Rilpivirine versus efavirenz in HIV-1-infected subjects receiving emtricitabine/tenofovir DF: pooled 96-week data from ECHO and THRIVE Studies

HIV Clin Trials. May-Jun 2013;14(3):81-91. doi: 10.1310/hct1403-81.

Abstract

Objectives: Week 96 efficacy and safety of the non-nucleoside reverse transcriptase inhibitor (NNRTI) rilpivirine (RPV) was compared to efavirenz (EFV) in subset of 1,096 subjects who received emtricitabine/tenofovir disoproxil fumarate (FTC/TDF) in pooled data from 2 phase 3 studies.

Methods: ECHO and THRIVE are double-blind, double-dummy, randomized, active-controlled, non-inferiority phase 3 studies of RPV versus EFV plus 2 NRTIs in antiretroviral-naïve adult subjects. The primary and secondary endpoints were the proportion of subjects with HIV-1 RNA <50 copies/ mL using an intent-to-treat, time to loss of virologic response (ITT-TLOVR) analysis at weeks 48 and 96, respectively. Safety, tolerability, immunologic response, adherence level, and other measures were also evaluated.

Results: At week 48, noninferior efficacy of RPV+FTC/TDF over EFV+FTC/TDF was established, and at week 96 RPV+FTC/TDF remained noninferior (77% overall response rate in both groups). Through week 96, rates of virologic failure were higher in the RPV+FTC/ TDF group, with low and similar rates of virologic failure and resistance mutations occurring during the second year of follow-up. Treatment with RPV+FTC/TDF was associated with a lower rate of discontinuation due to adverse events and grade 2-4 adverse events including dizziness, abnormal dreams/nightmares, rash, and lipid abnormalities.

Conclusions: The pooled ECHO and THRIVE studies demonstrated noninferiority of RPV+FTC/TDF in achieving virologic response with safety and tolerability advantages over EFV+FTC/TDF through 96 weeks. Higher rates of virologic failure in the RPV+FTC/TDF group were balanced with higher rates of discontinuations due to adverse events in the EFV+FTC/TDF group.

Publication types

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

MeSH terms

  • Adenine / administration & dosage
  • Adenine / analogs & derivatives
  • Adolescent
  • Adult
  • Aged
  • Alkynes
  • Anti-HIV Agents / administration & dosage
  • Anti-HIV Agents / therapeutic use*
  • Benzoxazines / administration & dosage
  • Cyclopropanes
  • Deoxycytidine / administration & dosage
  • Deoxycytidine / analogs & derivatives
  • Double-Blind Method
  • Drug Administration Schedule
  • Drug Therapy, Combination
  • Emtricitabine
  • Female
  • HIV Infections / drug therapy*
  • HIV Infections / virology
  • HIV Reverse Transcriptase / antagonists & inhibitors
  • HIV-1*
  • Humans
  • Male
  • Middle Aged
  • Nitriles / administration & dosage
  • Organophosphonates / administration & dosage
  • Pyrimidines / administration & dosage
  • Reverse Transcriptase Inhibitors / administration & dosage
  • Rilpivirine
  • Tenofovir
  • Young Adult

Substances

  • Alkynes
  • Anti-HIV Agents
  • Benzoxazines
  • Cyclopropanes
  • Nitriles
  • Organophosphonates
  • Pyrimidines
  • Reverse Transcriptase Inhibitors
  • Deoxycytidine
  • Tenofovir
  • HIV Reverse Transcriptase
  • Rilpivirine
  • Emtricitabine
  • Adenine
  • efavirenz