Objective: To evaluate the efficacy and safety of antiretroviral simplification from a ritonavir-boosted protease inhibitor-based regimen [protease inhibitor+RTV+two nucleos(t)ide reverse transcriptase inhibitors (NRTIs); ≥6 months of exposure prior to study entry with no prior treatment failure] to the single-tablet regimen (STR) rilpivirine/emtricitabine/tenofovir disoproxil fumarate (RPV/FTC/TDF) in virologically suppressed, HIV-1-infected participants.
Design: Phase 3b, randomized, open-label, international, 48-week switch study.
Methods: Participants were randomized 2 : 1 to switch to RPV/FTC/TDF immediately or stay on their baseline protease inhibitor+RTV+2NRTIs regimen with a delayed switch to RPV/FTC/TDF at week 24. The primary endpoint was noninferiority (12% margin) of RPV/FTC/TDF compared with protease inhibitor+RTV+ two NRTIs in maintaining plasma HIV-1 RNA less than 50 copies/ml at week 24 by Snapshot analysis.
Results: A total of 476 participants were randomized and received at least one dose of study drug. Demographics and baseline characteristics were similar between arms. The primary objective of noninferiority at week 24 was met: HIV-1 RNA less than 50 copies/ml by Snapshot analysis, 93.7% of RPV/FTC/TDF versus 89.9% of protease inhibitor+RTV+ two NRTIs (difference 3.8%, 95% confidence interval −1.6 to 9.1%). Through week 48, 89.3% of participants in the immediate switch group maintained virologic suppression. High rates of suppression were maintained with RPV/FTC/TDF regardless of participant's pre-antiretroviral HIV-1 RNA level. Overall development of resistance mutations after switching to RPV/FTC/TDF was low. Decreases in total cholesterol, low-density lipoprotein (LDL), and triglycerides were significantly greater among RPV/FTC/TDF recipients than those in the protease inhibitor+RTV+ two NRTIs group.
Conclusion: Switching to the STR RPV/FTC/TDF from an RTV-boosted protease inhibitor regimen in virologically suppressed, HIV-1-infected participants maintained virologic suppression with a low risk of virologic failure, while improving total cholesterol, LDL, and triglycerides.
aNorthwestern University, Feinberg School of Medicine, Chicago, Illinois, USA
bBrighton and Sussex University Hospitals, Brighton, UK
cUniversity of Pennsylvania, Division of Infectious Diseases, Clinical Trials Unit, Philadelphia, Pennsylvania, USA
dChelsea and Westminster Hospital Foundation Trust, London, UK
ePeter Ruane, MD, Inc., Los Angeles, California, USA
fUniversity Medical Center Hamburg-Eppendorf, Hamburg, Germany
gLa Playa Medical Group and Clinical Research, San Diego
hKaiser Permanente, Sacramento
iGilead Sciences Inc., Foster City, California, USA.
Correspondence to Todd Fralich, MD, 333 Lakeside Drive, Foster City, CA 94404, USA. E-mail: email@example.com
Received 28 March, 2013
Revised 28 August, 2013
Accepted 17 September, 2013
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