Current Status of HIV and Breastfeeding Research

Anna Coutsoudis Ph.D.

from Breastfeeding Abstracts, February 2005, Vol. 24, No. 2, pp. 11 & 12

Breastfeeding provides optimal nutrition for infants, as well as protection from disease, particularly infection. However, mother-to-child transmission of the human immunodeficiency virus (HIV) can occur through breastfeeding, if a mother is infected. This leads to difficult decisions, especially where HIV infection is common.

Risk of transmission of HIV through breastfeeding

Information on the risk of transmitting HIV through breastfeeding was reported by the Breastfeeding and HIV International Transmission Study (BHITS) Group,¹ in an individual patient data meta-analysis of 4085 predominantly breastfed children who participated in 9 trials. The overall risk of breastfeeding transmission was estimated as 0.74% per month of breastfeeding. This meta-analysis demonstrated that the risk of transmission was cumulative and roughly constant throughout the breastfeeding period, suggesting a 4% risk for every 6 months of breastfeeding.

These studies, however, did not investigate the risk of breastfeeding transmission during exclusive breastfeeding (EBF). Exclusive breastfeeding is defined as feeding an infant only breast milk, in contrast to mixed breastfeeding, defined as the feeding of breast milk along with complementary foods, other milks, and/or infant formula. The first study to prospectively examine the influence of EBF on risk of HIV transmission was conducted in South Africa² and found that the cumulative probability of HIV infection was similar among never breastfed and EBF infants up to 6 months, but was significantly higher for infants who received mixed breastfeeding.

Several large, well designed, prospective cohort studies in South Africa, Zimbabwe, Cote D’Ivoire, and Zambia are currently in progress to examine more closely the effect of EBF on the risk of HIV transmission via breastfeeding. Preliminary results of the Zimbabwean³ and Cote d’Ivoire⁴ studies presented at the recent International AIDS conference in Bangkok in July, 2004, have confirmed the finding that exclusive breastfeeding carries a much lower risk of HIV transmission than mixed breastfeeding. See the table for a summary of risk factors for HIV transmission during breastfeeding:

RISK FACTORS FOR BREASTFEEDING TRANSMISSION OF HIV
Strong Evidence	Limited Evidence
High plasma viral load	Non-exclusive breastfeeding in the first 6 months
Advanced disease/low CD4 count	High breast milk viral load
Breast pathology (mastitis, abscesses, cracked bleeding nipples)	Subclinical mastitis as evidenced by increased breast milk sodium levels
Primary infection/new infection	Low maternal levels of vitamins B, C, and E
Prolonged duration of breastfeeding (more than 6 months)	Infant oral candidiasis

Impact of breastfeeding on the HIV-infected mother

A study from Kenya reported that the 24-month maternal mortality among breast-feeding HIV-seropositive mothers was significantly increased relative to their formula-feeding counterparts.⁵ However, subsequently, a Tanzanian study,⁶ a Zambian study,⁷ and a meta-analysis involving 9 large studies⁸ have shown clearly that breastfeeding does not pose any mortality or other health risk to the HIV-infected mother.

Morbidity and mortality risks of not breastfeeding

Simply encouraging HIV-positive women not to breastfeed in order to prevent postnatal transmission of HIV carries its own risks. The objective of any strategy to prevent mother-to-child transmission of HIV must be to optimise overall survival, including that of children of women who are not infected with HIV. Central to this decision is determining the attendant risk of morbidity and death in breastfeeding versus non-breastfeeding infants and what impact the recommendation and/or provision of formula milk or other replacement feeds to HIV-infected women will have on the feeding practices of uninfected mothers.

Breast milk fulfils the healthy, full-term infant’s total nutrient requirements for the first 6 months of life and remains a valuable source of nutrition up to 2 years and beyond. Well known benefits of breastfeeding include reducing the infant’s risk of infection, especially diarrhea and pneumonia, and these have been reinforced by a recent meta-analysis.⁹ Reduction of mortality from infections is unlikely to be as important a consideration in well-resourced communities where the risks of artificial feeding can be minimized. However, even in developed countries, breastfeeding may protect against bacterial and viral infections and later onset of health problems such as diabetes, cardiovascular disease, and cancer.

Because of the paucity of well-designed prospective trials evaluating the long-term relative risks associated with breastfeeding and formula-feeding in settings of high HIV prevalence, several groups have designed mathematical models to assess the net mortality. In a recent modelling exercise Kuhn et al.¹⁰ estimate that when infant mortality rates are greater than about 40 per 1000 live births, providing formula milk to HIV-infected women would result in the excess number of deaths arising from formula use being the same or greater than the number of HIV infections that might be prevented.

Counselling and empowering women to make an informed choice on infant feeding is not simply a matter of informing them about the theoretical risks associated with different feeding options. Health workers need to assess an individual mother’s circumstances to ascertain what is most feasible and safe for her. Time is required to explain the factors that increase the risk of breastfeeding transmission of HIV or of morbidity from replacement feeds, and to give suggestions to reduce these risks. Counsellors need a deep understanding of the social issues and the household situation, as well as the ability to explain complex scientific concepts on risk in a way that is understood by women who do not ordinarily think in these terms. They need to express compassion and have the ability to emotionally support women in a decision that affects themselves, their children, and the rest of their family.¹¹

Now that there is growing evidence that mixed breastfeeding carries considerable risk for HIV transmission, implementers of Prevention of Mother-to-Child Transmission (PMTCT) programs should be cautious about the distribution of free formula milk, as this practice seems to encourage mixed breastfeeding.^{12, 13} A more equitable and safer approach would be to provide vouchers which could be exchanged either for formula milk for the infant or food for the mother.

For those mothers who choose to exclusively breastfeed, a second choice will need to be made at about 6 months of age. If the child is infected, or suspected to be infected, then the child should continue to breastfeed. If the child is uninfected, the mother should be encouraged to stop breastfeeding in a short period of about 1-2 weeks, providing that the child will have access to adequate complementary food. Mothers should be provided with specific guidance and support when they cease breastfeeding to avoid harmful nutritional and psychological consequences to the infant and to maintain their breast health. If the infant will not have access to adequate complementary food, the best option is probably for the mother to express and heat-treat her breast milk¹⁴ and use the money that would have been spent on formula milk to purchase complementary food.

Strategies to reduce breastfeeding transmission and improve child survival

Until more data is available to clarify these issues, what can be done to minimize breastfeeding transmission of HIV and optimize child survival? Health workers need improved counselling skills and more opportunities to assist women in making informed choices that they are committed to follow. For women who choose to breastfeed, experienced support should be available to ensure good exclusive breastfeeding practices that will minimize breast pathology, HIV viral load, and disruptions to the infant’s gut environment, thereby reducing risk of HIV transmission. Breastfeeding should be discouraged for those women who have progressed to AIDS and have very low CD4 counts.

Strategies to minimize risk of transmission include the following:

Exclusive breastfeeding during the first 6 months.
Shorter duration of breastfeeding – about 6 months.
Good lactation management so that breastfeeding problems such as cracked nipples, engorgement, and mastitis are prevented.
Where the mother does develop mastitis or abscesses, she must express milk from the affected side frequently and discard it and continue feeding from the unaffected side.
Condoms must be used throughout the lactation period.
If the infant has oral thrush, it must be treated promptly.

Pasteurisation of expressed breast milk, using a method that is practical and feasible even at home, can be used to effectively kill all cell-free HIV.¹⁴ This strategy is likely to be difficult to implement from birth but may be more relevant after 6 months or as a temporary measure to sustain exclusive breastfeeding when the mother is unwell or away from her child.

For those mothers who choose not to breastfeed, or who wean before 6 months postpartum, support should be available to demonstrate preparation and safe storage of commercial infant formula to minimize the risks of diarrheal morbidity and malnutrition.

Communities need to be encouraged to be supportive of mothers with HIV infection and accept the varied approaches to infant feeding that may occur.

Use of antiretrovirals to prevent HIV transmission during breastfeeding

As already mentioned, maternal HIV viral load has consistently been shown to be an important risk factor for breastfeeding transmission. It therefore seems likely that giving highly active anti-retroviral therapy (HAART) to the infant and/or mother during the lactation period could reduce transmission. Several studies are currently underway testing the use of HAART to the mother and single or dual antiretroviral drug regimens to the infant.¹⁵

Many women may already be on HAART, raising the question of whether a woman on HAART can safely breastfeed. Unfortunately, we do not yet have enough information to answer this question definitively. Given that the viral load in women on HAART will be very low (at undetectable levels), there should be no, or minimal risk of breastfeeding transmission. Other considerations to bear in mind in this decision would be medication safety issues. Most antiretrovirals will be excreted into the breast milk, and the infant will be exposed to small quantities. For those drugs which have been widely used in infants such as nevirapine (NVP), zidovudine (ZDV) and lamivudine (3TC), there are unlikely to be safety concerns. A remaining concern will be that infants will be exposed to subtherapeutic levels of antiretrovirals through breast milk. If some infants become HIV infected despite HAART, they may have developed resistance to these drugs. This could impact their future HIV treatment. There are several trials currently in progress investigating these issues.¹⁵

Conclusion

Based on current knowledge, the recommendations above should help to minimize mother-to-child transmission of HIV and maximize child survival. Research on mother-to-child transmission of HIV is ongoing, and future findings will inform, and possibly modify, the recommendations.

References

1. The Breastfeeding and HIV International Transmission Study Group. Late postnatal transmission of HIV-1 in breast-fed children: An individual patient data meta-analysis. JID 2004; 189:2154-66.

2. Coutsoudis, A., K. Pillay, L. Kuhn et al. Method of feeding and transmission of HIV-1 from mothers to children by 15 months of age: Prospective cohort study from Durban, South Africa. AIDS 2001; 15:379-87.

3. Piwoz, E., T. Iliff, N. Tavengwa et al. Early introduction of non-human milk and solid foods increases the risk of postnatal HIV-1 transmission in Zimbabwe. International AIDS Conference, Bangkok, July 2004, abstract MoPpB2008.

4. Leroy, V., R. Becquet, F. Rouet et al. Postnatal transmission risk according to feeding modalities in children born to HIV-infected mothers in a PMTCT project in Abidjan, Cote d’Ivoire. International AIDS Conference, Bangkok, July 2004, abstract MoPpB2007.

5. Nduati, R., B. Richardson, G. John et al. Effect of breastfeeding on mortality among HIV-1 infected women: A randomized trial. Lancet 2001; 357:1651-55.

6. Sedgh, G., D. Spiegelman, U. Larsen et al. Breastfeeding and maternal HIV-1 disease progression and mortality. AIDS 2004; 18:1043-49.

7. Kuhn, L., P. Kasonde, C. Vwalika et al. No increased risk of maternal mortality attributable to prolonged breastfeeding among HIV-positive women in Lusaka, Zambia. International AIDS Conference, Bangkok, July 2004, abstract ThPeB7010.

8. The Breastfeeding and HIV International Transmission Study Group. Mortality among HIV-1-Infected women according to children’s feeding: An individual patient data meta-analysis. AIDS 2004, in press.

9. WHO Collaborative Study Team on the Role of Breastfeeding on the Prevention of Infant Mortality. Effect of breastfeeding on infant and child mortality due to infectious diseases in less developed countries: A pooled analysis. Lancet 2000; 355:451-55.

10. Kuhn, L., Z. Stein, M. Susser. Preventing the mother-to-child HIV transmission in the new millennium: The challenge of breastfeeding. Paediatr Perinat Epidemiol 2004; 18:10-16.

11. WHO. New data on the prevention of mother-to-child transmission of HIV and their policy implications. Conclusions and recommendations. WHO technical consultation on behalf of the UNFPA/UNICEF/WHO/UNAIDS Inter-Agency Task Team on Mother-to-Child Transmission of HIV. Geneva. October 2000.

12. Jackson, D. J., M. Chopra, T. Doherty, and A. Ashworth. Quality of counseling of women in South African PMTCT pilot sites. International AIDS Conference, Bangkok, July 2004, abstract ThPeE7998.

13. Coutsoudis, A., A. E. Goga, N. Rollins et al. Free formula milk for infants of HIV-infected women: Blessing or curse? Health Policy and Planning 2002; 17(2):154-60.

14. Jeffrey, B., L. Weber, R. Makhondo, and D. Erasmus. Determination of effectiveness of inactivation of Human Immunodeficiency Virus by Pretoria pasteurisation. J Trop Paediatrics 2001; 47:345-49.

15. Gaillard, P., M.-G. Fowler, F. Dabis et al. Use of antiretroviral drugs to prevent HIV-1 transmission through breastfeeding: From animal studies to randomized clinical trials. J Acquir Immune Defic Syndr 2004; 35:178-87.

Page last edited Sun Oct 14 09:32:41 UTC 2007.