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 registration: ClinicalTrials.gov NCT01437241.

Conflict of interest statement

Competing Interests: The authors have read the journal’s policy and have the following conflicts: The authors have not conflicts of interest related to this manuscript. However, Luis F. López-Cortés, Pompeyo Viciana, José A. Girón-González, Manuel Márquez-Solero, Javier de la Torre-Lima, Marcial Delgado-Fernández, and Fernando Lozano have received honoraria for speaking at symposia organized on behalf of Abbott laboratories (Spain), Bristol-Myers Squibb, Glaxo Smithkline, Gilead Sciences, Janssen-Cilag España, Merck Sharp & Dohme España, Roche Pharma SA, and ViiV Healthcare. Also, they have received unrestricted funds for research from Abbott Laboratories (Spain), Bristol-Myers Squibb, Bristol-Myers Squibb, Gilead Sciences, Glaxo Smithkline, Roche Pharma S.A., and ViiV Healthcare.

Figures

Figure 1. Patient disposition.

ETV: etravirine. NRTIs, nucleos(t)ide reverse-transcriptase inhibitors. Group A: subjects without virologic failure on or no experience with non-nucleoside reverse-transcriptase inhibitors switched due to adverse effects. Group B: subjects switched after a virological failure on an efavirenz- or nevirapine-based regimen.

Figure 2. Proportion of patients with increased aminotransferases levels at any time-point throughout the follow-up.

Figure 3. Change in lipid plasma levels (mg/dL) throughout the follow-up.

A: patients with normal baseline values. B: patients with abnormal baseline values on previous NNRTIs- or PI/rtv-based regimens. CT: total cholesterol. HDL-C: high-density lipoprotein cholesterol. LDL-C: low-density lipoprotein cholesterol. TG: triglycerides.