The issue of breastfeeding infants of mothers with human immunodeficiency virus (HIV) infection has been a vexing problem for pediatricians in developing countries. On the one hand is the risk of the infant developing a chronic and fatal infection from breastfeeding and on the other is the increased risk of death from malnutrition or infectious diseases if breastfeeding is denied. The recommendation in developed countries is for HIV-infected women not to breastfeed. This is not an accept-able solution for most families in developing countries who cannot afford artificial feeds or are unable to provide artificial feeds in a safe manner. In 1996 the Joint United Nations Program on HIV/AIDS (UNAIDS) recom-mended that HIV seropositive women in resource poor areas be encouraged to make an informed choice about infant feeding, i.e., that considerations for risks and benefits be indivi-dualized for each women(1). However, in most situations, the "individual decision" is more a matter of necessity than choice and is based mainly on economic and social pressures rather than a choice dependent on risks and benefits. This leads to considerable anguish for the parents who may have to make less than optimal choice out of necessity. It is the responsibility of the physician to guide and support the family in making their decision. However, the lack of precise data on the excess risk of transmission from breast milk and the risk factors associated with such transmission makes the task of counseling families difficult. In the last one year, there has been considerable new information available on this subject, which provides new options to pediatricians dealing with HIV infected families. Since HIV/AIDS is threatning to become a major problem in children in India, it is essential that we evaluate the new information so that we are well equipped in assisting families in making this difficult decision.

The fact that HIV infection can be transmitted through breast milk is now un-disputed. The virus has been detected in breast milk both by culture(2) and polymerase chain reaction (PCR)(3). Though this finding in itself does not necessarily mean that infection is transmitted via breastfeeding, subsequent studies confirmed that this does occur(4). There were many who argued that this was an un-common phenomenon till a meta-analysis of retrospectively collected data showed that there was a 29% (95% CI 16-42%) risk of trans-mission through breastfeeding in a mother with primary HIV infection acquired during the early postnatal period and a 14% (95% CI 7-22%) increased risk of transmission through breast-feeding in a chronically infected woman, over and above intrauterine and intrapartum trans-mission(5). These data have been confirmed by the results of a recently published randomized clinical trial evaluating excess transmission of HIV via breastfeeding(6). This study showed that the risk of transmission of infection from breastfeeding was 16.2% (95% CI 6.5-25.9%) over and above other modes of vertical transmission(6). In industrialized countries this excess risk is not acceptable. But, in developing countries, the risk of transmission of HIV has to be weighed against the risk of morbidity and mortality from malnutrition and other infections due to lack of breastfeeding. It has been estimated that an infant in a developing country who is not breastfed has mortality 2 to 3 times higher than a breastfed infant(7). In the trial in Nairobi, the cumulative mortality at 24 months in formula fed infants and breastfed infants was not significantly different (20.0% and 24.4%, respectively)(6). However, children who sur-vive with HIV infection at 24 months have an increased risk of mortality later in life. There-fore, a more realistic estimate is HIV-free survival at 2 years, at which time breastfeeding has been discontinued. The HIV-free survival at 2 years in this trial was significantly lower in the breastfed group as compared to the formula fed group (58% vs. 70%, respectively, p = 0.02)(6). The improve HIV-free survival at 2 years in formula fed infants in this study is a case for recommending formula feeds for infants of HIV-infected mothers even in developing countries. But these results must be interpreted with caution since in this study formula feeding was done after extensive counseling about feed preparation and hygiene and strict follow up was maintained. This degree of counseling and monitoring may not be possible in a non-study situation and one may expect higher mortality in the formula fed infants than is reported in this study.

The early studies that provided estimates for the cumulative risk of transmission from breast-feeding did not provide information on the timing of transmission(5). It is now clear that transmission of infection can occur as long as breastfeeding is continued, though the risk of transmission at various periods postnatally may vary. A few studies that looked at late postnatal transmission of HIV showed that a significant proportion of infection occurred after 6 months of age(8,9). It was postulated that shorter duration of breastfeeding with early weaning might lead to less exposure and, therefore, a lower risk of transmission. Unfortunately, subsequent data on the timing of HIV infection from breastfeeding have been conflict-ing(6,10,11). The data from these studies are summarized in Table 1. The pooled multicentric study(10) and the study from Malawi(11) showed that the excess risk of transmission if breastfeeding was discontinued before 6 months was 0.7% and 3.5%, respectively. These data also suggested that a short period of breastfeeding followed by early weaning would tide the infant over the period in early infancy when breast milk was crucial for his/her well being and at the same time minimize the risk of transmission of HIV. However, data from the randomized controlled trial in Nairobi published early this year showed that 75% of transmission from breastfeeding occurred during the first 6 months of life, suggesting that breastfeeding for 6 months followed by early weaning would not substantially reduce mother-to-child transmission from breast-feeding(6). In the first two studies, which were cohort studies, the tests used to detect HIV infection in infants did not discriminate between intrapartum transmission and early neonatal transmission from breastfeeding. In these studies PCR positivity after 2.5 months(10) or 6 weeks(11) of age was taken as constituting postnatal infection. Infants who may have got infected through breastfeeding prior to this period would, therefore, not have been identified. Therefore, it is likely that these studies underestimated transmission from breastfeeding because they may have missed early postnatal transmission. In the trial from Kenya, where there was a comparative formula fed group, this was not a problem and this study probably provides a more accurate estimate on the timing of transmission. However, all the studies show that risk of transmission continues as long as breastfeeding continues. None of these studies specifically looked at differences in transmission between exclusively breastfed infants and infants fed breast milk along with formula feeds.

Table I - Timing on Mother-to-Child Infection of HIV-1 Through Breastfeeding

# Age = age till which the infant was breastfed.
* CER = Cumulative excess risk of transmission of HIV from breastfeeding (%).

Several studies have looked at the risk for factors for transmission of HIV-1 infection from breast milk. Increased maternal viral load, cracked nipples and introduction of other liquid food before weaning have been identified as potential risk factors(12,13). While one study found that even subclinical mastitis, as evidenced by elevated breast milk sodium, was associated with increased risk of transmission of infection(12), the other showed that mastitis in the absence of bleeding was not associated with higher risk of infection(13).

The risk of transmission of HIV-1 infection through colostrum has been another point of debate. The increased inflammatory cellular content of colostrum, the immature immune system of the neonate and achlorhydria in neonates are factors that favor increased transmission of HIV-1. On the other hand, the low proportion of infected cells, the low volume ingested, the high concentrations of IgA, IgM and other anti-infective factors and high concentrations of vitamin A make infection from colostrum less likely(14). Intake of colostrum was not found to be associated with increased risk of infection in one study that looked at this issue(13). However, more data is required before a definite conclusion can be made about risk of transmission from colostrum.

The concomitant use of other liquid feeds along with breast milk has been shown to be associated with an increased risk of transmission of HIV-1 infection(13). This effect was dramatically brought out in a recently published study from South Africa(15). In this cohort study the risk of transmission of HIV-1 in exclusively breastfed infants was no higher than formula fed infants at 3 months, whereas infants with mixed feeding had a significantly higher rate of transmission. Exclusive breast-feeding was defined as the administration of breast milk with the exclusion of all other liquid or solid food, including water. All infants who received any other oral feed in addition to breast milk were classified as mixed fed. The postulated explanation for this phenomenon is that breast milk contains several factors such as secretory leukocyte protease inhibitor, lactoferrin, complement and glycosamino-glycan that protect against infection. Moreover, breast milk contains epidermal growth factor and transforming growth factor b that may enhance the maturation and integrity of the epithelial barrier and hinder the entry of virus. These may be counteracted by the damage to the gut epithelium due to infection or allergy from mixed feeding. This is the only study that has closely examined the issue of exclusive breastfeeding versus mixed feeding using a strict a definition for exclusive feeding. The results have very important implication but need to be replicated in other studies to determine the validity of the finding. It must also be remembered that sweetened water or other feeds during the first few days after birth is a normal practice in many societies and that breastfeeding to the exclusion of all other oral feeds may be difficult to achieve, especially for working mothers.

Finally, even with the availability of new data, many unanswered questions remain. We need more definitive data on the timing of infection, the infectivity of colostrum, the role of protective factors in breast milk and other immunologic factors that enhance or reduce transmission from breast milk. The protective effect of exclusive breastfeeding, though very intriguing, needs to be confirmed by carefully conducted randomized clinical trials. Mean-while, the best option would be to avoid breast-feeding if it is a safe and economic option for the family. This would be particularly true for children born to mothers who have spent money and effort on antiretroviral therapy to prevent mother-to-child transmission or infants who have a negative PCR at 1 month of age. When artificial feeds are not a viable option or will pose a higher risk to the life of the infant than the risk of acquiring HIV, exclusive breast- feeding should be encouraged, with early weaning to minimize the risk of late postnatal transmission. A third option that has been suggested in resource poor settings is to combine breastfeeding with several weeks or months of antiretroviral therapy with weaning at six months of age(16). However, this strategy has never been tested and it is unlikely that mothers who cannot afford or safely give artificial feeds will have the motivation or be able to afford prolonged antiretroviral therapy.

It is time that the Academy formulated guidelines to assist pediatricians in counseling families with HIV. However, care should be taken to ensure that these guidelines would not counter the gains made by the promotion of breastfeeding by various programs. Such guidelines may also be subject to misinter-pretation and may be used by infant food manufacturers to promote their products. Thus, extreme caution has to be exercised in formulating and disseminating these guidelines.

Thomas Cherian,
Professor,
Department of Child Health,
Christian Medical College and Hospital,
Vellore 632 004, Tamil Nadu, India.
E-mail: [email protected]

Funding: None.

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