- Identify mechanisms of early on-set atherosclerosis with HIV and highly active antiretroviral therapy (HAART) and to identify low-cost diagnostics and effective prevention and treatment strategies for non-AIDS co-morbidities, with emphasis on populations in low-resource settings. The success of HAART has transformed HIV-infection from a terminal diagnosis to a manageable chronic disease. HIV patients on HAART, however, have shown elevated incidence of non-AIDS co-morbidities, including lipodystrophy, insulin resistance, diabetes mellitus, and cardiovascular disease (CVD); the latter includes higher prevalence of myocardial infarction and atherosclerotic lesions, as well as elevated subclinical markers atherosclerosis including increased carotid artery intima-media thickness (c-IMT), arterial stiffening, and impaired flow-mediated dilation (FMD). Markers of CVD have been shown to correlate with markers of dyslipidemia, systemic inflammation, and persistent immune activation and senescence. Of the five classes of HAART, protease inhibitors (PI’s) and nucleoside reverse transcriptase inhibitors (NRTI’s) have been implicated in HIV-associated CVD; our group was among the first to implicate the non-NRTI (NNRTI) efavirenz as a mediator of increased arterial stiffening and c-IMT and impaired FMD, using both mouse models and cross-sectional clinical data collected by our group in Ethiopia.
- Reducing maternal & perinatal mortality through low-cost, early diagnosis of risk in the rural developing world. Maternal and perinatal mortality rates in Ethiopia remain among the highest in the world. Cephalopelvic disproportion (CPD) is an inadequate size of the maternal pelvis, compared to the fetal head, which prevents the fetus from passing through the pelvic cavity during delivery. CPD is accountable for 8% of the maternal deaths worldwide and in many countries is almost as prevalent today as it was 30 years ago; in Ethiopia, 22% of maternal deaths are attributed to CPD. In the developed world, failure to progress due to CPD leads to a routine cesarean section; however, in low-resource settings around the world, cesarean section is often not available at the time of delivery and the consequence of CPD-related obstruction is often death to the mother and/or the fetus. The first aim of this research area is to develop and test a simple, ultra-low-cost portable technology using an off-the-shelf Microsoft Kinect sensor, combined with machine learning tools, to quantify an obstructive risk score to identify women at high risk for obstructed labor due to CPD. Timely diagnosis could lead to accurate referral of high risk mothers to seek improved health facilities. Preeclampsia/eclampsia syndrome is a leading cause maternal mortality and morbidity, preterm birth, perinatal death, and intrauterine growth restriction. In Ethiopia, 16% of maternal deaths occurred due to preeclampsia/eclampsia syndrome and the cause-specific case fatality rate was 3.6%. Delivery is the only curative treatment for preeclampsia; however, early prediction of preeclampsia risk could make way for improved management of pregnancies complicated with preeclampsia and introduction of emerging therapies to reduce the severity of vascular placental complications; e.g., early administration of aspirin to reduce risk of severe preeclampsia. The second aim of this research area is to test utility and usability of a portable technology to assess central arterial stiffness, measured via carotid-femoral pulse wave velocity and pulse wave analysis, as an early predictor of preeclampsia risk in Ethiopia.