Document 0730
 DOCN  M9650730
 TI    The appearance of drug resistance-associated point mutations in HIV type
       1 plasma RNA precedes their appearance in proviral DNA.
 DT    9605
 AU    Kaye S; Comber E; Tenant-Flowers M; Loveday C; Department of Virology,
       University College London Medical School,; U.K.
 SO    AIDS Res Hum Retroviruses. 1995 Oct;11(10):1221-5. Unique Identifier :
       AIDSLINE MED/96157210
 AB    Point mutations in the reverse transcriptase (RT) gene of human
       immunodeficiency virus type-1 (HIV-1) have been associated with reduced
       sensitivity of the virus to inhibition by the antiretroviral drug
       zidovudine (ZDV). During therapy we have previously observed the
       accumulation of these mutations, at codons 41, 67, 70, 215, and 219 of
       the RT gene, in proviral DNA sequences from infected peripheral blood
       mononuclear cells (PBMCs) and in cell-free virus RNA. Using a
       quantitative point mutation assay (PMA) we have been able to quantify
       the proportions of mutant and wild-type sequences at these points in
       mixed populations of viral RNA and DNA derived from clinical samples.
       Thus we have confirmed that the mutations can be detected earlier in
       cell-free virus RNA than in PBMC proviral DNA and their accumulation in
       RNA precedes that in DNA. We have analyzed serial samples from 10
       subjects undergoing zidovudine therapy and shown significantly higher
       levels of mutations in cell-free viral RNA than in PBMC proviral DNA at
       codons 41, 70, and 215 during the in vivo acquisition of the mutations.
       In the group of subjects studied the mean time delay between RNA and DNA
       reaching a given level of mutation was 25 days.
 DE    Antiviral Agents/*PHARMACOLOGY  Drug Resistance/GENETICS  DNA,
       Viral/GENETICS  Human  HIV Infections/BLOOD/*VIROLOGY  HIV-1/DRUG
       EFFECTS/ENZYMOLOGY/*GENETICS  *Point Mutation  Proviruses/*GENETICS
       Reverse Transcriptase Inhibitors/*PHARMACOLOGY  RNA-Directed DNA
       Polymerase/GENETICS/METABOLISM  RNA, Viral/BLOOD/GENETICS
       Zidovudine/*PHARMACOLOGY  JOURNAL ARTICLE

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