Simplification Therapy with Once Daily Emtricitabine, Didanosine, and Efavirenz in HIV Positive Adults with Viral Suppression Receiving a Protease Inhibitor-based Regimen

HIV-1 infection is now a chronic manageable disease that requires life-long therapy. However, the substantial benefits conferred by antiretroviral therapy require a high rate of adherence to treatment regimens, which were initially protease inhibitor (PI) based.

These regimens are often complex, and failure of antiretroviral therapy is often due to poor adherence. Also, antiretroviral therapy, including PI-based regimens, has been associated with morphologic changes and metabolic abnormalities that could further decrease adherence and that are potentially atherogenic.

Thus, strategies of simplifying antiretroviral therapy should increase adherence and the likelihood of treatment success. Reducing the pill burden by replacing the PI with a non nucleoside reverse-transcriptase inhibitor (NNRTI) has become an increasingly popular strategy.

In an effort to further optimize the convenience of antiretroviral therapy, the researchers have assessed a once-daily regimen combining emtricitabine (Emtriva), didanosine (Videx), and efavirenz (Sustiva). The results of a previous pilot study are encouraging. To confirm these observations, they designed a large, randomized, comparative trial in which patients successfully treated with a PI-based regimen were switched to this once-daily combination.

A total of 355 adults with plasma HIV-1 RNA levels <400 copies/mL were randomly assigned to either switch to once-daily emtricitabine, didanosine, and efavirenz (n = 178) or maintain their protease inhibitor (PI)–based regimens (n = 177).

The primary end point was sustained suppression of plasma HIV-1 RNA levels to <400 copies/mL.

Results   

At week 48, the proportion of patients meeting the end point was 87.6% in the PI group and 90.5% in the once-daily group, with a treatment difference of -2.9%. The proportion of patients with HIV-1 RNA levels <50 copies/mL was higher in the once-daily group (87%) than in the PI group (79%) (P < .05).

Resistance mutations to efavirenz and emtricitabine were detected in all patients in the once-daily group who experienced virologic failure while receiving study medication.

The proportion of patients discontinuing study medication because of adverse events was similar between the once-daily group (9%) and the PI group (10%) (P = .8).

Conclusions     

Substituting a convenient once-daily combination of emtricitabine, didanosine, and efavirenz for a PI-based regimen was well tolerated and associated with sustained virologic suppression.

Discussion

The present study has shown that, in HIV-1–infected patients with suppression of viral replication receiving a PI-based regimen, a switch to a simple once-daily combination of emtricitabine, didanosine, and efavirenz was successful in maintaining durable control of plasma HIV-1 RNA through week 48.

The switch to once-daily therapy was not, however, associated with better outcomes in either CD4 cell counts or disease progression. The once-daily regimen represented only 5 pills/day. The same regimen can be administered today with only 3 pills/day by use of the new formulation of efavirenz, and it has been proven to be efficacious in a large randomized trial in antiretroviral-naive patients.

Aalthough the risk of failure was low in the once-daily group, patients who experienced treatment failure while receiving study medication developed resistance mutations to almost all drugs in the combination. In the PI group, however, the selection of resistance mutations was less frequent.

This regimen offers the advantage of simplicity and low pill burden and, therefore, represents a new and attractive therapeutic option for HIV-1-infected patients.

Assistance-Publique Hôpitaux de Paris, Paris, Institut National de la Santé et de la Recherche Médicale U 593 Bordeaux, and Hôpital Saint-André, Bordeaux, Hôpital de l'Archet, Nice, and Hôpital Sainte Marguerite, Marseille, France.

02/18/05

Reference
J-M Molina and others (for the ALIZE (Agence Nationale de Recherches sur le SIDA 099) Study Team). Simplification Therapy with Once-Daily Emtricitabine, Didanosine, and Efavirenz in HIV-1–Infected Adults with Viral Suppression Receiving a Protease Inhibitor-based Regimen: A Randomized Trial. The Journal of Infectious Diseases 191(6) : 830-839. March 15, 2005.