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Relationship between mortality and feeding modality among children born to HIV-infected mothers in a research setting: the Kesho Bora Study

Cournil, Amandinea; De Vincenzi, Isabelleb; Gaillard, Philippeb; Cames, Cécilea; Fao, Paulinc; Luchters, Stanleyd,e,f; Rollins, Nigelg,h; Newell, Marie-Louisei; Bork, Kirstena; Read, Jennifer S.j,kfor the Kesho Bora Study Group

doi: 10.1097/QAD.0b013e32835d5226
Epidemiology and Social

Objective: To assess the relationship between infant feeding practices and mortality by 18 months of age among children born to HIV-infected mothers in the Kesho Bora trial (Burkina-Faso, Kenya and South Africa).

Methods: Enrolled HIV-infected women were counseled to choose between breastfeeding up to 6 months or replacement feeding from delivery. Multivariable Cox models were used to compare the infant mortality risks according to feeding practices over time defined as never breastfed, weaned or still breastfed. The category ‘still breastfed’ was disaggregated as exclusively, predominantly or partially breastfed to compare modes of breastfeeding. The relationship between weaning and mortality was also assessed using marginal structural models to control for time-dependent confounders, such as maternal or infant morbidity (reverse causality).

Results: Among 795 mothers, 618 (77.7%) initiated breastfeeding. Mortality rates by 18 months among uninfected and infected children were 6 and 38%, respectively. Never breastfed and weaned children were at greater risk of death compared with those still breastfed. Adjusted hazard ratios were 6.7 [95% confidence interval (CI)=2.5–17.9; P < 0.001] and 6.9 (CI = 2.8–17.2; P < 0.001) for never breastfed and weaned children, respectively. Estimation of the effect of weaning using marginal structural models led to similar results. No statistically significant differences were observed according to mode of breastfeeding (exclusive, predominant or partial).

Conclusion: Within 6 months after birth, weaned or never breastfed children were at about seven-fold higher risk of dying compared with children who were still breastfed despite a context in which interventions were provided to reduce risks associated with replacement feeding.

Supplemental Digital Content is available in the text

aInstitut de Recherche pour le Développement, University of Montpellier, Montpellier, France

bWHO, Reproductive Health and Research, Geneva, Switzerland

cCentre Muraz, Bobo-Dioulasso, Burkina Faso

dInternational Centre for Reproductive Health (ICRH), Mombasa, Kenya

eInternational Centre for Reproductive Health, Ghent University, Ghent, Belgium

fCentre for International Health, Burnet Institute, Melbourne, Victoria, Australia

gUniversity of KwaZulu-Natal, Durban, South Africa

hDepartment of Maternal, Newborn, Child and Adolescent Health, World Health Organization, Geneva, Switzerland

iAfrica Centre for Health and Population Studies, University of KwaZulu-Natal, Somkhele, South Africa

jEunice Kennedy Shriver National Institute of Child Health and Human Development, National Institutes of Health, Bethesda, Maryland

kNVPO/OASH/OS/DHHS, Washington, DC, USA.

*The Kesho Bora Study Group members are listed in the Appendix.

Correspondence to Amandine Cournil, Institut de Recherche pour le Développement, BP 64501, 34394 Montpellier Cedex 5, France. Tel: +33 4 67 41 63 22; fax: +33 4 67 41 63 30; e-mail:

Received 21 August, 2012

Revised 26 November, 2012

Accepted 29 November, 2012

Supplemental digital content is available for this article. Direct URL citations appear in the printed text and are provided in the HTML and PDF versions of this article on the journal's Website (

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Without interventions, the risk of breastmilk transmission of HIV after 4–6 weeks of age is about 0.8% per month of breastfeeding [1,2]. Complete avoidance of breastfeeding is the only way of totally preventing mother-to-child transmission (MTCT) of HIV through breastmilk. However, avoidance of breastfeeding and early cessation have been associated with increased risks of morbidity and mortality in resource-constrained settings [3–11]. Recently, clinical trials have demonstrated the efficacy of antiretroviral prophylaxis in reducing the risk of MTCT through breastmilk [12–16]. Providing maternal or infant antiretroviral drugs while breastfeeding thus appears to be a promising strategy to keep children alive while remaining HIV-uninfected in resource-constrained settings where formula feeding is not safe [17].

Meanwhile, several aspects of the association between infant feeding modality and mortality need further investigation. First, the contribution of infant and maternal morbidity as a determinant of both breastfeeding cessation and death of the child (i.e. reverse causality) has not been fully addressed. Second, it is unclear to what extent mortality is a consequence of a deleterious effect of the event of weaning or of the fact of receiving replacement feeding per se. Third, little information is available regarding the association between the degree of exclusivity of breastfeeding and mortality.

The present analysis aimed to address these issues using data collected in the Kesho Bora randomized controlled trial (RCT), conducted in three countries of sub-Saharan Africa. This trial assessed the efficacy of antiretroviral prophylaxis to reduce MTCT of HIV and followed mother-infant pairs from birth to 12–24 months postpartum with collection of detailed data on infant feeding practices and morbidity. Women were counselled to either breastfeed exclusively up to 6 months or to formula-feed from birth, but nonexclusive breastfeeding was common and many women breastfed for considerably less than 6 months. Feeding practices within the first 6 months were highly heterogeneous, providing a good opportunity to assess the relationship between mortality and infant feeding mode.

Specific objectives were: to compare mortality risks according to breastfeeding practices defined as never breastfed, weaned (stopped all breastfeeding) or still breastfed and according to breastfeeding type namely, exclusive, predominant and partial breastfeeding; and to assess whether child's or mother's health events prior to breastfeeding cessation contributed to any observed associations between breastfeeding cessation and mortality.

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The design of the Kesho Bora RCT has been described in detail previously [12,18]. Briefly, pregnant women were enrolled at antenatal clinics at five study sites (Bobo-Dioulasso, Burkina Faso; Mombasa, Kenya; Nairobi, Kenya; Durban, South Africa and Somkhele, South Africa). Enrolment criteria for the RCT were gestational age below 34 weeks, WHO clinical stage 1, 2, or 3, and a CD4 cell count of 200–500 cells/μl. Women were randomized to initiate either triple antiretroviral prophylaxis [combination of zidovudine (ZDV), lamiduvine, and lopinavir/ritonavir; = triple ARV] until cessation of breastfeeding or the South-African standard antiretroviral prophylaxis for MTCT [ZDV until delivery with single dose nevirapine (NVP) to women at the onset of labour and to the newborn infant; = ZDV/sdNVP].

Ethical clearance for the study was given by the ethical and regulatory committees in Burkina Faso, Kenya, and South Africa, and at the WHO and the US Centers for Disease Control and Prevention. All women provided written consent. The RCT was registered with Current Controlled Trials, ISRCTN71468401.

Infant feeding counselling based on 2004 WHO guidelines [19] was provided individually to all women by dedicated nutritionists or nurse counsellors [20,21].

Mother–infant pairs were seen at birth, every 2 weeks until 8 weeks after delivery, monthly until 12 months and every 3 months until 18 months to assess clinical, nutritional and biological characteristics. Infant-feeding patterns were assessed by interviewers, who were not involved in infant feeding counselling (with the exception of Bobo-Dioulasso study site) using an adaptation of the WHO infant-feeding assessment tool [22]. At each visit, mothers were asked if their child has been given breastmilk, replacement feeding or both. From the 2-week to the 6-month visit, an additional questionnaire was used for breastfeeding women to record foods or fluids ever given since the last scheduled visit.

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Inclusion criteria and definitions for this analysis

Women enrolled in the RCT and their live born infants were included in the analysis if at least one visit for which infant feeding was reported and at least one HIV PCR test result for the child was available. The mode of feeding was first defined as never breastfed for children who received only replacement feeding from birth and as ever breastfed for children who were ever breastfed, irrespective of the duration of breastfeeding. Second, ever-breastfed children were classified at each point of time as still breastfed or weaned. The time at weaning was defined as the last visit at which breastfeeding was reported. Children who died or were lost to follow-up before weaning were considered to have been breastfed up to the date of death (for those who died) or the date of the last contact (for those lost to follow-up). Third, still breastfed children were further classified at each timepoint from birth to 6 months as exclusively, predominantly or partially breastfed according to which fluids and foods they received [23–25]. A child who was breastfed at a given age while having never received any other food or drink with the exception of drops or syrups consisting of vitamins, mineral supplements or medicines, was considered as exclusively breastfed. A child who was breastfed at a given age having ever received food-based fluid, solid-food or nonhuman milk was considered as partially breastfed. Breastfed children having been given water or water-based drinks only were predominantly breastfed [26,27].

A protected source of water was defined as available if piped water into the house or compound was the main source of drinking water. A socioeconomic score was calculated by multiple correspondence analysis using eight household assets [28,29]. This score was categorized in tertiles of increasing economic level within each study site. Three periods of enrollment were defined: 2005–06, 2007 and 2008. Serious adverse events (SAEs) were defined as previously described [12]. Low birth weight was defined as a birth weight below 2500 g. Cotrimoxazole prophylaxis was defined as until 12 months versus less than 12 months (including none).

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Statistical analysis

Maternal and infant characteristics were compared between ‘never’ and ‘ever’ breastfed groups using Student's t-test and the χ2-test. Kaplan–Meier survival analyses were used to estimate cumulative child mortality. Log rank test was used to compare mortality between infant feeding groups (never versus ever breastfed).

Cox proportional hazards survival analyses were used to assess association of infant mortality with infant feeding patterns. Hazard ratios (HRs) and adjusted hazard ratios (aHRs) and 95% confidence intervals (CIs) were obtained. Infant-feeding mode was included as a fixed variable with two modalities (ever and never breastfed) [model 1]. Then, feeding practice (still breastfed, weaned and never breastfed) was tested as a time-varying variable [model 2]. In a third analysis, the modality ‘still breastfed’ was further split into three categories: exclusively, predominantly or partially ‘still breastfed’ [model 3]. Model three was run for the first 6 months of age in which these different feeding practices are defined. In addition to infant feeding variable, any available baseline variable (as listed in Table 1) was included in the models if its association with mortality in univariate analysis had a P-value below 0.25. Study sites were included in all models as a fixed effect. Missing data were considered as a specific category in all analyses to ensure stability of the sample sizes. Piece-wise time-varying covariates for age at complete breastfeeding cessation were introduced to assess whether the association between weaning and mortality were constant over time. Three age groups were considered: 0–2.9; 3–4.9; and 5 months and above. Interactions between any ‘baseline’ variable and infant-feeding variables were added in the model to identify effect modifiers. Some analyses were done separately according to HIV-infection status of the child, treatment allocation (triple ARV vs. ZDV/sdNVP prophylaxis) and cotrimoxazole prophylaxis, even in the absence of significant interaction terms. Estimated survival curves according to feeding practices (time-varying variables) were obtained using the Simon and Makuch method [30] (Fig. 1).

Table 1

Table 1

Fig. 1

Fig. 1

To address reverse causality, we reviewed data (i.e. routinely collected maternal recall of any infant feeding modification due to the illness leading to death) from the SAE form reporting the death of the child to determine whether the mother reported that she changed the way she fed her child as a result of health events. We also applied marginal structural models to estimate the effect of breastfeeding cessation on children's deaths by appropriate control for the effects of time-dependent confounders (i.e. the child's or the mother's health events) [31,32]. Three time-dependent covariates corresponding to the occurrence of an SAE for the child (excluding deaths) or for the mother and occurrence of a health event (diarrhea, vomiting or fever) for the child were considered. First, logistic regression models were fitted to predict patient-specific and time-specific probabilities of weaning as a function of baseline variables (as listed in Table 1) and health event variables as defined above. These predicted probabilities were then used to derive inverse probability weights (IPWs) for weaning. Second, these IPWs were used in a weighted pooled logistic model, which included baseline confounders and breastfeeding cessation variable, to estimate the parameters of a proportional hazards marginal structural model. The assumption of positivity was assessed by checking that all categories of exposure (weaned or not) were observed for the most important confounders. We also checked that stabilized weights satisfied the condition of small variability.

SAS (version 9.2; Cary, North Carolina, USA) and Stata (version 10.1; Stata Corp, College Station, Texas, USA) statistical software were used to conduct these analyses.

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Size and characteristics of the study population

Of 824 HIV-infected women enrolled in the Kesho Bora RCT, 805 delivered live born infants between June 2005 and August 2008. Of these 805 infants, six died before feeding initiation, two were lost to follow-up before recording information on the first feeding, and two died without a PCR test to determine HIV-infection status. Therefore, the study population for this analysis comprised 795 mother-infant pairs. Of these, 177 (22.3%) mothers never breastfed, whereas 618 (77.7%) initiated breastfeeding (Table 1). Compared with mothers who initiated breastfeeding, mothers who chose replacement feeding had a higher level of education and were more likely to have access to a protected source of water. They were also more likely to have a CD4+cell countless than 350 cells/μl and to have had a Caesarean delivery. Cumulative follow-up rates at the 18-month visit (excluding deaths) were similar in formula fed and ever-breastfed children (89.3 versus 87.1%; P = 0.43).

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Mortality among ever and never breastfed infants

A total of 63 children died within 18 months. The estimated overall mortality rate was 4.5% by 6 months, 7.4% by 12 months, and 8.3% by 18 months of age. The estimated cumulative mortality rate by 18 months was 10.5% in the never breastfed group compared with 7.7% among ever breastfed children, but the difference was not statistically significant (P-value for log-rank test = 0.20).

In univariate or multivariate analyses, study site, maternal age, maternal education, source of water, socioeconomic score, treatment allocation, maternal HIV-related characteristics at delivery (CD4 cell count and viral load), mode of delivery, infant characteristics (sex, birth weight) and cotrimoxazole prophylaxis were not associated with mortality. Period of enrollment showed a weak association with mortality in univariate analysis (see table, supplemental digital content 1, The risk of death tended to be higher for never-breastfed children compared with ever-breastfed children (Table 2, Model 1). HIV infection status of the child was strongly associated with the probability of death (aHR, 8.0; CI, 4.5;14.2; P < 0.001).

Table 2

Table 2

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Mortality and infant feeding practices over time

The median duration of breastfeeding was 4.9 months (interquartile range, 2.8;6.0). A total of 161 (26.1%) mothers stopped breastfeeding before their child reached 3 months of age, 162 (26.2%) mothers continued to breastfeed at 6 months of age. Weaned and never-breastfed children were at greater risk of death compared with still-breastfed children with similar adjusted HRs (Table 2, Model 2 and Fig. 1).

Interaction terms combining study arm, HIV infection status of the child or cotrimoxazole use with infant feeding modality were not statistically significant (P > 0.20) and HR estimates in adjusted analyses were similar across the different subgroups. The aHR of weaned versus still breastfed was 8.7 (CI: 2.7–28.5; P < 0.001) and aHR of never breastfed versus still breastfed was 7.8 (CI: 2.3–26.7; P = 0.001) among uninfected children. In infected children aHR of weaned versus still breastfed was equal to 4.8 (CI: 1.1–20.3; P = 0.03) and aHR of never breastfed versus still breastfed was 5.5 (CI: 0.9–31.6; P = 0.06). The excess of mortality among weaned or never-breastfed children compared with still breastfed was also observed in the ZDV/sdNVP arm [aHR (weaned): 8.9; CI: 2.7;29.8; P < 0.001; aHR(never breastfed): 8.7; CI: 2.4;31.1; P < 0.001] and to a lesser extent in the triple ARV arm [aHR (weaned): 4.4; CI: 1.1;17.8; P = 0.04; aHR (never breastfed): 3.7; CI: 0.8;16.4; P = 0.09]. Results were less homogeneous when stratifying by cotrimoxazole prophylaxis. An excess of mortality among weaned or never breastfed children compared with still breastfed children was found in those who received cotrimoxazole prophylaxis until 12 months [aHR (weaned): 6.2; CI: 2.2;17.3; P < 0.001; aHR(never breastfed): 5.7; CI: 1.7;18.9; P < 0.01] but not among children who did not receive the prophylaxis throughout infancy [aHR (weaned): 0.8; CI: 0.1;8.5; P = 0.83; aHR (never breastfed): 1.3; CI: 0.2;9.3; P = 0.76].

Gastroenteritis and pneumonia accounted for 71% of all causes of death in weaned and formula fed children, whereas gastroenteritis was never reported as a cause of death in children who were still breastfed at the time of death (Table 3).

Table 3

Table 3

To investigate whether the association between weaning and mortality varied with age, we assessed the effect of weaning before 3 months and between 3 and 4.9 months by introducing two time-varying covariates for these two periods in comparison with weaning from 5 months of age. Among ever breastfed children, weaning before 3 months was associated with a 3.5-fold increase in mortality (CI: 1.7;7.3; P < 0.001), whereas weaning at 3 to 4.9 months was associated with a 2.2-fold increase (CI: 0.9–5.4; P = 0.08) compared with weaning after 5 months.

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Reverse causality and time-varying confounders

Breastfeeding cessation as a consequence of a serious illness that led to death was reported in one case. Overall, the median period of time between breastfeeding cessation and death was 2.4 months [interquartile range (IQR): 1.4–5.4] and only one child died within 15 days after breastfeeding cessation.

Marginal structural models were used to account for time-dependent confounding. For ever-breastfed children, the unweighted model (i.e. without controlling for health event confounding) indicated that weaned children had a higher risk of mortality compared with still breastfed with an adjusted HR of 5.0 (CI: 1.8–13.6). The aHR obtained from the full weighted-model was slightly attenuated [4.4 (CI: 1.6–11.9)]. Similar HR attenuation was observed in uninfected and infected children (data not shown).

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Mortality and mode of breastfeeding over time

Of 618 women, who initiated breastfeeding, 246 (39.8%) and 137 (22.2%) were still exclusively breastfeeding at 3 and 5 months, respectively. One hundred and four (16.8%) practiced partial breastfeeding for more than 1 month, in the first 6 months. When disaggregated by breastfeeding type, there was no statistical difference in the risk of death within the first 6 months between children who were exclusively, predominantly or partially breastfed (Table 2, Model 3). Weaned and never-breastfed children were at a substantially higher risk of mortality in comparison with exclusively breastfed children.

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The relationship between infant feeding practices and mortality was investigated in 795 children born to HIV-infected mothers in three countries of sub-Saharan Africa. No evidence of difference in mortality risks was found when comparing never breastfed to ever-breastfed children. If mode of feeding was taken into account using time-dependent variables, weaned or never-breastfed children were at about a seven-fold higher risk of dying compared with children who were still breastfed. Additional results indicated that the adverse effect associated with breastfeeding cessation decreased with increasing age of infant between birth and 6 months of age. Moreover, although evaluating associations in sub-samples like infection status or trial arm may have been limited by the small number of events, breastfeeding appears to remain protective for HIV-infected infants as for HIV-uninfected ones, and whether or not the mother receives antiretroviral prophylaxis during breastfeeding.

Previous studies documenting an association between feeding modality and mortality among HIV-exposed children have shown that, at best, replacement feeding results in no benefit in survival [7,33–37] and, at worse, results in a six-fold increase in mortality by 12 months of age compared with breastfeeding [3,5]. Heterogeneity of findings between these reported studies can be explained by different socioeconomic and cultural settings. The definition of infant-feeding modality (fixed or time-dependent variable) used in studies might also have led to the different magnitude of effect; however the direction of effect was consistent in the various studies.

In agreement with observations made by Kuhn and colleagues [11], our results indicated a continuous adverse effect of receiving replacement feeding after cessation of breastfeeding, rather than a temporary deleterious effect of the event of weaning. First, deaths in weaned children were not concentrated in the period immediately following weaning but were homogeneously distributed in the whole period of replacement and complementary feeding. Second, HRs were similar in weaned and never breastfed children. The median time period between breastfeeding cessation and death was 2.4 months, which is longer than in a study in rural Uganda (i.e. 1.5 months) despite similar duration of follow-up, maybe because the level of schooling and hygiene were lower in the latter [3].

No evidence of difference between exclusive and predominant breastfeeding was found, and partial breastfeeding was associated with an intermediate risk between exclusive/predominant and replacement feeding. However, the number of events was limited in the partial category and the study was not powered to examine this question. Several studies have documented the relationship between breastfeeding mode and HIV transmission or HIV-free survival in HIV-exposed children [38–42] whereas others focused specifically on morbidity or mortality of children [3,9,39,43]. Overall, these studies indicated that exclusive breastfeeding is associated with the lowest risks of transmission, morbidity and mortality, and partial breastfeeding with the highest, but the difference between these two categories was reduced for mortality risk.

An important strength of this study lies in the effort made to control for confounding, notably of time-dependent variables. Indeed, the study of infant-feeding modality and mortality may be affected by a time-dependent confounding, which cannot be handled by traditional statistical means. Few studies have addressed this issue of reverse causality [11,44,45]. Some investigators tried to account for situations in which breastfeeding cessation and death both caused by a serious illness occurred within a short time, about 1 week. In this analysis, we addressed the issue of reverse causality by using marginal structural models. It allowed us to account for potential reverse causality situations wherein an illness episode, breastfeeding cessation, and death could occur over a long period. Although the child's and the mother's morbidity were determinants of weaning (results not shown), the amount of confounding was low. Marginal structural models are appropriate tools to explore causal relationships. However, estimation of the causal effect relies on several assumptions including the assumption of exchangeability, that is, all confounders are measured and appropriately taken into account in the models. Although we cannot exclude the possibility of unmeasured confounding, the great amount of information collected during the Kesho Bora trial allowed us to include all major potential confounders in the analysis.

It should be pointed out that breastfeeding durations were limited to approximately 6 months. Women were strongly encouraged to wean by that age in agreement with international and national recommendations at the time of the study. Our results cannot necessarily be generalized to longer periods of breastfeeding. However, it seems reasonable to hypothesize that the decrease in the protective effect of breastfeeding with increasing child age demonstrated within the 0–6-month age interval continues beyond the age of 6 months.

Four out of five of the Kesho Bora study sites were in urban African settings. Our results cannot be generalized to rural areas. However, it is likely that the detrimental effect of non or short-duration breastfeeding would be even larger in more remote rural areas.

In conclusion, the data presented here confirm the benefits of breastfeeding for survival of HIV-exposed children for the first 6 months in a context in which extensive counseling, support and other interventions were provided to reduce risks. Additionally, they confirm the potential risks of replacement feeding, independent of the event of weaning. In resource-constrained settings, it has long been recognized that promotion of breastfeeding is a key intervention for reducing the mortality among HIV-exposed and nonexposed children. In the context of antiretroviral drugs being available to reduce postnatal transmission through breastmilk, interventions to support HIV-infected mothers to exclusively breastfeed should be prioritized to promote HIV-free survival of HIV-exposed children.

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We thank all participants enrolled in the study. We acknowledge Pierre de Beaudrap for statistical advice.

Author contribution: J.S.R., A.C., I.D.V., K.B. conceived the analysis. A.C. performed the analysis with the contribution of P.G., C.C. and K.B. for infant feeding definitions implementation. A.C., J.S.R., K.B., I.D.V. wrote the article. All authors read, commented and approved the final version of the article.

The Kesho Bora Study Group and the study sites: Bobo Dioulasso, Burkina Faso (Centre Muraz): Nicolas Meda (Principal Investigator), Paulin Fao, Odette Ky-Zerbo, Clarisse Gouem (Study coordinators), Paulin Somda, Hervé Hien, Patrice Elysée Ouedraogo, Dramane Kania, Armande Sanou, Ida Ayassou Kossiwavi, Bintou Sanogo, Moussa Ouedraogo, Issa Siribie (Investigators), Diane Valéa (Laboratory Coordinator), Sayouba Ouedraogo & Roseline Somé (Data Managers), François Rouet (Inter-Site Laboratory Coordination); Durban, South Africa (University of KwaZulu Natal): Nigel Rollins (Principal Investigator), Lynne McFetridge, Kevi Naidu (Study Coordinators); Mombasa, Kenya (International Centre for Reproductive Health): Stanley Luchters, Marcel Reyners (Principal Investigators), Eunice Irungu (Study Coordinator), Christine Katingima, Mary Mwaura and Gina Ouattara (Investigators), Kishor Mandaliya, Sammy Wambua (Laboratory Coordinators), Mary Thiongo (Data Manager); Nairobi, Kenya (Network for AIDS Researchers in East and Southern Africa): Ruth Nduati (Principal Investigator), Judith Kose (Study Coordinator), Ephantus Njagi (Laboratory Coordinator), Peter Mwaura (Data Manager). Somkhele, South Africa (Africa Centre for Health and Population Studies, University of KwaZulu Natal): Marie-Louise Newell (Principal Investigator), Stephen Mepham (Study Coordinator), Johannes Viljoen (Laboratory Coordinator), Ruth Bland (Investigator), Londiwe Mthethwa (Data Manager).

Supporting institutions: Agence Nationale de Recherches sur le SIDA et les hépatites virales, France: Brigitte Bazin and Claire Rekacewicz (Sponsor Representatives); Centers for Disease Control and Prevention, USA: Allan Taylor (Sponsor Representative and Co-Investigator), Nicole Flowers, Michael Thigpen, Mary Glenn Fowler, Denise Jamieson (Co-Investigators); Eunice Kennedy Shriver National Institute of Child Health and Human Development, National Institutes of Health, USA: Lynne M. Mofenson (Sponsor Representative), Jennifer S. Read (Co-Investigator); Institut de Recherche pour le Développement (IRD), Montpellier, France: Kirsten Bork, Cécile Cames and Amandine Cournil (Nutrition Coordination); International Centre for Reproductive Health (ICRH), Ghent University, Ghent, Belgium: Patricia Claeys, Marleen Temmerman, Stanley Luchters (Sponsor Representatives); Université Montpellier 1, EA 4205 ‘Transmission, Pathogenèse et Prévention de l’infection par le VIH’ ; and CHU Montpellier, Laboratoire de Bactériologie-Virologie, Montpellier, France: Philippe Van de Perre, Pierre Becquart (until December 2006), Vincent Foulongne, Michel Segondy (Laboratory Coordination).

Study coordination: World Health Organization, Geneva, Switzerland: Isabelle de Vincenzi (Study Coordinator), Philippe Gaillard (Site Coordinator), Tim Farley (Project Manager), Ndema Habib (Study Statistician), Sihem Landoulsi (Study Analyst).

Financial support was provided by Agence Nationale de Recherches sur le SIDA et les hépatites virales (ANRS), Department for International Development (DFID), European and Developing Countries Clinical Trials Partnership (EDCTP), Thrasher Research Fund, Belgian Directorate General for International Cooperation, GlaxoSmithKline Foundation, Centers for Disease Control and Prevention, Eunice Kennedy Shriver National Institute of Child Health and Human Development, UNDP/UNFPA/UNICEF/World Bank/WHO Special Programme of Research, Development and Research Training in Human Reproduction and the Victorian Operational Infrastructure Support Program.

Funding: The Bobo-Dioulasso site was funded by l’Agence Nationale de Recherches sur le Sida et les Hépatites Virales (ANRS) and UNDP/UNFPA/World Bank/WHO Special Programme of Research, Development and Research Training in Human Reproduction (WHO/HRP).

The Mombasa site was funded by ANRS, WHO/HRP, European and Developing Countries Clinical Trials Partnership (EDCTP), Thrasher Research Fund, Belgian Directorate General for International Cooperation.

The Nairobi site was funded by the Centers for Disease Control and Prevention (CDC) and the Eunice Kennedy Shriver National Institute of Child Health and Human Development (NICHD) through a cooperative agreement.

The South-African sites were funded by the Department for International Development (DFID), EDCTP, UNICEF and WHO/HRP.

The Nutrition and laboratory coordination were funded by ANRS.

The overall coordination and external monitoring was funded by WHO/HRP.

The findings and conclusions in this report are those of the authors and do not necessarily represent the views of the World Health Organization, of the Centers for Disease Control and Prevention or of the National Institutes of Health

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Conflicts of interest

The authors have no conflict of interest to disclose.

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Africa; breastfeeding; HIV-exposed children; marginal structural models; mortality; replacement feeding

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