Abstract
Breastfeeding is a most valuable source of nutrition for infants. The anti-infective properties of breast milk are well documented and breastfeeding protects infants against gastrointestinal and respiratory illnesses. There is no disagreement that breastfeeding is the best form of nutrition for all infants everywhere. Exclusive breast-feeding for 6 months is recommended for the general population primarily because human milk can satisfy all of an infants' nutritional and hydration needs. New perinatal HIV infections in resource-rich countries have nearly been eliminated with the combination of universal, opt-out antenatal HIV testing, antiretroviral prophylaxis of the mother and infant, elective cesarean delivery, and avoidance of breastfeeding. Although effective interventions are available to reduce in utero and intrapartum transmission in resource-limited settings, postnatal transmission of HIV through breastfeeding has remained a significant problem. Acquisition of HIV through breast milk accounts for an estimated 40% of new infections in sub-Saharan Africa, where more than 90% of perinatal infection occurs. The studies performed during this PhD were part of a larger intervention program in KwaZulu-Natal that focused on the use of different forms of infant feeding within a rural setting. The Umkhanyakude district in northern KwaZulu-Natal, South Africa, is one of the areas worst affected by the HIV and AIDS pandemic, and has some of the highest prevalence figures in the world. Women were enrolled into this study prior to commencement of the South African national antiretroviral roll-out in 2005. This PhD research forms part of efforts to gain a better understanding of postnatal transmission of HIV-1 via breastfeeding, and to support the World Health Organization in their goal to reduce all forms of mother-to-child transmission (MTCT) to below five percent by the end of 2015. In the first study performed, we provide for the first time evidence that cumulative exposure to HIV-1 RNA in breast milk is a key risk factor associated with postnatal mother-to-child transmission, independent of maternal CD4 and plasma HIV-1 viral load. This data provides a better evaluation of the risk of HIV-1 MTCT and intra-breast viral load. In the second study we confirm that cell-associated virus load in breast milk is a stronger predictor of the risk of early postnatal MTCT than cell-free virus, independent of HIV-1 replication in blood and breast milk. In contrast, cell-free virus load is a stronger predictor of later postnatal HIV-1 transmission. We provide evidence that the HIV-1 reservoir is a main risk factor for post-natal MTCT of HIV-1. In the third study performed, we investigated the significance and impact of Cytomegalovirus (CMV) and Epstein-Barr virus (EBV) in breast milk from HIV-infected mothers, and MTCT of HIV-1. High levels of CMV is shed in breast milk, and frequently a significant level of EBV is shed in HIV-infected women. Hence, mothers whose breast milk contained high levels of CMV, were up to two and a half times more likely to transmit HIV-1 to her infant via breastfeeding compared to women with low levels. This is the first evidence of an association, independent of HIV-1 viral load, between CMV in breast milk and postnatal MTCT of HIV-1. In contemporary breastfeeding populations with access to antiretroviral prophylaxis, the residual HIV-1 transmission risk, especially in the early postpartum period, is explained in part by the persistence of cell-associated virus in breast milk. More studies are needed to further knowledge on the mechanism of HIV-1 transmission during lactation, and factors associated with compartmentalized shedding of HIV-1 in breast milk, and to help develop more effective drugs for use in resource-limited populations where avoidance of breastfeeding is almost impossible.