Human Immunodeficiency Virus Type 1 Quantitative Cell Microculture as a Measure of Antiviral Efficacy in a Multicenter Clinical Trial

Abstract

A Quantitative cell microculture assay (QMC) was used to measure the human immunodeficiency virus type 1 (HIV-1) peripheral blood mononuclear cell (PBMC)-associated titer in 109 subjects enrolled in an open-label phase I/II study of didanosine monotherapy or combination therapy with zidovudine, The titer was inversely correlated with C04⁺ cell count at baseline (r = .37,P = .001). After 12 weeks of therapy, subjects showed a significant decreases in virus titer and those with the highest baseline virus titers had the greatest increase in C04⁺ cell number (r = .430,P = .002). The QMC assay was more sensitive (98%) for assessing the antiretroviral effect of therapy than was immune complex-dissociated HIV p24 antigen (32%) or plasma culture (3.4%). Estimated sample sizes for phase I/II clinical trials were derived using the within-subject QMC SO of .72 log₁₀ infectious units per 10⁶ PMBC.