       Document 0101
 DOCN  M9630101
 TI    Kinetic analysis of intravirion reverse transcription in the blood
       plasma of human immunodeficiency virus type 1-infected individuals:
       direct assessment of resistance to reverse transcriptase inhibitors in
       vivo.
 DT    9603
 AU    Zhang H; Dornadula G; Wu Y; Havlir D; Richman DD; Pomerantz RJ; Dorrance
       H. Hamilton Laboratories, Department of Medicine,; Jefferson Medical
       College, Thomas Jefferson University,; Philadelphia, Pennsylvania 19107,
       USA.
 SO    J Virol. 1996 Jan;70(1):628-34. Unique Identifier : AIDSLINE
       MED/96099483
 AB    Intravirion reverse transcripts have been identified in the blood plasma
       of human immunodeficiency virus type 1 (HIV-1)-infected individuals. In
       the present studies, the kinetic processes of intravirion HIV-1 reverse
       transcription, in the blood plasma of HIV-1-infected persons treated
       with nevirapine, were investigated. Nevirapine is a nonnucleoside
       inhibitor of reverse transcriptase (RT) which decreases the level of
       HIV-1 viral particles in the blood plasma of infected individuals. By
       analyzing HIV-1 virions at different time points prior to and after
       initiation of nevirapine therapy in vivo, the levels of intravirion
       reverse transcripts have been demonstrated to be dramatically
       susceptible to this anti-RT agent, out of proportion to effects on
       plasma virion load. The intravirion reverse transcripts were also
       documented to rebound to the pretreatment levels, concomitant with the
       development of resistant viral mutants. In addition, the infectivity of
       HIV-1 virions dramatically decreased after nevirapine treatment, further
       indicating that the effects of this anti-RT agent begin within the
       cell-free virions. Since the levels of intravirion reverse transcripts
       were altered according to the susceptibility or resistance of the HIV-1
       RT enzyme to this inhibitor, these data demonstrate that the formation
       of intravirion reverse transcripts is a dynamic process in vivo.
       Moreover, because the alteration in ratios between intravirion HIV-1
       reverse transcripts and viral genomic RNA directly reflects the
       efficiency of reverse transcription, we propose that the determination
       of these ratios in the blood plasma of HIV-1-positive patients may be a
       useful and, most importantly, a direct assay to monitor the efficacy of
       anti-RT agents in vivo.
 DE    Base Sequence  Cohort Studies  Drug Resistance, Microbial  Human  HIV
       Infections/BLOOD/DRUG THERAPY/*VIROLOGY  HIV-1/DRUG EFFECTS/*GENETICS
       Kinetics  Longitudinal Studies  Molecular Sequence Data  Mutation
       Pyridines/*PHARMACOLOGY  Reverse Transcriptase Inhibitors/*PHARMACOLOGY
       Support, U.S. Gov't, Non-P.H.S.  Support, U.S. Gov't, P.H.S.
       *Transcription, Genetic/DRUG EFFECTS  Virion/METABOLISM  JOURNAL ARTICLE

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

