Efficacy and safety of once-daily regimens in the treatment of HIV infection

Abstract

Early versions of highly-active antiretroviral therapy (HAART) characteristically involved complicated combinations of different drugs, which were taken as varying numbers of pills and as multiple doses each day. With the recent availability of once-daily treatment drugs, simpler regimens are becoming increasingly popular because of increased convenience. To help physicians make informed decisions about updating their patients' treatment regimens, this article compares newer once-daily administration regimens with older twice-daily administration regimens in terms of efficacy, durability, potential for adverse effects and patient adherence. More than ten antiretroviral drugs or drug combinations are now approved for once-daily administration in some countries: abacavir, didanosine, emtricitabine, lamivudine, tenofovir disoproxil fumarate (DF), efavirenz, atazanavir, atazanavir plus ritonavir, fosamprenavir plus ritonavir and coformulated lopinavir/ritonavir. In addition, some drugs have been coformulated for once-daily administration (abacavir/lamivudine; emtricitabine/tenofovir DF; and efavirenz/emtricitabine/tenofovir DF). Clinical studies have validated the efficacy of HAART drug combinations 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 lowered viral load (percentage of patients with HIV RNA levels <400 copies/mL or <50 copies/mL), once-daily administration 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 relied on a combination of two nucleoside reverse transcriptase inhibitors plus a non-nucleoside reverse transcriptase inhibitor (NNRTI). Efavirenz was the most commonly-used NNRTI, and it was used in combination with lamuvidine or emtricitabine, plus didanosine, abacavir or tenofovir DF. In regimens that replaced efavirenz with once-daily protease inhibitors, those with atazanavir or lopinavir/ritonavir were similarly efficacious as either once-daily or twice-daily regimens. In terms of adherence to specific regimens, reviewed studies showed that once-daily HAART regimens were often superior and were at least non-inferior to twice-daily regimens, with no significant decrease in efficacy. In conclusion, once-daily HAART regimens have been validated in clinical trials as safely used, well tolerated and effective. Such regimens are likely to improve patient adherence because they are simpler and more convenient than earlier therapeutic regimens.