Immediate and delayed switches to tenofovir DF-containing, ainuovirine-based antiretroviral regimen: the SPRINT extensional study.

Abstract

Background: Ainuovirine (ANV) is a new-generation nonnucleoside reverse transcriptase inhibitor with potent antiviral activity and favorable neuropsychiatric and cardiometabolic safety. The SPRINT study showed that switching to fixed-dose ANV combined with lamivudine and tenofovir DF (ANV/3TC/TDF) provided non-inferior virologic efficacy and improved cardiometabolic conditions in virologically suppressed people living with HIV (PLWH) compared to that to cobicistat-boosted elvitegravir plus emtricitabine and tenofovir alafenamide (E/C/F/TAF) at 48 weeks.

Methods: In the base study (weeks 0-48), eligible virologically suppressed PLWH (n = 762) were randomized to receive ANV/3TC/TDF or E/C/F/TAF in a double-blind manner. In the extensional study (weeks 48-96), eligible participants on ANV/3TC/TDF continued the assigned regimen (immediate switch group, ISG), while those on E/C/F/TAF re-switched to ANV/3TC/TDF (delayed switch group, DSG). The original E/C/F/TAF group (weeks 0-48) was used as comparator for efficacy analysis. The primary efficacy endpoint was the proportion of PLWH with HIV RNA titer ≥ 50 copies/mL at week 96. Safety outcomes of primary interest included Changes in body weight and fasting serum lipids from weeks 48 to 96.

Results: The primary efficacy endpoints were both 3.4% with ISG and DSG at week 96, non-inferior to 1.6% for comparator at week 48. Estimated treatment differences were 1.8% (95% confidence interval [CI] - 0.5 to 4.3%) with ISG versus comparator and 1.9% (95%CI - 0.4 to 4.4%) with DSG versus comparator, respectively. Non-inferiority was established for both ISG and DSG as the upper limits of 95%CI were both below the prespecified margin of 5%. The treatment-emergent adverse events were generally similar between the two switch groups. DSG showed modest reduction in body weight (mean, - 0.59 kg), in contrast to ISG with a minimal weight loss (- 0.03 kg; DSG versus ISG, - 0.56 kg, [- 1.07 to - 0.05]). Fasting serum low-density lipoprotein cholesterol remained generally unchanged in ISG (0.01 mmol/L) but improved greatly in DSG at week 96 from week 48 (- 0.30 mmol/L; - 0.31 mmol/L [- 0.47 to - 0.16]).

Conclusions: Both ISG and DSG maintained high viral Suppression in PLWH through 96 weeks. DSG could offset weight gain and dyslipidemia associated with previous exposure to E/C/F/TAF.

Trial registration: Chinese Clinical Trial Register number, ChiCTR2100051605.