Journal Article

Rilpivirine versus efavirenz with tenofovir and emtricitabine in treatment-naive adults infected with HIV-1 (ECHO): a phase 3 randomised double-blind active-controlled trial

Walmsley, Sharon, Vanveggel, Simon, Supparatpinyo, Khuanchai, Rimsky, Laurence T, Cahn, Pedro, Lazzarin, Adriano, Molina, Jean-Michel, Saag, Michael, Grinsztejn, Beatriz, Mills, Anthony, Boven, Katia, Crauwels, Herta

2011

Overview

Efavirenz with tenofovir-disoproxil-fumarate and emtricitabine is a preferred antiretroviral regimen for treatment-naive patients infected with HIV-1. Rilpivirine, a new non-nucleoside reverse transcriptase inhibitor, has shown similar antiviral efficacy to efavirenz in a phase 2b trial with two nucleoside/nucleotide reverse transcriptase inhibitors. We aimed to assess the efficacy, safety, and tolerability of rilpivirine versus efavirenz, each combined with tenofovir-disoproxil-fumarate and emtricitabine. We did a phase 3, randomised, double-blind, double-dummy, active-controlled trial, in patients infected with HIV-1 who were treatment-naive. The patients were aged 18 years or older with a plasma viral load at screening of 5000 copies per mL or greater, and viral sensitivity to all study drugs. Our trial was done at 112 sites across 21 countries. Patients were randomly assigned by a computer-generated interactive web response system to receive either once-daily 25 mg rilpivirine or once-daily 600 mg efavirenz, each with tenofovir-disoproxil-fumarate and emtricitabine. Our primary objective was to show non-inferiority (12% margin) of rilpivirine to efavirenz in terms of the percentage of patients with confirmed response (viral load <50 copies per mL intention-to-treat time-to-loss-of-virological-response [ITT-TLOVR] algorithm) at week 48. Our primary analysis was by intention-to-treat. We also used logistic regression to adjust for baseline viral load. This trial is registered with ClinicalTrials.gov, number NCT00540449. 346 patients were randomly assigned to receive rilpivirine and 344 to receive efavirenz and received at least one dose of study drug, with 287 (83%) and 285 (83%) in the respective groups having a confirmed response at week 48. The point estimate from a logistic regression model for the percentage difference in response was −0·4 (95% CI −5·9 to 5·2), confirming non-inferiority with a 12% margin (primary endpoint). The incidence of virological failures was 13% (rilpivirine) versus 6% (efavirenz; 11% vs 4% by ITT-TLOVR). Grade 2–4 adverse events (55 [16%] on rilpivirine vs 108 [31%] on efavirenz, p<0·0001), discontinuations due to adverse events (eight [2%] on rilpivirine vs 27 [8%] on efavirenz), rash, dizziness, and abnormal dreams or nightmares were more common with efavirenz. Increases in plasma lipids were significantly lower with rilpivirine. Rilpivirine showed non-inferior efficacy compared with efavirenz, with a higher virological-failure rate, but a more favourable safety and tolerability profile. Tibotec.

• Publisher: Elsevier Ltd,Elsevier,Elsevier Limited
• Subject: Acquired Immunodeficiency Syndrome - drug therapy / Acquired Immunodeficiency Syndrome - ethnology / Acquired Immunodeficiency Syndrome - virology / Adenine - administration & dosage / Adenine - adverse effects / Adenine - analogs & derivatives / Adenine - therapeutic use / Adult / adults / Aged / Algorithms / Anti-HIV Agents - administration & dosage / Anti-HIV Agents - adverse effects / Anti-HIV Agents - therapeutic use / Antibiotics. Antiinfectious agents. Antiparasitic agents / Antiretroviral agents / Antiretroviral drugs / Antiviral agents / Benzoxazines - administration & dosage / Benzoxazines - adverse effects / Benzoxazines - therapeutic use / Biological and medical sciences / blood lipids / Clinical trials / Deoxycytidine - administration & dosage / Deoxycytidine - adverse effects / Deoxycytidine - analogs & derivatives / Deoxycytidine - therapeutic use / Double-Blind Method / Dreams / Drug Administration Schedule / Drug therapy / drugs / Efavirenz / Emtricitabine / Exanthema / Female / General aspects / HIV / HIV infections / HIV Reverse Transcriptase - antagonists & inhibitors / HIV-1 - drug effects / HIV-1 - genetics / Human immunodeficiency virus / Human immunodeficiency virus 1 / Human viral diseases / Humans / Infectious diseases / Internal Medicine / Lipids / Male / Medical sciences / Middle Aged / Mutation / Nitriles - administration & dosage / Nitriles - adverse effects / Nitriles - therapeutic use / non-nucleoside reverse transcriptase inhibitors / nucleosides / Nucleotides / Organophosphonates - administration & dosage / Organophosphonates - adverse effects / Organophosphonates - therapeutic use / patients / Pharmacology. Drug treatments / Pyrimidines - administration & dosage / Pyrimidines - adverse effects / Pyrimidines - therapeutic use / Regression analysis / Reverse Transcriptase Inhibitors - therapeutic use / Rilpivirine / RNA-directed DNA polymerase / screening / Tenofovir / Treatment Outcome / Viral diseases / Viral diseases of the lymphoid tissue and the blood. Aids / viral load / Viral Load - drug effects