CROI: Early weaning and formula feeding puts HIV-exposed infants in resource-limited settings at high risk of severe diarrhoea and death

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The wisdom of advising mothers with HIV in resource-limited settings to avoid breastfeeding — or to abruptly wean their infants sooner than they normally would — in order to keep from transmitting HIV to their infants has been called into question by several studies presented this week at the Fourteenth Conference on Retroviruses and Opportunistic Infections in Los Angeles.

There was a report about last year’s outbreak of diarrhoea among formula-fed infants in Botswana and more than one discussion of implications for infant feeding policy.

“This is telling you that you have to be really careful introducing formula in developing countries,” said Dr Hoosen Coovadia, of the University of KwaZulu Natal, in a plenary session.

Glossary

diarrhoea

Abnormal bowel movements, characterised by loose, watery or frequent stools, three or more times a day.

exclusive breastfeeding

Feeding an infant only breast milk, with no other liquids or solids, for the first six months of life.

mother-to-child transmission (MTCT)

Transmission of HIV from a mother to her unborn child in the womb or during birth, or to infants via breast milk. Also known as vertical transmission.

acute infection

The very first few weeks of infection, until the body has created antibodies against the infection. During acute HIV infection, HIV is highly infectious because the virus is multiplying at a very rapid rate. The symptoms of acute HIV infection can include fever, rash, chills, headache, fatigue, nausea, diarrhoea, sore throat, night sweats, appetite loss, mouth ulcers, swollen lymph nodes, muscle and joint aches – all of them symptoms of an acute inflammation (immune reaction).

antenatal

The period of time from conception up to birth.

In addition, new reports from Malawi, Uganda and Kenya each documented that when HIV-exposed babies are weaned early and abruptly, they are at a very high risk of life-threatening diarrhoeal illnesses.

In fact, one prospective randomised study, the Zambian Exclusive Breastfeeding Study (ZEBS) reported a high rate of mortality after early weaning (at four months). The study concluded that the strategy did not improve HIV-free survival at month 24. Weaning HIV-infected children early was especially harmful — with dramatically lower survival than the HIV-infected children who continued to be breastfed.

Previous guidance on infant feeding for HIV-positive mothers

Breastfeeding is by far, normally the best way to feed an infant. It is an excellent and readily available source of nutrition, and has immunological properties that help protect the infant (whose immune system is still immature) from potentially deadly infections. In fact, in studies in resource-limited settings where (or when) HIV was not a major problem, breastfeeding out to six months was repeatedly shown to result in better health and survival for babies.

“Exclusive breastfeeding for the first six months is one of the best preventive public health measure for reducing child mortality that we have,” said Dr. Peggy Henderson of WHO’s Department of Child and Adolescent Health and Development, during one of the opening sessions of the conference.

On the basis of such findings, the World Health Organization (WHO) and the United Nations Children’s Funds (UNICEF) developed a Global Strategy for Infant and Young Child Feeding. It recommended exclusive breastfeeding for the first six months and continued breastfeeding up to two years and beyond, with supplemental foods that are nutritionally adequate and safe from age six months, together with related nutrition and support for the mother.

However, when the mother has HIV, there is a significant risk that she can transmit HIV to her infant.

In industrialised countries, HIV-infected mothers can opt for safe and readily available alternatives to breastfeeding (and it also is easier to keep the infant’s home and environment hygienic). With the combination of antenatal antiretroviral therapy (ART or HAART) and breastfeeding avoidance, only about 1-2% of infants of HIV-positive mothers in industrialised countries are infected each year.

Antiretroviral prophylaxis and treatment for the prevention mother-to-child transmission (PMTCT), has also been shown to be quite effective in resource-limited settings, reducing transmission to levels similar to what has been seen in the Global North. However, several studies noted the HIV prevention benefit decreased over time — clearly associated with ongoing breastfeeding. According to a major meta-analysis of breastfeeding studies (the BHITS Group), that risk can be quite substantial in countries where prolonged breastfeeding is common, accounting for 42% of HIV infections in infants and young children in Africa. Overall, an estimated 5–20% of infants born to HIV-infected mothers are infected post-natally.

As a result, WHO and UNICEF amended the guidance in the Global Strategy for Infant and Young Child Feeding. They proposed that women with HIV should completely avoid breastfeeding when replacement feeding is “acceptable, feasible, affordable, sustainable and safe (AFASS).” Women who had no reliable access to formula feeding were not meant to starve their children but to continue breastfeeding until suitable replacement feeding could be obtained.

Over the last few years, the understanding of the risks of HIV transmission from breastfeeding has become more nuanced. Several studies have documented that mixed feeding (giving water or solid foods to the infant) resulted in much higher rates of transmission than if a mother exclusively breastfed.

And so in response, WHO and UNICEF amended their guidance once again to recommend that when replacement feeding wasn’t AFASS that women with HIV exclusively breastfeed for the “first months of life” and that as soon as replacement foods were available, that the infant be weaned abruptly, so as to avoid a prolonged period of mixed feeding (and therefore heightened risk of HIV transmission).

More recently this guidance has been changed yet again (see below).

Severe diarrhoea outbreak in Botswana

But the earlier guidance and the studies stressing the dangers of breastfeeding had the effect of making some of the nobler governments and programmes respond as though there was a moral imperative for them to provide formula to mothers with HIV. But in a developing country, this is easier said than done.

Even in Botswana, arguably the most stable, efficient and best-resourced democracy in Africa, keeping mothers all across the country well-stocked with a free and reliable supply of quality formula has proven a logistical nightmare, with frequent stock outs reported. But even if the provision of formula had been running perfectly smoothly, it is unlikely that anyone could have been prepared for the effect of the unusually heavy rains and floods that occurred in late 2005.

At a symposium at the very start of CROI, Dr Tracey Creek, of the US Centers for Disease Control, recounted a cautionary tale of a severe outbreak in diarrhoea and increase in infant mortality that followed within a month or two of flooding (which has previously been described in HIV and Treatment in Practice here. Although Botswana’s piped water is usually safe, the floods likely increased the risk of contamination of the water supply. In addition, latrines overflowed and standing pools of water nearby the homes served as possible sources of infection creating an environment that would be unsafe for any baby.

But the CDC analysis showed beyond any doubt that it was those infants who were not being breastfed, who were at greatest risk of being admitted into the emergency room with severe diarrhoea. Many infants were later readmitted with marasmus and kwashiorkor — severe malnutrition syndromes virtually unheard of in Botswana. And in the region of the outbreak, infant mortality for that period increased at least 25-fold over the previous year.

Both Dr Coovadia and Dr Henderson both stressed that, although the scale of the outbreak was shocking, these results were not totally unexpected. “We’ve known for sometime the dangers of not breastfeeding,” said Dr Henderson.

In fact, separate research conducted in Botswana, the Mashi study, had already shown that during the first year of life, mortality among HIV-exposed infants who were formula fed was higher than in those who were breastfed (especially when the baby was already HIV-infected). By 18 months of follow-up, HIV-free survival was more or less the same between the two arms.

New studies demonstrating the risks of early and abrupt weaning

Other programmes in resource-limited settings have instead opted for encouraging women to exclusively breastfeed, but as per the previous WHO/UNICEF guidance to wean HIV-exposed infants as early as possible. However, there were really very little data to suggest when might be the optimal time and way to wean the infant.

However, four new studies presented this week provided no support for the practice of early weaning.

"Studies from Malawi, Kenya, Uganda and Zambia, they are all making the same point,” said Dr Coovadia. “They found that when you stop breastfeeding, you risk an acute episode of diarrhoea and gastroenteritis.”

The studies will be discussed in more detail in a subsequent article.

Revised WHO/UNICEF guidance

According to Dr Henderson, WHO held a technical consultation last October to consider this new evidence and came up with three recommendations to update and clarify the earlier guidance:

  • The most appropriate infant feeding option for an HIV-infected mother continues to depend on her individual circumstances, including her health status and local situation but should take greater consideration of the health services available and the counselling and support she is likely to receive.
  • Exclusive breastfeeding is now recommended for HIV-infected for the first six months of life, unless replacement feeding is AFASS before that, and
  • When replacement feeding is acceptable, feasible, affordable, sustainable and safe avoidance of all breastfeeding by HIV-infected women is recommended.

However, although there was wide agreement with the clarification on how long infants should be exclusively breastfed, there appeared to be a range of opinion at the conference as to whether this guidance goes far enough, or could be put into practice in most settings

“For poor women in the developing world, there is no other choice [than to breastfeed],” said Dr Coovadia. “We shouldn’t devise policies for the rich few.”

[More of the discussion about how to make breastfeeding safer will be reviewed in subsequent reports]