ANTI-HUMAN-IMMUNODEFICIENCY-VIRUS (HIV) ACTIVITY, SAFETY, AND PHARMACOKINETICS OF ADEFOVIR DIPIVOXIL PIVALOYLOXYMETHYL)-PHOSPHONYLMETHOXYETHYL]ADENINE) IN HIV-INFECTED PATIENTS

A randomized, double-blind, placebo-controlled, dose-escalation study of adefovir dipivoxil, an oral prodrug of adefovir, was conducted in 3 6 human immunodeficiency virus (HIV)-infected subjects to evaluate its anti-HIV activity, safety, and pharmacokinetics, Subjects received pl acebo or one of three dosages of adefovir dipivoxil daily for 14 days. Median decreases in serum p24 antigen of 31% (P = .02), 25% (P = .31) , and 30% (P = .01) occurred in each drug-treated group, respectively, compared with an increase of 17% in the placebo group, Median decreas es in serum HIV RNA of 0.4-0.6 log(10) copies/mL occurred in the drug- treated groups (P = .03), compared with no change in the placebo group , Gastrointestinal complaints and reversible liver transaminase elevat ions were the most frequently noted adverse events. Decreases in serum free carnitine occurred in each drug-treated group during treatment. After 14 days of dosing, adefovir dipivoxil demonstrated anti-HIV acti vity and was best tolerated at the lowest dosage studied, 125 mg daily .