EFFECT OF FOSCARNET ON QUANTITIES OF CYTOMEGALOVIRUS AND HUMAN-IMMUNODEFICIENCY-VIRUS IN BLOOD OF PERSONS WITH AIDS

Four intravenous dosages of foscarnet given for 10 days were compared with no therapy in persons with AIDS who had asymptomatic cytomegalovi rus (CMV) viremia. CMV viremia was quantitated by endpoint cell diluti on microcultures, pp65 antigenemia assay, and measurement of CMV DNA i n peripheral blood leukocytes by a quantitative-competitive PCR, Human immunodeficiency virus type 1 (HIV-1) viremia was quantitated by endp oint cell dilution microculture; serum p24 antigen assay, and PCR for HIV-1 RNA in plasma. Twenty-seven subjects who had received a median o f 22 months of nucleoside antiretroviral therapy were enrolled. Twenty -two subjects received foscarnet, which was well tolerated and decreas ed 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 per cent 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 cop ies per 150,000 leukocytes (P = 0.02), and the level of CMV pp65 antig enemia decreased from 14.9 to 1.6 positive peripheral blood mononuclea r cells per 50,000 leukocytes (P = 0.008). A significant pharmacodynam ic 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 tr eatment, but the HIV-1 p24 antigen level in serum decreased significan tly, from 454 to 305 pg/ml (P = 0.01). Also, a significant pharmacodyn amic relationship was seen between plasma HIV-1 RNA concentrations and both peak foscarnet concentration (P < 0.01) and the area under the f oscarnet time-concentration curve (P < 0.05), Reductions in the levels of CMV and HIV-1 viremia correlated quantitatively with systemic expo sure to foscarnet, whereas control subjects actually experienced an in crease in CMV and HIV-1 burdens. The dual antiviral activity of foscar net shown in this trial encourages investigation of its use in combina tion with other antiretroviral therapies for persons with AIDS.