9412
 AU    Baxter JD; Gekowski KM; Rockoff TA; Parisi JM; Byrne BC; UMDNJ/RWJ
       Medical School, Camden 08103.
 SO    Int Conf AIDS. 1994 Aug 7-12;10(2):203 (abstract no. PB0826). Unique
       Identifier : AIDSLINE ICA10/94371450
 AB    OBJECTIVE: To use quantitative polymerase chain reaction (PCR) to
       determine the virologic effects of zidovudine (ZDV) on total HIV-1
       proviral load and circular proviral HIV-1 load in 10 treated patients.
       METHODS: Retrospectively selected serial peripheral blood mononuclear
       cell (PBMC) samples from 10 patients who had initiated ZDV were
       amplified by PCR for total proviral load (using inosine-substituted env1
       primers) and 2-LTR closed circular HIV DNA. Nested primers within the
       LTR were designed to amplify proviral 2-LTR circles. Product was
       measured quantitatively using 32P-labelled probe and a Betascope Blot
       Analyzer. RESULTS: Proviral DNA was detected by env1 primers in serial
       samples from all 10 patients. After the initiation of ZDV, total
       proviral load by env1 remained stable in 5 patients (after 7-16 weeks of
       ZDV), increased in 2 patients (after 10 and 11 weeks of ZDV) and
       decreased in 3 patients (after 8-31 weeks of ZDV). 2-LTR circular HIV-1
       DNA was detected in samples from 6 of the 10 patients. Three patients
       who had stable total proviral load by env1, had reductions in circular
       DNA after 7, 12, and 16 weeks of ZDV. One patient who had an increase in
       total proviral load after 10 weeks of ZDV also had a reduction in
       circular proviral load. Two patients had slight increases in circular
       DNA after 10 and 20 weeks of ZDV; one had no change in total proviral
       load (at 10 weeks) and the other had a decrease in total proviral load
       (at 20 weeks). CONCLUSION: Changes in 2-LTR circular HIV-1 proviral load
       may occur more rapidly in PBMCs then changes in total proviral load
       after the initiation of ZDV. Measurement of 2-LTR circles may be a
       useful virologic marker of the in vivo effects of reverse transcriptase
       inhibitors.
 DE    DNA, Circular/*DRUG EFFECTS  DNA, Viral/*DRUG EFFECTS  Human  HIV
       Infections/DRUG THERAPY/*MICROBIOLOGY  HIV-1/*DRUG EFFECTS/GENETICS
       Polymerase Chain Reaction  Proviruses/*DRUG EFFECTS/GENETICS
       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).