The Body PRO Covers: The 1st International AIDS Society Conference on HIV Pathogenesis and Treatment
July 9, 2001
- Comparison of the Plasma Pharmacokinetics of Lamivudine During Twice-Daily and Once-Daily Dosing in HIV-1 Infected Individuals (Poster 342)
Authored by Bruno, R.; Ciappina, V.; Villani, P.; Ragazzi, B. M.; Panebianco, R.; Fiuce, G.; Division Infectious and Tropical Diseases -- IRCCS. S. Matteo, University of Pavia, Italy
We have learned over the last several years that antiretroviral therapy has to be taken in an extremely rigorous manner. Nearly perfect adherence (taking all doses of all the medications every day) appears to be necessary to promote viral suppression as well as the prevention of antiviral resistance. Though adherence is certainly important in other conditions such as hypertension and diabetes, the degree of adherence required with antiretrovirals is much greater. Though we do tend to need to re-learn old lessons we have learned in the past -- that simplicity in dosing is the key to promoting medication adherence. And the pharmaceutical companies have responded by developing, among other examples, a myriad of antihypertensive medications that can be taken once daily with few adverse effects.
We have progressed from the times when AZT had to be taken every four hours around the clock (set those 4 a.m. alarms!) to the present when most antiretrovirals can be given in twice-daily regimens. But the Holy Grail in ART remains once-daily dosing.
So which of our antiretrovirals can be taken once a day? So far only ddI and efavirenz have FDA approval for once-daily dosing. Other antiretrovirals -- 3TC, abacavir, nevirapine, and certain protease inhibitors combined with ritonavir -- have potential for once-daily dosing in their current formulations. This study examined the pharmacokinetics of lamivudine (3TC) in standard twice-daily dosing (150mg every 12 hours) with once-daily dosing (300mg) in the same individuals. They measured a full battery of pharmacokinetic parameters and showed equivalence in half-life, steady-state concentration and AUC (area-under-the-curve). AUC is arguably the most important measurement in demonstrating pharmacokinetic equivalence. The once-daily regimen did show higher maximum and lower plasma trough concentrations. Other considerations include the knowledge that the antiviral activity of nucleosides such as 3TC occurs within the infected cells rather than in the blood. This actually lessens the impact of differences in these maximum and minimum blood concentrations.
So what does this mean? We have further support for the use of 3TC in once-daily fashion, 300mg every 24 hours. This adds to our ability to prescribe highly effective antiretroviral regimens on a once-daily schedule, and this should dramatically improve adherence -- which, of course, is the bottom line.
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