Simplification to single-tablet regimen of elvitegravir, cobicistat, emtricitabine, tenofovir DF from multi-tablet ritonavir-boosted protease inhibitor plus coformulated emtricitabine and tenofovir DF regimens: week 96 results of STRATEGY-PI

Abstract

Background: Antiretroviral therapy (ART) simplification to a single-tablet regimen can benefit HIV-1-infected, virologically suppressed, individuals on ART composed of multiple pills.

Objective: We assessed long-term efficacy and safety of switching to co-formulated elvitegravir, cobicistat, emtricitabine, and tenofovir disoproxil fumarate (E/C/F/TDF) from multi-tablet ritonavir-boosted protease inhibitor (PI + RTV) plus F/TDF (TVD) regimens.

Methods: STRATEGY-PI was a 96-week, phase 3b, randomized (2:1), open-label, non-inferiority study examining the efficacy, safety, and tolerability of switching to E/C/F/TDF from PI + RTV + TVD regimens in virologically suppressed individuals (HIV-1 RNA <50 copies/mL). Participants were randomized to switch to E/C/F/TDF (switch group) or to continue their PI + RTV + TVD regimens (no-switch group). Eligibility criteria included no resistance to F/TDF or history of virologic failure, and estimated creatinine clearance ≥70 mL/min.

Results: At week 96, 87% (252/290) of switch and 70% (97/139) of no-switch participants maintained HIV-1 RNA <50 copies/mL (difference: 17%, 95% CI 8.7–26.0%, p < 0.001). Superiority of the switch to E/C/F/TDF vs. no-switch was due to a smaller proportion of both virologic failures (switch, 1% [3/290]; no-switch, 6% [8/139]) and discontinuations for non-virologic reasons (switch, 11% [31/290]; no-switch, 24% [33/139]). No treatment-emergent resistance was observed in switch subjects with virologic failure. Discontinuation rates from adverse events were 3% in both groups (9/293, switch; 4/140, no-switch). Switching from PI + RTV + TVD to E/C/F/TDF was associated with significant improvements in patient-reported outcomes related to gastrointestinal symptoms (nausea and bloating).

Conclusion: E/C/F/TDF is a safe, effective long-term alternative to multi-tablet PI + RTV + TVD-based regimens in virologically suppressed, HIV-1-infected adults, and improves patient-reported gastrointestinal symptoms.

Keywords:

• HIV
• Switch
• Single-tablet regimen
• Simplification
• Protease inhibitor
• INSTI
• Randomized trial
• Superiority
• Patient-reported outcomes

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Addendum

Acknowledgements

We thank Martin Rhee (clinical support), Hoa Chu and Jennifer DeMorin (data organization, review and editing) and the members of the STRATEGY-PI study team including Andrew Plummer, Will Garner, Yu Ning, Eric Wang, Ting Bai, Sandy Shen and Desiree Benavente. We also thank all participating investigators and patients. Medical writing support was provided by Prescott Communications Group (Chicago, IL, USA). The authors wish to acknowledge the contributions of study investigator Professor Martin Fisher, from Brighton and Sussex University Hospital, who passed away on April 21st, 2015. He will be sadly missed.