 |
|
|
| |
Better 1-Month Safety With Rilpivirine Than Efavirenz in Treatment-Naive
|
| |
| |
51st Interscience Conference on Antimicrobial Agents and Chemotherapy (ICAAC), September 17-20, 2011, Chicago
Mark Mascolini
People starting their first antiretroviral regimen with rilpivirine had significantly fewer side effects than people starting efavirenz during the first month of treatment in the ECHO and THRIVE randomized trials [1]. Neurologic, psychiatric, and lipid problems affected more people taking efavirenz than rilpivirine in the first month, as did adverse events leading people to stop treatment.
The nonnucleoside rilpivirine (Edurant, TMC-278) won approval for treatment of antiretroviral-naive people on the basis of the phase 3 ECHO and THRIVE trials, which compared rilpivirine with efavirenz plus two nucleosides [2]. Response rates to the two nonnucleosides were similar at 48 weeks, but the virologic failure rate was higher with rilpivirine than with efavirenz in people starting therapy with a viral load above 100,000 copies. A 3-in-1 once-daily pill combining rilpivirine with tenofovir and emtricitabine, Complera, won FDA approval [3].
ECHO and THRIVE investigators combined safety results to compare adverse events in the rilpivirine and efavirenz arms during the first 12 weeks of those trials [1]. The analysis involved 1368 people. By several measures, adverse event rates were better in the rilpivirine group than in the efavirenz group during the first 4 weeks of treatment and sometimes from week 4 to 12:
At least possibly treatment-related grade 2 to 4 adverse events:
-- Weeks 0 to 4: 9.6% with rilpivirine, 22.3% with efavirenz
-- Weeks >4 to 8: 1.6% with rilpivirine, 3.4% with efavirenz
-- Weeks >8 to 12: 1.2% with rilpivirine, 2.5% with efavirenz
Adverse events leading to discontinuation:
-- Weeks 0 to 4: 0.7% with rilpivirine, 3.8% with efavirenz
-- Weeks >4 to 8: 0.3% with rilpivirine, 0.5% with efavirenz
-- Weeks >8 to 12: 0.6% with rilpivirine, 0.3% with efavirenz
Treatment-related psychiatric adverse events:
-- Weeks 0 to 4: 9.5% with rilpivirine, 17.7% with efavirenz
-- Weeks >4 to 8: 1.0% with rilpivirine, 2.0% with efavirenz
-- Weeks >8 to 12: 1.2% with rilpivirine, 0.9% with efavirenz
Treatment-related neurologic adverse events:
--Weeks 0 to 4: 14.7% with rilpivirine, 35.0% with efavirenz
-- Weeks 5 to 8: 0.6% with rilpivirine, 1.4% with efavirenz
-- Weeks 8 to 12: 0.3% with rilpivirine, 0.9% with efavirenz
Through the end of study week 4, incidence of adverse events of any grade affecting 5% or more of study participants was equivalent in the two study arms or favored the rilpivirine group: dizziness 7.6% with rilpivirine and 25.1% with efavirenz; nausea 8.7% with rilpivirine and 9.7% with efavirenz; abnormal dreams/nightmares 5.8% with rilpivirine and 10% with efavirenz; any rash 2.9% with rilpivirine, 13.6% with efavirenz; headache 5.1% with rilpivirine, 4.7% with efavirenz; and somnolence 2.9% with rilpivirine and 6.5% with efavirenz.
Treatment-related serious adverse events were rare in both study arms through week 12.
Lipid abnormalities were significantly worse with efavirenz than with rilpivirine in the first 12 weeks of ECHO and THRIVE. Total cholesterol, "bad" low-density lipoprotein cholesterol, and triglycerides all rose through 12 weeks with efavirenz but not with rilpivirine. However, at week 12 the rilpivirine and efavirenz groups did not differ in total to high-density lipoprotein cholesterol ratio, sometimes regarded as the single best overall lipid yardstick.
The analysis showed that serious adverse events, adverse events leading to discontinuation, and rash were more common in people who began rilpivirine with a viral load above 100,000 copies than in those who started rilpivirine with a lower load.
References
1. Rashbaum B, Girard P, Rachlis A, et al. Rilpivirine (RPV, TMC278) tolerability over the first 12 weeks of treatment in the phase 3 ECHO and THRIVE studies. 51st Interscience Conference on Antimicrobial Agents and Chemotherapy (ICAAC). September 17-20, 2011. Abstract H2-805.
2. FDA. Approval of Edurant (rilpivirine) a new NNRTI) for the treatment of HIV in treatment naive patients. May 20, 2011. http://www.fda.gov/ForConsumers/ByAudience/ForPatientAdvocates/HIVandAIDSActivities/ucm256151.htm.
3. FDA. Approval of Complera: emtricitabine/rilpivirine/tenofovir DF fixed dose combination. August 10, 2011. http://www.fda.gov/ForConsumers/ByAudience/ForPatientAdvocates/HIVandAIDSActivities/ucm267592.htm.
|
| |
|
|
|
|
|
