title: Clinical evaluation of branched DNA signal amplification for quantifying HIV type 1 in human plasma.
abstract: Quantification of HIV-1 RNA in human plasma has provided unique insight into AIDS pathogenesis and promises to hasten progress in antiretroviral therapy and vaccine research. However, no generally available HIV-1 RNA assay has yet been subjected to rigorous clinical testing or to comparative evaluation with research-based RNA assays using large numbers of well-characterized clinical specimens. In this study, the Chiron Quantiplex branched DNA (bDNA) signal amplification assay was used to measure viral RNA in the plasma of 152 HIV-1-positive individuals at all stages of infection and in 12 patients before and after initiating zidovudine therapy. Eighty-six percent of patients had bDNA assay results above the 10,000-RNA Eq/ml sensitivity cutoff. Branched DNA values were significantly correlated with plasma viral RNA levels determined by quantitative competitive polymerase chain reaction (QC-PCR) assay (Spearman rank correlation, r = 0.89), infectious plasma virus titers (r = 0.72), p24 antigen levels (r = 0.51), immune complex dissociated p24 antigen levels (r = 0.56), and CD4+ lymphocyte counts (r = -0.72; p < 0.0001 for all comparisons). Plasma viral RNA determinations by bDNA and QC-PCR assays were quantitatively similar in the range of 10(4) to 10(7) RNA molecules/ml [log bDNA = 0.93 + 0.80 (log QC-PCR); R2 = 0.81, p < 0.0001] and declined identically following the institution of zidovudine therapy (68-73% decrease from baseline). The close quantitative correlation between bDNA and QC-PCR results, and their significant association with other viral markers and CD4+ counts, support the use of plasma viral RNA measurement in HIV-1 clinical trials.
authors.affiliation: Aaron Diamond AIDS Research Center, New York, New York, USA.
authors.forename: Y
authors.initials: Y
authors.lastname: Cao
authors.forename: D D
authors.initials: DD
authors.lastname: Ho
authors.forename: J
authors.initials: J
authors.lastname: Todd
authors.forename: R
authors.initials: R
authors.lastname: Kokka
authors.forename: M
authors.initials: M
authors.lastname: Urdea
authors.forename: J D
authors.initials: JD
authors.lastname: Lifson
authors.forename: M
authors.initials: M
authors.lastname: Piatak
authors.forename: S
authors.initials: S
authors.lastname: Chen
authors.forename: B H
authors.initials: BH
authors.lastname: Hahn
authors.forename: M S
authors.initials: MS
authors.lastname: Saag
mesh_terms: D000163:Acquired Immunodeficiency Syndrome / Q000097:blood / Q000503:physiopathology* / Q000821:virology; D018791:CD4 Lymphocyte Count; D004247:DNA / Q000097:blood*; D016655:HIV Core Protein p24 / Q000097:blood; D015658:HIV Infections / Q000097:blood / Q000503:physiopathology* / Q000821:virology; D006679:HIV Seropositivity / Q000097:blood / Q000503:physiopathology* / Q000821:virology; D015497:HIV-1 / Q000302:isolation & purification*; D006801:Humans; D021141:Nucleic Acid Amplification Techniques; D016133:Polymerase Chain Reaction / Q000379:methods*; D012367:RNA, Viral / Q000097:blood*; D015203:Reproducibility of Results; D013997:Time Factors; D015215:Zidovudine / Q000627:therapeutic use
chemical_list: D016655:HIV Core Protein p24; D012367:RNA, Viral; D015215:Zidovudine; D004247:DNA