Effect of foscarnet on quantities of cytomegalovirus and human immunodeficiency virus in blood of persons with AIDS

Abstract

Four intravenous dosages of foscarnet given for 10 days were compared with no therapy in persons with AIDS who had asymptomatic cytomegalovirus (CMV) viremia. CMV viremia was quantitated by endpoint cell dilution microcultures, pp65 antigenemia assay, and measurement of CMV DNA in peripheral blood leukocytes by a quantitative-competitive PCR. Human immunodeficiency virus type 1 (HIV-1) viremia was quantitated by endpoint cell dilution microculture, serum p24 antigen assay, and PCR for HIV-1 RNA in plasma. Twenty-seven subjects who had received a median of 22 months of nucleoside antiretroviral therapy were enrolled. Twenty-two subjects received foscarnet, which was well tolerated and decreased the CMV burden, as reflected by all three indicator assays. During the 10 days of dosing, the level of CMV viremia, as measured by 50 percent tissue culture infective doses, decreased from 117.5 to 12.7 (P = 0.001), the amount of CMV DNA decreased from 20,328 copies to 622 copies per 150,000 leukocytes (P = 0.02), and the level of CMV pp65 antigenemia decreased from 14.9 to 1.6 positive peripheral blood mononuclear cells per 50,000 leukocytes (P = 0.008). A significant pharmacodynamic relationship was found between the peak foscarnet concentration and a decrease in the level of CMV antigenemia (P < 0.05). Foscarnet had no effect on quantitative HIV-1 microcultures during the 10 days of treatment, but the HIV-1 p24 antigen level in serum decreased significantly, from 454 to 305 pg/ml (P = 0.01). Also, a significant pharmacodynamic relationship was seen between plasma HIV-1 RNA concentrations and both peak foscarnet concentration (P < 0.01) and the area under the foscarnet time-concentration curve (P < 0.05). Reductions in the levels of CMV and HIV-1 viremia correlated quantitatively with systemic exposure to foscarnet, whereas control subjects actually experienced an increase in CMV and HIV-1 burdens. The dual antiviral activity of foscarnet shown in this trial encourages investigation of its use in combination with other antiretroviral therapies for persons with AIDS.