Didanosine (Videx-EC) + Emtricitabine (Emtriva) + Atazanavir (Reyataz) Inferior for Initial HIV Treatment: PEARLS Trial

For a variety of reasons, physicians may recommend an alternative initial antiretroviral regimen rather than one of the first-line regimens recommended by current treatmentguidelines. A once-daily regimen of didanosine (ddI; Videx-EC), emtricitabine (Emtriva), and unboosted atazanavir (Reyataz) has potential advantages over other alternative regimens, but the efficacy of this combination is unknown.

At the XVII International AIDS Conference this month in in Mexico City (August 3-8, 2008), Thomas Campbell presented results from the PEARLS study (ACTG A5175), a Phase IV, randomized, open-label, multinational clinical trial that included antiretroviral-naive participants with CD4 cell counts < 300 cells/mm3.

Participants were randomized to:

• Arm A: coformulated zidovudine/lamivudine (AZT/3TC; Combivir) twice daily + efavirenz (Sustiva) once daily;

• Arm B: ddI + emtricitabine + atazanavir, all once daily; or

• Arm C: coformulated tenofovir/emtricitabine (Truvada) + efavirenz, both once daily.

A total of 1045 participants (547 men and 498 women) from 8 developing countries and the U.S. received Arm A and B regimens. The median follow-up period was 72 weeks.

The primary efficacy endpoint was time from randomization to:

• 2 consecutive plasma HIV RNA measurements >1000 copies/mL from week 16 onward (virological failure);
• HIV disease progression (AIDS); or
• Death due to any cause.

Results

• The probability of reaching the primary endpoint in Arm B was 16.2% at 48 weeks and 23.9% at 96 weeks.

• Safety data were generally as expected.

• Sex, age, CD4 cell count, history of tuberculosis and AIDS, geographical location, and early adherence were independently associated with risk of virological failure Arm B.

• Follow-up in Arms A and Arm C is ongoing.

• A Data and Safety Monitoring Board planned interim review on May 6, 2008 recommended closure of the Arm B versus Arm A comparison.

Based on these findings, the study authors concluded that didanosine + emtricitabine + atazanavir "had inferior outcome" compared with zidovudine + 3TC + efavirenz. They noted that following the interim review, "study participants currently taking this regimen are switching to alternate antiretrovirals."

Abstract:
Powerpoint Slides [Steven: Please leave this link to the slides here AND post them in the AIDS 2008 Library of Posters and Slides]

8/19/08

Reference
T Campbell, L Smeaton, V De Grutolla, and others (for ACTG A5175 study group). PEARLS (ACTG A5175): a multinational study of didanosine-EC, emtricitabine and atazanavir vs. co-formulated zidovudine/lamivudine and efavirenz for initial treatment of HIV-1 infection. XVII International AIDS Conference (AIDS 2008). August 3-8, 2008. Mexico City.