Extended-dose nevirapine to 6 weeks of age for infants to prevent HIV transmission via breastfeeding in Ethiopia, India, and Uganda: An analysis of three randomised controlled trials

Abubaker Bedri, Berhanu Gudetta, Abdulhamid Isehak, Solomon Kumbi, Sileshi Lulseged, Yohannes Mengistu, Arvind V. Bhore, Ramesh Bhosale, Venkat Varadhrajan, Nikhil Gupte, Jayagowri Sastry, Nishi Suryavanshi, Srikanth Tripathy, Francis Mmiro, Michael Mubiru, Carolyne Onyango, Adrian Taylor, Philippa Musoke, Clemensia Nakabiito, Aida Abashawl & 20 others Rahel Adamu, Gretchen Antelman, Robert C. Bollinger, Patricia Bright, Mohammad A. Chaudhary, Jacqueline Coberly, Laura Guay, Mary Glenn Fowler, Amita Gupta, Elham Hassen, J. Brooks Jackson, Lawrence H. Moulton, Uma Nayak, Saad B. Omer, Lidia Propper, Malathi Ram, Vivian Rexroad, Andrea J. Ruff, Anita Shankar, Sheryl Zwerski

Research output: Contribution to journalArticle

Abstract

Background: UNICEF/WHO recommends that infants born to HIV-infected mothers who do not have access to acceptable, feasible, affordable, sustainable, and safe replacement feeding should be exclusively breastfed for at least 6 months. The aim of three trials in Ethiopia, India, and Uganda was to assess whether daily nevirapine given to breastfed infants through 6 weeks of age can decrease HIV transmission via breastfeeding. Methods: HIV-infected women breastfeeding their infants were eligible for participation. Participants were randomly assigned to receive either single-dose nevirapine (nevirapine 200 mg to women in labour and nevirapine 2 mg/kg to newborns after birth) or 6 week extended-dose nevirapine (nevirapine 200 mg to women in labour and nevirapine 2 mg/kg to newborn babies after birth plus nevirapine 5 mg daily from days 8-42 for the infant). The randomisation sequences were generated by computer at a central data coordinating centre. The primary endpoint was HIV infection at 6 months of age in infants who were HIV PCR negative at birth. Analyses were by modified intention to treat, excluding infants with missing specimens and those with indeterminate or confirmed HIV infection at birth. These studies are registered with ClinicalTrials.gov, numbers NCT00074399, NCT00061321, and NCT00639938. Findings: 2024 liveborn infants randomised in the study had at least one specimen tested before 6 months of age (1047 infants in the single-dose group and 977 infants in the extended-dose group). The modified intention-to-treat population included 986 infants in the single-dose group and 901 in the extended-dose group. At 6 months, 87 children in the single-dose group and 62 in the extended-dose group were infected with HIV (relative risk 0.80, 95% CI 0.58-1.10; p=0.16). At 6 weeks of age, 54 children in the single-dose group and 25 in the extended-dose group were HIV positive (0.54, 0.34-0.85; p=0.009). 393 infants in the single-dose group and 346 in the extended-dose group experienced grade 3 or 4 serious adverse events during the study (p=0.54). Interpretation: Although a 6-week regimen of daily nevirapine might be associated with a reduction in the risk of HIV transmission at 6 weeks of age, the lack of a significant reduction in the primary endpoint - risk of HIV transmission at 6 months - suggests that a longer course of daily infant nevirapine to prevent HIV transmission via breast milk might be more effective where access to affordable and safe replacement feeding is not yet available and where the risks of replacement feeding are high. Funding: US National Institutes of Health; US National Institute of Allergy and Infectious Diseases; Fogarty International Center.

LanguageEnglish (US)
Pages300-313
Number of pages14
JournalThe Lancet
Volume372
Issue number9635
DOIs
StatePublished - 2008

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Nevirapine
Ethiopia
Uganda
Breast Feeding
India
Randomized Controlled Trials
HIV
Parturition
HIV Infections
National Institute of Allergy and Infectious Diseases (U.S.)
Newborn Infant
United Nations
National Institutes of Health (U.S.)
Human Milk
Risk Reduction Behavior
Random Allocation

ASJC Scopus subject areas

  • Medicine(all)

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Extended-dose nevirapine to 6 weeks of age for infants to prevent HIV transmission via breastfeeding in Ethiopia, India, and Uganda : An analysis of three randomised controlled trials. / Bedri, Abubaker; Gudetta, Berhanu; Isehak, Abdulhamid; Kumbi, Solomon; Lulseged, Sileshi; Mengistu, Yohannes; Bhore, Arvind V.; Bhosale, Ramesh; Varadhrajan, Venkat; Gupte, Nikhil; Sastry, Jayagowri; Suryavanshi, Nishi; Tripathy, Srikanth; Mmiro, Francis; Mubiru, Michael; Onyango, Carolyne; Taylor, Adrian; Musoke, Philippa; Nakabiito, Clemensia; Abashawl, Aida; Adamu, Rahel; Antelman, Gretchen; Bollinger, Robert C.; Bright, Patricia; Chaudhary, Mohammad A.; Coberly, Jacqueline; Guay, Laura; Fowler, Mary Glenn; Gupta, Amita; Hassen, Elham; Jackson, J. Brooks; Moulton, Lawrence H.; Nayak, Uma; Omer, Saad B.; Propper, Lidia; Ram, Malathi; Rexroad, Vivian; Ruff, Andrea J.; Shankar, Anita; Zwerski, Sheryl.

In: The Lancet, Vol. 372, No. 9635, 2008, p. 300-313.

Research output: Contribution to journalArticle

Bedri, A, Gudetta, B, Isehak, A, Kumbi, S, Lulseged, S, Mengistu, Y, Bhore, AV, Bhosale, R, Varadhrajan, V, Gupte, N, Sastry, J, Suryavanshi, N, Tripathy, S, Mmiro, F, Mubiru, M, Onyango, C, Taylor, A, Musoke, P, Nakabiito, C, Abashawl, A, Adamu, R, Antelman, G, Bollinger, RC, Bright, P, Chaudhary, MA, Coberly, J, Guay, L, Fowler, MG, Gupta, A, Hassen, E, Jackson, JB, Moulton, LH, Nayak, U, Omer, SB, Propper, L, Ram, M, Rexroad, V, Ruff, AJ, Shankar, A & Zwerski, S 2008, 'Extended-dose nevirapine to 6 weeks of age for infants to prevent HIV transmission via breastfeeding in Ethiopia, India, and Uganda: An analysis of three randomised controlled trials' The Lancet, vol. 372, no. 9635, pp. 300-313. DOI: 10.1016/S0140-6736(08)61114-9
Bedri, Abubaker ; Gudetta, Berhanu ; Isehak, Abdulhamid ; Kumbi, Solomon ; Lulseged, Sileshi ; Mengistu, Yohannes ; Bhore, Arvind V. ; Bhosale, Ramesh ; Varadhrajan, Venkat ; Gupte, Nikhil ; Sastry, Jayagowri ; Suryavanshi, Nishi ; Tripathy, Srikanth ; Mmiro, Francis ; Mubiru, Michael ; Onyango, Carolyne ; Taylor, Adrian ; Musoke, Philippa ; Nakabiito, Clemensia ; Abashawl, Aida ; Adamu, Rahel ; Antelman, Gretchen ; Bollinger, Robert C. ; Bright, Patricia ; Chaudhary, Mohammad A. ; Coberly, Jacqueline ; Guay, Laura ; Fowler, Mary Glenn ; Gupta, Amita ; Hassen, Elham ; Jackson, J. Brooks ; Moulton, Lawrence H. ; Nayak, Uma ; Omer, Saad B. ; Propper, Lidia ; Ram, Malathi ; Rexroad, Vivian ; Ruff, Andrea J. ; Shankar, Anita ; Zwerski, Sheryl. / Extended-dose nevirapine to 6 weeks of age for infants to prevent HIV transmission via breastfeeding in Ethiopia, India, and Uganda : An analysis of three randomised controlled trials. In: The Lancet. 2008 ; Vol. 372, No. 9635. pp. 300-313
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abstract = "Background: UNICEF/WHO recommends that infants born to HIV-infected mothers who do not have access to acceptable, feasible, affordable, sustainable, and safe replacement feeding should be exclusively breastfed for at least 6 months. The aim of three trials in Ethiopia, India, and Uganda was to assess whether daily nevirapine given to breastfed infants through 6 weeks of age can decrease HIV transmission via breastfeeding. Methods: HIV-infected women breastfeeding their infants were eligible for participation. Participants were randomly assigned to receive either single-dose nevirapine (nevirapine 200 mg to women in labour and nevirapine 2 mg/kg to newborns after birth) or 6 week extended-dose nevirapine (nevirapine 200 mg to women in labour and nevirapine 2 mg/kg to newborn babies after birth plus nevirapine 5 mg daily from days 8-42 for the infant). The randomisation sequences were generated by computer at a central data coordinating centre. The primary endpoint was HIV infection at 6 months of age in infants who were HIV PCR negative at birth. Analyses were by modified intention to treat, excluding infants with missing specimens and those with indeterminate or confirmed HIV infection at birth. These studies are registered with ClinicalTrials.gov, numbers NCT00074399, NCT00061321, and NCT00639938. Findings: 2024 liveborn infants randomised in the study had at least one specimen tested before 6 months of age (1047 infants in the single-dose group and 977 infants in the extended-dose group). The modified intention-to-treat population included 986 infants in the single-dose group and 901 in the extended-dose group. At 6 months, 87 children in the single-dose group and 62 in the extended-dose group were infected with HIV (relative risk 0.80, 95{\%} CI 0.58-1.10; p=0.16). At 6 weeks of age, 54 children in the single-dose group and 25 in the extended-dose group were HIV positive (0.54, 0.34-0.85; p=0.009). 393 infants in the single-dose group and 346 in the extended-dose group experienced grade 3 or 4 serious adverse events during the study (p=0.54). Interpretation: Although a 6-week regimen of daily nevirapine might be associated with a reduction in the risk of HIV transmission at 6 weeks of age, the lack of a significant reduction in the primary endpoint - risk of HIV transmission at 6 months - suggests that a longer course of daily infant nevirapine to prevent HIV transmission via breast milk might be more effective where access to affordable and safe replacement feeding is not yet available and where the risks of replacement feeding are high. Funding: US National Institutes of Health; US National Institute of Allergy and Infectious Diseases; Fogarty International Center.",
author = "Abubaker Bedri and Berhanu Gudetta and Abdulhamid Isehak and Solomon Kumbi and Sileshi Lulseged and Yohannes Mengistu and Bhore, {Arvind V.} and Ramesh Bhosale and Venkat Varadhrajan and Nikhil Gupte and Jayagowri Sastry and Nishi Suryavanshi and Srikanth Tripathy and Francis Mmiro and Michael Mubiru and Carolyne Onyango and Adrian Taylor and Philippa Musoke and Clemensia Nakabiito and Aida Abashawl and Rahel Adamu and Gretchen Antelman and Bollinger, {Robert C.} and Patricia Bright and Chaudhary, {Mohammad A.} and Jacqueline Coberly and Laura Guay and Fowler, {Mary Glenn} and Amita Gupta and Elham Hassen and Jackson, {J. Brooks} and Moulton, {Lawrence H.} and Uma Nayak and Omer, {Saad B.} and Lidia Propper and Malathi Ram and Vivian Rexroad and Ruff, {Andrea J.} and Anita Shankar and Sheryl Zwerski",
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T1 - Extended-dose nevirapine to 6 weeks of age for infants to prevent HIV transmission via breastfeeding in Ethiopia, India, and Uganda

T2 - The Lancet

AU - Bedri,Abubaker

AU - Gudetta,Berhanu

AU - Isehak,Abdulhamid

AU - Kumbi,Solomon

AU - Lulseged,Sileshi

AU - Mengistu,Yohannes

AU - Bhore,Arvind V.

AU - Bhosale,Ramesh

AU - Varadhrajan,Venkat

AU - Gupte,Nikhil

AU - Sastry,Jayagowri

AU - Suryavanshi,Nishi

AU - Tripathy,Srikanth

AU - Mmiro,Francis

AU - Mubiru,Michael

AU - Onyango,Carolyne

AU - Taylor,Adrian

AU - Musoke,Philippa

AU - Nakabiito,Clemensia

AU - Abashawl,Aida

AU - Adamu,Rahel

AU - Antelman,Gretchen

AU - Bollinger,Robert C.

AU - Bright,Patricia

AU - Chaudhary,Mohammad A.

AU - Coberly,Jacqueline

AU - Guay,Laura

AU - Fowler,Mary Glenn

AU - Gupta,Amita

AU - Hassen,Elham

AU - Jackson,J. Brooks

AU - Moulton,Lawrence H.

AU - Nayak,Uma

AU - Omer,Saad B.

AU - Propper,Lidia

AU - Ram,Malathi

AU - Rexroad,Vivian

AU - Ruff,Andrea J.

AU - Shankar,Anita

AU - Zwerski,Sheryl

PY - 2008

Y1 - 2008

N2 - Background: UNICEF/WHO recommends that infants born to HIV-infected mothers who do not have access to acceptable, feasible, affordable, sustainable, and safe replacement feeding should be exclusively breastfed for at least 6 months. The aim of three trials in Ethiopia, India, and Uganda was to assess whether daily nevirapine given to breastfed infants through 6 weeks of age can decrease HIV transmission via breastfeeding. Methods: HIV-infected women breastfeeding their infants were eligible for participation. Participants were randomly assigned to receive either single-dose nevirapine (nevirapine 200 mg to women in labour and nevirapine 2 mg/kg to newborns after birth) or 6 week extended-dose nevirapine (nevirapine 200 mg to women in labour and nevirapine 2 mg/kg to newborn babies after birth plus nevirapine 5 mg daily from days 8-42 for the infant). The randomisation sequences were generated by computer at a central data coordinating centre. The primary endpoint was HIV infection at 6 months of age in infants who were HIV PCR negative at birth. Analyses were by modified intention to treat, excluding infants with missing specimens and those with indeterminate or confirmed HIV infection at birth. These studies are registered with ClinicalTrials.gov, numbers NCT00074399, NCT00061321, and NCT00639938. Findings: 2024 liveborn infants randomised in the study had at least one specimen tested before 6 months of age (1047 infants in the single-dose group and 977 infants in the extended-dose group). The modified intention-to-treat population included 986 infants in the single-dose group and 901 in the extended-dose group. At 6 months, 87 children in the single-dose group and 62 in the extended-dose group were infected with HIV (relative risk 0.80, 95% CI 0.58-1.10; p=0.16). At 6 weeks of age, 54 children in the single-dose group and 25 in the extended-dose group were HIV positive (0.54, 0.34-0.85; p=0.009). 393 infants in the single-dose group and 346 in the extended-dose group experienced grade 3 or 4 serious adverse events during the study (p=0.54). Interpretation: Although a 6-week regimen of daily nevirapine might be associated with a reduction in the risk of HIV transmission at 6 weeks of age, the lack of a significant reduction in the primary endpoint - risk of HIV transmission at 6 months - suggests that a longer course of daily infant nevirapine to prevent HIV transmission via breast milk might be more effective where access to affordable and safe replacement feeding is not yet available and where the risks of replacement feeding are high. Funding: US National Institutes of Health; US National Institute of Allergy and Infectious Diseases; Fogarty International Center.

AB - Background: UNICEF/WHO recommends that infants born to HIV-infected mothers who do not have access to acceptable, feasible, affordable, sustainable, and safe replacement feeding should be exclusively breastfed for at least 6 months. The aim of three trials in Ethiopia, India, and Uganda was to assess whether daily nevirapine given to breastfed infants through 6 weeks of age can decrease HIV transmission via breastfeeding. Methods: HIV-infected women breastfeeding their infants were eligible for participation. Participants were randomly assigned to receive either single-dose nevirapine (nevirapine 200 mg to women in labour and nevirapine 2 mg/kg to newborns after birth) or 6 week extended-dose nevirapine (nevirapine 200 mg to women in labour and nevirapine 2 mg/kg to newborn babies after birth plus nevirapine 5 mg daily from days 8-42 for the infant). The randomisation sequences were generated by computer at a central data coordinating centre. The primary endpoint was HIV infection at 6 months of age in infants who were HIV PCR negative at birth. Analyses were by modified intention to treat, excluding infants with missing specimens and those with indeterminate or confirmed HIV infection at birth. These studies are registered with ClinicalTrials.gov, numbers NCT00074399, NCT00061321, and NCT00639938. Findings: 2024 liveborn infants randomised in the study had at least one specimen tested before 6 months of age (1047 infants in the single-dose group and 977 infants in the extended-dose group). The modified intention-to-treat population included 986 infants in the single-dose group and 901 in the extended-dose group. At 6 months, 87 children in the single-dose group and 62 in the extended-dose group were infected with HIV (relative risk 0.80, 95% CI 0.58-1.10; p=0.16). At 6 weeks of age, 54 children in the single-dose group and 25 in the extended-dose group were HIV positive (0.54, 0.34-0.85; p=0.009). 393 infants in the single-dose group and 346 in the extended-dose group experienced grade 3 or 4 serious adverse events during the study (p=0.54). Interpretation: Although a 6-week regimen of daily nevirapine might be associated with a reduction in the risk of HIV transmission at 6 weeks of age, the lack of a significant reduction in the primary endpoint - risk of HIV transmission at 6 months - suggests that a longer course of daily infant nevirapine to prevent HIV transmission via breast milk might be more effective where access to affordable and safe replacement feeding is not yet available and where the risks of replacement feeding are high. Funding: US National Institutes of Health; US National Institute of Allergy and Infectious Diseases; Fogarty International Center.

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