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

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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.
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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",
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language = "English",
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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.

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