A PHASE I II STUDY OF 2'-DEOXY-3'-THIACYTIDINE (LAMIVUDINE) IN PATIENTS WITH ADVANCED HUMAN-IMMUNODEFICIENCY-VIRUS INFECTION/

In a phase I/II trial assessing the toxicity, pharmacokinetics, and ac tivity of the (-) enantiomer of 2'-deoxy-3'-thiacytidine (3TC, lamivud ine), 97 patients with AIDS or advanced human immunodeficiency virus ( HIV) disease were administered 3TC at 0.5-20.0 mg/kg/day. The cohort's median entry CD4 cell count was 128/mm(3) (range, 7-357). A toxic dos e was not reached, although some patients reported mild headache, inso mnia, and abdominal symptoms, and there was a general downward trend i n neutrophil counts at the highest doses. Although subjective and diff icult to interpret, increases in energy and appetite were noted, parti cularly in patients receiving greater than or equal to 8.0 mg/kg/day. Immunologic and virologic parameters showed evidence of at least trans ient anti-HIV activity at those higher doses. Although further studies of 3TC as monotherapy are needed, its favorable toxicity profile, evi dence of at least transient clinical activity, and results of in vitro resistance experiments support further clinical testing in combinatio n therapy.