Highlighted Research Activities
Biospecimen Resource ProjectsAt the George Washington University School of Medicine and Health Sciences, Dr. Sylvia Silver, Associate Dean and Professor for Health Sciences, oversees two biospecimen resource projects. Serving as the Principal Investigator for the East Coast AIDS and Cancer Specimen Resource (ACSR), Dr. Silver supports the work of this nationwide multi-site source for tissue and biological specimens serving investigators working in the fields of HIV/AIDS, cancer, virology, immunology, pathology, epidemiology, as well as others. As a repository for HIV-infected human biospecimens from a wide spectrum of HIV-associated diseases, the ACSR provides the research community with a wealth of well documented specimens. Furthering this work, Dr. Silver is also Co-Investigator of the Metropolitan Washington DC Women's Interagency HIV Study (WIHS), a study that is an ongoing national multicenter, prospective study to carry out investigations of the impact of HIV infection in women. Through a subcontract, funded by the National Cancer Institute, Dr. Silver and Co-Investigator, Dr. Jan Marc Orenstein, participate in the WIHS Cancer Pathology Working Group, and Dr. Silver oversees donations of specimens from WIHS women at the East Coast WIHS sites to the AIDS and Cancer Specimen Resource.
Clinical Research at the George Washington University Medical CenterThe Division of Infectious Diseases at the George Washington University Medical Center provides clinical care to more than 800 HIV-infected individuals in the outpatient setting. Dr. Gary Simon - Director of the Division of Infectious Diseases, Vice Chairman of the Department of Medicine, and Director of the Clinical Trials Unit in the Ambulatory Care Center - along with his colleagues in the infectious disease division oversee a number of clinical trials in which many of the HIV-infected individuals are enrolled. These patients participate in clinical trials of new antiretroviral agents, vaccine studies, epidemiological investigations, metabolic studies and provide whole blood and plasma samples for collaborative studies with basic science investigators. In order to facilitate these research studies, the clinical trials unit and the infectious disease clinics are located immediately adjacent to each other. Major areas of clinical HIV research studies include the following:
District of Columbia Department of Health & GWU PartnershipThe District of Columbia Department of Health (DC DOH) HIV/AIDS Administration requested technical assistance from the GWU SPHHS Department of Epidemiology and Biostatistics in 2006 to support surveillance and epidemiology activities in the District. Through the leadership of Dr. Alan Greenberg, the Principal Investigator for the Partnership, much as been accomplished to date to assist the District in improving our understanding of the current status of the HIV/AIDS epidemic in the city so as to better enable the roll-out of effective prevention and treatment programs. Initially, the Partnership focused on two main areas - to provide technical evaluation and subsequent assistance with core HIV/AIDS surveillance, and to conduct the heterosexual cycle of the National HIV Behavioral Surveillance project. In 2007, additional technical assistance was requested for two more projects - retrospective monitoring and evaluation of the DC DOH HIV Testing Campaign, and cleaning and epidemiologic evaluation of the DC Viral Hepatitis surveillance database. With six GW faculty members, five staff members and 12 graduate students having participated in the Partnership with staff at DOH, this public-academic partnership provides an excellent example what can be accomplished through collaboration.
Ethnographic ResearchThe ethnographic research of James Peterson plays a critical role in implementation of The National HIV Behavioral Surveillance (NHBS), which aims to identify behaviors that put people at risk for HIV in the District of Columbia. In studying the social and culture determinants that put people at risk for contracting HIV, Peterson employs an ethnographic methodology which includes a variety of methods and techniques, including observations, in-depth interviews and focus groups, to gather qualitative data that informs project decision making, provides perspectives about community details as a part of the formative research necessary to implement the study. As part of the heterosexual cycle of the NHBS study, Peterson initially conducted Windshield Tours in specific areas of the city which were identified through the review of complex data resources such as geographical information systems and an indexing of specific health and socioeconomic factors. Through these tours, Peterson gained a better understanding and in-depth knowledge of the community in terms of environment, who lives in certain areas, what risk behaviors they were engaged in and the dynamic processes that ensue as a result. This work also provided insight into new and emerging high risk networks in Washington, DC. This formative research was also able to identify a co-location site for the study based on finding out where community residents felt comfortable going for services. Additionally, focus groups allowed the study team to learn more about the community while also helping to identify participants for the study through Respondent Driven Sampling (RDS). The focus groups also provided richer data on hard-to-reach populations that the study needed to include in order to present a comprehensive picture of high risk behaviors in Washington, DC. Also, key informant interviews helped to test the validity of the data previously gathered through other means and to also help identify study participants. Much of this work throughout the community has provided integral interactions that have been useful for developing a Community Advisory Board (CAB). The NHBS-DC CAB is important to the ongoing activities and the future cycles of the study (e.g. Men who have sex with men (MSM) and injection drug users (IDU). In addition to his work with the NHBS study, Peterson is also involved in the monitoring and evaluation of the DC HIV testing campaign. The qualitative approach employed in this instance involves interviews with campaign staff, service providers and community members. This research obtains the multiple perspectives about such things as the various understandings about the implementation of the campaign among campaign staff, the tone of language being used when talking about routine testing among service providers, and how and whether there has been diffusion to the variety of community members about the testing campaign.
National HIV Behavioral Surveillance ProjectUnderstanding the variety and depth of epidemiologic expertise at GWU, in 2006 the District of Columbia Department of Health (DC DOH) HIV/AIDS Administration (HAA) sought technical assistance from the faculty in the Department of Epidemiology and Biostatistics in the GWU School of Public Health and Health Services to conduct the CDC-initiated National Behavioral Surveillance System in Washington, DC. In 2002, CDC developed the multi-site National HIV Behavioral Surveillance (NHBS) System to help health departments monitor selected behaviors and assess the use of prevention programs and services in groups at highest risk for HIV infection. The study is conducted in 25 metropolitan areas across the country, including Washington, DC. NHBS is a serial, cross-sectional survey focusing on three of the main populations at risk for HIV: men who have sex with men (MSM), injection drug users (IDU), and heterosexuals at high risk for HIV infection (HET). Conducting NHBS in Washington, DC enhances our understanding of HIV risk and testing behaviors in community-based populations and also the extent to which current HIV-prevention programs reach targeted communities. Findings from this study will help direct future HIV-prevention activities to reduce HIV transmission in the District. Through this partnership, GWU has worked closely with the DC DOH/HAA to successfully complete the heterosexual cycle of NHBS (NHBS-HET) in October 2007. Led by Principal Investigator, Dr. Manya Magnus and Project Director, Dr. Irene Kuo, a staff of eight GWU employees and graduate students work on this project in collaboration with DC DOH/HAA. Locally known as WORD UP (Washington Outreach Research Drive to Understand Prevention), overwhelming community support, including that of a strong Community Advisory Committee (CAB), allowed the study to succeed-a first for the District of Columbia. Preparations for the study occurred from June to November 2006, during which time study staff was hired, a comprehensive formative assessment was conducted, including a secondary data analysis of existing data and an ethnographic study of the study population. Recruitment of study participants began in early 2007, in which study participants completed the behavioral survey, which collected information about a variety of HIV risk and testing behaviors, and were offered HIV testing. In the Fall of 2007, the study was completed, with more than 750 participants recruited, an accrual target that was reached six weeks in advance of the required completion date. The GWU/DC DOH/HAA collaboration looks forward to continuing NHBS in 2008 as they together undertake the next data collection year, which focuses on men who have sex with men. Routine Testing Campaign of the DC Department of Health - Monitoring & EvaluationUnderstanding the variety and depth of epidemiologic expertise at GWU, in 2006 the District of Columbia Department of Health (DC DOH) HIV/AIDS Administration (HAA) sought technical assistance from the faculty in the Department of Epidemiology and Biostatistics in the GWU School of Public Health and Health Services to help with the monitoring and evaluation of the District's Routine HIV Testing Campaign. Technical assistance has been provided through conducting a retrospective monitoring and evaluation of the DC DOH's Routine HIV Testing Campaign, involving quantitative and qualitative methodology. The purpose of this study is to evaluate and monitor the HIV testing campaign, "Come together DC - get screened for HIV." A comprehensive understanding of effective methods and strategies for implementing and evaluating routine testing is necessary to improve the campaign in future cycles. In gaining a better understanding of the successes and challenges in implementing this campaign, this monitoring and evaluation project will help to determine where routine testing fits into HIV-public health related activities at both the local and national level. Surveillance of HIV/AIDS at the DC Department of HealthUnderstanding the variety and depth of epidemiologic expertise at GW, the District of Columbia Department of Health (DC DoH) HIV/AIDS Administration (HAA) approached the University in 2006 for technical assistance. Through this partnership, GW works with the DC DOH HAA to help improve HIV epidemiologic and surveillance activities, including core, incidence and behavioral surveillance. These surveillance efforts help to provide a comprehensive picture of the HIV/AIDS epidemic in the District of Columbia. Through the Partnership, which was launched in the spring of 2006, a doctoral-level epidemiologist, Dr. Amanda Castel, was recruited and hired to be embedded at HAA 80% of her time, as the "Chief Epidemiologist." To get the project off the ground, a comprehensive technical evaluation of the Bureau of Surveillance and Epidemiology was conducted in order to provide recommendations around core surveillance databases and case surveillance procedures, staffing structure and training, electronic laboratory reporting, transition to name-based reporting, and behavioral and incidence surveillance. After the submission of this report, much work has been done so that the structures and practices of the Bureau are in alignment with these recommendations. Dr. Castel and GWU faculty and staff had been involved in one of the major initiatives addressed in the recommendations-the transition from a code-based HIV surveillance system to a name-based system. Working alongside HAA staff, their involvement has included the development of a comprehensive plan to conduct the transition, leading de-duplication activities, training staff on name-based HIV reporting requirements, development of new case report forms and meeting with providers to update them on the new reporting requirements. Additionally, much technical work has been done around extracting incidence surveillance data collected by the Bureau and modifying it so that it meets the guidelines necessary for submission to the CDC. Finally, many of the activities conducted through the Partnership have allowed for the release of the first DC DOH HIV/AIDS Annual Surveillance Report, which sheds light on the burden of HIV and AIDS in the District of Columbia.
Forum for Collaborative HIV ResearchThe Forum for Collaborative HIV Research, an independent public-private partnership established in 1997, facilitates discussions on emerging issues in HIV and works to translate research results into patient care. Housed in the Department of Prevention and Community Health at the George Washington School of Public Health and Health Services (SPHHS), The Forum is comprised of representatives from all stakeholders in HIV clinical research and facilitates ongoing discussion and collaboration among these stakeholders to address critical unanswered questions about the optimal medical management of HIV disease and encourage coordination among public and private research efforts. As a result of these initiatives, the studies performed by the various research entities can begin faster; duplication of efforts reduced; patient enrollment and retention enhanced; the costs of getting answers to critical questions shared, and the results of research can be put to better and more expeditious use. As the Director of The Forum, Dr. Veronica Miller has emphasized the importance of involving all stakeholders in driving the field of HIV treatment forward. Under her leadership, the Forum has also expanded to include a focus on global HIV issues. Additionally, Dr. Miller has published extensively on HIV treatment strategies, especially on the immunological and virological impact of antiretroviral drug protocols through her appointment as Research Professor in the Department of Prevention and Community Health. Heavily involved in Institute activities, Dr. Miller serves as the Chair of the Institute's Continuing Medical Education Committee. In this role, she helps plan a series of seminars focusing on current scientific issues related to HIV treatment and care with a special focus on technology. Additionally, she teaches two courses for the Graduate Certificate in HIV/AIDS Studies - Issues in HIV Care and Treatment and HIV Prevention: An Interdisciplinary Approach. Lastly, she organizes and hosts an HIV Research Discussion Group, which is a "brown bag" informal seminar series bringing together non-laboratory based HIV Research at GW and organizations in the DC area.
Genomics, Proteomics and Bioinformatics Laboratory ResearchHoused in the GW School of Public Health and Health Services' Genomics, Proteomics and Bioinformatics Program, Dr. Fatah Kashanchi's HIV Laboratory Research relies on basic science studies to shed light on the proteomics of HIV-1 and HTLV-1 infected cells in an effort to develop more effective drugs to treat HIV-infected individuals and in the long term to work towards finding a vaccine for AIDS. Through functional genomics and various bioinformatics tools, the lab has recently been able to study alterations in cell pathways in order to better design cell cycle inhibitor drugs that specifically destroy both latent and activated HIV-1 infected cells, combating problems associated with drug resistance. Through a proteomic analysis, the lab has also been able to learn more about the HIV virus and the changes it goes through as a means for moving closer to designing antigenic domains for obtaining both innate and acquired immunity needed for AIDS vaccines. Additionally, an exciting small animal model has also been developed to advance vaccine studies. Utilizing human stem cells to repopulate an animal with human immune cells, this mouse-model innovation develops a fully functional human immune system. HIV can then be introduced into the organism and Dr. Kashanchi is able to study the response of these cells to the virus, leading to an investigation of how different drugs can inhibit entry of HIV into an immune cell. In collaborating with other basic scientists and other researchers across disciplines, the work of the lab will continue to further our insight and understanding of HIV-infected cells so as to contribute to the prevention, care and treatment of HIV/AIDS.
International Infectious Disease Clinical Training ProgramsAt the George Washington University School of Medicine and Health Sciences, Dr. Sylvia Silver, Associate Dean and Professor for Health Sciences, is involved in two international HIV-related research projects. Dr. Silver developed a Professional Development Program during a sabbatical year with the Aeras Global TB Vaccine Foundation and the University of Cape Town that focuses on building capacity for clinical research in developing countries where few professional development opportunities often exist. Dr. Silver's model provides a core foundation of knowledge and skills in clinical research to all levels of staff. The program functions to improve the quality of research and also provide the research personnel with professional development and career mobility for highly marketable skills in future research. In drawing upon this model of professional development, The Fogarty International Center (NIH) has funded, The South African Infectious Disease Clinical Research Training Program, that continues to build clinical research capacity beyond the scope of the Aeras projects. Led by the South African Tuberculosis Vaccine Initiative (SATVI), in partnership with George Washington University under the direction of Dr. Silver as Co-Principal Director, and the Aeras Global TB Vaccine Foundation, this Program allows individuals who are new to clinical research the opportunity to attend a programs based on the Aeras Professional Development Program. Additionally, clinical research mentoring programs and graduate level courses in the GW masters program in clinical research administration (distance education) with the goal of assisting the University of Cape Town having a similar masters program in clinical research in the future are available.
International Maternal, Pediatric, and Adolescent Clinical Trials Group (IMPAACT, formerly Pediatric AIDS Clinical Trials Group, PACTG)Children's National Medical Center (CNMC) represents the Department of Pediatrics at the George Washington University School of Medicine and offers pediatric residency training at its main location in downtown Washington, DC. According to the DC Department of Health (DOH), the Special Immunology Service (SIS) at CNMC provides counseling, testing and clinical care to >75% of HIV exposed and infected children in the metropolitan Washington DC area, including parts of Maryland and Virginia (unpublished data, DC Department of Health, HIV/AIDS Administration, July 2007). Since 1985, the Special Immunology Clinic (SPS) has diagnosed and cared for over 600 children with HIV and AIDS. The SIS is a site for the International Maternal Pediatric Adolescent AIDS Clinical Trials (IMPAACT) group, until recently the Pediatric AIDS Clinical Trials Group (PACTG). IMPAACT is a leadership group representing a merger of investigators from the Pediatric AIDS Clinical Trials Group (PACTG) and the Perinatal Scientific Working Group of the HIV Prevention Trials Network (HPTN/HIVNET) and works to significantly decrease the mortality and morbidity associated with HIV disease in pregnant women, children, and adolescents through the evaluation of treatments for HIV-infected children and complications of ARV drug toxicities. PACTG has conducted more than 55 primary therapy protocols for treatment of HIV infection, 28 protocols for the treatment of the complications of HIV infection and drug toxicities, and 28 perinatal protocols. As the Principal Investigator at CNMC, Dr. Steven Zeichner works with his colleagues at CNMC and with CNMC's subsites at the Washington Hospital Center and Johns Hopkins University to conduct a variety of IMPAACT protocols. A recent study showed that HIV infected infants and children can successfully mount an immune response to Pneumococcus. One current protocol looks at the safety and will help establish the correct dose of raltegravir in children that have failed other therapies. Another current protocol aims to understand how children metabolize certain anti-retroviral drugs when given in particular combinations. We also collaborate with our subsite at Washington Hospital Center to follow infants born to HIV-infected mothers and determine how antiretroviral drugs given to the mother and the infant to block HIV transmission to the infant may affect the infant. Several additional studies are under development, and we expect some of them to open within the year. Maternal and Child Health Care at Washington Hospital CenterAs a community medical center affiliated with Georgetown University through Medstar Health and The George Washington University School of Medicine through the HIV/AIDS Institute, The Washington Hospital Center (WHC) provides care to HIV positive pregnant women. Dr. Jennie Leslie, Assistant Clinical Professor at GTU and GWU and an Obstetrician and Gynecologist at WHC, focuses her attention on maternal and child health for HIV positive mothers through direct clinical care and research. The WHC OB High Risk Step-Down Integrated HIV clinic provides care to HIV positive women through comprehensive clinical management. Co-managed with the Infectious Disease Department, women receive interdisciplinary care by having access to social workers, nutritionists, patient advocates, psychologists, and an infectious disease adherence nurse. Every effort is made to prevent transmission of HIV from mother to child. After delivery, the child is transitioned to Children's National Medical Center for continuing pediatric care. WHC also serves as a clinical trial site evaluating drug management for HIV-infected women during pregnancy and determining the safety and effectiveness of HAART and other interventions intended to prevent vertical transmission and/or improve maternal health. Pregnant women experience unique physiological changes that may result in clinically significant alterations in drug pharmacokinetics (PK). Unfortunately, there have been few clinical trials to study the pharmacokinetics of antiretroviral (ARV) medications in pregnant women. The development of appropriate dosing regimens for HIV infected pregnant woman is critical to the health of both mother and fetus. To this end WHC serves as a part of the multi-center NICHD Pediatric and Maternal HIV Clinical Trials Network in partnership with Children's National Medical Center and John Hopkins University. It is a clinical site for several IMPAACT trials including P1025, an ongoing longitudinal cohort of infected women enrolled during pregnancy or up until 7 days after delivery and followed postpartum. This research consortium also is conducting a prospective PK substudy for women. Led by Dr. Leslie and Marla Shauer, CNM at WHC, this study seeks to describe the PK parameters during pregnancy of selected ARV drugs and to determine if therapeutic dosing regimens of these drugs produced adequate drug exposure during pregnancy.
Molecular Biological StudiesAs Associate Professor Microbiology and Tropical Medicine and Pediatrics, Dr. Steven Zeichner conducts molecular biological studies focusing on the HIV virus and on Kaposi's Sarcoma-associated Herpesvirus, the virus responsible for Kaposi's Sarcoma and other opportunistic cancers that afflict HIV patients. Through basic and translational research studies, Zeichner is able to explore viral pathogenesis at a molecular level, paying special attention to better understanding the interactions of viruses and their host cells. Dr. Zeichner studies how host cell functions contribute to the maintenance of HIV latency of cell lines. Because drug therapy is not able to have an effect on latent cells infected with HIV, the goal is to learn how to effectively activate the virus out of latency with the eventual hope of reducing or eliminating the long-lived reservoir of cells latently infected with HIV. Dr. Zeichner and his colleagues found that cell lines latently infected with HIV exhibit different gene expression patterns compared to their uninfected parental cells, which can help to identify cellular components that can be targeted with agents that activate HIV out of latency. Another molecular study currently underway looks at the Kaposi's Sarcoma-associated Herpesvirus (KSHV) and its replication process. In these studies, Dr. Zeichner's laboratory has developed microarray technologies that can show, in great detail, how each and every gene of the virus is expressed during the process of viral replication. These studies show how the virus is designed to replicate, and describe the pattern of KSHV gene expression during normal and abnormal viral replication. The studies help show which genes are required at different stages of viral replication to trigger the following stages of replication. Understanding these detailed mechanisms of KSHV replication will help in developing more effective therapies for the cancers caused by the virus.
Molecular Virology Laboratory ResearchHoused in the GW School of Public Health and Health Services' Department of Microbiology, Immunology & Tropical Medicine, Dr. Michael Bukrinsky's Laboratory of Molecular Virology focuses on the molecular mechanisms of virus-cell interactions which underlie the pathogenesis of HIV disease. A major research project that is currently underway involves the potential development of a new class of anti-HIV drugs for treating HIV-infected persons. At a time when incidences of drug resistance are increasing during long-term HIV treatment, it is important to think of innovative approaches to drug development. The ability of HIV to replicate in non-dividing cells underlies the extraordinary speed and efficiency of replication of this virus. Therefore, blocking the entry of the virus into a healthy cell's nucleus is an effective approach to inhibit HIV infection of all types of cells. Through computer modeling, Dr. Bukrinsky was able to find compounds that target one of the proteins responsible for nuclear translocation, thereby effectively decreasing the virus' ability to infect new cells. Another significant area of research of Dr. Bukrinsky's laboratory deals with the effects of HIV infection on cellular cholesterol metabolism. HIV infection is often associated with an increased risk of developing atherosclerosis. Previously, this risk was attributed to a side effect of anti-HIV drugs, in particular the protease inhibitors. However, due to Dr. Bukrinsky's research, there is now the understanding that the HIV- infected cells cannot release cholesterol into the plasma, as healthy cells do. By retaining the cholesterol in the cell, the virus ensures adequate delivery of cholesterol to new virus particles, thus making them capable of infecting other cells. The cholesterol-enriched cells, in particular macrophages, are likely participants in atherosclerotic plaque development. Dr. Bukrinsky is currently investigating what happens when HIV-infected cells are treated with drugs that stimulate cholesterol release from cells. His findings suggest that such drugs may not only prevent cholesterol accumulation in cells, thus reducing the risk of atherosclerosis, but also significantly reduce infectivity of the virus, suggesting potential usefulness of such drugs for treatment of HIV-infected patients. Pediatric AIDS and Public Health PartnershipThe Partnership for Pediatric AIDS and Public Health was created between the Elizabeth Glaser Pediatric AIDS Foundation (EGPAF) and the GWU SPHHS Department of Epidemiology and Biostatistics (DEB) in the spring of 2007 with the purpose of aligning the University's expertise in public health with the Foundation's work fighting pediatric AIDS around the world. Through this innovative partnership, the GW SPHHS will provide medical and scientific expertise to strengthen and expand the technical leadership capabilities of the EGPAF. This new partnership will promote opportunities to tie public health research more closely with delivery of AIDS prevention and treatment services in resource-poor settings, and also will create educational and internship opportunities for both EGPAF staff and SPHHS students. EGPAF staff will have the opportunity to contribute to the educational mission of the University, as well as to take advantage of educational opportunities at GW. The new, non-exclusive partnership is part of a trend to link the School of Public Health and Health Services more closely to the activities of public health organizations in the District of Columbia. It will include:
Dr. Alan E. Greenberg, Principal Investigator of the Partnership and also Chair of the Department of Epidemiology and Biostatistics at GW, works closely with Elizabeth Glaser Pediatric AIDS Foundation President and CEO Pamela W. Barnes to ensure a strong and ongoing partnership. Pediatric Clinical Care and Research at the Children's National Medical CenterChildren's National Medical Center represents the Department of Pediatrics at the George Washington University School of Medicine and offers pediatric residency training at its main location in downtown Washington, DC. Children's National Medical Center (CNMC) serves as the primary and tertiary pediatric care facility for the metropolitan DC area. According to the DC Department of Health (DOH), the Special Immunology Service (SIS) at CNMC provides counseling, testing and clinical care to >75% of HIV exposed and infected children in the metropolitan Washington DC area, including parts of Maryland and Virginia (unpublished data, DC Department of Health, HIV/AIDS Administration, July 2007). Since 1985, the Special Immunology Clinic has diagnosed and cared for over 600 children with HIV and AIDS. The SIS is a site for the IMPAACT/PACTG (International Maternal Pediatric Adolescent AIDS Clinical Trials /Pediatric AIDS Clinical Trials Group) network and Ryan White Titles I, II and IV in the nation's capital. CNMC is among leading NIH funded institutions where pediatric research is being conducted as a part of its mission to promote the advancement of research and education to improve child health and wellbeing. As an Assistant Professor of Pediatrics and the Clinic Director for Special Immunology/Infectious Diseases at Children's, Dr. Natella Rakhmanina, focuses her research on pharmacogenetics and pharmacokinetics of the HIV treatment in children and adolescents with the goal to optimize and individualize treatment of HIV-infected pediatric patients. Since 2004, Dr. Rakhmanina has lead a NIH sponsored Clinical Research Scholarship (K-12 award) to investigate role of pharmacogenetics and therapeutic drug monitoring in the treatment of HIV-infected children and adolescents. The results of this on differences in metabolism and drug response in HIV-infected children due to genetic variations have been presented at several National and International meetings and are scheduled to be presented at CROI meeting in Boston in February 2008. With the main location if the HIV pandemic on African continent, CNMC has expanded its pharmacogenetic research into the African population in collaboration with the University of Maryland. The group of Dr. Hoffman and Dr. Rakhmanina at CNMC has analyzed the samples collected by Dr. Sarah Tishkoff from 7 African populations in Kenya, Tanzania and Cameroon) to investigate the differences in drug metabolizing capacities among geographically and ethnically diverse African populations. The study has found high variability in genetic expression of certain drug metabolizing enzymes among different ethnic groups. Pharmacological HIV Research at Howard UniversityThrough pharmacological HIV research at Howard University College of Medicine, Dr. Keith Crawford, Assistant Professor in the Department of Pharmacology, works to identify host and virologic factors that my be predictors of HIV progression and that may also serve as markers for disease severity and response to treatment. Dr. Crawford is looking at C-reactive protein (CRP), a marker for inflammation, and its possible association with the stage of HIV disease, as some other studies suggest. He is trying to tease out whether CRP serves as a marker for HIV disease severity in a predominantly African American cohort that has many other co-morbidities that could also be playing a role in inflammation processes. He is also looking at chemokine receptor density (CCR5 and CXCR4) the quantity of receptors that are the targets that the HIV virus uses to enter the cell, and their association with stage of disease. Crawford is interested in exploring - 1) The relationship between CRP and chemokine receptor density; 2) Viral tropism (figuring out what receptor the virus is using to get in a cell) and its relationship to chemokine receptor density; and 3) The variability in HIV viral sequences and stage of HIV disease. By recruiting naive African-American HIV positive persons into his study and collecting blood specimens, Crawford is able to get a baseline sample and then track changes in these parameters once treatment begins. This methodology will help to uncover whether CRP and chemokine receptor density may be useful markers of disease stage and monitoring treatment response for this population. This type of research has potential applications for using CRP as a marker of HIV disease stage and response to therapy in resource poor settings without access to highly equipped laboratory facilities to measure CD4+ cells and viral loads. Having a better understanding of CRP could also give clinicians further indication as to whom may be at higher risk for complications from HIV disease or drug side-effects. Social-Behavioral HIV Research at George Washington UniversityThrough the Department of Psychology at the Columbian College of Arts and Sciences at George Washington University a significant amount of HIV-related social and behavioral research is being conducted by two primary investigators, Drs. Paul Poppen and Maria Cecilia Zea. Through a variety of research studies, they seek to gain a better understanding of the root causes and reasons why people behave in ways that increase their susceptibility to HIV infection. One five-year study, entitled "Contextual Influences on Sexual Risk among Latino Men Who Have Sex with Men," develops and tests a theoretical model of socio-cultural, psychosocial, and contextual influences on risk in three groups of Latino men in the U.S.-Dominicans, Colombians, and Brazilians. These groups represent understudied and growing immigrant populations at high risk. This application involves an innovative approach with a theoretical model that includes variables at two levels - the person level that includes between-subjects variables that describe socio-cultural and psychosocial characteristics of the person and the situation level that includes within-subjects variables. By focusing on situational characteristics of encounters, as well as on individual characteristics, this study provides a greater understanding of factors influencing risk among Latino men, which will aid in efforts to prevent the spread of the epidemic. A new study underway, entitled "HIV Prevalence, Sexual Behavior, and Attitudes toward Circumcision among Colombian MSM," looks at circumcision in Colombia, where very few men receive the procedure. While much of the attention on circumcision has been focused in Africa, this study focuses in on a different population of men living in another socio-cultural setting. This study grew out the ongoing study on Contextual Influences because circumcised Colombian men were less likely to be HIV-positive than uncircumcised men. These results piqued the need for further exploration in Colombia. Another study, entitled "Disclosure of HIV status among Latino gay men," explores the details of disclosure by HIV positive Latino gay men to their partners, family and friends. Who are they disclosing to, when, and under what circumstances? This study also examines the links between seroconcordance, disclosure of HIV status, and sexual risk. A minority supplement added to this study, examining disclosure of HIV status among Brazilian gay men, researched similar issues in a sample of Brazilian gay and bisexual men.
Women's Inter-Agency HIV Study (WIHS)The Women's Inter-Agency HIV Study (WIHS) is an ongoing multicenter, prospective study to carry out investigations of the impact of HIV infection in women. With its inception in 1993, 2,625 women were enrolled with an additional 1,143 women enrolled in 2001. The study follows women who are either infected with HIV (about 75%) or are considered to be at high risk for acquiring the disease (about 25%). A petition to the NIH to study the impact of HIV on women was the impetus for the WIHS study. At the start of the epidemic, research focused primarily on the male population known to be at highest risk for AIDS. However, by the mid-1990's, the epidemic shifted and there was a large increase in new AIDS cases among women. The study has since developed a large database and specimen repository that serve as resources for WIHS investigators as well as for nonaffiliated researchers working on HIV/AIDS and the promotion of women's health. There are six WIHS consortia, each made up of multiple clinical subsites. As Principle Investigator, Dr. Mary Young at Georgetown University leads the Washington, DC site. Three hundred and forty women are followed at the DC site with visits every six months. A number of linked RO-1's have been funded to further investigation into a variety of issues, including human papilloma virus, dynamics of virologic rebound and resistance, Hepatitis C, and AIDS associated malignancies. Local scientific intitatives have included collaborations on chemokines in HIV, iron status and survival, cardiovascular risk factors, and the utility of serum measurements of mitochondrial DNA as a predictor of metabolic abnormalities. The Washington, DC WIHS encourages the use of its data collection by local researchers as a means to promote collaboration and further research and understanding into the disease. World Health Organization "Task Shifting" ProjectThe George Washington University School of Public Health and Health Services (GWU-SPHHS) is working to support the World Health Organization (WHO) and its efforts to increase access to and delivery of HIV/AIDS services through the process of "task shifting" from more highly trained health professionals to less trained and non-traditional health workers in countries with severe health care worker shortages. The Co-Principal Investigators for this project, Dr. Alan E. Greenberg, MD, MPH (Epidemiology and Biostatistics Department) and Dr. John Palen PhD, MPH (Heath Policy and Global Health Departments), along with Co-Investigators Drs Anne Markus and Seble Frehywot (Health Policy Department) represent the core GWU team working on this project. GWU is working with WHO, the U.S. Office of the Global AIDS Coordinator, and government officials in selected PEPFAR countries to develop a regulatory (legal/policy) framework) to support task-shifting for health sector workforce strengthening and human capacity development. This complex project was conducted in multiple stages in 2007, including: the review of existing regulations (laws and policies) and other publicly available materials used for the purpose of "task shifting"; the construction and use of a survey tool to conduct an extensive situational analysis in five PEPFAR countries; data gathering of the regulations and the structure of the regulatory system and process within these countries; and the development of regulatory recommendations for the WHO guidelines to support task-shifting to accelerate the scale-up of HIV/AIDS prevention and treatment services in developing countries. An international meeting to present these guidelines to the 57 countries with severe health care worker shortages will be held in Ethiopia in January 2008, with the GWU core task-shifting team participating. |