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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): a randomised, double-blind, placebo-controlled trial.
Lancet 2012; 379(9812):221-8Lct

Abstract

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.

Authors+Show Affiliations

Maternal Adolescent and Child Health (MatCH), University of the Witwatersrand, Johannesburg, South Africa. hcoovadia@match.org.zaNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info available

Pub Type(s)

Clinical Trial, Phase III
Journal Article
Multicenter Study
Randomized Controlled Trial
Research Support, N.I.H., Extramural

Language

eng

PubMed ID

22196945

Citation

Coovadia, Hoosen M., et al. "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): a Randomised, Double-blind, Placebo-controlled Trial." Lancet (London, England), vol. 379, no. 9812, 2012, pp. 221-8.
Coovadia HM, Brown ER, Fowler MG, et al. 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): a randomised, double-blind, placebo-controlled trial. Lancet. 2012;379(9812):221-8.
Coovadia, H. M., Brown, E. R., Fowler, M. G., Chipato, T., Moodley, D., Manji, K., ... Maldonado, Y. (2012). 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): a randomised, double-blind, placebo-controlled trial. Lancet (London, England), 379(9812), pp. 221-8. doi:10.1016/S0140-6736(11)61653-X.
Coovadia HM, et al. 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): a Randomised, Double-blind, Placebo-controlled Trial. Lancet. 2012 Jan 21;379(9812):221-8. PubMed PMID: 22196945.
* Article titles in AMA citation format should be in sentence-case
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): 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, AU - ,, Y1 - 2011/12/22/ PY - 2011/12/27/entrez PY - 2011/12/27/pubmed PY - 2012/2/24/medline SP - 221 EP - 8 JF - Lancet (London, England) JO - Lancet VL - 379 IS - 9812 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. SN - 1474-547X UR - https://www.unboundmedicine.com/medline/citation/22196945/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_:_a_randomised_double_blind_placebo_controlled_trial_ L2 - https://linkinghub.elsevier.com/retrieve/pii/S0140-6736(11)61653-X DB - PRIME DP - Unbound Medicine ER -