Lipid-Lowering Effect and Efficacy After Switching to Etravirine in HIV-Infected Patients With Intolerance to Suppressive HAART

Casado, José L.; Santos, Ignacio; Palacio, M.; García‐Fraile, Lucio; Pérez-Elías, María Jesús; Sanz, Jesús; Moreno, Santiago

doi:10.1310/hct1401-1

Cited by 14 publications

(7 citation statements)

References 24 publications

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“…The incidence of mild-to-moderate rash (2.0%) was lower than previously reported [6] , and the transient grade 1 transaminase increases among the patients with chronic viral hepatitis and/or cirrhosis could be due to the natural evolution of chronic hepatitis rather than to pharmacological toxicity. Likewise, the incidence of abnormalities in lipid parameters among those patients with normal baseline values was negligible, and there was a substantial improvement in lipid profiles after switching to an ETV-based regimen in those patients with abnormal baseline values, as has been previously observed [6] , [19] .…”

Section: Discussionsupporting

confidence: 68%

“…In the first scenario, the Sense trial has evaluated, as a secondary objective, the efficacy of 400 mg ETV once daily vs. EFV plus two NRTIs in treatment-naïve patients up to 48 weeks; the primary objective was to assess neuropsychiatric tolerability at 12 weeks [17] . Two additional studies of switching in subjects with viral suppression but ongoing neuropsychiatric adverse events on EFV or toxicity under the previous regimen have also evaluated the efficacy of this combination for up to 24 weeks [18] , [19] . In the second setting, only the long-term virologic responses in four patients with isolated K103N mutations have been reported [20] .…”

Section: Introductionmentioning

confidence: 99%

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

et al. 2014

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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

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Section: Discussionsupporting

confidence: 68%

Section: Introductionmentioning

confidence: 99%

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

et al. 2014

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“…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.…”

Section: Discussionmentioning

confidence: 99%

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

Arathoon¹,

Bhorat

Silaghi

et al. 2017

SAGE Open Medicine

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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 AUC12h was 5390 ng h/mL and C0h 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.

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“…Interpretation of results of metabolic assessments are similarly limited by our small sample size of the substudy, yet our observations regarding lipids and glucose levels are, in general, consistent with findings in other larger studies. (4, 20, 23)…”

Section: Discussionmentioning

confidence: 99%

Antiretroviral Activity and Safety of Once-Daily Etravirine in Treatment-Naive HIV-Infected Adults: 48-Week Results

et al. 2016

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Background Etravirine (ETR), an NNRTI approved for 200 mg BID dosing in conjunction with other antiretrovirals (ARVs), has pharmacokinetic properties which support once-daily dosing. Methods In this single arm, open-label study, 79 treatment-naïve HIV-infected adults were assigned to receive ETR 400 mg plus tenofovir disoproxil fumarate/emtricitabine (TDF/FTC) 300/200mg once daily to assess antiviral activity, safety, and tolerability. Antiretroviral activity at 48 weeks was determined by proportion of subjects with HIV-1 RNA <50 copies/mL (intention-to-treat, missing = failure). Results Of 79 eligible subjects, 90% were men, 62% African-American and 29% Caucasian. At baseline, median (Q1, Q3) age was 29 years (23, 44) and HIV-1 RNA 4.52 log10 copies/mL (4.07, 5.04). Sixty-nine (87%) completed a week 48 visit and 61 (77%, 95% CI: 66 – 86%) achieved HIV-1 RNA <50 copies/mL at week 48. At time of virologic failure, genotypic resistance-associated mutations were detected in 3 participants, 2 with E138K (1 alone and 1 with additional mutations). Median (95% CI) CD4+ cell count increase was 163 (136, 203) cells/uL. Fifteen (19.0%) participants reported a new sign/symptom or lab abnormality ≥ Grade 3 and 3 participants (3.8 %) permanently discontinued ETR due to toxicity. Two participants had psychiatric symptoms of any grade. There were no deaths. Conclusions In this study of ARV-naïve HIV+ adults, once daily ETR with TDF/FTC had acceptable antiviral activity and was well-tolerated. Once daily ETR may be a plausible option as part of a combination ARV regimen for treatment-naïve individuals.

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Lipid-Lowering Effect and Efficacy After Switching to Etravirine in HIV-Infected Patients With Intolerance to Suppressive HAART

Cited by 14 publications

References 24 publications

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

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

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

Antiretroviral Activity and Safety of Once-Daily Etravirine in Treatment-Naive HIV-Infected Adults: 48-Week Results

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