EVALUATION OF SAFETY AND EFFICACY OF 3TC (LAMIVUDINE) IN PATIENTS WITH ASYMPTOMATIC OR MILDLY SYMPTOMATIC HUMAN-IMMUNODEFICIENCY-VIRUS INFECTION - A PHASE I/II STUDY

In a phase I/II study, 7 levels of 3TC therapy (from 0.5 to 20.0 mg/kg/day) were studied in 104 asymptomatic and mildly symptomatic human immunodeficiency virus-infected patients with CD4 cell counts less than or equal to 400 X 10(6)/L. Mild and transient episodes of diarrhea, headache, fatigue, nausea, and abdominal pain were the most frequent events reported. No dose-limiting toxicities were observed. Small and transient increases in CD4 cell counts were detected during the first 4 weeks of treatment. These were followed by progressive declines during prolonged therapy. Sustained decreases in beta(2)-microglobulin, neopterin, and p24 antigen levels were seen over the 52-week study, There was no consistent dose-response correlation for any surrogate marker, Penetration of 3TC into cerebrospinal fluid (CSF) was in the same range as reported for ddC and ddI; the mean CSF-to-serum ratio was 0.06. These findings indicate that 3TC exhibits an excellent safety profile and has antiretroviral activity at the dosages studied.