Clinical and Virological Efficacy of Etravirine Plus Two Active Nucleos(t)ide Analogs in an Heterogeneous HIV-Infected Population

• Published in: PloS one Vol. 9; no. 5; p. e97262
• Main Authors: López-Cortés, Luis F., Viciana, Pompeyo, Girón-González, José A., Romero-Palacios, Alberto, Márquez-Solero, Manuel, Martinez-Perez, Maria A., López-Ruz, Miguel A., de la Torre-Lima, Javier, Téllez-Pérez, Francisco, Delgado-Fernández, Marcial, Garcia-Lázaro, Milagros, Lozano, Fernando, Mohamed-Balghata, Mohamed O.
• Format: Journal Article
• Language: English
• Published: United States Public Library of Science 16.05.2014; Public Library of Science (PLoS)
• Subjects: Acquired immune deficiency syndrome; AIDS; Analogs; Antiretroviral drugs; Biology and Life Sciences; Drug resistance; Drug Therapy, Combination; Efavirenz; Effectiveness; Endpoint Determination; Failure analysis; Gene Expression Regulation, Viral - drug effects; HIV; HIV Infections - drug therapy; Human immunodeficiency virus; Humans; Kaplan-Meier Estimate; Medicine and health sciences; Motivation; Mutation; Nevirapine; Patients; Protease inhibitors; Proteinase inhibitors; Pyridazines - adverse effects; Pyridazines - pharmacology; Pyridazines - therapeutic use; Reverse Transcriptase Inhibitors - adverse effects; Reverse Transcriptase Inhibitors - pharmacology; Reverse Transcriptase Inhibitors - therapeutic use; Ribonucleic acid; RNA; RNA, Viral - metabolism; Salvage; Salvage Therapy - methods; Spain; Treatment Outcome; Spain
• ISSN: 1932-6203; 1932-6203
• DOI: 10.1371/journal.pone.0097262

Etravirine (ETV) is recommended in combination with a boosted protease inhibitor plus an optimized background regimen for salvage therapy, but there is limited experience with its use in combination with two nucleos(t)ide reverse-transcriptase inhibitors (NRTIs). This multicenter study aimed to assess the efficacy of this combination in two scenarios: group A) subjects without virologic failure on or no experience with non-nucleoside reverse-transcriptase inhibitors (NNRTIs) switched due to adverse events and group B) subjects switched after a virologic failure on an efavirenz- or nevirapine-based regimen. The primary endpoint was efficacy at 52 weeks analysed by intention-to-treat. Virologic failure was defined as the inability to suppress plasma HIV-RNA to <50 copies/mL after 24 weeks on treatment, or a confirmed viral load >200 copies/mL in patients who had previously achieved a viral suppression or had an undetectable viral load at inclusion. Two hundred eighty seven patients were included. Treatment efficacy rates in group A and B were 88.0% (CI95, 83.9-92.1%) and 77.4% (CI95, 65.0-89.7%), respectively; the rates reached 97.2% (CI95, 95.1-99.3%) and 90.5% (CI95, 81.7-99.3), by on-treatment analysis. The once-a-day ETV treatment was as effective as the twice daily dosing regimen. Grade 1-2 adverse events were observed motivating a treatment switch in 4.2% of the subjects. In conclusion, ETV (once- or twice daily) plus two analogs is a suitable, well-tolerated combination both as a switching strategy and after failure with first generation NNRTIs, ensuring full drug activity. ClinicalTrials.gov NCT01437241.