Once-Daily Administration of Antiretrovirals
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Once-Daily Administration of Antiretrovirals Pharmacokinetics of Emerging Therapies Anne-Marie Taburet,1 Sabine Paci-Bonaventure,1 Gilles Peytavin2 and JeanMichel Molina3 1 2 3
ˆ Hospital Bicˆetre, Assistance Publique-Hopitaux de Paris, France ˆ Hospital Bichat, Assistance Publique-Hopitaux de Paris, France ˆ Hospital Saint-Louis, Assistance Publique-Hopitaux de Paris, France
Abstract
Adherence to therapy is of critical importance for the long-term success of the treatment of HIV infection. Once-daily administration of antiretroviral agents is appealing, as it may increase patient’s adherence. The pharmaceutical industry is making huge efforts to develop drugs or combinations of drugs with pharmacokinetic properties allowing once-daily administration. The major pharmacokinetic requirement for once-daily administration is that the intracellular concentration of the antiretroviral or its active metabolite remains above the minimal concentration that can inhibit viral replication during the entire 24-hour period. Soon, all three major classes of antiretroviral agents will be available as once-daily formulations. However, only a few clinical trials have yet assessed the efficacy and safety of truly once-daily antiretroviral combinations. Preliminary results from these small pilot studies suggest that once-daily administration of antiretrovirals is a feasible approach. Large comparative trials are needed before the real benefits of such a strategy can be fully assessed.
The efficacy of highly active antiretroviral therapy (HAART), available since 1996, is now well established, and has provided extraordinary benefits to many patients with HIV infection.[1] The morbidity and mortality related to HIV infection have dramatically decreased in countries in which HAART has been available,[2] turning HIV infection into a chronic manageable disease. HAART is a combination of at least three antiretroviral agents, two nucleoside reverse transcriptase inhibitors (NRTIs) plus a third agent, a protease inhibitor (PI), a non-nucleoside reverse transcriptase inhibitor (NNRTI) or possibly a third NRTI.[1] However, HAART regimens have also shown some limitations, the major
one being the failure to eradicate HIV even after several years of therapy. Life-long antiretroviral treatment seems necessary, as viral replication and loss of CD4+ T cells resume as soon as HAART is interrupted. A number of issues have therefore recently emerged because of the need for long-term therapy and the complexity of current HAART regimens. Issues such as adherence to the regimen and serious toxicities associated with the long-term use of antiretrovirals have become increasingly important.[3-5] Prescription of convenient and well-tolerated regimens is a major challenge for all clinicians involved in the treatment of HIV-infected patients. Although at present most antiretroviral treatments
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are administered on a twice-daily basis, there is a need for further simplification. Whe
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