Evaluation of safety and efficacy of 3TC (lamivudine) in patients with asymptomatic or mildly symptomatic human immunodeficiency virus infection: a VOL

In a phase 1/11 study, 7 levels of3TC 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 ~400 X 106/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. Sus-tained decreases in Prmicroglobulin, neopterin, and p24 antigen levels were seen over the 52-week study. There was no consistent dose-response correlation for any surrogate marker. Pene-tration of 3TC into cerebrospinal fluid (CSF) was in the same range as reported for ddC and ddl; 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. Several 2'3'-dideoxynucleoside analogues are recognized as reverse transcriptase inhibitors; however, long-term clini-cal use of these drugs in human immunodeficiency virus (HIV)-infected patients may be limited by toxicity and th