SPIRIT: Simplification to Rilpivirine/Emtricitabine/Tenofovir DF Single-Tablet Regimen from Boosted Protease Inhibitor Maintains HIV-1 Suppression and Improves Fasting Lipids at Week 48

Background:

Antiretroviral regimen simplification improves quality of life and medication adherence while reducing the risk of HIV virologic failure and long-term drug-related toxicities. Rilpivirine/Emtricitabine/Tenofovir DF (RPV/FTC/TDF) is a well-tolerated, efficacious once daily single-tablet regimen (STR) treatment option.

Methods:

SPIRIT is a phase 3b, open-label, 48-week study to evaluate the safety and efficacy of simplifying from PI+RTV+2NRTI to RPV/FTC/TDF in virologically-suppressed HIV-1 infected subjects, who were randomized 2:1 to switch to RPV/FTC/TDF at baseline (n=317) or maintain their current PI+RTV+2NRTI regimen until a delayed switch to RPV/FTC/TDF at Week (W) 24 (n=159). The primary endpoint was non-inferiority (12% margin) of RPV/FTC/TDF to PI+RTV+2NRTI in maintaining plasma HIV-1 RNA <50 c/mL (virologic suppression; VS) at W24 by FDA snapshot analysis

Results:

The primary endpoint of non-inferiority at W24 was met (VS 93.7% RPV/FTC/TDF vs 89.9% PI+RTV+2NRTI; difference 3.8%, 95% CI [-1.6 to 9.1]). Through W48, 89.3% of subjects simplifying to RPV/FTC/TDF at baseline and 92.1% of subjects who simplified at W24 maintained VS.  Changes in fasting lipids and NCEP categories are in the table.

 

	Mean Change from Baseline				% of Patients in National Cholesterol Educational Program (NCEP) Target Categories
	RPV/FTCV/TDF (Immediate switch) at W24	PI+RTV+2NRTI at W24	RPV/FTCV/TDF (Delayed switch) W24 – W48	RPV/FTCV/TDF (Immediate switch) at W48	NCEP Category	RPV/FTCV/TDF (Immediate switch) at W24	PI+RTV+2NRTI at W24	RPV/FTCV/TDF (Delayed switch) W24 – W48	RPV/FTCV/TDF (Immediate switch) at W48
Total Cholesterol (mg/dL)	-25 p<0.001	-1	-24	-24	Desirable<200	83.9% p<0.001	57.5%	85.6%	83.0%
LDL (mg/dL)	-16 p<0.001	0	-14	-16	Optimal <100	45.1% p<0.001	21.4%	41.0%	44.0%
Triglycerides (mg/dL)	-53 p<0.001	+3	-80	-64	Normal <150	81.1% p<0.001	53.4%	84.9%	86.5%
HDL (mg/dL)	-4 p<0.001	-1	-2	-2	High ≥60	17.2% p=0.48	16.0%	15.4%	22.9%

Conclusion:

Through W48, VS was maintained regardless of whether subjects simplified to RPV/FTC/TDF at baseline or W24.  Simplifying to RPV/FTC/TDF also led to significant improvement in fasting total cholesterol, LDL, and triglycerides, including significant changes in those NCEP categories.