MATERNAL INFLAMMATION, DIET AND GUT MICROBIOME IN HIV: IMPACT ON INFANT OUTCOMES

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Preterm birth (PTB) is one of the leading causes of childhood morbidity and mortality. HIV-infected pregnant women have a greater incidence of PTB and this population warrants further studies to determine the risk factors. Some risk factors such as low maternal CD4 count, high viral load, co-infections, co-morbidities and treatment regimen are associated with increased preterm birth, but whether and the extent to which inflammation, a risk factor for PTB in HIV-uninfected populations, affects adverse birth outcomes among HIV- infected women remains to be studied. I am seeking the Pathway to Independence Award in order to gain additional training to meet my career goals: to become an independent investigator conducting research on maternal immune, microbiological and nutritional factors that affect maternal-child health in the context of infectious diseases, especially HIV/AIDS. In doing so, I will productively bridge the different disciplines of public health epidemiology, immunology, microbiology and nutrition. The training plan for this proposal combines various forms of learning methods including didactic courses, workshops, apprenticeships resulting in publications, directed readings and career development seminars and activities. These are designed for me to gain specific skills in: 1) Nutritional Epidemiology and Perinatal Nutrition, and 2) Microbiome data analyses. The competencies I learn from the training plan will then be applied to the research phase of the proposal (K99, and especially R00). The research component proposes to study the relationship between maternal diet, gut microbiome and inflammation and their association with PTB among HIV-infected pregnant women. Leveraging a recently funded NIH cohort immunology study of 400 HIV-infected and uninfected pregnant women, I will nest my study within this parent trial to collect dietary information and stool samples to address my specific aims: 1) Examine association between inflammation during pregnancy and incidence of adverse birth outcomes among HIV-infected pregnant women, and 2) Determine the relationship of a) dietary intake and b) gut microbiome with inflammation status among HIV-infected pregnant women. Given that diet and gut microbiome are two environmentally modifiable factors that can affect inflammation, my study will identify mechanisms to reduce inflammation and improve infant outcomes in HIV-infected populations. The proposed training and research plan will result in publications and conference presentations leading to career development to become an independent investigator during the R00 phase and with the ability to successfully compete for a R01 grant.