Maternal antibody transfer in HIV-1 infected women and impact on infant health : the role of antiretroviral prophylaxis and breastfeeding practices

Children born to human immunodeficiency virus type 1 (HIV-1) infected women are more vulnerable to infections and are more likely to die even when they are not HIV-1 infected. These adverse outcomes may blunt any gains made in escaping HIV-1 infection and could be ameliorated by improving maternal antibody transfer to the baby. The overall aim of this thesis was to study the role of antiretroviral prophylaxis and breastfeeding practices on maternal antibody transfer to their children and on the morbidity these children experience in the first year of life . Studies I and II examined the influence of antiretroviral treatment on antibody levels during pregnancy and delivery, in cord blood and breast milk. We used data from a randomized clinical trial in which HIV-1 infected pregnant women with CD4 counts between 200 and 500 were randomized to short-course zidovudine (ZDV) or triple antiretroviral therapy (ART) during pregnancy for prevention of HIV-1 transmission from mother to child. Antibody levels against measles, pneumococcus and rotavirus were measured in maternal plasma, infant cord blood and breast milk and compared between the trial arms. We found that maternal levels in plasma (Study I) and breast milk (Study II) were comparable between the two groups. Compared to women on short-course ZDV, women on triple ART transferred higher amounts of antibody via the placenta. In Study III, we compared infant morbidity, hospitalization, and mortality during the first year of life of HIV-1 exposed uninfected (HEU) children born to the women in Study I and II. Our morbidity outcomes of interest were those that cause significant mortality in these children namely diarrhea, pneumonia, and lower respiratory tract infection, and a composite measure of any infectious morbidity. We found important predictors for mortality in these children; however, we found no effect of the mother’s ART treatment regimen for any of these outcomes. Study IV used a real world setting in which HIV-1 infected women were enrolled during pregnancy into a clinic-level, before-after breastfeeding counseling intervention study. Women in the intervention arm were offered three counseling sessions that promoted exclusive breastfeeding (EBF), explained breastfeeding techniques and described its benefits. EBF prevalence was comparable between the two arms at 14 weeks postpartum. We found no differences between the groups for 6-week HIV-free survival or 14-week infant survival for the children born to these women. The results of this thesis show some benefit for maternal triple ART compared to short-course ZDV in passive antibody transfer via the placenta and that high EBF rates are attainable. The non-significant findings for impact on morbidity and mortality outcomes among HEU children highlight the complexity of unravelling the mechanisms that underlie the higher vulnerability that has been observed in these children. The findings from this thesis may be used to inform the design of future studies so that ultimately the health and survival of HEU children can be secured. LIST OF SCIENTIFIC PAPERS I. Bosire R, Farquhar C, Nduati R, Broliden K, Luchters S, Van De Perre P, De Vincenzi I, Merkel M, Wachuka V, Mbori-Ngacha D, John-Stewart G, LohmanPayne B, Reilly M. Higher transplacental pathogen specific antibody transfer among women randmomized to triple antiretroviral treatment versus shortcourse zidovudine. Pediatr Inect Dis J 2018;37:246252. II. Bosire R, Farquhar C, Ndiaye A, Nduati R, Broliden K, Luchters S, De Vincenzi I, Ichugu CG, Wachuka V, John-Stewart G, Reilly M, LohmanPayne B. Effect of pregnancy and postpartum antiretroviral prophylaxis on longitudinal breast milk IgA levels. (Manuscript). III. Bosire R, Ndiaye A, Reilly M, Nduati R, Luchters S, De Vincenzi I, MboriNgacha D, John-Stewart G, Lohman-Payne B, Farquhar C. Morbididty, hospitalization and mortality among infants born to women randomized to triple antiretroviral therapy vs shortcourse zidovudine in Kenya. (Manuscript). IV. Bosire R, Betz B, Aluisio A, Hughes JP, Nduati R, Kiarie J, Chohan BH, Merkel M, Lohman-Payne B, John-Stewart G, Farquhar C. High rates of exclusive breastfeeding in both arms of a peer counseling study promoting exclusive breastfeeding among HIV-infected Kenyan women. Breastfeed Med 2016:11(2) 56-63. The papers will be referred to throughout the text by their Roman numerals. Related Articles (not included in the thesis) Odeny BM, Pfeiffer J, Farquhar C, Igonya EK, Gatuguta A, Kagwaini F, Nduati R, Kiarie J, Bosire R. The stigma of exclusive breastfeeding among HIV-positive and HIV-negative women in Nairobi, Kenya. Breastfeed Med 2016;11:252-8 Aluisio AR, Bosire R, Betz B, Gatuguta A, Kiarie JN, Nduati R, John-Stewart G, Farquhar C. Male partner participation in antenatal clinic services is associated with improved HIV-free survival among infants in Nairobi, Kenya: A prospective cohort study. J Acquir Immune Defic Syndr 2016;73(2):169-76