Once-Daily Complera as Effective as Atripla, Though with Fewer Side Effects

Study results presented at the 2013 United States Conference on AIDS show that Complera (rilpivirine/emtricitabine/tenofovir DF) is significantly better tolerated than Atripla (efavirenz/emtricitabine/tenofovir DF) by HIV patients. Both Complera and Atripla are daily single-tablet regimen (STaR) therapies that previous studies have shown are similar in efficacy in treating antiretroviral-therapy (ART)-naïve patients.

The goal of the new study was to compare the efficacy, safety, and tolerability of Complera and Atripla, according to presenter Calvin Cohen, MD, Director of Research at Community Research Initiative of New England.

In this randomized, open-label IIIb trial, patients were given once-daily doses of either Complera or Atripla. No placebo was given. The primary endpoint was an undetectable viral load of HIV-1 RNA<50 c/ml, expressed as a percentage at 48 weeks, representing efficacy of treatment. Secondary endpoints included change in CD4+ levels at Week 48 and Week 96, treatment safety, severity and types of HIV symptoms, and patient satisfaction with treatment.

The study enrolled 786 ART-naïve patients who had an HIV-1 viral load of at least 2500 c/ml and no resistance to the test drugs. Patients were divided into two test groups. Of the 394 patients in the Complera STR group, median age was 37, 93% were male. Sixty-eight percent of patients were white, 25% were black, and 15% Latino. Mean baseline CD4 count was 396, mean baseline viral load was 4.8.

Of the 392 patients in the Atripla STR group, median age was 35, 93% were male. Sixty-seven percent of patients were white, 24% were black, and 19% were Latino. Mean CD4 count was 385, and mean viral load was 4.8.

At Week 48, the Complera group showed a mean change in CD4+ levels of +200, with 338 (86%) patients showing an undetectable viral load. The Atripla group showed similar efficacy, experiencing a mean change in CD4+ levels of+191, with 320 (82%) patients showing an undetectable viral load.

In the first group, 10 (2.5%) patients were taken off therapy due to treatment-emergent adverse events (including dizziness, depression, insomnia, and abnormal dreams); in the second group, 34 (8.7%) stopped therapy. In the first group, 117 (29.7%) patients experienced nervous system events (including dizziness, insomnia, somnolence, and headaches), 62 (15.7%) had psychiatric events (abnormal dreams, depression, anxiety), and 68 (17.3%) experienced skin rash. In the second group, 198 (50.5%) patients experienced nervous system events, 147 (37.5%) had psychiatric events, and 83 (21.2%) experienced rash.

In the first group, 68 patients (17.3%) had abnormal lab tests (such as glycosuria, hematuria, liver enzymes, creatine kinase levels); in the second group, 63 patients (16.1%) had abnormal tests.

Summarizing patient questionnaires about changes in HIV symptoms, there were no statistically significant differences reported by the two groups at Week 48 for psychiatric or nervous system symptoms. There were fewer subjects in the Complera group reporting symptoms of diarrhea and pain, numbness, or tingling in the extremities, compared to the Atripla group. In neither group were any symptoms reported in significantly more subjects at Week 48 than on Day 1. Subjects in both groups expressed similar satisfaction with treatment.

The researchers concluded that Complera and Atripla have similar efficacy through Week 48 for the primary endpoint of subjects achieving an undetectable viral load. Complera was more effective than Atripla in controlling symptoms of diarrhea, pain, numbness, or tingling in the extremities. Also, tolerance and safety were superior on Complera, resulting in fewer adverse events and discontinuations.

This study was sponsored by Gilead Sciences