ASSESSMENT OF ANTIRETROVIRAL THERAPY BY PLASMA VIRAL LOAD TESTING - STANDARD AND ICD HIV-1 P24 ANTIGEN AND VIRAL-RNA (QC-PCR) ASSAYS COMPARED

To assess the utility of quantitative competitive-polymerase chain rea ction (QC-PCR) measurements of plasma human immunodeficiency virus typ e 1 (HIV-1) RNA and other viral load markers for assessment of antiret roviral therapy, we used archived cryopreserved specimens from a rando mized controlled clinical trial of 135 patients (CD4(+) T cell count l ess than or equal to 500/mm(3)), comparing zidovudine (500 mg/day) ver sus the nonnucleoside reverse transcriptase inhibitor L-697,661 (50, 3 00, or 1,000 mg daily). We evaluated treatment-associated changes in p lasma 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 basel ine, HIV-1 RNA was quantifiable by QC-PCR in all patients tested (100% ), whereas standard and ICD HIV-1 p24 antigen tests were positive (gre ater than or equal to 30 pg/ml) in 42% and 56%, respectively. All vira l 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 eit her 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 w ere sustained for the duration of treatment, plasma viral markers ofte n returned to pretreatment levels despite ongoing L-697,661 treatment, with evidence of the emergence of drug-resistant virus. Whereas stand ard p24, ICD p24, and viral RNA levels changed similarly in response t o treatment, the superior sensitivity and available dynamic range of p lasma viral RNA assays like QC-PCR analysis provide an advantage for c linical monitoring of plasma viral load, allowing tracking of treatmen t-related changes even in patients with earlier stage disease and lowe r levels of viral load.