Rilpivirine vs. efavirenz in HIV-1 patients with baseline viral load 100 000 copies/ml or less: week 48 phase III analysis

• Published in: AIDS (London) Vol. 27; no. 6; pp. 889 - 897
• Main Authors: MOLINA, Jean-Michel, CLUMECK, Nathan, PEDANT, Karla, RIMSKY, Laurence, VANVEGGEL, Simon, STEVENS, Marita
• Format: Journal Article
• Language: English
• Published: Hagerstown, MD Lippincott Williams & Wilkins 27.03.2013
• Subjects: Adult; Aged; AIDS/HIV; Anti-HIV Agents - administration & dosage; Anti-HIV Agents - adverse effects; Antibiotics. Antiinfectious agents. Antiparasitic agents; Antiviral agents; Benzoxazines - administration & dosage; Benzoxazines - adverse effects; Biological and medical sciences; Cholesterol; Double-Blind Method; Drug Resistance, Viral; Female; HIV Infections - drug therapy; HIV Infections - virology; HIV-1 - drug effects; HIV-1 - isolation & purification; Human immunodeficiency virus 1; Human viral diseases; Humans; Immunodeficiencies; Immunodeficiencies. Immunoglobulinopathies; Immunopathology; Infectious diseases; Male; Medical sciences; Middle Aged; Nitriles - administration & dosage; Nitriles - adverse effects; Pharmacology. Drug treatments; Pyrimidines - administration & dosage; Pyrimidines - adverse effects; Rilpivirine; Treatment Outcome; Viral diseases; Viral diseases of the lymphoid tissue and the blood. Aids; Viral Load; Young Adult; Phase III trial; treatment-naive; Antiretroviral agent; Benzoxazine derivatives; RNA-directed DNA polymerase; Acetylenic compound; Rilpivirine; Non nucleoside compound; nonnucleoside reverse transcriptase inhibitor; Efavirenz; Microbiological investigation; Reverse transcriptase inhibitor; Antiviral; TMC278; Viral load; Immunopathology; Enzyme; Transferases; Enzyme inhibitor; AIDS; Immune deficiency; Infection; Allosteric inhibitor; Nucleotidyltransferases; Viral disease; baseline viral load; Comparative study
• ISSN: 0269-9370; 1473-5571
• DOI: 10.1097/QAD.0b013e32835e1554

To compare efficacy, resistance development, and safety between rilpivirine and efavirenz in treatment-naive, HIV-1-infected adults with baseline viral load 100,000 copies/ml or less in the pooled 48-week dataset of the ECHO (Efficacy Comparison in treatment-naive HIV-infected subjects Of TMC278 and EFV) and THRIVE (TMC278 against HIV, in a once-daily RegImen Vs. Efavirenz) trials. Phase III, double-blind, double-dummy, randomized trials. Patients received rilpivirine 25 mg once daily (q.d.) or efavirenz 600 mg q.d. with two nucleoside/tide reverse transcriptase inhibitors [N(t)RTIs]. This analysis considers the subpopulation of 368 rilpivirine and 330 efavirenz patients with baseline viral load 100,000 copies/ml or less. Significantly higher 48-week response rates (viral load <50 copies/ml, intent-to-treat-time-to-loss-of-virological response) were observed with rilpivirine vs. efavirenz [90 vs. 84%, respectively; difference 6.6% (95% confidence interval 1.6-11.5%)]. The proportion of patients experiencing virological failure (VF(res)) was 5% in each treatment group. A comparable proportion of VF(res) patients in each group developed nonnucleoside reverse transcriptase inhibitor resistance-associated mutations (RAMs) [rilpivirine: 6/16 (38%) vs. efavirenz: 5/12 (42%)]. A numerically higher proportion of rilpivirine VF(res) patients developed N(t)RTI RAMs [7/16 (44%)] vs. efavirenz [2/12 (17%)]; P = 0.2232. A significantly lower incidence for rilpivirine vs. efavirenz was observed for the following events: treatment-related grade 2-4 overall adverse events (17 vs. 30%; P <0.0001), rash (any type; 2 vs. 12%; P <0.0001), and neurological adverse events (19 vs. 40%; P <0.0001), including dizziness (10 vs. 29%; P <0.0001). There was no significant difference between groups in the total cholesterol/high-density lipoprotein cholesterol ratio. In treatment-naive patients with baseline viral load 100,000 copies/ml or less, rilpivirine along with two N(t)RTIs achieved a high response, with a comparable frequency of VF(res) and more favorable tolerability than efavirenz.