CLINICAL-EVALUATION OF BRANCHED DNA SIGNAL AMPLIFICATION FOR QUANTIFYING HIV TYPE-1 IN HUMAN PLASMA

Quantification of HIV-1 RNA in human plasma has provided unique insigh t into AIDS pathogenesis and promises to hasten progress in antiretrov iral 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 num bers of well-characterized clinical specimens, In this study, the Chir on Quantiplex branched DNA (bDNA) signal amplification assay was used to measure viral RNA in the plasma of 152 HIV-1-positive individuals a t all stages of infection and in 12 patients before and after initiati ng zidovudine therapy. Eighty-six percent of patients had bDNA assay r esults above the 10,000-RNA Eq/ml sensitivity cutoff. Branched DNA val ues were significantly correlated with plasma viral RNA levels determi ned by quantitative competitive polymerase chain reaction (QC-PCR) ass ay (Spearman rank correlation, r = 0.89), infectious plasma virus tite rs (r = 0.72), p24 antigen levels (r = 0.51), immune complex dissociat ed p24 antigen levels (r = 0.56), and CD4+ lymphocyte counts (r = -0.7 2; 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); R( 2) = 0.81, P < 0.0001] and declined identically following the institut ion of zidovudine therapy (68-73% decrease from baseline). The close q uantitative correlation between bDNA and QC-PCR results, and their sig nificant association with other viral markers and CD4(+) counts, suppo rt the use of plasma viral RNA measurement in HIV-1 clinical trials.