A phase I/II study of the safety and pharmacokinetics of nevirapine in HIV-1-infected pregnant Ugandan women and their neonates (HIVNET 006)

Philippa Musoke, Laura A. Guay, Danstan Bagenda, Mark Mirochnick, Clemensia Nakabiito, Thomas Fleming, Terry Elliott, Scott Horton, Kevin Dransfield, Joseph W. Pav, Amal Murarka, Melissa Allen, Mary Glenn Fowler, Lynne Mofenson, David Hom, Francis Mmiro, J. Brooks Jackson

Research output: Contribution to journalArticle

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Abstract

Objective: To determine the safety, pharmacokinetics, tolerance, antiretroviral activity, and infant HIV infection status after giving a single dose of nevirapine to HIV-1-infected pregnant women during labor and their newborns during the first week of life. Design: An open label phase I/II study. Setting: Tertiary care hospital, Kampala, Uganda. Patients and interventions: Nevirapine, 200 mg, was given as a single dose during labor to 21 HIV-1-infected pregnant Ugandan women. In cohort 1, eight infants did not receive nevirapine whereas in cohort 2, 13 infants received a single dose of nevirapine, 2 mg/kg, at 72 h of age. Outcomes: The number and type of adverse events; nevirapine concentrations in the plasma and breast milk; maternal plasma HIV-1 RNA copy number before and up to 6 weeks after delivery; and HIV-1 infection status of the infants were monitored. Results: Nevirapine was well tolerated by women and infants; no serious adverse events that were related to nevirapine were observed. Median nevirapine concentration in the women at delivery was 1623 ng/ml (range 238-2356 ng/ml); median cord/maternal blood ratio of 0.75 (0.37-0.93). The median half-life in women was 61.3 h (27-90 h) and the transplacental nevirapine half-life in infants who did not receive a neonatal dose was 54 h. The median half-life after a single dose at 72 h in infants was 46.5 h. During the first week of life, the median colostrum/breast milk to maternal plasma nevirapine concentration was 60.5% (25-122%). The median nevirapine concentration in breast milk 1 week after delivery was 103 ng/ml (25-309 ng/ml). Plasma nevirapine concentrations were above 100 ng/ml in all infants from both cohorts tested at age 7 days. Maternal HIV-1 RNA levels decreased by a median of 1.3 logs at 1 week postpartum, and returned to baseline by 6 weeks postpartum. Detectable plasma HIV-1 RNA was observed in one out of 22 (4.5%) infants at birth; three out of 21 (14%) at 6 weeks; and four out of 21 (19%) at 6 months of age. Conclusion: The administration of a single dose of nevirapine to women during labor and to their newborns at 72 h was well tolerated and showed potent antiretroviral activity in the women at 1 week after dosing without rebound above baseline 6 weeks after a single dose. The nevirapine concentration was maintained above the target of 100 ng/ml in infants at age 7 days, even in those infants not receiving a neonatal dose. This regimen has promise as prophylaxis against intrapartum and early breast milk transmission in a breastfeeding population.

Original languageEnglish (US)
Pages (from-to)479-486
Number of pages8
JournalAIDS
Volume13
Issue number4
DOIs
StatePublished - Jan 1 1999

Fingerprint

Nevirapine
HIV-1
Pregnant Women
Pharmacokinetics
Newborn Infant
Safety
Human Milk
Mothers
Half-Life
RNA
Postpartum Period
HIV Infections
Colostrum
Uganda
Tertiary Healthcare
Breast Feeding
Fetal Blood
Tertiary Care Centers

Keywords

  • HIV vertical transmission
  • Nevirapine
  • Pharmacokinetics
  • Uganda

ASJC Scopus subject areas

  • Immunology and Allergy
  • Immunology
  • Infectious Diseases

Cite this

Musoke, P., Guay, L. A., Bagenda, D., Mirochnick, M., Nakabiito, C., Fleming, T., ... Jackson, J. B. (1999). A phase I/II study of the safety and pharmacokinetics of nevirapine in HIV-1-infected pregnant Ugandan women and their neonates (HIVNET 006). AIDS, 13(4), 479-486. https://doi.org/10.1097/00002030-199903110-00006

A phase I/II study of the safety and pharmacokinetics of nevirapine in HIV-1-infected pregnant Ugandan women and their neonates (HIVNET 006). / Musoke, Philippa; Guay, Laura A.; Bagenda, Danstan; Mirochnick, Mark; Nakabiito, Clemensia; Fleming, Thomas; Elliott, Terry; Horton, Scott; Dransfield, Kevin; Pav, Joseph W.; Murarka, Amal; Allen, Melissa; Fowler, Mary Glenn; Mofenson, Lynne; Hom, David; Mmiro, Francis; Jackson, J. Brooks.

In: AIDS, Vol. 13, No. 4, 01.01.1999, p. 479-486.

Research output: Contribution to journalArticle

Musoke, P, Guay, LA, Bagenda, D, Mirochnick, M, Nakabiito, C, Fleming, T, Elliott, T, Horton, S, Dransfield, K, Pav, JW, Murarka, A, Allen, M, Fowler, MG, Mofenson, L, Hom, D, Mmiro, F & Jackson, JB 1999, 'A phase I/II study of the safety and pharmacokinetics of nevirapine in HIV-1-infected pregnant Ugandan women and their neonates (HIVNET 006)', AIDS, vol. 13, no. 4, pp. 479-486. https://doi.org/10.1097/00002030-199903110-00006
Musoke, Philippa ; Guay, Laura A. ; Bagenda, Danstan ; Mirochnick, Mark ; Nakabiito, Clemensia ; Fleming, Thomas ; Elliott, Terry ; Horton, Scott ; Dransfield, Kevin ; Pav, Joseph W. ; Murarka, Amal ; Allen, Melissa ; Fowler, Mary Glenn ; Mofenson, Lynne ; Hom, David ; Mmiro, Francis ; Jackson, J. Brooks. / A phase I/II study of the safety and pharmacokinetics of nevirapine in HIV-1-infected pregnant Ugandan women and their neonates (HIVNET 006). In: AIDS. 1999 ; Vol. 13, No. 4. pp. 479-486.
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abstract = "Objective: To determine the safety, pharmacokinetics, tolerance, antiretroviral activity, and infant HIV infection status after giving a single dose of nevirapine to HIV-1-infected pregnant women during labor and their newborns during the first week of life. Design: An open label phase I/II study. Setting: Tertiary care hospital, Kampala, Uganda. Patients and interventions: Nevirapine, 200 mg, was given as a single dose during labor to 21 HIV-1-infected pregnant Ugandan women. In cohort 1, eight infants did not receive nevirapine whereas in cohort 2, 13 infants received a single dose of nevirapine, 2 mg/kg, at 72 h of age. Outcomes: The number and type of adverse events; nevirapine concentrations in the plasma and breast milk; maternal plasma HIV-1 RNA copy number before and up to 6 weeks after delivery; and HIV-1 infection status of the infants were monitored. Results: Nevirapine was well tolerated by women and infants; no serious adverse events that were related to nevirapine were observed. Median nevirapine concentration in the women at delivery was 1623 ng/ml (range 238-2356 ng/ml); median cord/maternal blood ratio of 0.75 (0.37-0.93). The median half-life in women was 61.3 h (27-90 h) and the transplacental nevirapine half-life in infants who did not receive a neonatal dose was 54 h. The median half-life after a single dose at 72 h in infants was 46.5 h. During the first week of life, the median colostrum/breast milk to maternal plasma nevirapine concentration was 60.5{\%} (25-122{\%}). The median nevirapine concentration in breast milk 1 week after delivery was 103 ng/ml (25-309 ng/ml). Plasma nevirapine concentrations were above 100 ng/ml in all infants from both cohorts tested at age 7 days. Maternal HIV-1 RNA levels decreased by a median of 1.3 logs at 1 week postpartum, and returned to baseline by 6 weeks postpartum. Detectable plasma HIV-1 RNA was observed in one out of 22 (4.5{\%}) infants at birth; three out of 21 (14{\%}) at 6 weeks; and four out of 21 (19{\%}) at 6 months of age. Conclusion: The administration of a single dose of nevirapine to women during labor and to their newborns at 72 h was well tolerated and showed potent antiretroviral activity in the women at 1 week after dosing without rebound above baseline 6 weeks after a single dose. The nevirapine concentration was maintained above the target of 100 ng/ml in infants at age 7 days, even in those infants not receiving a neonatal dose. This regimen has promise as prophylaxis against intrapartum and early breast milk transmission in a breastfeeding population.",
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T1 - A phase I/II study of the safety and pharmacokinetics of nevirapine in HIV-1-infected pregnant Ugandan women and their neonates (HIVNET 006)

AU - Musoke, Philippa

AU - Guay, Laura A.

AU - Bagenda, Danstan

AU - Mirochnick, Mark

AU - Nakabiito, Clemensia

AU - Fleming, Thomas

AU - Elliott, Terry

AU - Horton, Scott

AU - Dransfield, Kevin

AU - Pav, Joseph W.

AU - Murarka, Amal

AU - Allen, Melissa

AU - Fowler, Mary Glenn

AU - Mofenson, Lynne

AU - Hom, David

AU - Mmiro, Francis

AU - Jackson, J. Brooks

PY - 1999/1/1

Y1 - 1999/1/1

N2 - Objective: To determine the safety, pharmacokinetics, tolerance, antiretroviral activity, and infant HIV infection status after giving a single dose of nevirapine to HIV-1-infected pregnant women during labor and their newborns during the first week of life. Design: An open label phase I/II study. Setting: Tertiary care hospital, Kampala, Uganda. Patients and interventions: Nevirapine, 200 mg, was given as a single dose during labor to 21 HIV-1-infected pregnant Ugandan women. In cohort 1, eight infants did not receive nevirapine whereas in cohort 2, 13 infants received a single dose of nevirapine, 2 mg/kg, at 72 h of age. Outcomes: The number and type of adverse events; nevirapine concentrations in the plasma and breast milk; maternal plasma HIV-1 RNA copy number before and up to 6 weeks after delivery; and HIV-1 infection status of the infants were monitored. Results: Nevirapine was well tolerated by women and infants; no serious adverse events that were related to nevirapine were observed. Median nevirapine concentration in the women at delivery was 1623 ng/ml (range 238-2356 ng/ml); median cord/maternal blood ratio of 0.75 (0.37-0.93). The median half-life in women was 61.3 h (27-90 h) and the transplacental nevirapine half-life in infants who did not receive a neonatal dose was 54 h. The median half-life after a single dose at 72 h in infants was 46.5 h. During the first week of life, the median colostrum/breast milk to maternal plasma nevirapine concentration was 60.5% (25-122%). The median nevirapine concentration in breast milk 1 week after delivery was 103 ng/ml (25-309 ng/ml). Plasma nevirapine concentrations were above 100 ng/ml in all infants from both cohorts tested at age 7 days. Maternal HIV-1 RNA levels decreased by a median of 1.3 logs at 1 week postpartum, and returned to baseline by 6 weeks postpartum. Detectable plasma HIV-1 RNA was observed in one out of 22 (4.5%) infants at birth; three out of 21 (14%) at 6 weeks; and four out of 21 (19%) at 6 months of age. Conclusion: The administration of a single dose of nevirapine to women during labor and to their newborns at 72 h was well tolerated and showed potent antiretroviral activity in the women at 1 week after dosing without rebound above baseline 6 weeks after a single dose. The nevirapine concentration was maintained above the target of 100 ng/ml in infants at age 7 days, even in those infants not receiving a neonatal dose. This regimen has promise as prophylaxis against intrapartum and early breast milk transmission in a breastfeeding population.

AB - Objective: To determine the safety, pharmacokinetics, tolerance, antiretroviral activity, and infant HIV infection status after giving a single dose of nevirapine to HIV-1-infected pregnant women during labor and their newborns during the first week of life. Design: An open label phase I/II study. Setting: Tertiary care hospital, Kampala, Uganda. Patients and interventions: Nevirapine, 200 mg, was given as a single dose during labor to 21 HIV-1-infected pregnant Ugandan women. In cohort 1, eight infants did not receive nevirapine whereas in cohort 2, 13 infants received a single dose of nevirapine, 2 mg/kg, at 72 h of age. Outcomes: The number and type of adverse events; nevirapine concentrations in the plasma and breast milk; maternal plasma HIV-1 RNA copy number before and up to 6 weeks after delivery; and HIV-1 infection status of the infants were monitored. Results: Nevirapine was well tolerated by women and infants; no serious adverse events that were related to nevirapine were observed. Median nevirapine concentration in the women at delivery was 1623 ng/ml (range 238-2356 ng/ml); median cord/maternal blood ratio of 0.75 (0.37-0.93). The median half-life in women was 61.3 h (27-90 h) and the transplacental nevirapine half-life in infants who did not receive a neonatal dose was 54 h. The median half-life after a single dose at 72 h in infants was 46.5 h. During the first week of life, the median colostrum/breast milk to maternal plasma nevirapine concentration was 60.5% (25-122%). The median nevirapine concentration in breast milk 1 week after delivery was 103 ng/ml (25-309 ng/ml). Plasma nevirapine concentrations were above 100 ng/ml in all infants from both cohorts tested at age 7 days. Maternal HIV-1 RNA levels decreased by a median of 1.3 logs at 1 week postpartum, and returned to baseline by 6 weeks postpartum. Detectable plasma HIV-1 RNA was observed in one out of 22 (4.5%) infants at birth; three out of 21 (14%) at 6 weeks; and four out of 21 (19%) at 6 months of age. Conclusion: The administration of a single dose of nevirapine to women during labor and to their newborns at 72 h was well tolerated and showed potent antiretroviral activity in the women at 1 week after dosing without rebound above baseline 6 weeks after a single dose. The nevirapine concentration was maintained above the target of 100 ng/ml in infants at age 7 days, even in those infants not receiving a neonatal dose. This regimen has promise as prophylaxis against intrapartum and early breast milk transmission in a breastfeeding population.

KW - HIV vertical transmission

KW - Nevirapine

KW - Pharmacokinetics

KW - Uganda

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