Duration, Pattern of Breastfeeding and Postnatal Transmission of HIV: Pooled Analysis of Individual Data from West and South African Cohorts Renaud Becquet 1,2,3 *, Ruth Bland 1,4 , Vale ´ riane Leroy 2,3 , Nigel C. Rollins 1,5 , Didier K. Ekouevi 2,3,6 , Anna Coutsoudis 5 , Franc ¸ois Dabis 2,3 , Hoosen M. Coovadia 7 , Roger Salamon 2,3 , Marie-Louise Newell 1,8 1 Africa Centre for Health and Population Studies, University of KwaZulu-Natal, Somkhele, South Africa, 2 INSERM, unite ´ 897, Centre de recherche ‘‘Epide ´miologie et Biostatistique’’, Bordeaux, France, 3 Institut de Sante ´ Publique Epide ´miologie De ´veloppement (ISPED), Universite ´ Victor Segalen Bordeaux 2, Bordeaux, France, 4 Division of Developmental Medicine, University of Glasgow, Glasgow, United Kingdom, 5 Department of Paediatrics and Child Health, University of KwaZulu-Natal, Durban, South Africa, 6 ANRS site in Co ˆ te d’Ivoire (PAC-CI), Centre Hospitalier Universitaire de Treichville, Abidjan, Co ˆ te d’Ivoire, 7 Centre for HIV/AIDS Networking, University of KwaZulu- Natal, Durban, South Africa, 8 Centre for Paediatric Epidemiology and Biostatistics, Institute of Child Health, University College London, London, United Kingdom Abstract Background: Both breastfeeding pattern and duration are associated with postnatal HIV acquisition; their relative contribution has not been reliably quantified. Methodology and Principal Findings: Pooled data from 2 cohorts: in urban West Africa where breastfeeding cessation at 4 months was recommended but exclusive breastfeeding was rare (Ditrame Plus, DP); in rural South Africa where high rates of exclusive breastfeeding were achieved, but with longer duration (Vertical Transmission Study, VTS). 18-months HIV postnatal transmission (PT) was estimated by Kaplan-Meier in infants who were HIV negative, and assumed uninfected, at age .1 month. Censoring with (to assess impact of mode of breastfeeding) and without (to assess effect of breastfeeding duration) breastfeeding cessation considered as a competing event. Of 1195 breastfed infants, not HIV-infected perinatally, 38% DP and 83% VTS children were still breastfed at age 6 months. By age 3 months, 66% of VTS children were exclusively breastfed since birth and 55% of DP infants predominantly breastfed (breastmilk+water-based drinks). 18-month PT risk (95%CI) in VTS was double that in DP: 9% (7–11) and 5% (3–8), respectively (p = 0.03). However, once duration of breastfeeding was allowed for in a competing risk analysis assuming that all children would have been breastfed for 18- month, the estimated PT risk was 16% (8–28) in DP and 14% (10–18) in VTS (p = 0.32). 18-months PT risk was 3.9% (2.3–6.5) among infants breastfed for less than 6 months, and 8.7% (6.8–11.0) among children breastfed for more than 6 months; crude hazard ratio (HR): 2.1 (1.2–3.7), p = 0.02; adjusted HR 1.8 (0.9–3.4), p = 0.06. In individual analyses of PT rates for specific breastfeeding durations, risks among children exclusively breastfed were very similar to those in children predominantly breastfed for the same period. Children exposed to solid foods during the first 2 months of life were 2.9 (1.1–8.0) times more likely to be infected postnatally than children never exposed to solids this early (adjusted competing risk analysis, p = 0.04). Conclusions: Breastfeeding duration is a major determinant of postnatal HIV transmission. The PT risk did not differ between exclusively and predominantly breastfed children; the negative effect of mixed breastfeeding with solids on PT were confirmed. Citation: Becquet R, Bland R, Leroy V, Rollins NC, Ekouevi DK, et al. (2009) Duration, Pattern of Breastfeeding and Postnatal Transmission of HIV: Pooled Analysis of Individual Data from West and South African Cohorts. PLoS ONE 4(10): e7397. doi:10.1371/journal.pone.0007397 Editor: Landon Myer, University of Cape Town, South Africa Received June 26, 2009; Accepted August 22, 2009; Published October 16, 2009 Copyright: ß 2009 Becquet et al. This is an open-access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited. Funding: This work was supported by the French charity Sidaction, the Agence Nationale de Recherches sur le Sida et les Hepatites Virales (ANRS) and the Wellcome Trust. Renaud Becquet was funded until the end of 2008 by the French charity SIDACTION as a visiting scientist at the Africa Centre for Health and Population Studies (University of KwaZulu-Natal, South Africa). The primary sponsor of the Ditrame Plus study was the ANRS. The Africa Centre for Health and Population Studies was supported by a core centre grant from the Wellcome Trust (050524), and the Vertical Transmission Study by an additional grant (Wellcome Trust, UK 063009/Z/00/2). This pooled analysis was funded by an additional grant from the French charity SIDACTION. The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript. Competing Interests: The authors have declared that no competing interests exist. * E-mail: Renaud.Becquet@isped.u-bordeaux2.fr Introduction HIV can be transmitted from mother to infant during pregnancy, delivery or postnatally through breastfeeding, and is a major cause of child mortality in sub-Saharan Africa [1]. Mother-to-child transmission of HIV occurring around delivery can be largely prevented by peri-partum antiretroviral regimens [2]. As a consequence, HIV transmission through breastmilk has emerged as a more important mode of paediatric acquisition in African breastfeeding populations [3], and its prevention remains challenging [4]. Exclusive breastfeeding has been reported to carry a lower postnatal HIV transmission risk than breastfeeding while concur- rently feeding other milks, non-milk fluids, and solid foods [5–7]. PLoS ONE | www.plosone.org 1 October 2009 | Volume 4 | Issue 10 | e7397