Early HAART regimens characteristically involved complicated combinations of drugs, which often were taken as varying numbers of pills and as multiple doses each day. With the recent availability of once-daily drugs, simpler regimens have becoming increasingly popular because of increased convenience.

To help physicians and their patients make informed decisions about updating treatment regimens, a review described in a recent issue of Drugs compared newer once-daily administration regimens against older twice-daily administration regimens in terms of efficacy, durability, potential for adverse effects, and patient adherence.

More than 10 antiretroviral agents or drug combinations are now approved for once-daily administration in some countries: abacavir (Ziagen), didanosine (ddI; Videx), emtricitabine (Emtriva), lamivudine (3TC; Epivir), tenofovir (Viread), efavirenz (Sustiva), atazanavir (Reyataz), ritonavir-boosted atazanavir, boosted fosamprenavir (Lexiva), and co-formulated lopinavir/ritonavir (Kaletra).

In addition, some drugs have been co-formulated for once-daily administration: abacavir/lamivudine (Epzicom), tenofovir/emtricitabine (Truvada), and tenofovir/emtricitabine/efavirenz (Atripla).

Clinical trials have validated the efficacy of HAART combination regimens for once-daily or twice-daily administration in patients who were treatment-naive or who required salvage therapy.

On the basis of efficacy measures reflecting reduced viral load (percentage of patients with HIV RNA levels <400 or <50 copies/mL), once-daily regimens were consistently found to be at least as effective as twice-daily regimens, and sometimes more effective.

Most of the regimens studied for efficacy consisted of a combination of two nucleoside/nucleotide reverse transcriptase inhibitors (NRTIs) plus a non-nucleoside reverse transcriptase inhibitor (NNRTI). Efavirenz was the most commonly used NNRTI, and it was typically used in combination with either lamivudine or emtricitabine plus either didanosine, abacavir, or tenofovir.

In regimens that replaced efavirenz with a once-daily protease inhibitor, those that included atazanavir or lopinavir/ritonavir has similar efficacy as either once-daily or twice-daily regimens.

In terms of adherence to specific regimens, reviewed studies demonstrated that once-daily HAART regimens were at least non-inferior, and were often superior, to twice-daily regimens, with no significant decrease in efficacy.

In conclusion, according the review author Jean-Michel Molina, once-daily HAART regimens have been validated in clinical trials as safe, effective, and well tolerated. Such combinations are likely to improve patient adherence because they are simpler and more convenient than earlier therapeutic regimens.

Department of Infectious Diseases, Assistance Publique-Hôpitaux de Paris, Hôpital Saint-Louis, Université Paris Diderot, Paris 7, France.

4/25/08

Reference

JM Molina. Efficacy and Safety of Once-daily Regimens in the Treatment of HIV Infection. Drugs 68(5): 567-78. 2008.

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