TY - JOUR
T1 - Efficacy and safety of an extended nevirapine regimen in infant children of breastfeeding mothers with HIV-1 infection for prevention of postnatal HIV-1 transmission (HPTN 046)
T2 - A randomised, double-blind, placebo-controlled trial
AU - Coovadia, Hoosen M.
AU - Brown, Elizabeth R.
AU - Fowler, Mary Glenn
AU - Chipato, Tsungai
AU - Moodley, Dhayendre
AU - Manji, Karim
AU - Musoke, Philippa
AU - Stranix-Chibanda, Lynda
AU - Chetty, Vani
AU - Fawzi, Wafaie
AU - Nakabiito, Clemensia
AU - Msweli, Lindiwe
AU - Kisenge, Roderick
AU - Guay, Laura
AU - Mwatha, Anthony
AU - Lynn, Diana J.
AU - Eshleman, Susan H.
AU - Richardson, Paul
AU - George, Kathleen
AU - Andrew, Philip
AU - Mofenson, Lynne M.
AU - Zwerski, Sheryl
AU - Maldonado, Yvonne
N1 - Funding Information:
The HIV Prevention Trials Network (HPTN) 046 study was funded by the US National Institutes of Health (NIH), initially through the HPTN and later through the International Maternal Pediatric Adolescent AIDS Clinical Trials (IMPAACT) group. The HPTN (U01AI46749) has been funded by the National Institute of Allergy and Infectious Diseases (NIAID), the Eunice Kennedy Shriver National Institute of Child Health and Human Development (NICHD), National Institute of Drug Abuse (NIDA), and National Institute of Mental Health (NIMH). The IMPAACT Group (U01AI068632) has been funded by NIAID, NICHD, and NIMH. The study products were provided for free by Boehringer-Ingelheim. We thank the mothers and their children who participated in the study; the HPTN 046 study coordinators, counsellors, clinicians, pharmacists, data quality and laboratory staff, and those responsible for recruitment and retention for their dedication and hard work on site; Thomas R Fleming (University of Washington/Fred Hutchinson Cancer Research Center) for his contributions to study design and his strong support throughout study conduct; Scharla Estep (NIAID protocol pharmacist) for her help on pharmaceutical matters; and Avinash Shetty (Wake Forest University Health Sciences) for his contribution to study development and safety data review.
PY - 2012
Y1 - 2012
N2 - Background: Nevirapine given once-daily for the first 6, 14, or 28 weeks of life to infants exposed to HIV-1 via breastfeeding reduces transmission through this route compared with single-dose nevirapine at birth or neonatally. We aimed to assess incremental safety and efficacy of extension of such prophylaxis to 6 months. Methods: In our phase 3, randomised, double-blind, placebo-controlled HPTN 046 trial, we assessed the incremental benefit of extension of once-daily infant nevirapine from age 6 weeks to 6 months. We enrolled breastfeeding infants born to mothers with HIV-1 in four African countries within 7 days of birth. Following receipt of nevirapine from birth to 6 weeks, infants without HIV infection were randomly allocated (by use of a computer-generated permuted block algorithm with random block sizes and stratified by site and maternal antiretroviral treatment status) to receive extended nevirapine prophylaxis or placebo until 6 months or until breastfeeding cessation, whichever came first. The primary efficacy endpoint was HIV-1 infection in infants at 6 months and safety endpoints were adverse reactions in both groups. We used Kaplan-Meier analyses to compare differences in the primary outcome between groups. This study is registered with ClinicalTrials.gov, number NCT00074412. Findings: Between June 19, 2008, and March 12, 2010, we randomly allocated 1527 infants (762 nevirapine and 765 placebo); five of whom had HIV-1 infection at randomisation and were excluded from the primary analyses. In Kaplan-Meier analysis, 1·1 (95 CI 0·3-1·8) of infants who received extended nevirapine developed HIV-1 between 6 weeks and 6 months compared with 2·4 (1·3-3·6) of controls (difference 1·3, 95 CI 0-2·6), equating to a 54 reduction in transmission (p=0·049). However, mortality (1·2 for nevirapine vs 1·1 for placebo; p=0·81) and combined HIV infection and mortality rates (2·3 vs 3·2; p=0·27) did not differ between groups at 6 months. 125 (16) of 758 infants given extended nevirapine and 116 (15) of 761 controls had serious adverse events, but frequency of adverse events, serious adverse events, and deaths did not differ significantly between treatment groups. Interpretation: Nevirapine prophylaxis can safely be used to provide protection from mother-to-child transmission of HIV-1 via breastfeeding for infants up to 6 months of age. Funding: US National Institutes of Health.
AB - Background: Nevirapine given once-daily for the first 6, 14, or 28 weeks of life to infants exposed to HIV-1 via breastfeeding reduces transmission through this route compared with single-dose nevirapine at birth or neonatally. We aimed to assess incremental safety and efficacy of extension of such prophylaxis to 6 months. Methods: In our phase 3, randomised, double-blind, placebo-controlled HPTN 046 trial, we assessed the incremental benefit of extension of once-daily infant nevirapine from age 6 weeks to 6 months. We enrolled breastfeeding infants born to mothers with HIV-1 in four African countries within 7 days of birth. Following receipt of nevirapine from birth to 6 weeks, infants without HIV infection were randomly allocated (by use of a computer-generated permuted block algorithm with random block sizes and stratified by site and maternal antiretroviral treatment status) to receive extended nevirapine prophylaxis or placebo until 6 months or until breastfeeding cessation, whichever came first. The primary efficacy endpoint was HIV-1 infection in infants at 6 months and safety endpoints were adverse reactions in both groups. We used Kaplan-Meier analyses to compare differences in the primary outcome between groups. This study is registered with ClinicalTrials.gov, number NCT00074412. Findings: Between June 19, 2008, and March 12, 2010, we randomly allocated 1527 infants (762 nevirapine and 765 placebo); five of whom had HIV-1 infection at randomisation and were excluded from the primary analyses. In Kaplan-Meier analysis, 1·1 (95 CI 0·3-1·8) of infants who received extended nevirapine developed HIV-1 between 6 weeks and 6 months compared with 2·4 (1·3-3·6) of controls (difference 1·3, 95 CI 0-2·6), equating to a 54 reduction in transmission (p=0·049). However, mortality (1·2 for nevirapine vs 1·1 for placebo; p=0·81) and combined HIV infection and mortality rates (2·3 vs 3·2; p=0·27) did not differ between groups at 6 months. 125 (16) of 758 infants given extended nevirapine and 116 (15) of 761 controls had serious adverse events, but frequency of adverse events, serious adverse events, and deaths did not differ significantly between treatment groups. Interpretation: Nevirapine prophylaxis can safely be used to provide protection from mother-to-child transmission of HIV-1 via breastfeeding for infants up to 6 months of age. Funding: US National Institutes of Health.
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U2 - 10.1016/S0140-6736(11)61653-X
DO - 10.1016/S0140-6736(11)61653-X
M3 - Article
C2 - 22196945
AN - SCOPUS:84856080219
SN - 0140-6736
VL - 379
SP - 221
EP - 228
JO - The Lancet
JF - The Lancet
IS - 9812
ER -