Week 48 results from a randomized clinical trial of rilpivirine/emtricitabine/tenofovir disoproxil fumarate vs. efavirenz/emtricitabine/tenofovir disoproxil fumarate in treatment-naive HIV-1-infected adults

AIDS. 2014 Apr 24;28(7):989-97. doi: 10.1097/QAD.0000000000000169.


Objectives: To compare the safety and efficacy of the two single-tablet regimens (STRs), rilpivirine/emtricitabine/tenofovir disoproxil fumarate (RPV/FTC/TDF) and efavirenz/emtricitabine/tenofovir DF (EFV/FTC/TDF), in HIV-1-infected, treatment-naive adults.

Design: This is a phase 3b, randomized, open-label, multicenter, international, 96-week study.

Methods: Participants were randomized 1:1 to receive either RPV/FTC/TDF or EFV/FTC/TDF. The primary endpoint was the proportion of participants with HIV-1 RNA less than 50 copies/ml at week 48 by the Snapshot algorithm.

Results: A total of 786 participants were randomized. RPV/FTC/TDF was noninferior to EFV/FTC/TDF (85.8 vs. 81.6%) at week 48 for HIV-1 RNA less than 50 copies/ml [difference 4.1%, 95% confidence interval (CI) -1.1 to 9.2%]. A statistically significant difference in efficacy favoring RPV/FTC/TDF was demonstrated for participants with baseline HIV-1 RNA 100000 copies/ml or less [(n=510) 88.8% RPV/FTC/TDF vs. 81.6% EFV/FTC/TDF (difference 7.2%, 95% CI 1.1-13.4%)]. In participants with baseline HIV-1 RNA more than 100000 copies/ml (n=276), RPV/FTC/TDF demonstrated noninferior efficacy compared with EFV/FTC/TDF (79.9 vs. 81.7%, respectively, difference -1.8%, 95% CI -11.1 to 7.5%). In the RPV/FTC/TDF arm, more virologic failure was observed as baseline HIV-1 RNA levels increased. There were more participants with emergent resistance in the RPV/FTC/TDF arm than in the EFV/FTC/TDF arm (4 vs. 1%, respectively). There were fewer discontinuations because of adverse events with RPV/FTC/TDF (2.5%) than with EFV/FTC/TDF (8.7%).

Conclusion: In treatment-naive participants, RPV/FTC/TDF demonstrated noninferior efficacy and improved tolerability compared with EFV/FTC/TDF, as well as a statistically significant difference in efficacy for participants with baseline HIV-1 RNA 100000 copies/ml or less at week 48.

Publication types

  • Clinical Trial
  • Clinical Trial, Phase III
  • Comparative Study
  • Multicenter Study
  • Randomized Controlled Trial
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adult
  • Anti-Retroviral Agents / adverse effects*
  • Anti-Retroviral Agents / therapeutic use*
  • Antiretroviral Therapy, Highly Active / methods*
  • Drug-Related Side Effects and Adverse Reactions
  • Female
  • HIV Infections / drug therapy*
  • HIV-1 / isolation & purification
  • Humans
  • International Cooperation
  • Male
  • Middle Aged
  • RNA, Viral / blood
  • Treatment Outcome
  • Viral Load


  • Anti-Retroviral Agents
  • RNA, Viral