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

Week 48 Safety, Efficacy, Virology and Pharmacokinetics

Johan Lombaard, Torsak Bunupuradah, Patricia M. Flynn, John Ramapuram, Francis Ssali, Herta Crauwels, Annemie Hoogstoel, Veerle Van Eygen, Marita Stevens

Research output: Contribution to journalArticle

3 Citations (Scopus)

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/mm 3 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 (AUC 24h and C 0h) 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.

Original languageEnglish
Pages (from-to)1215-1221
Number of pages7
JournalPediatric Infectious Disease Journal
Volume35
Issue number11
DOIs
Publication statusPublished - 01-11-2016

Fingerprint

Rilpivirine
Virology
Pharmacokinetics
HIV
Safety
Therapeutics
HIV-1
Reverse Transcriptase Inhibitors
CD4 Lymphocyte Count
Nucleosides

All Science Journal Classification (ASJC) codes

  • Pediatrics, Perinatology, and Child Health
  • Microbiology (medical)
  • Infectious Diseases

Cite this

Lombaard, Johan ; Bunupuradah, Torsak ; Flynn, Patricia M. ; Ramapuram, John ; Ssali, Francis ; Crauwels, Herta ; Hoogstoel, Annemie ; Van Eygen, Veerle ; Stevens, Marita. / Rilpivirine as a Treatment for HIV-infected Antiretroviral-naïve Adolescents : Week 48 Safety, Efficacy, Virology and Pharmacokinetics. In: Pediatric Infectious Disease Journal. 2016 ; Vol. 35, No. 11. pp. 1215-1221.
@article{9f966e76458d48f78c2fa4f4c99023a6,
title = "Rilpivirine as a Treatment for HIV-infected Antiretroviral-na{\"i}ve Adolescents: Week 48 Safety, Efficacy, Virology and Pharmacokinetics",
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-na{\"i}ve 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/mm 3 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 (AUC 24h and C 0h) 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-na{\"i}ve HIV-1-infected adolescents and adults, supporting use of rilpivirine 25 mg qd, plus other antiretrovirals, in treatment-na{\"i}ve adolescents with VL ≤100,000 copies/mL at treatment initiation.",
author = "Johan Lombaard and Torsak Bunupuradah and Flynn, {Patricia M.} and John Ramapuram and Francis Ssali and Herta Crauwels and Annemie Hoogstoel and {Van Eygen}, Veerle and Marita Stevens",
year = "2016",
month = "11",
day = "1",
doi = "10.1097/INF.0000000000001275",
language = "English",
volume = "35",
pages = "1215--1221",
journal = "Pediatric Infectious Disease Journal",
issn = "0891-3668",
publisher = "Lippincott Williams and Wilkins",
number = "11",

}

Rilpivirine as a Treatment for HIV-infected Antiretroviral-naïve Adolescents : Week 48 Safety, Efficacy, Virology and Pharmacokinetics. / Lombaard, Johan; Bunupuradah, Torsak; Flynn, Patricia M.; Ramapuram, John; Ssali, Francis; Crauwels, Herta; Hoogstoel, Annemie; Van Eygen, Veerle; Stevens, Marita.

In: Pediatric Infectious Disease Journal, Vol. 35, No. 11, 01.11.2016, p. 1215-1221.

Research output: Contribution to journalArticle

TY - JOUR

T1 - Rilpivirine as a Treatment for HIV-infected Antiretroviral-naïve Adolescents

T2 - Week 48 Safety, Efficacy, Virology and Pharmacokinetics

AU - Lombaard, Johan

AU - Bunupuradah, Torsak

AU - Flynn, Patricia M.

AU - Ramapuram, John

AU - Ssali, Francis

AU - Crauwels, Herta

AU - Hoogstoel, Annemie

AU - Van Eygen, Veerle

AU - Stevens, Marita

PY - 2016/11/1

Y1 - 2016/11/1

N2 - 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/mm 3 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 (AUC 24h and C 0h) 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.

AB - 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/mm 3 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 (AUC 24h and C 0h) 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.

UR - http://www.scopus.com/inward/record.url?scp=84974691404&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=84974691404&partnerID=8YFLogxK

U2 - 10.1097/INF.0000000000001275

DO - 10.1097/INF.0000000000001275

M3 - Article

VL - 35

SP - 1215

EP - 1221

JO - Pediatric Infectious Disease Journal

JF - Pediatric Infectious Disease Journal

SN - 0891-3668

IS - 11

ER -