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Once-Daily Etravirine Effective Through 24 Weeks in Three-Center Study
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IDWeek, October 2-6, 2013, San Francisco
Mark Mascolini
Etravirine taken once daily with tenofovir/emtricitabine (TDF/FTC) controlled HIV well, with only 1 toxicity dropout, through 24 weeks in a single-arm, 80-person study [1].
The nonnucleoside etravirine is licensed for dosing at 200 mg twice daily, but its 30- to 40-hour half-life and pharmacokinetic studies in antiretroviral-naive adults [2,3] suggest a 400-mg once-daily dose may be feasible. To test that hypothesis, researchers from the University of North Carolina and two other North Carolina infectious disease clinics recruited adults with a viral load of at least 1000 copies and with fewer than 11 days of total antiretroviral exposure. The study excluded people with who had taken etravirine, dapivirine, or rilpivirine and those with TDF- or FTC-related resistance mutations. At IDWeek the investigators reported a planned 24-week analysis of this ongoing 96-week trial.
Seventy-one of the 80 study participants (89%) were men, 63% were black, 29% white, and 6% Hispanic. Median age stood at 29 years (interquartile range [IQR] 23 to 45) and median viral load at 4.52 log (about 33,000 copies). One quarter of study participants had a pretreatment viral load above 100,000 copies. Median CD4 count was 382 (IQR 248 to 470).
At week 24 a missing-equals-failure analysis determined that 69 people (86%) had a viral load below 50 copies. Of the 11 other study participants, 5 (6%) had a load above 50 copies and 6 (7.5%) did not complete the 24 weeks and counted as failures. Among those 6 people, 1 missed the week-24 visit and 5 discontinued early, including 1 with grade 2 rash, 1 admitted to the hospital with vomiting, 1 who began chemotherapy, 1 lost to follow-up, and 1 who never started treatment.
Only 1 of 5 people with virologic failure had detectable resistance mutations at failure: V75I, E138K, M184V, Y181C, K219E, M230L. The researchers did not report how many people with virologic failure had a pretreatment viral load above or below 100,000 copies.
Among 73 people with 24-week CD4 data available, CD4 counts rose by a median 156 (IQR 67 to 245).
Among all 80 study participants, 7 (9%) had a grade 3 adverse event and 2 (2.5%) a grade 4 event. There were 3 grade 2 rashes and no grade 3 or 4 rashes. Grade 3 or 4 events included neuropsychiatric problems in 1 and aminotransferase elevations in 1, a patient coinfected with HBV. Five people had grade 2 aminotransferase elevations.
As the trial continues, the investigators proposed that "once-daily dosing may improve acceptability of etravirine for antiretroviral-naive HIV-infected patients" and that "results support further investigation of once-daily etravirine dosing."
References
1. Floris-Moore M, Mollan K, Wilkin A, et al. Antiretroviral activity and safety of once-daily etravirine in treatment-naive HIV-infected adults. IDWeek 2013. October 2-6, 2013. San Francisco. Abstract 170.
2. Di Perri G, Green B, Morrish G, et al. Pharmacokinetics and pharmacodynamics of etravirine 400 mg once daily in treatment-naive patients. HIV Clin Trials. 201;14:92-98.
3. Gutierrez-Valencia A, Martin-Pena R, et al. Intracellular and plasma pharmacokinetics of 400 mg of etravirine once daily versus 200 mg of etravirine twice daily in HIV-infected patients. J Antimicrob Chemother. 2012;67:681-684.
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