Rilpivirine as a Treatment for HIV-infected Antiretroviral-naïve Adolescents: Week 48 Safety, Efficacy, Virology and Pharmacokinetics : The Pediatric Infectious Disease Journal

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Rilpivirine as a Treatment for HIV-infected Antiretroviral-naïve Adolescents

Week 48 Safety, Efficacy, Virology and Pharmacokinetics

Lombaard, Johan MB, ChB; Bunupuradah, Torsak MD; Flynn, Patricia M. MD; Ramapuram, John MD; Ssali, Francis MMED; Crauwels, Herta PhD; Hoogstoel, Annemie MSc; Van Eygen, Veerle MSc; Stevens, Marita MD

Author Information

From the *Josha Research, Bloemfontein, South Africa; †HIV-NAT, Thai Red Cross AIDS Research Centre, Bangkok, Thailand; ‡St Jude Children’s Research Hospital, Memphis, Tennessee; §Kasturba Medical College Hospital, Mangalore, India; Joint Clinical Research Centre, Kampala, Uganda; and ‖Janssen Pharmaceutica NV, Beerse, Belgium.

Accepted for publication February 15, 2016.

Data were previously presented by Johan Lombaard, Torsak Bunupuradah, Patricia M. Flynn, John Ramapuram, Francis Ssali, Herta Crauwels, Annemie Hoogstoel, Veerle Van Eygen, Marita Stevens and Katia Boven. Week 48 safety and efficacy of a rilpivirine (TMC278)-based regimen in HIV-infected treatment-naïve adolescents: PAINT phase II trial. 8th IAS 2015. Abstract MOAB0106 and 7th HIV Pediatrics Workshop 2015. Abstract O10. Veerle Van Eygen, Annemie Hoogstoel, Marita Stevens, Sandra De Meyer and Johan Vingerhoets. 48-week resistance analysis of treatment-naïve, HIV-1-infected adolescents on a rilpivirine-containing regimen in the PAINT phase II study. XXIVth International HIV Drug Resistance Workshop, Seattle, WA, USA, February 21–22, 2015. Abstract/Poster Number: 34.

P.M.F. has received grants from Janssen, consultancy fees from Merck and royalties from UpToDate; H.C., V.V.E. and M.S. are full-time employees of Janssen. A.H. is an insourced consultant for Janssen. This study was sponsored by Janssen Research and Development, Ireland. Medical writing support was provided by Ian Woolveridge of Zoetic Science, an Ashfield company, Macclesfield, UK; this support was funded by Janssen Pharmaceuticals. The authors have no other funding or conflicts of interest to disclose. All authors were involved in the development of the primary manuscript, interpretation of data, have read and approved the final version and have met the criteria for authorship as established by the International Committee of Medical Journal Editors (ICMJE).

Address for correspondence: Johan Lombaard, MB, ChB, Josha Research, Box 3530, Bloemfontein 9300, South Africa. E-mail: [email protected].

The Pediatric Infectious Disease Journal 35(11):p 1215-1221, November 2016. | DOI: 10.1097/INF.0000000000001275

Abstract

Background: 

Rilpivirine 25 mg qd yields similar exposure in adolescents and adults (Pediatric study in Adolescents Investigating a New NNRTI TMC278 [PAINT] Cohort 1, Part 1). We report rilpivirine safety, efficacy, virology and pharmacokinetics in adolescents during 48 weeks of treatment (Cohort 1, Part 2).

Methods: 

PAINT (NCT00799864) is a phase II, ongoing, open-label, single-arm trial of rilpivirine plus 2 investigator-selected nucleoside/nucleotide reverse-transcriptase inhibitors. Cohort 1 of PAINT includes treatment-naïve HIV-1-infected adolescents (≥12 to <18 years). Following approval in adults and after Part 1a in Cohort 1, enrollment was restricted to screening viral load (VL) ≤100,000 copies/mL.

Results: 

Overall, 20 (56%) of 36 patients were women, 18 (50%) were aged ≥12 to <15 years, 32 (89%) were Black or African American, mostly from South Africa or Uganda, and 28 (78%) had baseline VL ≤100,000 copies/mL. At week 48, adverse events considered possibly related to treatment occurred in 13 (36%) patients, mostly (excluding investigations) somnolence (n = 5, 14%) and nausea (n = 2, 6%). Most adverse events were grade 1 or 2, and 7 (19%) patients had grade 3 or 4 adverse events. Week 48 virologic response (VL <50 copies/mL, time-to-loss-of-virologic-response) was achieved in 26 of the 36 (72%) patients: 22 of the 28 (79%) with baseline VL ≤100,000 copies/mL and 4 of the 8 (50%) with baseline VL >100,000 copies/mL. Median (range) CD4+ count increased by 184 (−135 to 740) cells/mm3 at week 48. Eight patients experienced virologic failure, including 5 who developed rilpivirine resistance-associated mutations, mostly E138K, K101E and M230L. Mean (standard deviation) rilpivirine area-under-the-concentration-time curve from 0 to 24 hours (AUC24h and C0h) were 2391 (991) ng·h/mL and 83.5 (38.7) ng/mL, respectively.

Conclusions: 

Rilpivirine safety, virologic and pharmacokinetic profiles were similar in treatment-naïve HIV-1-infected adolescents and adults, supporting use of rilpivirine 25 mg qd, plus other antiretrovirals, in treatment-naïve adolescents with VL ≤100,000 copies/mL at treatment initiation.

Copyright © 2016 Wolters Kluwer Health, Inc. All rights reserved.

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