Background to study:
Phosphonovir (PZT or 3'-azido-2', 3'dideoxythymine-5'-H-phosphonate) is a phosphonated nucleoside analog. It has been shown to have potent in vitro anti-HIV activity, and preliminary pre-clinical and clinical studies revealed it to be well tolerated and safe.

Objectives:
To establish an optimum daily dose and to compare the BID and TID dosing frequencies for equivalence.

Study Design:
A phase I open label, 12 week, dose escalating study. Eligibility criteria included no previous antiretroviral drug therapy and no active opportunistic infections. 42 patients (11 women and 31 men) were recruited and randomized to four treatment groups. (A) 200mg BID (B) 200mg TID (C) 400mg BID and (D) 400mg TID. The drug was supplied in 200mg oral tablets. Thirty-one men, mean age 22 y.o. range (17- 40yrs), 11 women, mean age 27 y.o. range (18-59yrs) were enrolled. All patients were asymptomatic at time of entry. Mean baseline CD4 was 413 (range 65-1104) cells/mm3 in men, and 459 (range 160-1135) cells/mm3 in women.

Results:
The data on 36 patients who completed all 12 weeks of therapy were analyzed. A dose response effect was noted as early as two weeks post therapy. The mean drop in HIV-RNA in Group A was -0.31 log10copies/mL (range -0.13 to -0.63) and in Group B was -0.38 log 10copies/mL (range -0.21 to -0.66). In Group C -0.70 log10copies/mL (range 0 to -1.73) Group D -0.78 log10copies/mL (range -0.27 to -1.97).

Conclusions:
No major toxicities were noted, all dosage levels were very well tolerated during the study period. The higher doses had the most potent antiviral activity. Group C (400mg BID dosing) showed equivalence to group D (400mg TID dosing). This compound merits further study in combination with other antiretroviral therapies.

Back to Publications