STaR Study: Association of Efficacy Outcomes with Baseline HIV-1 RNA and CD4 Count and Adherence Rate for the Single-Tablet Regimens Rilpivirine/Emtricitabine/Tenofovir DF and Efavirenz/Emtricitabine/Tenofovir DF in ART-Naïve Adults

Background:

Simplified antiretroviral regimens improve quality of life and adherence. Rilpivirine/Emtricitabine/Tenofovir DF (RPV/FTC/TDF) is a well-tolerated once-daily single-tablet regimen (STR) treatment option. This is the first study to directly compare the two STRs, RPV/FTC/TDF and Efavirenz/FTC/TDF (EFV/FTC/TDF) in treatment-naïve adults.

Methods:

STaR is a randomized, open-label, 96-week study to evaluate the safety and efficacy of the STR RPV/FTC/TDF to the STR EFV/FTC/TDF in treatment-naïve HIV-1 infected subjects, who were randomized 1:1 to RPV/FTC/TDF or EFV/FTC/TDF. Randomization was stratified by HIV-1 RNA level (≤100,000 c/mL or >100,000 c/mL) at screening. The primary endpoint was the proportion of subjects with HIV-1 RNA <50 c/mL (virologic suppression; VS) at Week (W) 48 (FDA snapshot algorithm; 12% pre-specified non-inferiority margin).

Results:

786 subjects were randomized and received at least 1 dose of study drug (394 RPV/FTC/TDF; 392 EFV/FTC/TDF). Baseline characteristics were similar in both treatment arms with mean CD4 count 391 cells/mm³ and HIV-1 RNA 4.8 log10 c/mL. RPV/FTC/TDF was non-inferior to EFV/FTC/TDF (86% vs 82%) at W48 for VS (difference 4.1%, 95% CI [-1.1%, 9.2%]). Overall, virologic failure (VF) was 8% RPV/FTC/TDF vs 6% EFV/FTC/TDF (difference 2.7%, 95% CI [-0.9%, 6.2%]). VS results by ordinal levels of adherence rate and baseline HIV-1 RNA and CD4 count at W48 are summarized in Table 1 (excluding 9 subjects with missing adherence measure).

                            Table 1*

				VS
HIV-1 RNA	CD4	Adherence	N	RPVFTC/TDF	EFV/FTC/TDF
≤100,000	>200	≥95%	357	93% (171/184)	89% (154/173)
		<95%	112	82% (46/56)	68% (38/56)
	≤200	≥95%	23	80% (8/10)	77% (10/13)
		<95%	12	67% (6/9)	67% (2/3)
>100,000	>200	≥95%	163	87% (69/79)	90% (76/84)
		<95%	42	70% (14/20)	72% (16/22)
	≤200	≥95%	53	77% (20/26)	81% (22/27)
		<95%	15	50% (4/8)	29% (2/7)

 

*Subjects with missing data were excluded

Conclusion:

RPV/FTC/TDF demonstrated overall non-inferior efficacy compared to EFV/FTC/TDF in treatment-naïve HIV-1-infected subjects.  The analysis showed the subgroup with adherence rate ≥95% had better virologic outcomes across both treatment arms and all HIV-1 RNA and CD4 categories, with most favorable results in the strata consisting of those with baseline HIV-1 RNA ≤100,000 c/mL, CD4 >200 cells/mm³ and adherence rate ≥95%.