A phase I/II randomized, controlled study of FTC versus 3TC in HIV-infected patients.
Originally Published on February 1, 2000
Delehanty, A., Waldman, S., Hulett, L., Quinn, J., McCreedy, B., Almond, M., Miralles, D., and Rousseau, F.
6th.Conf.Retrovir.Oppor.Infect., Chicago, IL, 1999. Abstract 16.
ABSTRACT:
FTC ([1-beta-L-FTC] 2',3'-dideoxy-5-fluoro-3'-thiacytidine) possesses potent in vitro activity against HIV-1 (EC50 10-20nM) and HBV(EC50 10-40nM). The in vitro activity against HIV-1 is approximately 4-10 fold greater than with 3TC. This phase I/II randomized study evaluated antiviral activity, as measured by plasma HIV RNA over 12 days. Patients were randomized to either 25, 100, 200 mg QD of FTC or 3TC 150 mg BID. HIV RNA was monitored frequently (Amplicor TMAssay) over the 12-day study period. The study was powered to detect a difference of 0.5 log10 in AAUCMB between FTC 200 mg QD and 3TC 150 mg BID. Eighty-one antiretroviral naive HIV-infected patients, mean age 32, 47% female, mean CD4 437, mean HIV RNA 4.4 log10, were randomized in the study. FTC at 200 mg QD had a significantly greater antiviral activity than 3TC as measured by AAUCMB over the study period (p= 0.047) or slope of RNA decay over the first week of treatment (p= 0.03). At the end of the study, HIV RNA decreases from baseline were respectively 1.45, 1.48, 1.60, 1.70 log10 for 3TC 150 mg BID, FTC 25, 100 and 200 mg QD. FTC at both 25 and 100 mg QD had similar antiviral activity to 3TC 150 mg BID. Preliminary safety assessment showed that all regimens were well tolerated; two patients developed asymptomatic elevation of CPK in the FTC 200-mg group. The results of this 12-day randomized clinical trial confirm in vitro findings that FTC has superior antiviral activity as compared to 3TC. These results also confirm the potent antiviral activity of FTC as a QD drug. Further confirmatory long-term studies are underway.
