- Category: HIV Treatment
- Published on Tuesday, 20 November 2012 00:00
- Written by Liz Highleyman
The Complera (rilpivirine/tenofovir/emtricitabine) single-tablet regimen suppressed HIV as well as the Atripla (efavirenz/tenofovir/emtricitabine) combination pill in treatment-naive people, but led to fewer adverse events -- in particular neuropsychiatric side effects associated with efavirenz, according to a report at the 11th International Congress on Drug Therapy in HIV Infection (HIV11) last week in Glasgow.
Once-daily single-tablet regimens offer maximum convenience and promote good adherence for people with HIV, but as new coformulations come online, other factors come into play when comparing one against another.
Cal Cohen from the Community Research Initiative of New England and colleagues conducted the first head-to-head study directly comparing the safety and efficacy of the Complera and Atripla single-tablet regimens, both marketed by Gilead Sciences. (Gilead also makes the only other approved single-tablet regimen, the 4-in-1 Stribild pill).
The STaR trial was an open-label, multicenter, international study. It enrolled 786 previously untreated people with HIV. More than 90% were men and the median age was 36 years -- younger than many HIV treatment trials. About 68% were white, 25% were black, and about 17% identified as Latino. At baseline the mean CD4 T-cell count was approximately 390 cells/mm3, 65% had HIV RNA < 100,000 copies/mL,and they were not resistant to any of the study drugs according to genotypic testing.
Participants were randomly assigned (1:1) to receive either Complera or Atripla. The primary study endpoint was undetectable HIV viral load (< 50 copies/mL) at 48 weeks, with randomized treatment continuing through 96 weeks. The pre-specified non-inferiority margin was set at 12%. Randomization was stratified by HIV level at study entry (< 100,000 or >100,000 copies/mL).
- At 48 weeks, 86% of participants in the Complera arm and 82% in the Atripla arm achieved undetectable HIV RNA in an intent-to-treat analysis, not a statistically significant difference.
- This difference fell well within the 12% margin, indicating that Complera was non-inferior to Atripla.
- 8% of Complera recipients and 6% of Atripla recipients experienced virological failure.
- CD4 T-cell gains were also similar, +200 and +191 cells/mm3, respectively.
- Breaking down the virological response results by baseline viral load:
o HIV RNA < 100,00 copies/mL: 89% with Complera vs 82% with Atripla, making Complera was statistically superior;
o HIV RNA > 100,00 copies/mL: 80% with Complera vs 82% with Atripla, indicating that Complera was non-inferior.
- Breaking the viral load stratification down even further in a post hoc analysis without pre-specified non-inferiority criteria:
o HIV RNA 100,00-500,000 copies/mL: 83% with Complera vs 82% with Atripla;
o HIV RNA > 500,00 copies/mL: 72% with Complera vs 80% with Atripla.
- Among the small number of participants with available drug resistance data through week 48:
o 4% in the Complera arm and 1% in the Atripla arm showed any antiretroviral resistance;
o 4% and 1%, respectively, had primary NNRTI resistance mutations;
o 19% and 4%, respectively, developed resistance in the highest viral load strata (> 500,000 copies/mL).
- Overall, Complera performed significantly better than Atripla when considering adverse events:
o Grade 3 or 4 adverse events: 7% vs 14%, respectively;
o Adverse events leading to study discontinuation: 3% vs 9%, respectively;
o Nervous system events (including dizziness, vertigo, insomnia, headache): 30% vs 51%, respectively;
o Psychiatric events (including abnormal dreams, depression, anxiety): 16% vs 38%, respectively;
- No serious adverse events or related discontinuations occurred more often in the Complera arm.
- Fasting total cholesterol, LDL "bad" cholesterol, and triglycerides rose more in the Atripla arm, but so did HDL "good" cholesterol.
- Changes in estimated glomerular filtration rate (a marker of impaired kidney function, with higher being better) were worse in the Complera arm, -5.4 mL/min vs +4.6 mL/min.
Overall, the researchers concluded, "[rilpivirine/tenofovir/emtricitabine] was non-inferior to [efavirenz/emtricitabine/tenofovir] through week 48 for the primary endpoint of virological suppression."
"[Rilpivirine/tenofovir/emtricitabine] is significantly better tolerated than [efavirenz/emtricitabine/tenofovir]," they added, with "fewer nervous system and psychiatric adverse events" and "fewer discontinuations due to adverse events."
These findings indicate that Complera is an equally effective option for first-line HIV treatment, with better tolerability overall, though caution may be warranted for people starting therapy with a very high viral load.
Interestingly, the researchers noted that there was less emergent resistance in the STaR comparison of single-tablet regimens than observed in the ECHO and THRIVE trials, which compared the same drugs as separate components instead of coformulated.
Abstracts from the HIV11 Congress have been published in a supplement of the Journal of the International AIDS Society, which can be viewed online or downloaded at www.jiasociety.org/index.php/jias/issue/view/1461.
C Cohen, D Wohl, J Arribas, et al. STAR Study: single tablet regimen emtricitabine/rilpivirine/tenofovir DF is non-inferior to efavirenz/emtricitabine/tenofovir DF in ART-naive adults. 11th International Congress on Drug Therapy in HIV Infection (HIV11). Glasgow, November 11-15, 2012. Abstract O425.
Gilead Sciences. Gilead ’s Complera Non-Inferior to Atripla Among Treatment-Naive HIV Patients. Press release. November 15, 2012.