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 < or = 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.
van Leeuwen
R
R
Department of Internal Medicine (Clinical AIDS Unit), University of Amsterdam, Academic Medical Centre, Netherlands.
Katlama
C
C
Kitchen
V
V
Boucher
C A
CA
Tubiana
R
R
McBride
M
M
Ingrand
D
D
Weber
J
J
Hill
A
A
McDade
H
H
D000328:Adult; D000998:Antiviral Agents / Q000008:administration & dosage / Q000134:cerebrospinal fluid / Q000493:pharmacokinetics / Q000627:therapeutic use*; D015415:Biomarkers; D001708:Biopterins / Q000031:analogs & derivatives / Q000097:blood; D018791:CD4 Lymphocyte Count; D018450:Disease Progression; D004305:Dose-Response Relationship, Drug; D016655:HIV Core Protein p24 / Q000097:blood; D015658:HIV Infections / Q000188:drug therapy*; D006801:Humans; D019259:Lamivudine; D008297:Male; D008875:Middle Aged; D019798:Neopterin; D016047:Zalcitabine / Q000009:adverse effects / Q000031:analogs & derivatives* / Q000134:cerebrospinal fluid / Q000493:pharmacokinetics / Q000627:therapeutic use; D001613:beta 2-Microglobulin / Q000032:analysis
D000998:Antiviral Agents; D015415:Biomarkers; D016655:HIV Core Protein p24; D001613:beta 2-Microglobulin; D001708:Biopterins; D019259:Lamivudine; D019798:Neopterin; D016047:Zalcitabine