For Answers in the Bronx, a Look at Rwanda
Elizabeth M. Kiefer, MD
As antiretroviral therapy (ART) becomes more available and people with HIV live longer, the combination of HIV and cardiovascular disease have created an epidemic that is projected to surpass infectious disease as the leading cause of mortality in Sub-Saharan Africa. Better understanding is needed of how HIV/AIDS and ART affect cardiovascular disease. Dr. Elizabeth Kiefer, a general internist with an interest in international health, is working to identify patients in Rwanda at risk for heart attack and stroke so that physicians can recognize and treat cardiovascular disease before its devastating consequences. She is principal investigator of an American Heart Association Clinical Research Program Award for her work entitled “Cardiovascular Risk Inflammation and Antiretroviral Therapy in HIV-infected Rwandan Women.”
While Dr. Kiefer’s clinical practice in the Bronx helps to inform her research abroad, she also hopes the knowledge gained from her global investigation will aid the patients she treats in New York. “As antiretroviral therapy becomes more available in Africa and people live longer with HIV they are dealing with some of the same issues that we see in this country, like hypertension, cardiovascular disease, and diabetes,” she said. “This research in Rwanda allows me to merge two interests: the patients with cardiovascular disease I care for every day and the serious health issues emerging in the developing world.”
Two Regions at Risk
Sub-Saharan Africa (SSA) accounts for 67% of the world’s HIV infection, with 60% of the estimated HIV infections occurring in women. Cardiovascular disease is rapidly climbing in this region due to urbanization and shifting lifestyle factors such as increasingly sedentary jobs and exposure to different diets. HIV and its treatment have been shown to further raise the risk for these diseases. Although the correlation between HIV and higher risk of cardiovascular disease is still unclear, evidence is emerging that HIV infection and antiretroviral treatment may create a high inflammatory state which may increase cardiovascular disease risk. Malnutrition, a prevalent issue in developing countries, may also cause inflammation, and nearly a quarter of the cohort that Kiefer is studying has a body mass index under 18.5.
About two percent of Bronx residents are HIV-positive, the second highest prevalence in the nation. A recent study by Dr. Yehuda Cohen, an internal medicine resident, shows that diagnoses of acute myocardial infarction have been increasing among patients seen at the Montefiore AIDS Center’s Center for Positive Living/Infectious Diseases Clinic, mirroring trends seen nationwide. Contributors to this trend include high rates of cardiovascular disease risk factors (including smoking, hypertension, diabetes, obesity, hyperlipidemia), and living longer with HIV. “We look forward to the information that studies by Dr. Kiefer and others will reveal about cardiovascular disease risk factors in people with HIV, especially more information on the role of HIV itself and resultant inflammation,” said Dr. Barry Zingman, director of the AIDS Center.
Exploring the Role of a Protein
Dr. Kiefer will measure C-reactive protein (CRP), which is released into the bloodstream during inflammation and thought to be a predictor of cardiovascular disease. CRP levels are elevated in HIV-infected individuals, and independently predict HIV mortality, HIV disease progression, and risk for AIDS and non-AIDS events. Antiretroviral therapy has been shown to decrease the risk of death from cardiovascular disease, possibly as a result of decreased inflammation. However, it is unclear how CRP levels change with ART use in HIV-infected individuals, or whether they are related to cardiovascular disease risk factors before or after ART. Dr. Kiefer will use the high-sensitivity CRP test (hsCRP), an inexpensive blood test ($10-120, depending on where it is performed), to evaluate the relationship between CRP and cardiovascular disease risk factors in both HIV-infected and -uninfected women, and to examine the change in CRP and its relationship to traditional cardiovascular risk factors (such as BMI and cholesterol) in HIV-infected women before and after antiretroviral therapy.
Capitalizing on Einstein’s Global Health Presence
In the course of her study, Dr. Kiefer will measure CRP from collected, stored serum obtained through the Rwanda Women’s Interassociation Study and Assessment (RWISA), a longitudinal cohort study developed by her mentor Dr. Kathryn Anastos, Professor of Medicine and of Epidemiology & Population Health. RWISA was initiated in 2005, enrolling and following nearly a thousand women with and without HIV, 50% of whom are survivors of rape during the country’s 1994 genocide.
RWISA is an observational prospective cohort study investigating the effectiveness and toxicity of antiretroviral therapy (ART) and the effect of traumatic rape, HIV infection and immune suppression on multiple clinical outcomes in Rwandan women. RWISA partners with community-based Rwandan women’s organizations that recruited participants. Trauma counselors are located in the community to maintain contact with participants, know their vital status, and ensure follow-up visits. This connection has been a critical factor in the program’s success in recruiting and retaining patients for research studies. The large majority (about 89%) of the HIV-positive women in the RWISA cohort now receive ART, and the collected biologic samples are being used for several research projects including Dr. Anastos’s investigations of HIV and hepatitis C's relationship with insulin resistance and lipoprotein abnormalities, as well as translational research in vaginal immunology by Drs. Marla Keller (Infectious Diseases) and Betsy Herold (Pediatrics).
RWISA also provides data to several Rwandan physicians enrolled in Einstein’s AIDS International Training and Research Program (AITRP), led by Dr. Vinayanka Prasad. Currently two Rwandan physicians are enrolled in Einstein’s Clinical Research Training Program, and another twelve receive in-country training via the AITRP. All of these physicians are using RWISA data.
"Dr. Kiefer's new studies address extremely important clinical and public health questions for Africans living with HIV," said Dr. Anastos. "Very little is known about the interactions of inflammation, malnutrition, and HIV disease or treatment, and Dr. Kiefer’s work can help elucidate the pathophysiology of these processes."
"The work that we’re doing in Rwanda is one piece of the puzzle of what happens when people start antiretroviral therapy," Dr. Kiefer said. "We hope it will be helpful in determining what happens to peoples’ cardiovascular risk profiles as they stay longer on antiretroviral therapy."