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

Abstract

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.Trial registrationClinicalTrials.gov NCT01437241

Etravirine combined with antiretrovirals other than darunavir/ritonavir for HIV-1-infected, treatment-experienced adults: Week 48 results of a phase IV trial

“…In previously reported studies of virologically suppressed patients experiencing AEs who then switched to an etravirine-based regimen not including darunavir/r, viral suppression was well maintained (range: 77%-100%). [30][31][32][33][34][35][36] In this study, while patient numbers were low in patients with baseline VL < 50 copies/mL (N = 56), 75% of patients maintained virologic suppression at week 48. Poor adherence had minimal impact on virologic response in this subpopulation compared with the subpopulation with baseline VL ⩾ 50 copies/mL.…”

Liver toxicity and risk of discontinuation in HIV/hepatitis C virus‐coinfected patients receiving an etravirine‐containing antiretroviral regimen: influence of liver fibrosis

“…More recently, in a similar study in a clinical setting, Lopez‐Cortés et al . [16] reported no cases of liver toxicity grade 3–4 in 103 patients with chronic HCV infection receiving ETR plus two NRTIs, and <1% of patients with grade 2 increases in transaminases.…”

Therapy-Emergent Drug Resistance to Integrase Strand Transfer Inhibitors in HIV-1 Patients: A Subgroup Meta-Analysis of Clinical Trials

“…Many human immunodeficiency virus (HIV) therapies aim to inhibit multiple targets in the viral replication cycle. The application of antiviral drugs is widespread and includes nuclear nucleoside reverse transcriptase inhibitors (NRTIs), non-nucleoside reverse transcriptase inhibitors (NNRTIs), protease inhibitors (PIs), and fusion inhibitors; however, all of these drug classes have met with high resistance rates [ 1 – 4 ]. The resistance to anti-HIV-1 drugs not only renders existing therapies ineffective but also could cause that new patients who did not experienced therapy resistanted to existing agents.…”