A phase I/II study of 3TC in HIV positive, asymptomatic or mild ARC patients.
Int Conf AIDS 1992 Jul 19-24; 8:We47 (abstract no. WeB 1014) Van Leeuwen R, Boucher C, Katlama C, Ingrand D, Kitchen V, Weber J, McDade H; Academic Medical Centre & National AIDS Therapy Evaluation Centre, Amsterdam.
INTRODUCTION. 3TC (GR109714X) is the single (-) enantiomer of the racemic mixture 2'-deoxy-3'-thiacytidine (BCH189), a nucleoside analogue originally synthesised by Biochem Pharma Inc (formerly IAF Biochem), Montreal. 3TC has been shown to have activity against a wide spectrum of laboratory and clinical strains of HIV-1 in several cell lines with IC50 = 0.003-1.14 microM. In vitro activity has also been demonstrated against zidovudine-resistant isolates. Pre-clinical in vivo toxicology studies have shown 3TC to be well tolerated. In a phase I single-dose pharmacokinetic study bioavailability after oral administration was found to be good (greater than 75%). METHODS. A phase I/II dose escalating study to evaluate the safety, pharmacokinetics and preliminary activity of 3TC in HIV positive, asymptomatic or mild ARC patients with screening CD4 counts less than or equal to 400/mm3 commenced in August 1991 at 3 centres in Europe. Fifteen patients are being enrolled successively to each of 6 dose levels (0.5, 1.0, 2.0, 4.0, 8.0, 12.0mg/kg/day). 3TC is administered orally BID. Activity is being assessed by serial analyses of CD4, p24-ag, Neopterin, beta 2 microglobulin, clinical measurements and quantitative whole blood and plasma viraemia. RESULTS. Currently 75 patients have been recruited into the study at doses up to 8.0mg/kg/day. Mean baseline CD4 count was 225 (range 10-460). Patients have been on study for up to 28 weeks and results to date suggest that 3TC is well tolerated in this population. Three patients have withdrawn from the study, none for drug-related reasons. Patient recruitment continues. Preliminary activity data and interim safety data will be presented.
Keywords: AEGIS, Lamivudine, AIDS-Related Complex, HIV Infections, Zidovudine, HIV, CD4 Lymphocyte Count, HIV Seropositivity, Reverse Transcriptase Inhibitors, HIV-1, Anti-HIV Agents, HIV Core Protein p24, HIV-1 Reverse Transcriptase, Clinical Trials, Viremia, Europe, In Vitro, Human, ICA8
920719
WeB1014
