Author Interviews, Heart Disease, HIV / 05.01.2017
Types of Myocardial Infarction Among HIV–Infected Individuals
MedicalResearch.com Interview with:
Heidi M. Crane MD, MPH
Associate Professor of Medicine
Associate Director Clinical Epidemiology and Health Services Research Core
Center for AIDS Research
University of Washington
MedicalResearch.com: What is the background for this study? What are the main findings?
Response: Studies have suggested that rates of myocardial infarction (MI) are higher in those with HIV, likely for a variety of reasons. However, prior studies have not been able to distinguish MIs by type. The Universal Definition of MI has been recommended by cardiology societies and classifies MIs into types with Type 1 MIs resulting spontaneously from atherosclerotic plaque instability and Type 2 MIs occurring secondary to causes other than atherosclerotic plaque rupture, including hypotension, hypoxia, and stimulant induced spasm resulting in increased oxygen demand or decreased supply. Understanding MI types is likely important as they may indicate a different prognosis and need for different prevention approaches.
Dr. James M. Smith[/caption]
Dr. James M. Smith Ph.D
Laboratory Branch, Division of HIV/AIDS Prevention
Centers for Disease Control and Prevention
Atlanta, Georgia
MedicalResearch.com: What is the background for this study?
Dr. Smith: Our laboratory has been developing a macaque model for testing drug release, safety and efficacy of intravaginal rings (IVR) for preexposure prophylaxis (PrEP) against HIV for several years. The initial studies involved both matrix rings, where the drug is dispersed in the silicone matrix of the device, and reservoir rings, which are essentially a polymer tube filled with drug. In collaboration with the Oak Crest Institute of Science and Auritec Pharmaceuticals, Inc., we began testing a new type of intravaginal ring, the pod-IVR. In this innovative design the ring itself is a scaffold that contains compressed polymer-coated drug tablets, or pods, within the ring. Each pod is separate, allowing for a customizable release rate for each drug by varying the number and diameter of the drug release ports for each individual pod. The macaque pod-IVR can accommodate up to six pods whereas the human pod-IVR can accommodate up to 10 pods. The IVR design was developed to allow the delivery of drug combinations and for simple, cost-effective manufacturing.
Dr. Joseph Alvarnas[/caption]
Joseph Alvarnas, MD
Associate clinical professor
Department of hematology and Director of value-based analytics
City of Hope National Medical Center
Duarte, CA
MedicalResearch.com: What is the background for this study?
Dr. Alvarnas: Patients with HIV infection have a significantly increased risk of non-Hodgkin lymphoma and Hodgkin lymphoma. Prior to the availability of effective anti-retroviral therapy, HIV-infected patients with lymphoma had very poor treatment outcomes. Following the availability of effective anti-HIV therapy, patient outcomes for HIV-infected patients now parallel those of non-infected patients. Historically, however, HIV infection has been used as a criterion for not offering patients autologous blood stem cell transplantation outside of centers with unique expertise. The purpose of this trial was to evaluate outcomes, complication rates, and immunological reconstitution of HIV-infected patients following autologous blood stem cell transplantation.
Dr. Steven Kyle Grinspoon[/caption]
Steven Grinspoon, MD
Professor of Medicine, Harvard Medical School
MGH Endowed Chair in Neuroendocrinology and Metabolism
Director, MGH Program in Nutritional Metabolism
and Nutrition Obesity Research Center at Harvard
MGH
Boston, MA 02114
MedicalResearch.com: What is the background for this study? What are the main findings?
Dr. Grinspoon: Numerous epidemiologic studies have shown that people living with HIV face a 1.5 to 2-fold increased risk of heart attack, or myocardial infarction, as compared to individuals without the virus. Mechanisms underlying the increased risk of myocardial infarction in HIV are incompletely understood. It is possible that among people living with HIV, increased systemic immune activation fuels arterial inflammation. Arterial inflammation may, in turn, promote the development of high-risk morphology coronary atherosclerotic plaque, which is liable to rupture and result in myocardial infarction.
For people diagnosed with HIV, the overall health benefits of immediate antiretroviral therapy (ART) are clear. However, the effects of newly-initiated antiretroviral therapy on arterial inflammation have not previously been studied. In this study, we set out to assess among a cohort of treatment-naive HIV-infected subjects, the effects of newly-initiated ART with a contemporary regimen on both immune function and arterial inflammation. We found that among treatment-naive HIV-infected individuals without clinical cardiovascular disease, newly initiated combined antiretroviral therapy has discordant effects to restore immune function without reducing the degree of arterial inflammation.
Robert Bonacci[/caption]
Robert Bonacci MPH, MD Candidate’16
University of Pennsylvania School of Medicine
MedicalResearch.com: What is the background for this study?
Response: During the mid-2000’s, the HIV incidence rate stubbornly persisted around 50,000 infections per year. Responding to this trend, President Obama released the first comprehensive US National HIV/AIDS Strategy (NHAS) in 2010. The NHAS hoped to spur a more coordinated national response and set ambitious targets for reducing HIV incidence (25 percent) and the transmission rate (30 percent), among other goals, by 2015.
To evaluate whether the U.S. achieved the NHAS goals by 2015, we used mathematical models drawing on data from the U.S. Centers for Disease Control and Prevention (CDC) on HIV prevalence and mortality for 2007 to 2012, and our own previously published incidence estimates from 2008-2012. Changes seen from 2010 through 2012 were extrapolated for the time period 2013 through 2015.
Dr. Martin Hoenigl[/caption]
Martin Hoenigl, MD
Postdoctoral Fellow
AntiViral Research Center, Department of Medicine
University of California, San Diego
Medical Research: What is the background for this study?
Response: The detection of acute HIV infection (AHI) is critical to HIV prevention and treatment strategies. Many field-based testing programs rely on point-of-care HIV antibody testing, which will reliably identify persons with established infection, but fail to detect persons with AHI. In many of these programs additional tests for AHI are only performed / recommended in persons presenting with signs and symptoms consistent with an acute retroviral syndrome (ARS). These signs and symptoms are unspecific and include fatigue, headache, pharyngitis, skin rash, GI symptoms, night sweats and others. However, the proportion of persons with 
Dr. Christina Polyak[/caption]
MedicalResearch.com Interview with:
Dr. Christina Polyak MD MPH
Acting Instructor with the University of Washington
Clinical research physician at the U.S. Military HIV Research Program
Walter Reed Army Institute of Research at WRAIR
Bethesda, MD 20817
Medical Research: What is the background for this study? What are the main findings?
Dr. Polyak: Today, 35 million people are infected with HIV, the virus that causes AIDS. (CTX) is low-cost and widely utilized broad spectrum antibiotic used to prevent opportunistic infections in patients with HIV. CTX prophylaxis is recommended by the World Health Organization (WHO) for HIV infected adults in settings with high infectious disease prevalence. In these settings, the threshold for CTX discontinuation is undefined. We designed a study to determine whether CTX discontinuation was non-inferior to continued CTX-prophylaxis in decreasing morbidity in adults with evidence of immune reconstitution (CD4 >350 and 18 months on ART). Our findings show that combined morbidity/mortality was significantly higher in the CTX discontinuation arm (RR=2.27, 95% CI 1.52-3.38;p<0.001), driven by malaria morbidity. This suggests that CTX discontinuation among ART-treated, immune-reconstituted adults in malaria-endemic regions resulted in increased incidence of malaria but not pneumonia or diarrhea. These data helped inform and support the 2014 WHO CTX guidelines.
Dr. Meyerhans[/caption]
MedicalResearch.com Interview with:
Andreas Meyerhans, PhD
ICREA Research Professor at the University Pompeu Fabra
Infection Biology Group
Department of Experimental and Health Sciences
Universitat Pompeu Fabra
Barcelona Spain
Medical Research: What is the background for this study? What are the main findings?
Dr. Meyerhans: In brief, chronic HIV infections lead to a dampening of HIV-specific killer cells. This phenomenon is named exhaustion and is mediated by inhibitory proteins, such as PD-1, on the cell surface. A consequence of exhaustion is a reduction of the immune control over virus expansion.
We have studied the effect of blocking the negative signaling from the inhibitory proteins by means of PD-1/PD-L1 pathway inhibition on effector and regulatory T cells (Treg). We found that one can augment antiviral immune control only when the virus load was well controlled in the HIV-infected individuals i.e. by antiviral drugs. In that case, PD-1/PD-L1 pathway blockage led to an expansion of anti-HIV killer cells over Treg cells. This latter are suppressive white blood cells also subject to the same inhibitory pathway regulation. In contrast, when blood cells from viremic HIV-infected individuals were analyzed, Treg cells expanded efficiently and thus reduced the effector to regulatory T cell ratio that controls HIV. Taken together, our data point to Treg cells as an important component in the outcome of PD-1/PD-L1 pathway inhibitor therapies and suggest a net gain in anti-HIV immune responses only when the HIV loads are well controlled during the administration of these novel compounds.