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1996-01-30
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Document 0626
DOCN M9610626
TI Assessment of antiretroviral therapy by plasma viral load testing:
standard and ICD HIV-1 p24 antigen and viral RNA (QC-PCR) assays
compared.
DT 9601
AU Kappes JC; Saag MS; Shaw GM; Hahn BH; Chopra P; Chen S; Emini EA;
McFarland R; Yang LC; Piatak M Jr; et al; Department of Medicine,
University of Alabama at Birmingham, USA.
SO J Acquir Immune Defic Syndr Hum Retrovirol. 1995 Oct 1;10(2):139-49.
Unique Identifier : AIDSLINE MED/96007275
AB To assess the utility of quantitative competitive-polymerase chain
reaction (QC-PCR) measurements of plasma human immunodeficiency virus
type 1 (HIV-1) RNA and other viral load markers for assessment of
antiretroviral therapy, we used archived cryopreserved specimens from a
randomized controlled clinical trial of 135 patients (CD4+ T cell count
< or = 500/mm3), comparing zidovudine (500 mg/day) versus the
nonnucleoside reverse transcriptase inhibitor L-697, 661 (50, 300, or
1,000 mg daily). We evaluated treatment-associated changes in plasma
viral load by standard and immune complex-dissociated (ICD) HIV-1 p24
antigen assays, and, in a representative subset of patients (n = 46), by
QC-PCR determination of virion-associated HIV-1 RNA. At baseline, HIV-1
RNA was quantifiable by QC-PCR in all patients tested (100%), whereas
standard and ICD HIV-1 p24 antigen tests were positive (> or = 30 pg/ml)
in 42% and 56%, respectively. All viral load parameters showed
significant decreases from baseline within 1 week of initiation of
zidovudine, as measured by standard p24 antigen assay, ICD p24 assay,
and QC-PCR. At 1 week, patients treated with either 300 or 1,000 mg/day
of L-697,661 showed significant decreases from baseline in plasma
standard and ICD p24 antigen and QC-PCR-determined HIV-1 RNA levels.
Whereas viral load decreases seen with zidovudine were sustained for the
duration of treatment, plasma viral markers often returned to
pretreatment levels despite ongoing L-697,661 treatment, with evidence
of the emergence of drug-resistant virus. Whereas standard p24, ICD p24,
and viral RNA levels changed similarly in response to treatment, the
superior sensitivity and available dynamic range of plasma viral RNA
assays like QC-PCR analysis provide an advantage for clinical monitoring
of plasma viral load, allowing tracking of treatment-related changes
even in patients with earlier stage disease and lower levels of viral
load.
DE Antiviral Agents/*THERAPEUTIC USE Benzoxazoles/THERAPEUTIC USE
Biological Markers Comparative Study CD4 Lymphocyte Count
Double-Blind Method Human HIV Core Protein p24/*ANALYSIS HIV
Infections/DRUG THERAPY/*VIROLOGY HIV-1/DRUG
EFFECTS/GENETICS/IMMUNOLOGY/*ISOLATION & PURIF Immunoassay Polymerase
Chain Reaction Prospective Studies Pyridones/THERAPEUTIC USE Reverse
Transcriptase Inhibitors/THERAPEUTIC USE RNA, Viral/*ANALYSIS Support,
Non-U.S. Gov't Support, U.S. Gov't, Non-P.H.S. Support, U.S. Gov't,
P.H.S. Viremia/DRUG THERAPY/*VIROLOGY Zidovudine/THERAPEUTIC USE
CLINICAL TRIAL JOURNAL ARTICLE RANDOMIZED CONTROLLED TRIAL
SOURCE: National Library of Medicine. NOTICE: This material may be
protected by Copyright Law (Title 17, U.S.Code).