I am applying for a K24 award with the goals of expanding the scope of two NIH-funded research studies in Botswana and creating a combined dataset to maximally utilize existing data and specimens from clinical cohorts. In the past 18 years, I have built a successful research program in Botswana with a focus on the prevention of mother-to-child HIV transmission (PMTCT), understanding adverse birth outcomes among infants exposed to antiretrovirals in utero, and improving survival among HIV-infected and HIV-exposed children. I have successfully mentored or co-mentored over 30 young investigators in my career, but through a K24 mechanism I can improve my mentoring expertise and expand opportunities for mentees. My K24-supported research will have the following aims: 1) to expand analyses of the virologic and immunologic predictors of successful outcomes following use of a broadly neutralizing monoclonal antibody as an ART-sparing intervention in a cohort of early-treated HIV-infected children; 2) to expand the objectives of existing NIH- funded nationwide birth surveillance in Botswana by adding first-ever birth outcomes surveillance of Dolutegravir-exposed infants and marginal structural modeling to simulate a clinical trial comparing birth outcomes by ART regimens used in pregnancy; and 3) to combine data from 6 large research cohorts to evaluate the reasons for declining mortality among HIV-exposed uninfected children in Botswana. My training plan will specifically expand my expertise in maternal-fetal medicine, and my mentoring plan will involve a team approach in Boston and Botswana to efficiently utilize opportunities within both large clinical trials and existing datasets and specimens.
My current research program in Botswana is aimed at improving survival in HIV-infected and HIV-exposed infants, and understanding the epidemiology and underlying mechanisms that link antiretroviral exposure in pregnancy with adverse birth outcomes. A K24 award will allow me to expand mentorship of young investigators interested in international HIV, and to expand opportunities for researchers in Botswana. My mentoring plan will involve a team approach in Boston and Botswana that utilizes opportunities within larger clinical trials while also making efficient use of datasets and specimens stored from ongoing research studies.
|Zash, Rebecca; Jacobson, Denise L; Diseko, Modiegi et al. (2018) Comparative safety of dolutegravir-based or efavirenz-based antiretroviral treatment started during pregnancy in Botswana: an observational study. Lancet Glob Health 6:e804-e810|
|Zash, Rebecca; Rough, Kathryn; Jacobson, Denise L et al. (2018) Effect of Gestational Age at Tenofovir-Emtricitabine-Efavirenz Initiation on Adverse Birth Outcomes in Botswana. J Pediatric Infect Dis Soc 7:e148-e151|