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 activity of the (-)enantiomer of 2'-deoxy-3'-thiacytidine (3TC, lamivudine), 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/mm3 (range, 7-357). A toxic dose was not reached, although some patients reported mild headache, insomnia, and abdominal symptoms, and there was a general downward trend in neutrophil counts at the highest doses. Although subjective and difficult to interpret, increases in energy and appetite were noted, particularly in patients receiving > or = 8.0 mg/kg/day. Immunologic and virologic parameters showed evidence of at least transient anti-HIV activity at those higher doses. Although further studies of 3TC as monotherapy are needed, its favorable toxicity profile, evidence of at least transient clinical activity, and results of in vitro resistance experiments support further clinical testing in combination therapy.