Simplification of antiretroviral therapy to a single-tablet regimen consisting of efavirenz, emtricitabine, and tenofovir disoproxil fumarate versus unmodified antiretroviral therapy in virologically suppressed HIV-1-infected patients

J Acquir Immune Defic Syndr. 2009 Jun 1;51(2):163-74. doi: 10.1097/QAI.0b013e3181a572cf.

Abstract

Objective: To evaluate a simplification strategy for HIV-1-infected patients virologically suppressed on antiretroviral therapy (ART) by switching to a single-tablet regimen consisting of efavirenz/emtricitabine/tenofovir disoproxil fumarate (EFV/FTC/TDF).

Design: : Prospective, randomized, controlled, open-label, multicenter study.

Methods: Patients on stable ART with HIV-1 RNA <200 copies per milliliter for > or = 3 months were stratified by prior nonnucleoside reverse transcriptase inhibitor-based or protease inhibitor-based therapy and randomized (2:1) to simplify treatment to EFV/FTC/TDF or to stay on their baseline regimen (SBR). Efficacy and safety assessments were performed at baseline and at weeks 4, 12, 24, 36, and 48. Additional patient-reported outcomes included the following: adherence by visual analog scale, quality of life by SF-36 (v2) survey, HIV Symptom Index, and the Preference of Medication and Perceived Ease of the Regimen for Condition questionnaires.

Results: Three hundred patients (EFV/FTC/TDF 203, SBR 97) were evaluated (prior protease inhibitor-based ART, 53%; nonnucleoside reverse transcriptase inhibitor-based ART, 47%). The arms were well balanced at baseline with 88% males, 29% blacks, and a mean age of 43 years; CD4 was 540 cells per cubic millimeter, 96% had HIV-1 RNA <50 copies per milliliter, and 88% were on their first ART regimen. Through 48 weeks, 89% vs. 88% in the EFV/FTC/TDF vs. SBR arms, respectively, maintained HIV-1 RNA <200 copies per milliliter by time to loss of virologic response algorithm (intent to treat, noncompleters = failures) with the difference (95% confidence interval) between arms of 1.1% (-6.7% to 8.8%), indicating noninferiority of EFV/FTC/TDF vs. SBR. Similarly, maintenance of HIV-1 RNA <50 copies per milliliter by time to loss of virologic response algorithm was 87% vs. 85% for EFV/FTC/TDF vs. SBR, respectively [difference (95% confidence interval) 2.6% (-5.9% to 11.1%)]. Discontinuation rates were similar (EFV/FTC/TDF 11%, SBR 12%); more discontinuations for adverse events occurred in the EFV/FTC/TDF arm vs. SBR (5% vs. 1%), most commonly for nervous system symptoms. More patients withdrew consent in the SBR arm vs. EFV/FTC/TDF (7% vs. 2%). Estimated glomerular filtration rate (by Modification of Diet in Renal Disease) remained unchanged over 48 weeks in both arms (median change < 1 mL.min.1.73 m). A decrease in fasting triglycerides was observed at 48 weeks in the EFV/FTC/TDF vs. SBR arm (-20 vs. -3.0 mg/dL; P = 0.035). Adherence of > or = 96% was reported by visual analog scale in both arms at baseline and at all study visits.

Conclusion: Simplification to EFV/FTC/TDF maintained high and comparable rates of virologic suppression vs. SBR through 48 weeks.

Trial registration: ClinicalTrials.gov NCT00365612.

Publication types

  • Multicenter Study
  • Randomized Controlled Trial

MeSH terms

  • Adenine / administration & dosage
  • Adenine / adverse effects
  • Adenine / analogs & derivatives*
  • Adenine / therapeutic use
  • Adult
  • Alkynes
  • Anti-HIV Agents / administration & dosage
  • Anti-HIV Agents / adverse effects
  • Anti-HIV Agents / therapeutic use*
  • Benzoxazines / administration & dosage
  • Benzoxazines / adverse effects
  • Benzoxazines / therapeutic use*
  • Cyclopropanes
  • Deoxycytidine / administration & dosage
  • Deoxycytidine / adverse effects
  • Deoxycytidine / analogs & derivatives*
  • Deoxycytidine / therapeutic use
  • Drug Combinations
  • Emtricitabine
  • Female
  • HIV Infections / drug therapy*
  • HIV-1*
  • Humans
  • Male
  • Middle Aged
  • Organophosphonates / administration & dosage
  • Organophosphonates / adverse effects
  • Organophosphonates / therapeutic use*
  • Patient Compliance
  • Tenofovir

Substances

  • Alkynes
  • Anti-HIV Agents
  • Benzoxazines
  • Cyclopropanes
  • Drug Combinations
  • Organophosphonates
  • Deoxycytidine
  • Tenofovir
  • Emtricitabine
  • Adenine
  • efavirenz

Associated data

  • ClinicalTrials.gov/NCT00365612