There is a diversity of research activities within the Section of Infectious Diseases and Global Health. Investigations range from basic laboratory studies, outbreak investigations-often utilizing state-of-the-art molecular methods for strain typing, clinical trials, and hospital epidemiology. Basic lab investigations into the mechanisms of probiotic formulations in inflammatory bowel disease are being conducted in a collaborative effort with the Section of Gastroenterology. Clinical studies include determining factors that affect adherence with antiretroviral regimens, studies of new antiretroviral therapies for HIV infection, and studies of the safety and efficacy of new antimicrobial agents. The section is collaborating with Transplant Surgery in a multi-center study of solid organ transplantation of HIV-infected patients. There is also translational research in immunodeficiency states, with laboratory studies of ex vivo leukocyte apoptosis and immune reconstitution in HIV infection and phagocytic cell function in transplant recipients. Active epidemiologic investigations include the epidemiology of VRE in the Bone Marrow Transplant unit, epidemiology of other antibiotic-resistant pathogens, and risk factor analysis for hospital-acquired fungal infections.
Several investigations with a bench laboratory component are being conducted by faculty members in the Section of Infectious Diseases.
Effects of Probiotic Formulation
Probiotics are ingestible microorganisms having health benefit beyond their intrinsic nutritive value. Probiotics have been used to treat a variety of gastrointestinal ailments including inflammatory bowel disease, rotavirus and antibiotic-associated diarrhea, to name a few. They appear to have protective, trophic and anti-inflammatory effects on bowel mucosa. However, the exact mechanisms by which probiotics act to protect against mucosal injury have yet to be fully elucidated.
Activation of the NF-kB pathway is thought to be a key molecular event involved in the pathogenesis of many conditions of intestinal inflammation. We have shown that certain probiotics inhibit the NF-kB pro-inflammatory pathway, which may account for some of their anti-inflammatory effects. In addition, we have demonstrated that probiotics induce the expression of certain cytoprotective heat shock proteins (HSPs) which belong to a family of highly conserved proteins and play an important role in protecting cells against physiologic and pathogenic stressors in the environment. In intestinal epithelial cells, these inducible HSPs convey a degree of cytoprotection, prolong viability under conditions of stress and preserve the integrity of intestinal epithelial cell barrier function under hostile conditions. Efforts are currently underway to more fully characterize the microbial-epithelial cell interactions involved and to isolate the probiotic bioactive factor(s) responsible for these effects.
Bench laboratory studies are also part of the clinical studies of immune reconstitution in HIV and epidemiology of VRE on the transplant units described under Clinical Research.
A number of clinical studies are being conducted by faculty members of the Section of Infectious Diseases. This includes investigations of outpatient therapy for HIV infection and inpatient studies of newer antibacterial agents. Some studies are part of NIH-funded trials consortia, while others are multi-center studies of new agents or approaches to therapy being sponsored by industry. There are also investigator-initiated trials, some of which have a translational laboratory research component.
Current Global research areas include epidemiologic and social network studies of HIV, HSV-2 and Chlamydia infection in India and China, Novel HIV prevention strategies in Asia, HIV and STI seroepidemiologic studies in high-risk male cohorts such as truck-drivers and men who have sex with men. Cost-effectiveness of HIV therapy in Uganda. Cardiovascular and diabetes disease prevention in South Asia. Health worker migration patterns (“brain drain”), and pharmaceutical industry policy in India. These and other collaborative projects have been funded in part by the NIH, CDC, Lancet, foreign government, and private foundation and pharmaceutical support.
In addition, opportunities for global infectious disease operational research projects have been established by clinical training and research relationships established in Andhra Pradesh, India and in Wuhan, China. Specific projects under consideration are HIV prevention and health worker training in India and operational research in infectious disease and public health training in China.
The listing below is limited to studies being conducted by the Infectious Diseases Section that are actively accruing study participants.
- Chicago Center for HIV Elimination
- Community Programs for Clinical Research on AIDS(CPCRA)
The AIDS Research Alliance of Chicago (ARAC) is the Chicago site of the CPCRA. The University of Chicago joined this trials consortium this year. The major trial that is ongoing and recruiting patients is the SMART (Strategies for Management of Anti-Retroviral Therapy) study. This is a management strategy study comparing two approaches to antiretroviral therapy that compares intermittent therapy based on immunologic status versus continuous therapy. This is a large, long-term study that could greatly impact on the use of antiretroviral therapy in the future.
- Solid Organ Transplantation in HIV: Multi-Site Study
A multi-center study of solid organ transplantation in HIV infection is supported by the NIH. The University of Chicago is a site, and Dr. Pursell from our section is a site Co-Investigator for this trials. This study will focus on liver and renal transplantation in HIV patients as an option for organ failure. The study is designed to examine the effects of HIV on graft survival and the effects of immune suppression for the transplant on the progression of HIV disease.
- Chicago Department of Public Health, Office of HIV/AIDS Surveillance
The University of Chicago is a site for the CDPH study “Estimating HIV Incidence by Using a Population-Based Serologic Method to Detect Recent HIV-1 Infection, Chicago, IL.” Previous antibody tests were only able to detect chronic HIV infection without any ability to determine if the infection was recent, having been contracted in the past 6 months to 1 year. This type of information is important in tracking the HIV epidemic and determining the efficacy of prevention measures. This study uses a de-tuned serologic test to determine if patients have had recent infection. This study will also have a component looking at the incidence of transmission of drug-resistant HIV, a growing concern for clinicians across the country.
- HIV Studies
Switching HIV Patients with a Viral Load of < 50 copies/mL on a Twice Daily or More Frequent Initial HAART Regimen to a Once Daily Regimen Including Stavudine XR, Lamivudine, and Efavirenz.
Therapy for HIV has been plagued by non-compliance due to the complexity of the regimens. There has been a move to reduce the number of pills and doses, and now a number of medications have been developed as once daily drugs. However, there is little data the efficacy of regimens where all the medications are taken once a day. This study is a proof of concept study that once daily regimens can be as efficacious as regimens where medications are taken multiple times a day.