Intrapartum and neonatal single-dose nevirapine compared with zidovudine for prevention of mother-to-child transmission of HIV-1 in Kampala, Uganda

18-Month follow-up of the HIVNET 012 randomised trial

J. Brooks Jackson, Philippa Musoke, Thomas Fleming, Laura A. Guay, Danstan S Bagenda, Melissa Allen, Clemensia Nakabiito, Joseph Sherman, Paul Bakaki, Maxensia Owor, Constance Ducar, Martina Deseyve, Anthony Mwatha, Lynda Emel, Corey Duefield, Mark Mirochnick, Mary Glenn Fowler, Lynne Mofenson, Paolo Miotti, Maria Gigliotti & 2 others Dorothy Bray, Francis Mmiro

Research output: Contribution to journalArticle

401 Citations (Scopus)

Abstract

Background: In 1999, we reported safety and efficacy data for short-course nevirapine from a Ugandan perinatal HIV-1 prevention trial when 496 babies were followed up to age 14-16 weeks. Safety and efficacy data are now presented for all babies followed up to 18 months of age. Methods: From November, 1997, to April, 1999, HIV-1 infected pregnant women in Kampala, Uganda, were randomly assigned nevirapine (200 mg at labour onset and 2mg/kg for babies within 72 h of birth; regimen A) or zidovudine (600 mg orally at labour onset and 300 mg every 3 h until delivery, and 4 mg/kg orally twice daily for babies for 7 days, regimenB). Infant HIV-1 testing was done at birth, age 6-8 and 14-16 weeks, and age 12 months by HIV-1 RNA PCR, and by HIV-1 antibody at 18 months. HIV-1 transmission and HIV-1-free survival were assessed using Kaplan-Meier analysis. We recorded adverse experiences through 6-8 weeks postpartum for mothers, and 18 months for babies. Efficacy analyses were by intention to treat. Findings: We enrolled 645 mothers to the study: 313 were assigned regimen A, 313 regimen B, and 19 placebo. Eight mothers were lost to follow-up before delivery. 99% of babies were breastfed (median duration 9 months). Estimated risks of HIV-1 transmission in the zidovudine and nevirapine groups were 10·3% and 8·1% at birth (p=0·35); 20·0% and 11·8% by age 6-8 weeks (p=0·0063); 22·1% and 13·5% by age 14-16 weeks (p=0·0064); and 25·8% and 15·7% by age 18 months (p=0·0023). Nevirapine was associated with a 41% (95% CI 16-59) reduction in relative risk of transmission through to age 18 months. Both regimens were well-tolerated with few serious side-effects. Interpretation: Intrapartum/neonatal nevirapine significantly lowered HIV-1 transmission risk in a breastfeeding population in Uganda compared with a short intrapartum/neonatal zidovudine regimen. The absolute 8·2% reduction in transmission at 6-8 weeks was sustained at age 18 months (10·1% [95% CI 3·5-16·6]). This simple, inexpensive, well-tolerated regimen has the potential to significantly decrease HIV-1 perinatal transmission in less-developed countries.

Original languageEnglish (US)
Pages (from-to)859-868
Number of pages10
JournalLancet
Volume362
Issue number9387
DOIs
StatePublished - Sep 13 2003

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Nevirapine
Uganda
Zidovudine
HIV-1
Mothers
Labor Onset
Parturition
Safety
HIV Antibodies
Intention to Treat Analysis
Lost to Follow-Up
Kaplan-Meier Estimate
Breast Feeding
Postpartum Period
Developing Countries
Pregnant Women
Placebos
RNA

ASJC Scopus subject areas

  • Medicine(all)

Cite this

Intrapartum and neonatal single-dose nevirapine compared with zidovudine for prevention of mother-to-child transmission of HIV-1 in Kampala, Uganda : 18-Month follow-up of the HIVNET 012 randomised trial. / Jackson, J. Brooks; Musoke, Philippa; Fleming, Thomas; Guay, Laura A.; Bagenda, Danstan S; Allen, Melissa; Nakabiito, Clemensia; Sherman, Joseph; Bakaki, Paul; Owor, Maxensia; Ducar, Constance; Deseyve, Martina; Mwatha, Anthony; Emel, Lynda; Duefield, Corey; Mirochnick, Mark; Fowler, Mary Glenn; Mofenson, Lynne; Miotti, Paolo; Gigliotti, Maria; Bray, Dorothy; Mmiro, Francis.

In: Lancet, Vol. 362, No. 9387, 13.09.2003, p. 859-868.

Research output: Contribution to journalArticle

Jackson, JB, Musoke, P, Fleming, T, Guay, LA, Bagenda, DS, Allen, M, Nakabiito, C, Sherman, J, Bakaki, P, Owor, M, Ducar, C, Deseyve, M, Mwatha, A, Emel, L, Duefield, C, Mirochnick, M, Fowler, MG, Mofenson, L, Miotti, P, Gigliotti, M, Bray, D & Mmiro, F 2003, 'Intrapartum and neonatal single-dose nevirapine compared with zidovudine for prevention of mother-to-child transmission of HIV-1 in Kampala, Uganda: 18-Month follow-up of the HIVNET 012 randomised trial', Lancet, vol. 362, no. 9387, pp. 859-868. https://doi.org/10.1016/S0140-6736(03)14341-3
Jackson, J. Brooks ; Musoke, Philippa ; Fleming, Thomas ; Guay, Laura A. ; Bagenda, Danstan S ; Allen, Melissa ; Nakabiito, Clemensia ; Sherman, Joseph ; Bakaki, Paul ; Owor, Maxensia ; Ducar, Constance ; Deseyve, Martina ; Mwatha, Anthony ; Emel, Lynda ; Duefield, Corey ; Mirochnick, Mark ; Fowler, Mary Glenn ; Mofenson, Lynne ; Miotti, Paolo ; Gigliotti, Maria ; Bray, Dorothy ; Mmiro, Francis. / Intrapartum and neonatal single-dose nevirapine compared with zidovudine for prevention of mother-to-child transmission of HIV-1 in Kampala, Uganda : 18-Month follow-up of the HIVNET 012 randomised trial. In: Lancet. 2003 ; Vol. 362, No. 9387. pp. 859-868.
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abstract = "Background: In 1999, we reported safety and efficacy data for short-course nevirapine from a Ugandan perinatal HIV-1 prevention trial when 496 babies were followed up to age 14-16 weeks. Safety and efficacy data are now presented for all babies followed up to 18 months of age. Methods: From November, 1997, to April, 1999, HIV-1 infected pregnant women in Kampala, Uganda, were randomly assigned nevirapine (200 mg at labour onset and 2mg/kg for babies within 72 h of birth; regimen A) or zidovudine (600 mg orally at labour onset and 300 mg every 3 h until delivery, and 4 mg/kg orally twice daily for babies for 7 days, regimenB). Infant HIV-1 testing was done at birth, age 6-8 and 14-16 weeks, and age 12 months by HIV-1 RNA PCR, and by HIV-1 antibody at 18 months. HIV-1 transmission and HIV-1-free survival were assessed using Kaplan-Meier analysis. We recorded adverse experiences through 6-8 weeks postpartum for mothers, and 18 months for babies. Efficacy analyses were by intention to treat. Findings: We enrolled 645 mothers to the study: 313 were assigned regimen A, 313 regimen B, and 19 placebo. Eight mothers were lost to follow-up before delivery. 99{\%} of babies were breastfed (median duration 9 months). Estimated risks of HIV-1 transmission in the zidovudine and nevirapine groups were 10·3{\%} and 8·1{\%} at birth (p=0·35); 20·0{\%} and 11·8{\%} by age 6-8 weeks (p=0·0063); 22·1{\%} and 13·5{\%} by age 14-16 weeks (p=0·0064); and 25·8{\%} and 15·7{\%} by age 18 months (p=0·0023). Nevirapine was associated with a 41{\%} (95{\%} CI 16-59) reduction in relative risk of transmission through to age 18 months. Both regimens were well-tolerated with few serious side-effects. Interpretation: Intrapartum/neonatal nevirapine significantly lowered HIV-1 transmission risk in a breastfeeding population in Uganda compared with a short intrapartum/neonatal zidovudine regimen. The absolute 8·2{\%} reduction in transmission at 6-8 weeks was sustained at age 18 months (10·1{\%} [95{\%} CI 3·5-16·6]). This simple, inexpensive, well-tolerated regimen has the potential to significantly decrease HIV-1 perinatal transmission in less-developed countries.",
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TY - JOUR

T1 - Intrapartum and neonatal single-dose nevirapine compared with zidovudine for prevention of mother-to-child transmission of HIV-1 in Kampala, Uganda

T2 - 18-Month follow-up of the HIVNET 012 randomised trial

AU - Jackson, J. Brooks

AU - Musoke, Philippa

AU - Fleming, Thomas

AU - Guay, Laura A.

AU - Bagenda, Danstan S

AU - Allen, Melissa

AU - Nakabiito, Clemensia

AU - Sherman, Joseph

AU - Bakaki, Paul

AU - Owor, Maxensia

AU - Ducar, Constance

AU - Deseyve, Martina

AU - Mwatha, Anthony

AU - Emel, Lynda

AU - Duefield, Corey

AU - Mirochnick, Mark

AU - Fowler, Mary Glenn

AU - Mofenson, Lynne

AU - Miotti, Paolo

AU - Gigliotti, Maria

AU - Bray, Dorothy

AU - Mmiro, Francis

PY - 2003/9/13

Y1 - 2003/9/13

N2 - Background: In 1999, we reported safety and efficacy data for short-course nevirapine from a Ugandan perinatal HIV-1 prevention trial when 496 babies were followed up to age 14-16 weeks. Safety and efficacy data are now presented for all babies followed up to 18 months of age. Methods: From November, 1997, to April, 1999, HIV-1 infected pregnant women in Kampala, Uganda, were randomly assigned nevirapine (200 mg at labour onset and 2mg/kg for babies within 72 h of birth; regimen A) or zidovudine (600 mg orally at labour onset and 300 mg every 3 h until delivery, and 4 mg/kg orally twice daily for babies for 7 days, regimenB). Infant HIV-1 testing was done at birth, age 6-8 and 14-16 weeks, and age 12 months by HIV-1 RNA PCR, and by HIV-1 antibody at 18 months. HIV-1 transmission and HIV-1-free survival were assessed using Kaplan-Meier analysis. We recorded adverse experiences through 6-8 weeks postpartum for mothers, and 18 months for babies. Efficacy analyses were by intention to treat. Findings: We enrolled 645 mothers to the study: 313 were assigned regimen A, 313 regimen B, and 19 placebo. Eight mothers were lost to follow-up before delivery. 99% of babies were breastfed (median duration 9 months). Estimated risks of HIV-1 transmission in the zidovudine and nevirapine groups were 10·3% and 8·1% at birth (p=0·35); 20·0% and 11·8% by age 6-8 weeks (p=0·0063); 22·1% and 13·5% by age 14-16 weeks (p=0·0064); and 25·8% and 15·7% by age 18 months (p=0·0023). Nevirapine was associated with a 41% (95% CI 16-59) reduction in relative risk of transmission through to age 18 months. Both regimens were well-tolerated with few serious side-effects. Interpretation: Intrapartum/neonatal nevirapine significantly lowered HIV-1 transmission risk in a breastfeeding population in Uganda compared with a short intrapartum/neonatal zidovudine regimen. The absolute 8·2% reduction in transmission at 6-8 weeks was sustained at age 18 months (10·1% [95% CI 3·5-16·6]). This simple, inexpensive, well-tolerated regimen has the potential to significantly decrease HIV-1 perinatal transmission in less-developed countries.

AB - Background: In 1999, we reported safety and efficacy data for short-course nevirapine from a Ugandan perinatal HIV-1 prevention trial when 496 babies were followed up to age 14-16 weeks. Safety and efficacy data are now presented for all babies followed up to 18 months of age. Methods: From November, 1997, to April, 1999, HIV-1 infected pregnant women in Kampala, Uganda, were randomly assigned nevirapine (200 mg at labour onset and 2mg/kg for babies within 72 h of birth; regimen A) or zidovudine (600 mg orally at labour onset and 300 mg every 3 h until delivery, and 4 mg/kg orally twice daily for babies for 7 days, regimenB). Infant HIV-1 testing was done at birth, age 6-8 and 14-16 weeks, and age 12 months by HIV-1 RNA PCR, and by HIV-1 antibody at 18 months. HIV-1 transmission and HIV-1-free survival were assessed using Kaplan-Meier analysis. We recorded adverse experiences through 6-8 weeks postpartum for mothers, and 18 months for babies. Efficacy analyses were by intention to treat. Findings: We enrolled 645 mothers to the study: 313 were assigned regimen A, 313 regimen B, and 19 placebo. Eight mothers were lost to follow-up before delivery. 99% of babies were breastfed (median duration 9 months). Estimated risks of HIV-1 transmission in the zidovudine and nevirapine groups were 10·3% and 8·1% at birth (p=0·35); 20·0% and 11·8% by age 6-8 weeks (p=0·0063); 22·1% and 13·5% by age 14-16 weeks (p=0·0064); and 25·8% and 15·7% by age 18 months (p=0·0023). Nevirapine was associated with a 41% (95% CI 16-59) reduction in relative risk of transmission through to age 18 months. Both regimens were well-tolerated with few serious side-effects. Interpretation: Intrapartum/neonatal nevirapine significantly lowered HIV-1 transmission risk in a breastfeeding population in Uganda compared with a short intrapartum/neonatal zidovudine regimen. The absolute 8·2% reduction in transmission at 6-8 weeks was sustained at age 18 months (10·1% [95% CI 3·5-16·6]). This simple, inexpensive, well-tolerated regimen has the potential to significantly decrease HIV-1 perinatal transmission in less-developed countries.

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