Human immunodeficiency virus type 1 quantitative cell microculture as a measure of antiviral efficacy in a multicenter clinical trial.
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 rolled in an open-label phase I/II study of didanosine monotherapy or combination therapy with zidovudine. The titer was inversely correlated with CD4+ 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 CD4+ 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 SD of .72 log10 infectious units per 10(6) PMBC.
Fiscus
S A
SA
Department of Microbiology and Immunology, University of North Carolina, Chapel Hill.
DeGruttola
V
V
Gupta
P
P
Katzenstein
D A
DA
Meyer
W A
WA
LoFaro
M L
ML
Katzman
M
M
Ragni
M V
MV
Reichelderfer
P S
PS
Coombs
R W
RW
D018791:CD4 Lymphocyte Count; D016049:Didanosine / Q000627:therapeutic use*; D004359:Drug Therapy, Combination; D016655:HIV Core Protein p24 / Q000097:blood; D015658:HIV Infections / Q000188:drug therapy* / Q000821:virology; D015497:HIV-1 / Q000187:drug effects* / Q000254:growth & development; D006801:Humans; D007963:Leukocytes, Mononuclear / Q000821:virology; D016896:Treatment Outcome; D014776:Virus Cultivation / Q000379:methods*; D015215:Zidovudine / Q000627:therapeutic use*
D016655:HIV Core Protein p24; D015215:Zidovudine; D016049:Didanosine