Infectious Diseases

Center for AIDS Intervention Research

Dr. Andrew Petroll is a clinical Infectious Disease Specialist and a faculty researcher at the Center for AIDS Intervention Research (CAIR). CAIR is a multidisciplinary HIV prevention research center that is supported by an AIDS research grant from the National Institute of Mental Health. CAIR also receives grant support from other sources, including the Centers for Disease Control and Prevention, the Wisconsin AIDS/HIV Program, and the Medical College of Wisconsin. The research center is based in the Department of Psychiatry and Behavioral Medicine of the Medical College of Wisconsin. The research mission of the CAIR is to develop, conduct, and evaluate new interventions to prevent HIV among persons most vulnerable to the disease.

Dr. Petroll's research interests include how patients' risk behaviors for HIV transmission are addressed in clinical settings, how patient-physician interactions affect the disclosure and discussion of HIV risk behaviors, and how patient and physician characteristics influence such discussions. He is interested in studying the effectiveness of interventions aimed at improving HIV risk behavior discussions between health care providers and both HIV-negative and HIV-positive patients, assessing HIV testing behaviors within high-risk populations, and intervening to increase HIV testing. He is currently conducting a study that is evaluating medical providers' attitudes and experience with prescribing HIV pre-exposure prophylaxis (PrEP) to patients at risk for acquiring HIV. Recent Publications

Research in the Coburn laboratory focus on pathogenic spirochetes, a group of bacteria that are able to cause persistent, disseminated infections in immunocompetent animals, including humans. We are currently working with Borrelia burgdorferi, which is maintained in a tick-animal cycle in nature. We also work with another pathogenic spirochete, Leptospira interrogans. Leptospires are maintained in infected animals in nature, but can also survive in water and mud. Since both pathogens are maintained in animal reservoirs in nature, both are referred to as zoonotic infections. The focus of our work with both Borrelia and Leptospira is to identify and then test the biologic significance of bacterial proteins that help the bacteria bind to mammalian cell surface receptors, to identify the mammalian cell surface receptors recognized by the bacteria, and ultimately the biological and pathologic significance of the bacterial-mammalian receptor interaction.

In the Borrelia work, we have two main projects ongoing in the lab. In one, we are trying to understand the mechanisms behind the requirement for the B. burgdorferi protein, P66, for the bacteria to cause infection in mammals. P66 binds to mammalian cell surface receptors called integrins and serves as a porin in the bacterial outer membrane. We know that the integrin binding function is important for the bacteria to cross endothelial layers and disseminate to different sites in the body. In another Borrelia project, we developed a new experimental model to determine the roles of bacterial adhesive proteins in how the bacteria colonize different tissues in mammals, and how they survive the mammalian defenses in the bloodstream.

In the Leptospira work, we also focus in how the bacteria interact with endothelial cells. In severe cases of leptospirosis, widespread endothelial damage is seen, and this is associated with hemorrhage. L. interrogans binds to an endothelial cell surface receptor called VE-cadherin, which helps the endothelial cells form cell-cell junctions that maintain the integrity of small blood vessels. We are currently determining how the bacteria disrupt cadherin-cadherin interactions, and determining whether the bacterial proteins that bind VE-cadherin are responsible for the endothelial disruption caused by the bacteria. In a second Leptospira project, we are working to identify the bacterial proteins that help the bacteria bind to kidney cells, as the kidneys are where the bacteria reside in a chronically infected animal and from where they are released into the environment.

Learn more about the Center for Infectious Disease Research.

As an academic institution, the Froedtert Hospital Infectious Disease clinic is able to offer opportunities to participate in a variety of clinical trials. MCW faculty are engaged in a variety of clinical research trials conducted in collaboration with research networks and industry sponsored-trials. Faculty also practice at the AIDS Resource Center of Wisconsin and are able to offer most of the clinical trials through that location as well.

INSIGHT | PI: Michael Frank, MD

The Medical College of Wisconsin's Division of Infectious Diseases has been an affiliate site for the International Network for Strategic Initiatives in Global HIV Trials (INSIGHT) as an enrolling site for the SMART trial (Strategies for the Management of Anti-Retroviral Therapy) which investigated whether it was better to treat patients with HIV continuously with antiretrovirals or to treat them episodically based on immune function.

In 2010, the START trial (Strategic Timing of Anti-Retroviral Treatment) began in order to determine the optimal timing of initiation of antiretroviral therapy (ART) with regard to morbidity and mortality among HIV-1 infected patients who are naïve to ART and have CD4 + cell counts greater than 500 cells/mm3. The START study has enrolled over 4,600 participants worldwide. This study randomizes participants into two study arms:

1. Immediate initiation of ART
2. Deferred ART until the participant’s CD4+ cell count decreases to less than 350 cells/mm3

Enrollment began in April 2009 and ended on December 23rd, 2013 with 4,688 participants. In May 2015, enough data was collected to determine the optimal time to initiate antiretroviral therapy. Previous guidelines recommended earlier initiation of ART, but no randomized-control trials had been done to address this important question prior to the START study.

INSIGHT is one of six HIV/AIDS clinical trial networks funded in 2006 by the National Institute of Allergy and Infectious Diseases, a component of the National Institutes of Health. INSIGHT's mission is to define optimal strategies for the management of HIV and other infectious diseases through a global clinical research network. INSIGHT conducts studies worldwide.

REPRIEVE Study | PI: Michael Frank, MD

In 2015, enrollment in a random trial to prevent cardiovascular disease (CVD) in people with HIV began at MCW’s division of Infectious Diseases. People living with HIV are 50-100% more likely to develop CVD than people who do not have HIV.

MCW is working with the AIDS Clinical Trials Group (ACTG) and National Institute of Allergy and Infectious Diseases (NIAID) on this trial. Pitavastatin is FDA approved to lower cholesterol along with diet and exercise. The REPRIEVE trial tests whether Pitavastatin can prevent heart disease in people living with HIV.

Up to 6,500 people between the ages of 40 and 75, who have been on ART for at least six months, and who have no history of heart disease will enroll in this study. Participants are expected to make three visits per year for four years. The study is expected to run for 72 months (6 years).

Please visit the REPRIEVE Trial website for more information.

Industry Sponsored Trials

A number of faculty serve as Principal Investigators for industry-sponsored trials. These trials are often done to determine if drugs are safe and effective. Ongoing trials involve the following investigational agents:

• Stribild for HIV | PI: Andrew Petroll, MD
• STR Containing Tenofovir Alafenamide | PI: Andrew Petroll, MD

For more information about any of our HIV clinical trials, please contact Sonija Parker, Research Coordinator, at (414) 955-0492 or at smparker@mcw.edu or Nancy Grey, Research Assistant, at (414) 955-0491 or at ngrey@mcw.edu.

DISCOVER-PrEP Study

With an estimated 37 million people in the world infected with the virus, HIV is a major medical problem. In 2015, there were more than 2 million new HIV infections estimated world-wide even though there is widespread knowledge of how to prevent acquiring the virus.

DISCOVER is a new clinical study for men who have sex with men and trans women who have sex with men. This study is to evaluate if a once-daily investigational medicine can help reduce the risk of getting HIV infection from sex (“PrEP”, or Pre-exposure Prophylaxis).

Eligible participants must be at least 18 years of age and must be HIV negative.

In this study 2 HIV prevention regimens will be compared. One regimen is Truvada®, which is already approved in the US and Canada for PrEP. The other regimen is one pill containing two drugs, emtricitabine (F) and tenofovir alafenamide (TAF). F/TAF is approved in the United States, Canada, and Europe for the treatment of HIV infection, but is not yet approved for PrEP.

The purpose of this study is to see if F/TAF is safe and effective for use as PrEP against HIV-1 infection in healthy adults.

Dr. Aldrete's research interest is to better understand why some people living with HIV have poor CD4 cell recovery even while they are taking antiretroviral therapy. These individuals are known as immune non-responders (INR). However, it remains unclear what factors should define a person as an INR, since not enough is known regarding which factors are associated with poor health outcomes. She is interested in looking at how different CD4+ metrics predict the development of AIDS and non-AIDS related outcomes. She is performing a retrospective study that aims to compare the various definitions of INRs currently found in the literature in order to determine which definitions are most effective in identifying true risk for poorer long-term outcomes. This study is also identifying the CD4+ T-cell count recovery pattern most predictive of adverse events using a complex modeling approach. By providing a better definition for which patients are immune non-responders, this work has the potential to more precisely identify individuals at risk for increased morbidity and mortality and allow clinicians to focus their efforts on reducing these poor health outcomes.

Dr. Leslie Cockerham is an Infectious Disease Specialist and conducts HIV clinical and translational research. Dr. Cockerham’s research interests include better understanding HIV immunopathogenesis by studying the processes that lead to immune dysfunction and viral persistence, and exploring strategies that target these mechanisms, with the goal of bringing us closer to achieving the eradication of HIV. She is also interested in identifying individuals in early HIV infection and linking and retaining them in care as early treatment is beneficial in limiting the HIV reservoir size and preserving immune function. Dr. Cockerham is the recipient of an MCW New Faculty Pilot Grant and currently investigating whether there is variation in HIV reservoir levels over the course of the day and potential underlying mechanisms for this. In her role as Medical Director at the AIDS Resource Center of Wisconsin, she will also be working on strategies that improve HIV clinical outcomes and retention to care.

Our aim is to understand the disruptions of the intestinal microbiome during hospitalization and how these alterations are associated with C. difficile fecal loads, C. difficile acquisition, and C. difficile colitis. With our internal and external collaborators we are planning to explore the structure of the microbiome using 16S rRNA, metabolomics, and transcriptomics. In the future we aim to be able to predict the risk of acquisition of C. difficile by measuring indexes in the stool of an individual patient. This will allow us to tailor novel prevention interventions to patients at highest risk.

In order to accomplish these aims Drs. Munoz-Price and Uhrig collaborate with a multidisciplinary team including the Infection Control Department (Drs. Mary Beth Graham and Figueroa Castro), the Antimicrobial Stewardship team (Drs. Sara Revolinski and Wainaina), the Froedtert's Clinical Microbiology Department, the MCW's Center for Infectious Diseases Research (Dr. Jenifer Coburn), the Divisions of Hematology-Oncology (Drs. Hari, Charlson, Shaw, Horowitz) and Gastroenterology (Dr. Stein), the Departments of Pathology (Drs. Ledeboer and Buchan), Pediatrics (Dr. Nita Salzman) and Pharmacology (Dr. Thomas).

Jenifer Coburn, PhD

John Fangman, MD

Carlos Figueroa Castro, MD

Mary Beth Graham, MD

Christine Hogan, MD

Michael Kron, MD

Andrew Petroll, MD

Peter Sohnle, MD