Share this article on:

Acceptability of Formula-Feeding to Prevent HIV Postnatal Transmission, Abidjan, Côte d'Ivoire: ANRS 1201/1202 Ditrame Plus Study

Leroy, Valériane MD, PhD*; Sakarovitch, Charlotte PhD*; Viho, Ida MD; Becquet, Renaud PhD*; Ekouevi, Didier Koumavi MD, PhD*†; Bequet, Laurence MD; Rouet, François PharmD, PhD; Dabis, François MD, PhD*; Timite-Konan, Marguerite MD§the ANRS 1201/1202 Ditrame Plus Study Group

JAIDS Journal of Acquired Immune Deficiency Syndromes: January 1st, 2007 - Volume 44 - Issue 1 - p 77-86
doi: 10.1097/01.qai.0000243115.37035.97
Epidemiology and Social Science

Objective: To describe the maternal acceptability of formula-feeding proposed to reduce postnatal HIV transmission in Abidjan, Côte d'Ivoire.

Methods: Each consenting HIV-infected pregnant women, age ≥18 years, who received a perinatal antiretroviral prophylaxis was eligible. Two hierarchical infant-feeding options were proposed antenatally: exclusive formula-feeding or short-term exclusive breast-feeding. Formula-feeding was provided free up to age 9 months. Determinants of acceptability were analyzed using a logistic regression. Formula-feeding failure was defined as having breast-fed one's child at least once.

Results: Between March 2001 and March 2003, 580 women delivered: 97% expressed their infant-feeding choice before delivery; 53% chose formula-feeding. Significant prenatal determinants for refusing formula-feeding were: living with her partner, being Muslim, having a low educational level, being followed in one of the study sites, having not disclosed her HIV status, and having been included within the first 6 months of the project. Among the 295 mothers who formula-fed, the Kaplan-Meier probability of success of the formula-feeding option was 93.6% at Day 2 (95% confidence interval [CI]: 90.7% to 96.3%) and 84.2% at 12 months (95% CI: 79.9% to 88.5%): 46 of 295 (15.6%) women breast-fed at least once, of whom 41% temporarily practiced mixed-feeding at Day 2 because of social stigma or newborn poor health.

Conclusions: In settings with general access to clean water, structured antenatal counseling, and sustained provision of free formula, slightly over half of HIV-infected women chose to artificially feed their newborn infant. Low mixed-feeding rates were observed. This social acceptability must be balanced with mother-child long-term health outcomes to guide safe recommendations on infant-feeding among HIV-infected women in African urban settings.

From *INSERM, 593 Institut de Santé Publique, Epidémiologie et Développement (ISPED), Université Victor Segalen, Bordeaux, France; †Projet ANRS Ditrame Plus, Programme PACCI, Centre Hospitalier Universitaire de Treichville, Abidjan, Côte d'Ivoire; ‡Centre de Diagnostic et de Recherches sur le SIDA (CeDReS), CHU de Treichville, Abidjan; and §Service de Pédiatrie, Centre Hospitalier Universitaire de Yopougon, Abidjan.

Received for publication April 27, 2006; accepted August 18, 2006.

The primary sponsor of the ANRS 1201/1202 Ditrame-Plus study was the Agence Nationale de Recherches sur le Sida (ANRS). Renaud Becquet was a fellow of the French Ministry of Education, Research and Technology and is now a post-doctoral fellow of the French charity SIDACTION. Didier K. Ekouevi was a fellow of the French charity SIDACTION and is now a post-doctoral fellow of the European Clinical Trial Partnership (EDCTP). Laurence Bequet was supported by the French Ministry of Foreign Affairs.

None of the authors have any conflict of interest to declare.

This study was presented in part at the 14th International AIDS Conference, July 7-12, 2002 (Barcelona, Spain) [Abstract MoPeD3677] and at the 16th International AIDS Conference, August 13-18, 2006 (Toronto, Canada) [Abstract CDC0512].

¶See appendix.

Reprints: Valériane Leroy, MD, PhD, INSERM U593, ISPED, Université Victor Segalen Bordeaux2, 146 Rue Léo Saignat, 33076 Bordeaux Cedex, France (e-mail:

Every day, 1900 children acquire HIV infection from their mother during the pregnancy, the delivery, or postnatally in Africa.1 Since 1998, different short-course antiretroviral interventions have proven their efficacy in preventing peri-partum mother-to-child transmission (PMTCT) of HIV.1,2 However, postnatal transmission (PT) of HIV through breast milk remains of great concern in Africa where breast-feeding is a common practice with the longer the duration of breast-feeding, the higher the risk of PT.3,4 Moreover, this subsequent PT risk reduced the long-term overall efficacy of peri-partum antiretroviral regimens at age 2 years.4 A Kenyan randomized trial comparing breast-feeding to formula-feeding in the absence of any use of antiretroviral therapy showed an additional PT risk of 16% at age 2 years.5 Most breast milk transmission occurred early, with 75% of the risk difference between the 2 arms occurring by 6 months.5 The overall risk of PT was estimated to be 8.9 new cases per 100 child-years of breast-feeding (95% CI: 7.8 to 10.2) in a recent pooled analysis.6

Peri-partum antiretroviral interventions aimed to PMTCT should be rapidly implemented on a large-scale basis to control the pediatric epidemic in Africa.7 In such a context, it is also urgent to evaluate safe interventions to reduce PT of HIV and maximize the effect of perinatal interventions. Among them, alternatives to prolonged breast-feeding such as formula-feeding could constitute an option in African settings where clean water is widely available.8 In the selected setting of the randomized Kenyan trial, formula-feeding prevented 44% of MTCT infections and was associated with significantly improved HIV-1-free survival compared with breast-feeding.5 However, the social acceptability and whether breast milk PT risk exceeds the potential risk of formula-associated mortality remains unknown and must be assessed in a more generalized population. Indeed, the social acceptability of such a public health intervention representing a real risk of stigmatization is a key issue in assessing its field effectiveness. This information is needed in the scaling-up process of PMTCT programs in Africa.7

The ANRS 1201/1202 Ditrame-Plus program conducted in Abidjan, Côte d'Ivoire from 2001-2005 aimed at evaluating the field effectiveness of a package of interventions targeted on HIV-infected pregnant women and their children to prevent MTCT and its consequences.9,10 In this specific urban setting, which guaranteed a generalized access to municipal water of good quality,11 our program included a postpartum component with a systematic proposal of alternatives to prolonged breast-feeding.

The objective of the present study is to describe the uptake of formula-feeding from birth as an alternative to prolonged and predominant breast-feeding in HIV-infected women observed over 2 years in the Ditrame-Plus program.

Back to Top | Article Outline


Study Sites

The ANRS 1201/1202 Ditrame-Plus project was conducted in the two most densely populated districts of Abidjan, Côte d'Ivoire. We selected the Yopougon University Hospital and 6 community-run health facilities to set up HIV counseling and testing services within the antenatal clinics. Two of them were upgraded to serve as study clinics for inclusion and follow-up of mother-child pairs. HIV seroprevalence estimates in pregnant women have consistently been in the range of 11% to 12% in these parts of Abidjan during the study period.12,13

Back to Top | Article Outline

Study Design

The study design was a nonrandomized open-label prospective cohort with a peri-partum antiretroviral intervention9 then a postpartum intervention including the promotion of alternatives to prolonged breast-feeding and the case management of HIV-infected children.

Back to Top | Article Outline

Inclusion Procedures

Between March 6, 2001 and March 6, 2003, all consenting pregnant women attending the selected prenatal clinics, living within the city limits, presenting at <36 weeks of gestation and aged at least 18 years were tested for HIV infection.9,14 HIV infection was defined by 2 sequential positive rapids tests (Determine, Abbot Laboratories, Abbot Park, IL and Genie II, Bio-Rad, Marnes-La-Coquette, France) performed onsite later confirmed using enzyme-linked immunosorbent assays (ELISA).15 Posttest counseling and announcement of the seropositive status were made if both test results were positive. HIV-infected women (HIV-1 or dually reactive HIV-1 + 2) were systematically eligible for the program if hemoglobinemia was ≥7 g/dL.

Back to Top | Article Outline

Study Interventions

Those women who fulfilled all the above inclusion criteria, accepted the study principles, and signed an informed consent were included from 32 weeks of gestation and received a short-course peri-partum antiretroviral combination of zidovudine (ZDV) ± lamivudine and nevirapine single dose.9 The child received a neonatal prophylaxis of nevirapine single dose combined with a 7-day course of ZDV.

Women received a supplementation in multivitamins,16 iron and folates, and malaria chemoprophylaxis according to Ivorian guidelines.

At inclusion, pregnant women were individually counseled about the advantages of breast milk and the risk of PT during 30 minutes. They were systematically and hierarchically proposed 2 alternatives to prolonged breast-feeding: exclusive formula-feeding from birth or exclusive breast-feeding with early cessation within the fourth month. The advantages of these interventions-the reduction of the risk of HIV transmission through breast milk-and their disadvantages-the possible stigmatization and the potential risks for infant health-were fully discussed during the subsequent weekly prenatal visits until delivery. This semidirective counseling proposed a hierarchical choice: first, formula-feeding, and if not acceptable for the woman, exclusive short-term breast-feeding. Both interventions were presented to women as conceivable and reasonable interventions to control the postnatal risk that must be balanced with infant health.

The first option, formula-feeding from birth, was proposed free of charge up to 9 months of age and facilitated by the use of a single oral dose of cabergoline for inhibiting lactation.17 The second option proposed, the practice of a short exclusive breast-feeding period followed by early weaning to obtain complete cessation of breast-feeding between 3 and 4 months of age completed, was further described elsewhere.10 All women could express their feeding choice until birth and the staff supported their choice and counseled them accordingly. The following material was provided free of charge to women willing to refrain from breast-feeding: bottles, teats, bottles brush, pan to sterilize, thermos to keep safely clean water, and a controlled distribution of local powdered infant formula (1 box at each follow-up visit) until 9 months of age. These women were also trained to prepare and store correctly and hygienically bottles, and to feed in nutritionally adequate quantities their child, with clean hands and using clean utensils.18 Cup-feeding was encouraged after 3 months of age. Material was delivered prenatally when the choice was expressed.

At the beginning of the project, daily life in Abidjan was compatible with the use of a locally available formula-milk; we chose it to reduce stigmatization.

A systematic vitamin A supplementation was provided to children according to WHO recommendations.

Condoms were freely provided whenever needed. Contraceptive methods according to infant feeding practices were systematically proposed to the women: injectable and oral contraceptives were available to all women, and emphasis was placed on the Lactational Amenorrhea Method among breast-feeding mothers.19

Back to Top | Article Outline

Follow-Up Procedures

Two clinics were exclusively dedicated to the follow-up of the mother-infant pairs of the Ditrame Plus study, with 60 healthcare workers recruited from the local area specifically trained for this program.

Pregnant women were observed weekly until delivery and mother-infant pairs were seen 48 hours after birth, weekly until 6 weeks of age, monthly until 9 months of age, and every 3 months until their second birthday. At each scheduled visit, clinical, nutritional, psychosocial, and biological follow-up of both mothers and infants was proposed. Care services dispensed were also available whenever needed between scheduled visits. All transport costs were reimbursed and all care expenses related to any scheduled visit or clinical event were entirely supported by the project.

Four nutritionists individually counseled the women about infant-feeding practices whenever needed. Collective sessions were frequently organized to explain to non-breast-feeding mothers how to safely prepare artificial feeding, use appropriate complementary feeding, or cook the baby food. If a woman had declared her intent to formula feed her child and had received the formula-feeding material but thereafter decided to implement breast-feeding for any reason, the material was picked-up again to avoid mixed feeding practices or a spill-over effect. To identify possible undeclared breast-feeding practices to the team among women who chose to formula feed, medical examination of mother's breast was performed to look for breast milk discharge at each scheduled visit, and the child was snuggled-up in her/his mother arms to observe her/his suckling behavior during the interview. A maternal blood sample was taken at Day 2 in women who declared to formula feed to measure the blood prolactinemia. We used this biological indicator as a proxy of the compliance to formula-feeding; low values (<40 ng/mL) were expected in those women who had taken cabergoline after delivery and not breast-fed.

Blood samples were collected at Day 2, Week 4, 6, 12 then every 3 months until 18 months or until 2 months after complete cessation of breast-feeding if the child was ever breast-fed. A serology was systematically performed at age 18 months in all children. Pediatric HIV infection was initially diagnosed using a commercial plasma HIV-1 RNA assay (Versant bDNA HIV RNA kit version 3.0, Bayer Diagnostics, Emeryville, CA).20 From 2003, a TaqMan HIV-1 RNA real-time PCR test was used for this purpose.21 HIV-infected children systematically received a cotrimoxazole prophylaxis (25 mg/kg per day) from 6 weeks of age until at least their first birthday.

Back to Top | Article Outline

Ethical Considerations

The study protocol was approved by the Ethical Committee of the National AIDS Control Program in Côte d'Ivoire and the Institutional Review Board of the French Agence Nationale de Recherches sur le SIDA (ANRS), the primary sponsor.

Women were included in the Ditrame-Plus study from March 2001 to July 2003. From April 2003, we have decided to temporarily stop proposing the formula-feeding option to the women because of the political turmoil in Côte d'Ivoire: the risk of breakdown distribution of the breast milk substitutes was becoming unacceptable. The evaluation of the alternatives to prolonged breast-feeding was thus made among women included from March 2001 to March 2003.

Back to Top | Article Outline

Data Collection

At each scheduled visit, clinical events that occurred in both mothers and children since the last visit were documented and infant-feeding practices were recorded via structured questionnaires by trained social workers who were not involved in nutritional counseling. Women were asked if their child had been given breast milk, artificial milk, or both since the last visit. Fluids and foods other than any milk were documented using a 24-hour and a 7-day recall history. Social workers went over a detailed list of 15 commonly used fluids or foods. Women were asked if these fluids, foods, or some other items not listed had been given in the previous 7 days, and if so in what amount (24-hour recall history) and how frequently in the past 7 days. The first liquid given after birth was recorded at the Day 2 visit.

Infants were classified at each scheduled visit as breast-fed, mixed fed, or artificial fed using these recall histories.22 We used the following WHO definitions to allow a better comparability of results between studies:23,24 Exclusive breast-feeding means giving a child no other food or drink, including no water, in addition to breast-feeding with the exception of medicines, vitamin drops or syrups, and mineral supplements; Predominant breast-feeding means breast-feeding a child but also giving small amounts of water or water-based drinks; Artificial feeding means feeding a child on artificial foods (including infant formula and powdered animal milk), and not breast-feeding at all. Mixed feeding means breast-feeding while giving nonhuman milk such as infant formula or food-based fluid, or solid food.

Back to Top | Article Outline

Statistical Analysis

Among all HIV-infected pregnant women enrolled, we described the maternal infant-feeding choice formulated antenatally if any, then the feeding option implemented at Day 2 after delivery. Results were expressed in percentages with their 95% confidence interval (CI). Determinants for prenatal refusal of the formula-feeding option were explored using a logistic regression with the following variables: maternal age, parity, gestational age, living with a partner, with her mother-in-law, being a cospouse, educational level, personal income, access to clean piped water, ethnic group, religion, maternal WHO clinical staging at entry, and maternal CD4 cell count and viral load at entry. A stepwise descendant multivariate analysis included all variables with P < 0.25 in the univariate analysis.

Women whose live-born infants were formula-fed at least once at Day 2 were classified in the formula-fed group whatever their prenatal choice. The behavioral compliance to the formula-feeding option was described among these women. The Kaplan-Meier probabilities of formula-feeding success at given ages were computed until 12 months. Formula-feeding failure was defined as having breast-fed at least once, based on one of the following criteria: reporting of any breast-feeding from feeding recall histories or maternal breast milk discharge, or child breast-feeding behavior during visit. Determinants for failure of the formula-feeding option were explored using a multivariate logistic regression including the variables associated with the prenatal choice and the prenatal choice itself. Reasons for feeding switches over time were described. All statistical analyses were carried out with the SAS software (version 8.2; SAS Institute, Inc., Cary, NC).

Back to Top | Article Outline


Prenatal Infant-Feeding Choice

From March 6, 2001 to March 6, 2003, 643 HIV-infected pregnant women were consecutively enrolled in the cohort (Fig. 1). Nineteen women with HIV-2 infection only and 44 lost-to-follow-up before delivery were excluded from the analysis. Among the 580 pregnant women who delivered, 309 (53%) had expressed their willingness to formula-feed, 256 (44%) had planned to breast feed, and only 15 (3%) had not expressed any choice before delivery. The prenatal acceptability of formula-feeding was thus estimated to be 53% (95% CI: 49% to 57%). Women who expressed their infant-feeding choice before delivery had a significant longer median duration of prenatal follow-up than those who did not formulate their choice before delivery: 34 days versus 16 days, respectively (Wilcoxon test, P = 0.01). Women who expressed their choice before delivery had a similar median duration of prenatal follow-up according to their option chosen: 34 days in the formula-feeding group and 35 days among those who chose breast-feeding (Wilcoxon test, P = 0.67). Overall, 93 women of the 580 (16%) reported hesitation in making their infant-feeding choice at the time of inclusion. The main reasons of hesitation for choosing the formula-feeding option reported by 88 women were as follows: fear from their partner reaction (39%), fear from their family circle reaction (31%), constraints of organization (13%), fear for their infant health (7%), logistic constraints (2%), and other reason (8%). Among these 88 uncertain women, 8% did not express any choice before delivery, 41% decided to formula-feed, and 51% to breast feed before delivery.



Back to Top | Article Outline

Prenatal Determinants for Refusing Formula-Feeding

Among the 565 pregnant women who expressed a prenatal choice (Table 1), living with her partner, being foreigner, or native from the North Mande or Gur ethnic groups, being Muslim, having a low educational level, living in a shared housing, having no access to tap water, being observed in the clinic based in Abobo district, and not having shared her HIV status with someone else were significantly associated with refusal of the formula-feeding option in a univariate logistic regression analysis (Table 1). Neither maternal clinical stage nor CD4 cell count were associated with the prenatal choice (Table 1). In a multivariate adjusted analysis, a few sociodemographic variables remained significantly associated with the maternal refusal of the formula-feeding option (Table 2): living with her partner, being Muslim, having a low educational level, being observed in the Abobo center, not having shared her HIV status with someone else, and having been included in the project after September 2001 (in the first 6-month period of the project). There was no longer significant association with the type of access to water.





There was a significant center affect on the acceptability of formula-feeding, even adjusted on the other sociodemographic variables. In Abobo, there was a significant evolution of the refusal rate of formula-feeding over time, ranging from 34% in the March to August 2001 period, 51% in the September 2001 to February 2002 period, 52% in the March to August 2002 period, up to 63% during the September 2002 to March 2003 period (χ2 for trend, P = 0.0008). While in Yopougon, a site opened 1 year after the Abobo site, in March 2002, the refusal rate was lower and did not vary over time (P = 0.45). When pooling the two centers, the time varying effect was no longer significant (P = 0.078). The study site was a confounding factor in the analysis of the evolution of acceptability over time.

Back to Top | Article Outline

Neonatal Implementation of Infant-Feeding Option According to the Prenatal Choice

Among the 309 mothers who had chosen formula-feeding prenatally, 1 woman was lost to follow-up after birth, and 13 women could not implement any infant-feeding choice because their child died before their first feed (4%); they were excluded from the analysis of postnatal acceptability (Fig. 1). At Day 2, 267 of the 295 women (91%) who had chosen formula-feeding before birth had actually initiated this practice after birth in agreement with their prenatal choice, and 28 (9%) changed their mind and decided to breast feed from birth (Fig. 1). At Day 2, among those 267 who formula-fed consistently with their prenatal choice, 93% were exclusively formula-feeding while 7% initiated mixed-feeding temporarily from birth. Among those 19 uncertain women at birth, 11 (58%) finally succeeded in implementing a definitely exclusive formula-feeding practice from Day 8, 5 (26%) decided to switch for the exclusive breast-feeding option, and recurrent practice of mixed feeding were reported in 3 children (16%).

Among the 557 mothers whose live-born child was fed at least once, 295 (53%) initiated formula-feeding (267 women who had chosen formula-feeding prenatally + 22 women who had chosen exclusive breast-feeding prenatally + 6 who had not expressed their prenatal choice) and constituted the formula-feeding group for the present analysis (Fig. 1). Postnatal acceptability of the exclusive breast-feeding option and its determinants were described elsewhere.10

The baseline maternal sociodemographic, clinical, biological, and delivery characteristics of the 295 women of the formula-feeding group are shown in Table 3. Overall, 63% lived with their partner, 33% with their in-law family, 25% were illiterate, and half of them had shared their HIV status with someone else. All but 3 had electricity at home, 59% lived in a shared housing, and all had access to tap water with 38% who had an individual access. Their baseline median CD4 count was 386/cell mm3 (IQR 239-583).



Back to Top | Article Outline

Postnatal Acceptability of Formula-Feeding

In the formula-feeding group, from birth to 12 months, 46 (15.6%) women failed to maintain exclusive formula-feeding and breast-fed at least once. The Kaplan-Meier probabilities of success of the formula-feeding practice were 93.6% at Day 2 (95% CI: 90.7% to 96.5%); 86.7% at 1 month (95% CI: 82.7% to 90.7%); and 84.2% at 12 months (95% CI: 79.9% to 88.5%). Failures occurred before the tenth day in median (range: birth to 319 days). Overall, 85% of these failures occurred in the neonatal period and 19 of 46 women (41%) mixed breast-fed at Day 2 for the following reasons: forgot their formula-feeding material at delivery in maternity (n = 6), family pressure (n = 5), baby cry (n = 4), midwife's advice (n = 3), unknown (n = 1). Beyond the early neonatal period, the reasons for switching to breast-feeding were as follows: probable family pressure not admitted (n = 12), family pressure admitted (n = 10), logistic constraints (n = 2), desire to breast feed (n = 2). One child had not been breast-fed by his mother but was considered as a failure because he had been breast-fed by his aunt, whose HIV status was unknown.

Back to Top | Article Outline

Determinants of Formula-Feeding Failure after Birth

In univariate analysis, none of the baseline prenatal variables was significantly associated with the subsequent failure of formula-feeding, but having a multiple birth or a low birthweight newborn were significantly associated (Table 3). In an adjusted multivariate analysis, the only variables explaining the failure of formula-feeding were having a low birthweight newborn: adjusted odds ratio (aOR: 2.4, 95% CI: 1.1 to 5.4), and a multiple birth (aOR: 2.0, 95% CI: 0.7 to 6.1).

Back to Top | Article Outline

Prolactin Blood Level as a Biological Marker of Compliance

Among the 267 women who received it before delivery, 263 women declared they had taken cabergoline after birth and had a blood sample taken for prolactin measurement at their first visit. Of these, 191 (73%) were precisely collected after Day 2, the other ones having been collected before. Of the 158 mothers who succeeded in formula-feeding and had a blood sample available for prolactin measurement, 87% had a low prolactin level (<40 ng/L) from Day 2, which was consistent with their compliance to this option. Of the 32 women who failed in practicing exclusive formula-feeding and had a prolactin measurement, 62% had a low prolactin level at Day 2 (P = 0.0009).

Back to Top | Article Outline


The Ditrame-Plus project was an open-label cohort, proposing systematically and hierarchically during the prenatal period 2 alternatives to prolonged breast-feeding to reduce mother-to-child transmission of HIV. By providing semidirective counseling to HIV-infected pregnant women, supporting their infant-feeding choice and offering them all the equipment and formula free of charge to implement properly this option at birth, we were able to pragmatically capture its social acceptability and determinants, excluding the economical constraint reported to be one major limitation in low-income countries.24

We show that the uptake of formula-feeding was high in this population usually practicing prolonged breast-feeding.25,26 Almost all HIV-infected women expressed their infant-feeding choice before delivery. The formula-feeding option was better accepted than anticipated: slightly over half of HIV-infected women chose it in the prenatal period whereas our baseline hypothesis was estimated around 20%.26 Women living with their partner, who were illiterate, Muslim, had not disclosed their HIV status, and included over the first 6 months of the project were more likely to refuse the formula-feeding option before delivery. For pregnant women who chose formula-feeding, the postnatal compliance to their prenatal choice was high-over 90%. Most failures occurred early in the early neonatal period (85%) and were mainly related to stigma (partner, familial, or health worker environment) or newborn health concerns (low birthweight). Very few newborns were exposed to mixed feeding in this population of mothers who had chosen not to breast feed-6% within the first week of life and on a very transitory period.

Our cohort was conducted among HIV-infected pregnant women attending the community-run health facilities of 2 poor districts: a quite representative population of all social categories in Abidjan.10,26 Our findings could be extrapolated to the same unselected population. This cohort also provided prospective data on infant feeding practices carefully collected from birth until 12 months of age. Standardized questionnaires were used to perform recall histories administered by trained healthcare workers other than those who counseled the women on infant feeding practices. As the interval between 2 visits was 1 week over the first 2 months then 1 month up to 9 months, then 3 months, we believe we provide an unbiased overview of the infant-feeding practices. In addition, by crossing information between the declared infant-feeding practices with the maternal breast examination and the child behavior with her mother's breast during the maternal interview at each clinical visit, we were able to detect quite precisely and early the mixed-feeding practices not recommended by the project. Finally, although not strictly sensitive, the high proportion of low blood prolactin level reaching 87% in formula-feeders was also consistent with the compliance to the non-breast-feeding option.

Several arguments justified our methodological choices and our proposition of formula-feeding in this African urban setting. First, we proposed a cohort study design instead of a randomized clinical trial with a random allocation of the infant-feeding group to minimize ethical considerations and the risk of noncompliance inducing at-risk mixed feeding-practices already reported in the Kenya trial.5,27 Second, in Abidjan, municipal water of good quality was widely available but water storage was a common practice in most households, which might contribute to the contamination of drinking water.11 This fact justifies both the need for a timely counseling of pregnant women as early as possible before delivery to teach them how to safely prepare formula-feeding, and also the furniture of the material needed to prepare bottles and to store the boiled water. Third, we decided to provide formula-feeding free of charge to avoid the practice of mixed feeding in women who would like to avoid breast-feeding but with too limited resources to buy the correct amount of breast milk substitutes. This contributed to the low rate of mixed feeding observed within our study. Indeed, in another study where formula-feeding was not provided for free, the proportion of mixed feeding practices reached 30% among those who opted not to breast-fed, and was related to low socioeconomic status.28 Fourth, we accepted to provide the breast milk substitutes until 9 months of age only to avoid the introduction of such substitutes in children old enough to be fed with diversified food and to limit the spill-over effect of formula-feeding practice.

Overall, our study provides useful knowledge underlining that alternatives to breast-feeding are acceptable and feasible in this West African urban population with access to tap water. In East Africa, Magoni et al. 29 reported a 40% neonatal acceptance rate of formula-feeding offered free of charge in 306 mothers enrolled in a PMTCT program in an urban hospital center in Kampala, Uganda. Failure to maintain exclusive formula-feeding was reported in 11% of the women up to 6 months of age, and consistent with our findings. These two studies argue in favor of providing formula-feeding free of charge to women who opt for this option in such urban settings.

The main weakness of our research study concerns the extrapolation of our results, particularly with regard to the formula subsidization, the clinical and counseling support provided, and to the trained staff required to implement such complex interventions in operational settings. The infrastructure of the Ditrame-Plus study would all be expected to lead to more optimal outcomes for alternatives to prolonged breast-feeding in contrast to what was observed in less well-structured or well-supported programs. Maternal perceptions of stigma impairing the acceptability of formula-feeding were indeed reported within some operational African settings.30,31 However, our research study is helpful is identifying important key components of implementing such intervention in a generalized unselected population, given pre-required conditions (eg, access to clean water, free formula given, counseling information in the prenatal period, clinical and nutritional support in the postnatal period).

Our findings show that women who refused the formula-feeding option prenatally or failed to maintain exclusive formula-feeding up to 12 months were under the social pressure of the partner's family. The fear of stigma could also explain the association reported between this prenatal refusal and the lack of prenatal disclosure of the woman's HIV-status. These social factors must be carefully taken into account when counseling mothers on infant feeding options, with a clear emphasis on issues regarding confidentiality.32 Finally, we interpret the association between refusal of the formula-feeding option and the fact of being followed in the Abobo clinic or the fact of being included during the initial phase of the project as an expression of the lack of self-confidence of healthcare workers during the initial phase of the project. These difficulties in proposing alternatives to prolonged breast-feeding were already reported by the Ditrame-Plus team33 and reflect field difficulties that may be encountered, even in a well-structured context.

These findings lead to formulate several practical recommendations. First, there is a need for an adequate counseling and training of healthcare workers on infant-feeding counseling, including the involvement of midwives in the delivery room to avoid mixed feeding practices in HIV-infected women who opt for formula-feeding.33 One should bear in mind that healthcare workers have a key role to play in reaching successful practices of alternatives to prolonged breast-feeding, even if this counseling remains difficult to standardize. Second, there is an urgent need to find innovative approaches to involve positively fathers and partners in PMTCT programs so that the communication within couples could be improved and the infant-feeding choice facilitated as soon as before delivery. Third, reducing overall stigmatization of people living with HIV/AIDS should be useful in helping HIV-infected pregnant women regarding their infant-feeding choice and practice. Finally, it should be also acknowledged that non-breast-feeding women of low socioeconomic status require support to avoid compromising the nutritional status of their infants.28 The free provision of the breast milk substitutes and the material needed for HIV-infected women who choose not to breast feed in settings where this practice could be safely conducted should be a strategic public health decision, as important as the universal access to antiretroviral interventions to reduce MTCT.34

This social acceptability must be balanced with mother-child long-term health outcomes evaluated at age 2 years, accounting for PT, morbidity, and mortality events in children to guide safe recommendations on alternatives to breast-feeding among HIV-infected women in urban African settings.

Back to Top | Article Outline


We gratefully acknowledge the women and children included in the Ditrame-Plus cohort and give a special thanks to Suzanne Kouadio and Zénica Goulheon for their devotion and helpful support in nutritional counseling of the team and the cohort. This study was sponsored by the French National AIDS Research Agency (ANRS, Paris, France). It was conducted in partnership with the French Ministry of Foreign Affairs and the Ministry of Health of Côte d'Ivoire. Glaxo-Wellcome France and International provide ZDV and 3TC. Pr. M. C. Saux, Pr. D. Breihl, and Mr. B. Fallourd (Bordeaux University Hospital) provided drug packaging.

Back to Top | Article Outline


1. Dabis F, Ekpini ER. HIV-1/AIDS and maternal and child health in Africa. Lancet. 2002;359:2097-2104.
2. Leroy V, Sakarovitch C, Cortina-Borja M, et al. Is there a difference in the efficacy of peripartum antiretroviral regimens in reducing mother-to-child transmission of HIV in Africa? AIDS. 2005;19:1865-1875.
3. Leroy V, Newell M, Dabis F, et al. International multicentre pooled analysis of late postnatal mother-to-child transmission of HIV-1 infection. Lancet. 1998;352:597-600.
4. Alioum A, CortinaBorja M, Dabis F, et al. Estimating the efficacy of interventions to prevent mother-to-child transmission of human immunodeficiency virus in breastfeeding populations: comparing statistical methods. Am J Epidemiol. 2003;158:596-605.
5. Nduati R, John G, Mbori-Ngacha D, et al. Effect of breastfeeding and formula-feeding on transmission of HIV-1. A randomized clinical trial. JAMA. 2000;283:1167-1174.
6. The Breastfeeding and HIV International Transmission Study Group (BHITS), Coutsoudis A, Dabis F, et al. Late postnatal transmission of HIV-1 in breast-fed children: an individual patient data meta-analysis. J Infect Dis. 2004;189:2154-2166.
7. World Health Organization. HIV and Infant Feeding Counselling: From Research to Practice. Geneva: WHO, UNICEF; 2005.
8. Rollins N, Meda N, Becquet R, et al. Preventing postnatal transmission of HIV-1 through breast-feeding: modifying infant feeding practices. J Acquir Immune Defic Syndr. 2004;35:188-195.
9. Dabis F, Bequet L, Ekouevi DK, et al. Field efficacy of zidovudine, lamivudine and single-dose nevirapine to prevent peripartum HIV transmission. AIDS. 2005;19:309-318.
10. Becquet R, Ekouevi DK, Viho I, et al. Acceptability of exclusive breast-feeding with early cessation to prevent HIV transmission through breast milk, ANRS 1201/1202 Ditrame Plus, Abidjan, Cote d'Ivoire. J Acquir Immune Defic Syndr. 2005;40:600-608.
11. Dunne EF, Angoran-Benie H, Kamelan-Tano A, et al. Is drinking water in Abidjan, Cote d'Ivoire, safe for infant formula? J Acquir Immune Defic Syndr. 2001;28:393-398.
12. Dabis F, Msellati P, Meda N, et al. Six months efficacy, tolerance and acceptability of a short regimen of oral zidovudine in reducing vertical transmission of HIV in breast-fed children. A double blind placebo controlled multicentre trial, ANRS049a, Côte d'Ivoire and Burkina Faso. Lancet. 1999;353:786-792.
13. Msellati P, Sakarovitch C, Bequet L, et al. Decrease of human immunodeficiency virus prevalence in antenatal clinics in Abidjan, Cote d'Ivoire, 1995-2002. Int J STD AIDS. 2006;17:57-60.
14. Ekouevi D, Leroy V, Viho I, et al. Acceptability and update of a package to prevent mother-to-child transmission using rapid HIV testing in Abidjan, Côte d'Ivoire. AIDS. 2004;18:697-700.
15. Rouet F, Ekouevi DK, Inwoley A, et al. Field evaluation of a rapid human immunodeficiency virus (HIV) serial serologic testing algorithm for diagnosis and differentiation of HIV type 1 (HIV-1), HIV-2, and dual HIV-1-HIV-2 infections in west African pregnant women. J Clin Microbiol. 2004;42:4147-4153.
16. Fawzi W, Msamanga G, Spiegelman D, et al. Randomised trial of effect of vitamin supplements on pregnancy outcomes and T cell counts in HIV-1 infected women in Tanzania. Lancet. 1998;351:1477-1482.
17. European Multicentre Study Group for Cabergoline in Lactation Inhibition. Single dose cabergoline versus bromocriptine in inhibition of puerperal lactation: randomised, double blind, multicentre study. BMJ. 1991;302:1367-1371.
18. UNICEF, UNAIDS, WHO. HIV and Infant Feeding-A Guide for Health-Care Managers and Supervisors. Geneva: WHO; 1998.
19. Van Look PFA, von Hertzen H, Glasier A, et al. The World Health Organization Multinational Study of Breast-feeding and Lactational Amenorrhea. III. Pregnancy during breast-feeding. Fertil Steril. 1999;72:431-440.
20. Rouet F, Montcho C, Rouzioux C, et al. Early diagnosis of paediatric HIV-1 infection among African breast-fed children using a quantitative plasma HIV RNA assay. AIDS. 2001;15:1849-1856.
21. Rouet F, Ekouevi DK, Chaix ML, et al. Transfer and evaluation of an automated, low-cost real-time reverse transcription-PCR test for diagnosis and monitoring of human immunodeficiency virus type 1 infection in a West African resource-limited setting. J Clin Microbiol. 2005;43:2709-2717.
22. Gaillard P, Piwoz E, Farley TMM. Collection of standardized information on infant feeding in the context of mother-to-child transmission of HIV. Stat Med. 2001;20:3525-3537.
23. World Health Organization UNICEF. Breastfeeding Counselling: A Training Course. Geneva:WHO, UNICEF; 1993.
24. World Health Organization UNAIDS. UNICEF. HIV and Infant Feeding. A Guide for Health Care Managers and Supervisors. Geneva, WHO, 1998, WHO/FRH/NUT/CHD 98.2. 36p.
25. Leroy V, Karon JM, Alioum A, et al. Twenty-four month efficacy of a maternal short-course zidovudine regimen to prevent mother-to-child transmission of HIV-1 in West Africa. AIDS. 2002;16:631-641.
26. Becquet R, Castetbon K, Viho I, et al. Infant feeding practices before implementing alternatives to prolonged breastfeeding to reduce HIV transmission through breastmilk in Abidjan, Cote d'Ivoire. J Trop Pediatr. 2005;51:351-355.
27. Mbori Ngacha D, Nduati R, John G, et al. Morbidity and mortality in breastfed and formula-fed infants of HIV-1-infected women-A randomized clinical trial. JAMA. 2001;286:2413-2420.
28. Kiarie JN, Richardson BA, Mbori-Ngacha D, et al. Infant feeding practices of women in a perinatal HIV-1 prevention study in Nairobi, Kenya. J Acquir Immune Defic Syndr. 2004;35:75-81.
29. Magoni M, Bassani L, Okong P, et al. Mode of infant feeding and HIV infection in children in a program for prevention of mother-to-child transmission in Uganda. AIDS. 2005;19:433-437.
30. Abiona TC, Onayade AA, Ijadunola KT, et al. Acceptability, feasibility and affordability of infant feeding options for HIV-infected women: a qualitative study in south-west Nigeria. Matern Child Nutr. 2006;2:135-144.
31. Doherty T, Chopra M, Nkonki L, et al. Effect of the HIV epidemic on infant feeding in South Africa: “When they see me coming with the tins they laugh at me”. Bull World Health Organ. 2006;84:90-96.
32. Eide M, Myhre M, Lindbaek M, et al. Social consequences of HIV-positive women's participation in prevention of mother-to-child transmission programmes. Patient Educ Couns. 2006;60:146-151.
33. Becquet R, Ekouevi DK, Sakarovitch C, et al. Knowledge, attitudes, and beliefs of health care workers regarding alternatives to prolonged breast-feeding (ANRS 1201/1202, Ditrame Plus, Abidjan, Cote d'Ivoire). J Acquir Immune Defic Syndr. 2005;40:102-105.
34. World Health Organization. Antiretroviral Drugs and the Prevention of Mother-to-Child Transmission in Resource-Limited Settings. Recommendations for a Public Health Approach (2005 revision). Technical Reference Group; Geneva, Switzerland; June 28-29, 2005:4.
Back to Top | Article Outline


Composition of the ANRS 1201/1202 Ditrame-Plus Study Group

Principal investigators: François Dabis, Valériane Leroy, Marguerite Timite-Konan, Christiane Welffens-Ekra. Coordination in Abidjan: Laurence Bequet, Didier K. Ekouévi, Besigin Tonwe-Gold, Ida Viho. Methodology, biostatistics and data management: Gérard Allou, Renaud Becquet, Katia Castetbon, Laurence Dequae-Merchadou, Charlotte Sakarovitch, Dominique Touchard. Clinical team: Clarisse Amani-Bosse, Ignace Ayekoe, Gédéon Bédikou, Nacoumba Coulibaly, Christine Danel, Patricia Fassinou, Apollinaire Horo, Ruffin Likikouët, Hassan Toure. Laboratory team: André Inwoley, François Rouet, Ramata Touré. Psychosocial team: Hortense Aka-Dago, Alphonse Sihé. Social sciences team: Hélène Agbo, Hermann Brou, Annabel Desgrées-du-Loû, Annick Tijou-Traoré, Benjamin Zanou. Scientific committee: Stéphane Blanche, Jean-François Delfraissy, Philippe Lepage, Laurent Mandelbrot, Christine Rouzioux, Roger Salamon.

Back to Top | Article Outline

Ethical Permissions

The ANRS 1201/1202 Ditrame-Plus study was granted ethical permission in Côte d'Ivoire from the ethical committee of the National AIDS Control Program, and in France from the institutional review board of the French Agence Nationale de Recherches sur le Sida (ANRS).

Back to Top | Article Outline

Author Contributions

Study concept and design: VL, MTK, FD. Field work and data collection: RB, LB, DKE, IV. Statistical analysis: CS, VL. Interpretation of results: RB, VL, CS. First drafting of the manuscript: VL. Critical revision of the manuscript for important intellectual content: RB, VL, CS. Obtained funding: FD, VL.


Africa; behavioral research; cohort study; formula-feeding; HIV infections; mother-to-child transmission acceptability

© 2007 Lippincott Williams & Wilkins, Inc.