Impact of adherence and anthropometric characteristics on nevirapine pharmacokinetics and exposure among HIV-infected Kenyan children

Rachel Vreeman, Winstone M. Nyandiko, Edward A. Liechty, Naftali Busakhala, Imke H. Bartelink, Rada M. Savic, Michael L. Scanlon, Samual O. Ayaya, Terry F. Blaschke

Research output: Contribution to journalArticle

4 Citations (Scopus)

Abstract

Background: There are insufficient data on pediatric antiretroviral therapy (ART) pharmacokinetics (PK), particularly for children in low- and middle-income countries. Methods: We conducted a prospective nevirapine (NVP) PK study among HIV-infected Kenyan children aged 3-13 years initiating an NVP-based ART regimen. NVP dose timing was measured through medication event monitors. Participants underwent 2 inpatient assessments: 1 at 4-8 weeks after ART initiation and 1 at 3-4 months after ART initiation. Allometric scaling of oral clearance (CL)/bioavailability (F) and volume of distribution (Vd)/F values were computed. Nonlinear mixed-effects modeling using the first-order conditional estimation with interaction method was performed with covariates. The impact of adherence on time below minimum effective concentration was assessed in the final PK model using medication event monitors data and model-estimated individual parameters. Results: Among 21 children enrolled, mean age was 5.4 years and 57% were female. CL/F was 1.67 L/h and Vd/F was 3.8 L for a median child weighing 15 kg. Participants' age had a significant impact on CL/F (P < 0.05), with an estimated decrease in CL of 6.2% for each 1-year increase in age. Total body water percentage was significantly associated with Vd/F (P < 0.001). No children had >10% of time below minimum effective concentration when the PK model assumed perfect adherence compared with 10 children when adherence data were used. Conclusions: Age and body composition were significantly associated with children's NVP PK parameters. ART adherence significantly impacted drug exposure over time, revealing subtherapeutic windows that may lead to viral resistance.

Original languageEnglish
Pages (from-to)277-286
Number of pages10
JournalJournal of Acquired Immune Deficiency Syndromes
Volume67
Issue number3
StatePublished - 2014

Fingerprint

Nevirapine
Pharmacokinetics
HIV
Therapeutics
Body Composition
Biological Availability
Inpatients
Pediatrics
Pharmaceutical Preparations

Keywords

  • Adherence
  • HIV-infected children
  • Pharmacokinetics
  • Resource-limited settings

ASJC Scopus subject areas

  • Infectious Diseases
  • Pharmacology (medical)
  • Medicine(all)

Cite this

Vreeman, R., Nyandiko, W. M., Liechty, E. A., Busakhala, N., Bartelink, I. H., Savic, R. M., ... Blaschke, T. F. (2014). Impact of adherence and anthropometric characteristics on nevirapine pharmacokinetics and exposure among HIV-infected Kenyan children. Journal of Acquired Immune Deficiency Syndromes, 67(3), 277-286.

Impact of adherence and anthropometric characteristics on nevirapine pharmacokinetics and exposure among HIV-infected Kenyan children. / Vreeman, Rachel; Nyandiko, Winstone M.; Liechty, Edward A.; Busakhala, Naftali; Bartelink, Imke H.; Savic, Rada M.; Scanlon, Michael L.; Ayaya, Samual O.; Blaschke, Terry F.

In: Journal of Acquired Immune Deficiency Syndromes, Vol. 67, No. 3, 2014, p. 277-286.

Research output: Contribution to journalArticle

Vreeman, R, Nyandiko, WM, Liechty, EA, Busakhala, N, Bartelink, IH, Savic, RM, Scanlon, ML, Ayaya, SO & Blaschke, TF 2014, 'Impact of adherence and anthropometric characteristics on nevirapine pharmacokinetics and exposure among HIV-infected Kenyan children', Journal of Acquired Immune Deficiency Syndromes, vol. 67, no. 3, pp. 277-286.
Vreeman, Rachel ; Nyandiko, Winstone M. ; Liechty, Edward A. ; Busakhala, Naftali ; Bartelink, Imke H. ; Savic, Rada M. ; Scanlon, Michael L. ; Ayaya, Samual O. ; Blaschke, Terry F. / Impact of adherence and anthropometric characteristics on nevirapine pharmacokinetics and exposure among HIV-infected Kenyan children. In: Journal of Acquired Immune Deficiency Syndromes. 2014 ; Vol. 67, No. 3. pp. 277-286.
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abstract = "Background: There are insufficient data on pediatric antiretroviral therapy (ART) pharmacokinetics (PK), particularly for children in low- and middle-income countries. Methods: We conducted a prospective nevirapine (NVP) PK study among HIV-infected Kenyan children aged 3-13 years initiating an NVP-based ART regimen. NVP dose timing was measured through medication event monitors. Participants underwent 2 inpatient assessments: 1 at 4-8 weeks after ART initiation and 1 at 3-4 months after ART initiation. Allometric scaling of oral clearance (CL)/bioavailability (F) and volume of distribution (Vd)/F values were computed. Nonlinear mixed-effects modeling using the first-order conditional estimation with interaction method was performed with covariates. The impact of adherence on time below minimum effective concentration was assessed in the final PK model using medication event monitors data and model-estimated individual parameters. Results: Among 21 children enrolled, mean age was 5.4 years and 57{\%} were female. CL/F was 1.67 L/h and Vd/F was 3.8 L for a median child weighing 15 kg. Participants' age had a significant impact on CL/F (P < 0.05), with an estimated decrease in CL of 6.2{\%} for each 1-year increase in age. Total body water percentage was significantly associated with Vd/F (P < 0.001). No children had >10{\%} of time below minimum effective concentration when the PK model assumed perfect adherence compared with 10 children when adherence data were used. Conclusions: Age and body composition were significantly associated with children's NVP PK parameters. ART adherence significantly impacted drug exposure over time, revealing subtherapeutic windows that may lead to viral resistance.",
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AU - Nyandiko, Winstone M.

AU - Liechty, Edward A.

AU - Busakhala, Naftali

AU - Bartelink, Imke H.

AU - Savic, Rada M.

AU - Scanlon, Michael L.

AU - Ayaya, Samual O.

AU - Blaschke, Terry F.

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N2 - Background: There are insufficient data on pediatric antiretroviral therapy (ART) pharmacokinetics (PK), particularly for children in low- and middle-income countries. Methods: We conducted a prospective nevirapine (NVP) PK study among HIV-infected Kenyan children aged 3-13 years initiating an NVP-based ART regimen. NVP dose timing was measured through medication event monitors. Participants underwent 2 inpatient assessments: 1 at 4-8 weeks after ART initiation and 1 at 3-4 months after ART initiation. Allometric scaling of oral clearance (CL)/bioavailability (F) and volume of distribution (Vd)/F values were computed. Nonlinear mixed-effects modeling using the first-order conditional estimation with interaction method was performed with covariates. The impact of adherence on time below minimum effective concentration was assessed in the final PK model using medication event monitors data and model-estimated individual parameters. Results: Among 21 children enrolled, mean age was 5.4 years and 57% were female. CL/F was 1.67 L/h and Vd/F was 3.8 L for a median child weighing 15 kg. Participants' age had a significant impact on CL/F (P < 0.05), with an estimated decrease in CL of 6.2% for each 1-year increase in age. Total body water percentage was significantly associated with Vd/F (P < 0.001). No children had >10% of time below minimum effective concentration when the PK model assumed perfect adherence compared with 10 children when adherence data were used. Conclusions: Age and body composition were significantly associated with children's NVP PK parameters. ART adherence significantly impacted drug exposure over time, revealing subtherapeutic windows that may lead to viral resistance.

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