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Rilpivirine 48-Week Results in Naive Adolescents Similar to Adult Findings
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IAS 2015, July 19-22, 2015, Vancouver
Mark Mascolini
At the standard dose of 25 mg once daily, the nonnucleoside rilpivirine plus two nucleos(t)ides yielded pharmacokinetic results and virologic suppression rates similar to those seen in adults, according to a 48-week analysis of the PAINT Trial [1]. The findings confirm 24-week pharmacokinetic results in adolescents [2].
Rilpivirine is licensed at the 25-mg once-daily dose in combination with other antiretrovirals for treatment-naive adults. Some countries limit use to adults with a pretreatment viral load below 100,000 copies. Complera, a single-tablet once-daily formulation of rilpivirine with tenofovir/emtricitabine (TDF/FTC), is available.
PAINT is a phase 2 trial of 25-mg rilpivirine with two nucleos(t)ides for antiretroviral-naive adolescents 12 to 18 years old. After 24 weeks of treatment, 75% of participants had a viral load below 50 copies, as did 86% with a pretreatment load below 100,000 copies.
Study participants had to weigh at least 32 kg and have HIV sensitive to nucleos(t)ides and nonnucleosides. They took rilpivirine with an investigator-selected background regimen of TDF/FTC (67%), TDF/lamivudine (22%), or zidovudine/lamivudine (11%). Of the 36 adolescents enrolled, 20 were from South Africa, 11 from Uganda, 3 from India, and 1 each from Thailand and the United States. Median age stood at 14.5 years (range 12 to 17) and median weight at 45 kg (range 33 to 93). Thirty-two youngsters were black and 4 Asian. Median pretreatment viral load measured 4.76 log10 (about 57,500 copies) and median CD4 count 414. Twenty-eight participants (78%) began treatment with a viral load below 100,000 copies. These 36 adolescents had been infected for a median of 1.3 years (range 0 to 11), 30 of them via vertical infection.
At 48 weeks a time-to-loss-of-virologic-response analysis determined that 72% of adolescents had a viral load below 50 copies, including 79% with a pretreatment load below 100,000 copies and 50% (4 of 8) with a pretreatment load above 100,000 copies. The investigators recorded virologic failure in 5 adolescents (18%) with a pretreatment load below 100,000 copies and in 3 (38%) with a higher pretreatment load. Of the 8 participants with virologic failure, rilpivirine resistance mutations emerged in 5. Four of these 5 also had nucleos(t)ide mutations, usually M184V. The investigators noted that this resistance pattern is consistent with that seen in adults. Median CD4 count rose by 184 cells through 48 weeks.
One youngster with a pretreatment load above 100,000 copies discontinued treatment because of an adverse event (pulmonary TB), and one with a sub-100,000 pretreatment load quit for other reasons. Through an averaged 71.6 weeks of treatment, 7 grade 3 or 4 adverse events developed (19%), including 6 serious adverse events (17%). Thirteen youngsters (36%) had any adverse event at least possibly related to rilpivirine. Grade 3 lab abnormalities included 2 cases of decreased neutrophils, 2 cases of increased amylase, and 1 case of hypophosphatemia. The two grade 4 abnormalities were increased creatinine and decreased neutrophils.
Adherence measured by pill count averaged 97.5% through 48 weeks. Eight participants (22%) had adherence at or below 95%. Among the 8 adolescents with virologic failure, 2 had adherence below 95%. Week 24 and 48 area under the concentration-time curve and trough concentrations were similar to adult values in the ECHO and THRIVE trials.
The PAINT team proposed that these findings support use of rilpivirine at the 25-mg once-daily dose for antiretroviral-naive 12- to 18-year-olds with a pretreatment viral load below 100,000 copies.
References
1. Lombaard J, Bunupuradah T, Flynn P, et al. Week 48 safety and efficacy of a rilpivirine (TMC278)-based regimen in HIV-infected treatment-naïve adolescents: PAINT phase II trial. IAS 2015. 8th Conference on HIV Pathogenesis, Treatment and Prevention. July 19-22, 2015. Vancouver. Abstract MOAB0106.
2. Crauwels H, Hoogstoel A, Vanveggel S, Yarnall W, Stevens M, Boven K. Rilpivirine pharmacokinetics in HIV-1-infected adolescents: a substudy of PAINT (phase II trial). CROI 2014. March 3-6, 2014. Boston. Abstract 900. http://www.croiconference.org/sessions/rilpivirine-pharmacokinetics-hiv-1-infected-adolescents-substudy-paint-phase-ii-trial
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