This is the first study reporting the field efficacy of two concomitant PMTCT interventions to reduce postnatal transmission of HIV. Whereas FF has been the recommended option in developed countries, this intervention is not feasible for many African women and carries a higher risk of morbidity and mortality in resource-limited settings that needs to be balanced against its benefits in preventing postnatal transmission. With the antiretroviral era in Africa since 2004, providing HAART to women while BF is another conceivable option, offering a culturally appropriate alternative. In our study, following a backbone of maternal HAART according to 2006 WHO criteria[25
], both postnatal approaches were found to be safe and effective, with similar nine-month HIV-free survival of about 95%. The overall nine-month transmission rate was about 1.3%, one of the lowest MTCT rate ever reported from low-income countries[29
] and similar to those reported from industrialized countries. We attribute this strong effect to the combination of starting HAART prior to delivery, antiretroviral prophylaxis to the newborn and continued HAART for six months while BF.
In a meta-analysis, the risk of HIV transmission by EBF was estimated around 0.7% per child-month of BF follow-up[6
]. In other recent African studies, the lowest reported rates of transmission with EBF by 3–6 months have varied between 1.3 % and 5.6%[2
]. Although these studies are difficult to compare directly, our postnatal transmission rate for women BF under HAART would suggest a significant reduction in postnatal transmission. We found only one other published report (DREAM Program), assessing the efficacy of BF combined with maternal HAART to reduce postnatal transmission (additional 0.8% postnatal transmission in the BF group with HAART), but without a FF comparison group at the same period of time[2
The results with FF were also encouraging, showing an overall mortality lower than in infants born to HIV-uninfected mothers in Rwanda[32
]. The total mortality of children followed in the AMATA trial was 4.7% at 9 months, without statistically significant differences between the BF and FF groups. This is in contrast with some studies that have shown an overall increased mortality in FF infants and we suggest that this is because both studies (DREAM and AMATA) were strongly focused on patients’ counseling, education, and good quality of care and adaptation of the feeding option to the mother’s choice. These data also confirm the importance of postnatal follow-up for exposed children, very often neglected when PCR-testing is not available, resulting in limited access to care and information.
We chose a cohort design instead of a randomized clinical trial to avoid the ethical problems associated with a fixed allocation of the infant feeding practices[33
]. In addition, this design helped to assess the mother’s choice of feeding method with FF with a close follow-up and education for the preparation of milk. We believe this was a key factor in encouraging good adherence[34
]. To be able to offer women a culturally acceptable method of feeding, that matched HIV transmission rates using FF, resulted in very important public health implications.
This study had several limitations. First, while adjusting for the cohort design our findings remained essentially unchanged in multivariate analysis, residual confounding may still be possible. Second, these outcomes were obtained within a specific study research setting with high quality of care and follow-up. Consequently, these findings could not be generalized to the country level. Third, even though the overall tolerance of HAART was very good in this study, toxicity of HAART could be problematic in settings with fewer resources for follow-up.
Finally, this study did not have the power to detect small differences in postnatal HIV-1 infection or mortality between the two approaches.
There are some public health caveats, as well. In most low-income countries, access to HAART services is still limited and particularly challenging for pregnant women during the last trimester of pregnancy. Even if accessible everywhere, cost implications of dissemination of this PMTCT model will have to be considered in each country. There is also the potential of an increased risk of infection with resistant viruses for those newborns infected while breastfed from mothers taking HAART[35
]. This issue may become less problematic now since, based on a recent pediatric study, WHO currently recommends to treat all young HIV infected children with protease inhibitors in case of recent exposure to NVP[36
Several relevant questions remain to be addressed. How will mixed feeding affect the postnatal transmission rate, even if HAART is taken? If HAART does protect against transmission during mixed feeding, then could HAART be continued for longer periods (e.g. up to 1 year) or during all the BF period? It also remains to be seen whether sufficient levels of adherence to prophylactic HAART can be achieved to avoid emergence of drug-resistance, especially when HAART is given for a longer period.
There may be several alternatives to replacement feedings such as diluted, boiled cow’s milk or heated expressed breast milk[38
] that might be more easily implemented in remote places where provision of HAART or FF can be problematic.
We conclude that BF when combined with maternal HAART can be associated with a minimal risk of postnatal transmission, similar to the FF one in our cohort, and with HIV transmission rates as low as those in high-income countries. A key implication of this study is that women can be offered a choice in infant feeding options, both of which could be safe and effective, given regular postnatal follow-up and counseling. This information would be useful in guiding recommendations on the safest and best infant feeding modalities according to the different African contexts combined with the full spectrum of antiretroviral strategies, including ART for those in need.