The Body Covers: The 43rd Interscience Conference on Antimicrobial Agents and Chemotherapy
FTC Compares Well to 3TC in Triple-NRTI Regimens
September 15, 2003
More user-friendly antiretroviral (ARV) regimens are greatly needed to aid in improving adherence. In this regard, once-daily (QD) regimens are being evaluated with increasing frequency and have now been incorporated into the recent DHHS Guidelines for the first time. There remains, however, concern on the part of physicians that once-daily regimens may be less "forgiving" than twice-daily regimens if a patient misses a dose. This is clearly a misconception as long as the pharmacokinetics of the drug supports once-daily dosing. Medication dosing is based upon a number of factors, especially the half-life of the drug. The bottom line is the blood level of the drug that remains at the end of the dosing interval prior to the next dose. This level needs to be above the drug concentration necessary for the drug to have its intended effect for the entire dosing interval. Once-daily drugs may actually be more forgiving than twice-daily medications if these properties are present.Reference Abstract: Evaluation of Emtricitabine Within a Triple-NRTI HAART Regimen (Poster H-868)
FTC (emtricitabine, Emtriva) is the latest NRTI to be approved. Very similar to 3TC (lamivudine, Epivir), FTC is a well-tolerated one pill once-daily NRTI. However, unlike 3TC, FTC has a much longer half-life that truly makes it a once-daily medication. In an attempt to provide more information on the efficacy and safety of this new nuke, Sanne et al. compared the triple-nuke regimen of FTC/d4T (stavudine, Zerit)/abacavir (ABC, Ziagen) to the three-NRTI regimen 3TC/abacavir/AZT (zidovudine, Retrovir) in six previously completed clinical trials. The analysis of the adult antiretroviral-naive patients was performed retrospectively. It compared the antiretroviral activity between these two three-nuke regimens by examining the proportion (%) of patients achieving HIV RNA levels below both 400 and 50 copies/mL at the end of 48 weeks, the median change in CD4 cell counts, the incidence of virologic failure, and the incidence of the M184V/I mutations when virologic failure occurred.
Baseline characteristics were generally similar between the various study groups; baseline HIV RNA levels ranged from 4.2-5.0 log10 copies/mL and CD4 cell counts were 350-400 cells/mm3. Comparisons between the FTC-containing three-nuke group and the six 3TC/abacavir/AZT groups revealed similar percentages of patients having HIV RNA levels less than 400 and less than 50 copies/mL and increases in CD4 cell counts (177 vs. 118-215 cells/mm3). However, fewer patients in the FTC arm experienced virologic failure (9 percent) at 48 weeks compared to the other three-nuke regimens (18 percent, p<0.01). In addition, the incidence of the M184V/I mutations in those patients experiencing virologic failure was significantly lower in the FTC arm (52 percent) than in the other combined three-nuke regimens (74 percent, p<0.02).
What, then, does this report add to our knowledge about FTC and once-daily regimens? Firstly, cross comparisons between trials is fraught with many limitations; nevertheless, they may provide us with important information that we may otherwise not be able to obtain. That being said, the results reported here confirm that FTC is at least as efficacious as 3TC in those studies that directly compared the two drugs. In the analysis reported in this study, the FTC-containing three-nuke regimen had fewer virologic failures and a lesser incidence of the signature resistance-associated mutation(s) than the 3TC-containing regimens when virologic failure occurred. Unfortunately, this study does very little to add to our knowledge of the comparative efficacy of once-daily antiretroviral regimens with the more usual twice-daily regimens. Nor do the results tell us much about how FTC's longer half-life (compared to 3TC) allows for true once-daily dosing.
Authored by: I. Sanne, J. Anderson, D. Kargl, C. Wakeford, J. B. Quinn, C. Moxham, F. Rousseau, for the MKC-401 Study Team
Affiliations: Clinical Trials Unit, Parktown, South Africa; Gilead Sciences, Inc., Durham, NC
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