- Category: Approved HIV Drugs
- Published on Friday, 03 August 2012 00:00
- Written by Liz Highleyman
People who switched to the all-in-one Complera (rilpivirine/tenofovir/emtricitabine) combination pill from a boosted protease inhibitor continued to have undetectable viral load and on average had improved lipid profiles associated with lower cardiovascular risk, according to study findings presented at the XIX International AIDS Conference (AIDS 2012) last week in Washington, DC.
Antiretroviral regimens containing ritonavir-boosted protease inhibitors can be highly effective at suppressing HIV, but they can also cause side effects including metabolic abnormalities.
The Complera single-tablet regimen, approved in August 2011, contains the next-generation non-nucleoside reverse transcriptase inhibitor (NNRTI) rilpivirine, sold separately as Edurant, plus the NRTIs tenofovir and emtricitabine (the drugs in Truvada). Studies to date have shown Complera to be effective and well-tolerated both for previously untreated people and for those switching from the Atripla coformulation containing another NNRTI, efavirenz, plus tenofovir/emtricitabine.
As described by Frank Palella from Northwestern University, the SPIRIT study was a an open-label clinical trial in which participants taking a ritonavir-boosted protease inhibitor plus 2 NRTIs were randomly assigned to either remain on their current regimen or switch to the simplified Complera regimen. Simpler regimens have the potential to improve quality of life and adherence, and to reduce side effects and risk of virological failure.
The study included 476 participants on a stable first or second boosted protease inhibitorregimen with no prior use of NNRTIs and no known resistance to the study drugs. 37% started on atazanavir (Reyataz), 33% on lopinavir/ritonavir (Kaletra), and 20% on darunavir (Prezista); as for NRTIs, about 80% were taking tenofovir/emtricitabine.
About 90% of participants were men and three-quarters were white. The average CD4 T-cell count was approximately 600 cells/mm3 and they had been on ART for a median of about 2.8 years.
- Switching to Complera was found to be non-inferior to staying on a ritonavir-boosted protease inhibitor regimen.
- 93.7% of participants who switched to Complera vs 89.9% who stayed on their protease inhibitor regimen had viral load < 50 copies/mL at 24 weeks.
- Response rates were similar for people who originally started ART with low viral load < 100,000 copies/mL (95.0% vs 89.2%, respectively) or higher viral load (95.5% vs 92.3%, respectively).
- All 17 participants with the pre-existing K103N NNRTI resistance mutation who switched to Complera maintained undetectable viral load.
- Fewer people taking Complera experienced virologic failure in a 24-week "snapshot" analysis (0.9% vs 5.0%, respectively).
- Among participants with non-suppressed viral load, 2 people taking Complera and 1 staying on a protease inhibitor had newly emergent drug resistance mutations.
- CD4 cell gains were similar in both arms, 20 vs 32 cells/mm3, respectively.
- Both treatment strategies were generally well-tolerated.
- 1.9% of Complera switchers and no protease inhibitor maintainers discontinued treatment due to adverse events.
- 5.0% vs 6.9%, respectively, experienced serious (grade 3 or 4) adverse events, while 6.3% vs 11.3% experienced grade 3 or 4 laboratory abnormalities.
- Significantly fewer people taking Complera reported diarrhea (17.4% vs 45.3%) or stomach upset (18.3% vs 32.1%), though frequency of nausea and vomiting were similar.
- Complera switchers had larger decreases in lipid levels than those remaining on boosted protease inhibitors:
o Total cholesterol: -25 vs -1 mg/dL, respectively;
o LDL "bad" cholesterol: -16 vs 0 mg/dL, respectively;
o HDL "good" cholesterol: -4 vs -1 mg/dL, respectively;
o Triglycerides: -53 vs +3 mg/dL, respectively;
o Total-to-HDL ratio: -0.27 vs +0.08, respectively.
- Switching to Complera led to a greater improvement in 10-year Framingham cardiovascular risk scores at week 24.
- Estimated GFR (a measure of kidney function) was significantly lower (105.4 vs 108.9 mL/min) and the decrease was greater (-4.4 vs +0.1 mL/min) in the Complera arm.
Based on the findings, the researchers concluded that switching to Complera was non-inferior to remaining on boosted protease inhibitor regimens, regardless of viral load prior to treatment initiation. A lower rate of virological non-suppression was observed in participants switching to Complera, and switching resulted in improvement in fasting lipids and Framingham risk scores.
F Palella, P Tebas, B Gazzard, et al. SPIRIT study: switching to emtricitabine/rilpivirine/tenofovir DF (FTC/RPV/TDF) single-tablet regimen (STR) from a ritonavir-boosted protease inhibitor and two nucleoside reverse transcriptase inhibitors (NRTIS) maintains HIV suppression. XIX International AIDS Conference (AIDS 2012). Washington, DC, July 22-27, 2012. Abstract TUAB0104.
Gilead Sciences. Gilead ’s Once-Daily Single Tablet Regimen Complera Maintains HIV Suppression Among Patients Switching From Protease Inhibitor-Based Regimens. Press release. July 24, 2012.