PHASE-I PHASE-II STUDY OF 3TC (LAMIVUDINE) IN HIV-POSITIVE, ASYMPTOMATIC OR MILD AIDS-RELATED COMPLEX PATIENTS - SUSTAINED REDUCTION IN VIRAL MARKERS/

Objective: To evaluate the efficacy of 3TC (lamivudine), a synthetic n ucleoside analogue that inhibits HIV reverse transcriptase in vitro, a s treatment for HIV-positive, asymptomatic or mild AIDS-related comple x patients. Design: Open-label, multinational and multicentre, non-com parative, escalating dose study. Methods: Patients who meet the select ion criteria (n = 104) were enrolled in three European countries. Ten to 15 patients were included at each of the six dose levels of 3TC (0. 5, 1.0, 2.0, 4.0, 8.0, 12.0 and 20.0 mg/kg daily in two divided doses every 12 h). Virological parameters - immune-complex dissociation (ICD ) assay for HIV p24 antigenaemia, plasma HIV RNA load, whole blood ass ay and cellular viraemia - were evaluated at weeks 0, 4, 12 and 24. Re sults: Sustained reductions in HIV RNA load and in ICD p24 antigen lev els were observed and maintained over the 12-week assessment period. G reater reductions were noted at higher doses but this trend did not re ach statistical significance. In 38 patients, reductions of cell virae mia were significantly greater at 4 weeks for patients treated at high er doses of 3TC. Conclusion: These virological data show that 3TC is a potent inhibitor of HIV replication in HIV-positive, asymptomatic or mild ARC patients as assessed by ICD p24 antigenaemia, plasma HIV RNA load and cell viraemia.