• Comparable Antiviral Efficacy and Safety of Lamivudine Administered 300 mg Once-Daily (QD) Versus 150 mg BID Both in Combination With Zidovudine (300 mg BID) and Efavirenz (600 mg QD) in HIV-1 Infected, Antiretroviral-Naive Adults: EPV20001 (Abstract H-161)
  Authored by E. DeJesus, B. Grinsztejn, K. Gough, D. McCarty, D. Shortino, D. Thomas, S. Castillo, S. Madison, S. Hetherington
  View the original abstract

In recent years, an improving appreciation for the way that HIV medications function and are metabolized has led to a reevaluation of the frequency with which some medications are administered. This understanding has led to an entire group of medications that can be dosed once-daily. Once-daily dosing is thought to improve adherence and certainly can improve the convenience of antiretroviral treatments.

The EPV20001 study, presented by Dr. Edwin DeJesus of the U.S. on behalf of an international group of investigators, compared the efficacy and safety of once-daily (QD) to twice-daily (BID) lamivudine (3TC, Epivir) in combination with zidovudine (ZDV, Retrovir) and efavirenz (EFV, Sustiva). The study was double-blinded and placebo-controlled, meaning that all study participants took lamivudine study pills twice daily (whether placebo or active). Five hundred fifty four participants were randomized to receive one of the two doses. The study showed comparable antiviral and immunologic potency between the QD and BID lamivudine arms, with about 60 percent of both groups having undetectable viral loads (less than 50 copies) at 48 weeks. CD4 cell increases were about 145 cells. Interestingly, there were more medication discontinuations (due to adverse events) among the BID (13 percent) then the QD group (7 percent).

The results of this study provide further corroboration of the ability to dose lamivudine once-daily. Indeed, both the European Medical Evaluation Agency (EMEA) and U.S. Food and Drug Administration (FDA) have recently approved the QD use of the medication. I look forward to the U.S. introduction of the 300 mg lamivudine tablet (already available in Europe). Clearly, the era of once-daily medications has arrived.

Other medications approved to be dosed once daily include didanosine (ddI, Videx), tenofovir (TDF, Viread) and efavirenz, while several others have ongoing studies to evaluate QD dosing -- abacavir (ABC, Ziagen) and zidovudine, as well as several protease inhibitors.

What do these data mean to persons with HIV infection? In our practice, if the entire current drug regimen can be given QD, then lamivudine is readily switched to QD. Should patients taking lamivudine with zidovudine in the fixed dose combination pill, Combivir (COM), be switched off of zidovudine? In my practice, this has not been done with any frequency, unless there are ongoing significant zidovudine side effects. The observation that there is no side effect profile cost with QD lamivudine (indeed, this study shows less side effects with QD) is very important and encouraging. Does this mean that QD dosing will be the principle reason for picking a treatment regimen? I'd think that this would be overly simplistic. There are many factors that go into the choice of medications (side effects, toxicity, pill burden, sequencing), but these easier-to-take options will definitely play a big role in treatment decisions.