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

Eduardo Arathoon; Asad Bhorat; Rodica Silaghi; Herta Crauwels; Ludo Lavreys; Lotke Tambuyzer; Ben Van Baelen; Simon Vanveggel; Magda Opsomer

doi:10.1177/2050312116686482

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

SAGE Open Med. 2017 Jan 18:5:2050312116686482. doi: 10.1177/2050312116686482. eCollection 2017.

Authors

Eduardo Arathoon¹, Asad Bhorat², Rodica Silaghi³, Herta Crauwels⁴, Ludo Lavreys⁴, Lotke Tambuyzer⁴, Ben Van Baelen⁴, Simon Vanveggel⁴, Magda Opsomer⁴

Affiliations

¹ La Clinica Familiar de Luis Angel Garcia, Guatemala City, Guatemala.
² Soweto Clinical Trials Centre, Johannesburg, South Africa.
³ Infectious Diseases Hospital, Braşov, Romania.
⁴ Janssen Pharmaceutica NV, Beerse, Belgium.

Abstract

Objective: VIOLIN (TMC125IFD3002; NCT01422330) evaluated the safety, tolerability, and pharmacokinetics of etravirine with antiretrovirals other than darunavir/ritonavir in HIV-1-infected patients.

Methods: In a 48-week, phase IV, single-arm, multicenter study, patients on prior antiretroviral therapy (⩾8 weeks) who needed to change regimen for virologic failure (viral load ⩾ 500 copies/mL) or simplification/adverse events (viral load < 50 copies/mL) received etravirine 200 mg bid with ⩾1 other active antiretroviral, excluding darunavir/ritonavir or only nucleoside/tide reverse transcriptase inhibitors.

Results: Of 211 treated patients, 73% (n = 155) had baseline viral load ⩾ 50 copies/mL and 27% (n = 56) had baseline viral load < 50 copies/mL. Protease inhibitors were the most common background antiretrovirals (83%). Diarrhea was the most frequent adverse event (17%). Serious adverse events (no rash) occurred in 5% of patients; none were etravirine related. Overall, median etravirine AUC_12h was 5390 ng h/mL and C_0h was 353 ng/mL (N = 199). Week 48 virologic response rates (viral load < 50 copies/mL; Food and Drug Administration Snapshot algorithm) were 48% (74/155) (baseline viral load ⩾ 50 copies/mL) and 75% (42/56) (baseline viral load < 50 copies/mL). Virologic failure rates were 42% and 13%, respectively. The most frequently emerging etravirine resistance-associated mutations in virologic failures were Y181C, E138A, and M230L. Virologic response rates for patients with baseline viral load ⩾ 50 copies/mL were 38% (30/79) (non-adherent) versus 64% (44/69) (adherent subset).

Conclusion: Etravirine 200 mg bid in combination with antiretrovirals other than darunavir/ritonavir was well tolerated in the studied treatment-experienced HIV-1-infected population. The overall etravirine safety and tolerability profile and pharmacokinetics (specifically in those patients who were adherent) were similar to those previously observed for etravirine in HIV-1-infected adults. The relatively high level of non-adherence, also observed in the pharmacokinetic assessments, negatively impacted virologic response, especially in patients with ⩾50 copies/mL at baseline.

Keywords: Etravirine; efficacy; pharmacokinetics; safety; virology.