1. An Employee-Owned Research Corporation 7/7/2016 Overall and Diarrhea- or Lower Respiratory Infections-Related Mortality Among Formula-Fed and Breast-Fed Children of HIV1-Infected Women in Africa: A Meta-Analysis Moussa Sarr 1, Birahim P. Ndiaye 2, Hugues Loemba 3, Mwenda Yasa 4 1 Westat, Inc., Rockville, MD, United States, 2 Cheikh Anta Diop University, Dakar, Senegal, 3 University of Ottawa Health Services, Ottawa, Canada, 4 University of New Mexico, New Mexico, United States

2. An Employee-Owned Research Corporation 7/7/2016 BACKGROUND In 2006, 2.3 million children under the age of 15 years were living with HIV/AIDS and an additional 530,000 children became newly infected with HIV through vertical transmission of the virus from their mothers. Vertical transmission of HIV from mother to child has been shown to occur in approximately three time periods: during pregnancy (intrauterine), labor and delivery (intrapartum), and through breastfeeding (postpartum).

3. An Employee-Owned Research Corporation 7/7/2016 Background Under current UNAIDS recommendations, women who are HIV positive and live in developed countries should formula feed their infants to avoid transmission of HIV via breastfeeding. n However, in resource-poor settings breast milk avoidance may result in an increase in infant mortality related to diarrhea and LRIs, and offsetting most of the gains related to using formula feeding.

4. An Employee-Owned Research Corporation 7/7/2016 Background n Many studies have reported some contradictory results on these issues, however, there has been no formal systematic review and meta-analysis comparing the mortality among formula-fed and breastfed children of HIV infected women in Africa.

5. An Employee-Owned Research Corporation 7/7/2016 Patients and Methods We searched for the MEDLINE database articles published in French or English in the last 20 years (1987 to 2007) and the reference lists of reviews and retrieved articles. The Web sites of major HIV conferences also were also searched. We used the following key search terms: formula feeding, breastfeeding, HIV, diarrhea, respiratory infections, and mortality. We included studies in the analysis if mortality and/or morbidity of formula and breastfed infants of HIV infected women were assessed. Only studies conducted in Africa were selected.

6. An Employee-Owned Research Corporation 7/7/2016 Patients and Methods Two reviewers independently assessed the quality and relevance of the data, which were analyzed using the Cochrane Collaboration’s Review Manager software (RevMan), version 4.2.7 (Oxford, England). Homogeneity of the data was calculated using a Chi-square test on N-1 degrees of freedom. Because heterogeneity tests have low power especially with a small number of studies, we used an alpha-level of 0.20 to reject the null hypothesis of homogeneity. To allow for heterogeneity, the summary estimate was obtained using a random effect model. We assessed the presence of publication bias by examining Funnel plots for asymmetry.

7. An Employee-Owned Research Corporation 7/7/2016 Eligible Studies

8. An Employee-Owned Research Corporation 7/7/2016 Cumulative Infant Mortality at 6 – 7 months of age

9. An Employee-Owned Research Corporation 7/7/2016 Cumulative Infant Mortality or HIV infection at 6 – 7 months of age Only one study with cumulative infant mortality or HIV infection at 6 – 7 months: –Breastfed vs. formula-fed hazard ratio of 1.30 (P=.28; 95% CI, 0.81- 2.10). Thior et al, 2006

10. An Employee-Owned Research Corporation 7/7/2016 Cumulative Infant Mortality at 18 – 24 month of age

11. An Employee-Owned Research Corporation 7/7/2016 Cumulative Infant Mortality or HIV infection at 18 - 24 month of age

12. An Employee-Owned Research Corporation 7/7/2016 Cumulative Diarrhea Related Mortality at 18 – 24 months

13. An Employee-Owned Research Corporation 7/7/2016 Cumulative Pneumonia Related Mortality at 18 – 24 month of age

14. An Employee-Owned Research Corporation 7/7/2016 Summary The incidence of overall infant death by month 6-7 was higher, but not significantly different in the formula-fed vs. the breastfed children, but this difference diminished beyond month 7, such that overall infant mortality were no longer in favor of breastfeeding by 18-24 months of age. The incidence of overall diarrhea and pneumonia related mortality were not also significantly different by 18–24 months of age between the two groups.

15. An Employee-Owned Research Corporation 7/7/2016 Conclusion Intervention to reduce mortality related to diarrheal and respiratory diseases during the first 6 months of infants life could help optimize the potential benefits of formula feeding for HIV infected mothers who opt for that feeding option.