Formula feed is `medicine to prevent HIV`

With growing evidence that formula feed can be provided safely to babies born to HIV positive women in many African settings, health researchers are calling for formula feed to be provided free of charge to HIV positive women who need it, can use it safely, and currently do not have the resources to access it.

New evidence presented this week at the 2nd IAS Conference on HIV Pathogenesis and Treatment in Paris includes findings from the Ditrame Plus study sponsored by the French AIDS research agency ANRS in Abidjan, Côte d'Ivoire, and a survey of HIV positive women attending clinics in Khayelitsha, Cape Town, South Africa.

According to Dr Francois Dabis, one of the leading researchers in this field and a presenter of Ditrame Plus, formula feeding should now be considered as a medicine, which means it should be:

• adequately subsidised
• supplied continuously
• provided complete with support and counselling
• targeted towards women who need it

He said there also needed to be monitoring of adherence and side effects.

Given that there is strong evidence that women with lower CD4 counts are at substantially higher risk of transmitting HIV to their babies, CD4 testing (when available) should be used to guide the provision of alternatives to breast feeding as well as to identify those who could benefit from ARV treatment.

The implication of what Dr Dabis is saying about targeting is that it might be reasonable to think in terms of promoting exclusive breast feeding (with or without antiretrovirals given to the baby – as indicated in the SIMBA study here) when CD4 counts were over 350, and to provide formula feed when they were lower.

The Ditrame Plus study

Ditrame Plus is a major research project that is being carried out with support from the French ANRS by a team of Ivoirian and international researchers, looking at a range of interventions to reduce HIV transmission from mothers to babies and to safeguard the health of mothers and babies. The use of antiretrovirals in this project has been reported separately on aidsmap here. This report focusses on the mothers' infant feeding choices (Becquet).

Women who were recruited into this study between March 2001 and August 2002, in Abidjan, Côte d'Ivoire, were strongly encouraged to choose between exclusive formula feeding and exclusive breast feeding (with early weaning) for their babies. Those who chose formula were provided with free formula, with training in how to use it, and with drugs to suppress their milk production. 398 children and their mothers were enrolled into the study; 393 children survived long enough to be fed at least once. 17 babies were considered to have received mixed feeding and were excluded from the analysis. A total of 28 children died in the course of the study, of whom 11 were HIV positive at age 6 weeks.

The assessment compared mortality rates for HIV negative babies during the period when children were actually breast fed or being provided with formula. Four deaths among 187 babies, formula fed for an average of 215 days were compared with two deaths among 166 babies, exclusively breast fed for an average of 123 days. The respective annual mortality rates among HIV negative babies fed at least once were 30.4 per thousand and 34.2 per thousand, which were not significantly different.

While Abidjan is the commercial capital of Côte d'Ivoire, this population was predominantly of very low income and most of the women had received little or no formal education. There might therefore still be a question about how sustainable formula feeding would be, given the level of support they needed to use it safely. However, the researchers were confident that this service can safely be provided in this urban African setting.

The Khayelitsha survey

As part of their work with the government of the Western Cape Province, to introduce and evaluate the use of ARVs in public health clinics, the NGO Medecins Sans Frontieres has interviewed 113 women who had been provided with short course AZT at the time of their baby’s birth, to find out how they were responding to advice to use formula rather than breast feeding and to describe the experiences of the mothers and babies (Coetzee).

The majority of the women said they had chosen for themselves to use formula feed exclusively, and a further proportion had made this decision on the advice of clinic staff. In all, 95% of the women had used formula feed exclusively and the remainder had breast fed only very briefly, during the baby's first week.

All were offered formula free of charge by the clinic for nine months, and given training and support in making it up and giving it to their babies. They also participated in a support group for mothers, held at the clinic, and babies were provided with cotrimoxazole prophylaxis from 6 weeks of age until discharged from the programme.

Many of the women had not disclosed their HIV status to people in their own household and interpreted questions about why they were choosing not to breastfeed as questions about their HIV status.

The most common explanations mothers used included:

• "I am taking anti-TB drugs"
• "I have had a caesarian section"
• "I have 'bad milk' "

The women were asked about the incidence of diarrhoea in the month before they were interviewed, and 70% reported that there had been no diarrhoea; only 3% of children had two episodes of diarrhoea. Separate analysis of clinic records for the district had found no evidence of any increase in diarrhoea among babies, since formula feed began to be provided to HIV positive women.

Although Khayelitsha has clean water supplies and good access to electricity compared to many African cities, the majority of the women in this population were unemployed, and on very low incomes.

The baby milk controversy

For many years, international public health campaigns have stressed the importance of breast feeding, especially in developing countries, and have sought to restrain commercial interests which promoted formula feeding.

Among the many problems associated with formula feed were that:

• women would buy it for their babies, at the expense of their own nutrition
• it was mixed with water that was not clean or had been stored in unclean containers
• bottles and teats were used without sterilising them (which is why cup-feeding is always advocated these days, when babies have to be given formula in limited-resource settings)
• the babies were deprived of antibodies from their mothers’ milk which are critically needed
• the contraceptive, birth-spacing effect of breast feeding was lost, so women had more babies than they wanted or could support
• families did not have the fuel to heat water properly

It was commonly observed that babies fed on formula suffered more diarrhoea and respiratory infections than breast-fed babies, and were more likely to die in infancy. There are also serious concerns about the development of allergies which can affect a child’s nutritional status and development.

These adverse effects of formula feeding occurred despite the efforts of international companies which promoted formula feed by offering it free of charge to hospitals and advertised it with images implying medical approval. Unfortunately, this was not sufficient to protect the babies or their mothers.

With the advent of AIDS, it was still observed that babies that were not breast fed did considerably worse than babies given formula. However, there has been a radical shift in professional opinion since it was realised that they did worse because their mothers were more seriously unwell. In a setting where breast feeding is a very strongly established norm, mothers who don’t breast feed are likely to be those who cannot do so.

A randomised controlled trial of breast feeding vs formula was carried out, in the face of great difficulties in recruiting HIV-positive women to take part, in Kenya by a team led by the paediatrician, Prof Ruth Nduati of Nairobi University. Although a significant proportion of ‘formula fed’ babies still received some breast milk, this trial showed that when formula feeding was “chosen” rather than driven by a mother’s health status, overall mortality was similar in breastfed and formula-fed babies in an urban African population. However, the rate of HIV transmission was significantly lower with formula feeding.

Does breast feeding disadvantage positive women?

Another key finding of the Nairobi trial was that women who breast fed appeared to be more likely to die during the period of the trial than women who were provided with formula and assistance to use it.

This finding has not been supported by other studies, although since none have followed the same design, this is not surprising.

A meta-analysis of African studies which recorded the survival of mothers and babies and described their feeding choices was presented in Paris by Marie-Louise Newell of the Institute of Child Health in London. Unfortunately, this failed to resolve the question raised in the Nairobi trial, since the majority of the studies included were observational and subject to the bias described above. Worse, the study did not exclude women who died of obstetric complications shortly after their child was born – whose welfare clearly would not have been affected in any way by the impact of breastfeeding.

As Dr Newell observed, the only kind of study which is likely to appear in the next few years and could shed light on this issue will be studies of nutritional supplementation for pregnant and breastfeeding women.