During 2001, ~800,000 children worldwide acquired human immunodeficiency virus type 1 (HIV-1), 90% via mother-to-child transmission [1
]. In the absence of treatment, approximately one-third to one-half of HIV-1 infections in infants occur via breast-feeding [2
]. Although antiretroviral therapy has been effective in reducing perinatal transmission of HIV-1, no therapeutic regimen has yet been developed that, throughout lactation, significantly reduces transmission via breast-feeding [6
]. In developing countries, where 90% of HIV-1–exposed children live, alternatives to breast-feeding are often unaffordable, and, in settings where clean water in unavailable, their use may cause an increased susceptibility to other infectious diseases. Therefore, breast-feeding, regardless of maternal HIV-1 infection status, continues to be the most prevalent form of infant feeding in resource-constrained settings.
Antiretroviral drugs reduce transmission of HIV-1, presumably by decreasing its levels in both maternal blood and maternal mucosal secretions, resulting in reduced infant exposure to the virus. It is possible that antiretroviral therapy given to the mother during the breast-feeding period might be effective in preventing transmission of HIV-1 via breast milk; however, it is not known how much a reduction in breast-milk virus levels would affect the risk of transmission, nor is it known whether there is an optimal time to administer antiretroviral therapy that, throughout lactation, would prevent transmission via breast feeding. To better understand how antiretroviral therapy might prevent transmission via breast milk, the association between breast-milk virus levels and transmission of HIV-1, as well as the fluctuation in breast-milk virus load throughout the period of lactation, need to be well characterized.
Previous studies have indicated that HIV-1 is present in breast milk and that breast-milk virus levels are associated with mother-to-child transmission [13
]. A study of 334 Malawian women reported that virus load in breast milk collected 6 weeks after delivery was associated with perinatal transmission [14
]. A smaller study of South African women (n
= 79), which included the collection of up to 3 breast-milk samples from 1 week to 15 months after delivery, also reported that breast-milk virus levels were associated with transmission [15
]. The latter study reported no significant change, over time, in breast-milk virus levels in the women from whom 2 (n
= 24) or 3 (n
= 17) samples were collected. Because that study did not include breast-milk samples collected earlier than 1 week after delivery (i.e., colostrum/early milk), and because the sample size and frequency of sample collection were low, a more thorough study is necessary to define the changes, over time, of breast-milk virus levels in HIV-1–infected women.
In 1992 in Nairobi, Kenya, our group initiated a randomized clinical trial of breast-feeding and formula feeding in 425 HIV-1–seropositive mothers who were followed for up to 2 years after delivery [2
]. The incidence of transmission via breast milk was 16.2% (95% confidence interval [CI], 6.5%–25.9%); 44% of all transmission was attributable to breast-feeding. The majority of transmission via breast-feeding occurred early, with the infection-rate difference between the breast-feeding group and the formula-feeding group being 63% by 6 weeks after delivery, 75% by 6 months after delivery, and 87% by 12 months after delivery. As in other studies, prenatal maternal plasma virus levels, prenatal maternal CD4 T cell count, and breast-feeding were associated with mother-to-child transmission [17
]. Up to 7 serial breast-milk samples were collected from 275 women participating in the trial, and, in a preliminary study, cell-free viral RNA and cell-associated proviral DNA were detected in breast-milk supernatant and in cell-pellet fractions, respectively [16
]. Because of the large number of participants and the frequency of sample collection, this trial provided a unique opportunity to investigate both the fluctuation in breast-milk virus load during the first 2 years of lactation and the association between breast-milk virus load and both transmission and maternal disease. These analyses are presented here.