Robert L. Cook, MD, MPH – Grants and Contracts

Current Grants

Southern HIV Alcohol Research Consortiium (SHARC) Admin and Sesearch Support Core
5U24AA022002-02 (Septmeber 25, 2012 – August 31, 2017)
PI: Cook

The State of Florida has the highest rate of new HIV diagnoses in the US. Its ongoing epidemic is characterized by significant racial disparities and special populations including women and men who have sex with men. The Southern HIV Alcohol Research Consortium (SHARC) was created as a CHAART in 2011 to address the impact of high-risk alcohol consumption on HIV outcomes in Florida. The consortium consists of three independently-funded research projects: a randomized clinical trial of naltrexone in HIV-infected women with high-risk drinking, an ongoing cohort study focusing on the impact of alcohol on neurocognition and aging in HIV, and an immunology study of the direct impact of alcohol (and naltrexone) on immune senescence over time. The projects build upon a successful research infrastructure that has already recruited over 800 persons with HIV in Miami, Florida, share clinical research resources, and have overlapping aims. However, the consortium lacks a central administrative infrastructure or mechanism to support new research as a whole. The SHARC Administrative and Research Support Core, submitted in response to RFA-AA-12-010, is critically needed to ensure coordination and communication across our consortium projects, to form new, multidisciplinary research collaborations, and to extend our research into additional public health settings within Florida. The specific aims of this Core are (1) to create a self-sustaining, transdisciplinary research consortium addressing HIV and risky alcohol use in Florida (administrative core); (2) to expand our research and clinical trial capacities (research support); and (3) to expand multidisciplinary research and to mentor a new generation of scientists (education). Our investigators bring expertise in clinical trials methodology, clinical epidemiology, immunology, cognitive function, health services research, and exercise. Overall, the Core will support research that has significant impact by maximizing overall research productivity, increasing capacity to conduct clinical trials, enhancing collaborations, mentoring new researchers, and translating findings into clinical practice and public health settings that will improve health outcomes in persons with HIV and high-risk alcohol comorbidities

Pharmacotherapy for alcohol consumption in HIV-infected women: Randomized trial
U01AA020797 (September 25, 2011 – August 31, 2016)
PI: Cook

Hazardous alcohol consumption is common in HIV-infected women and is associated with significant harm. The primary objective of this application is to evaluate whether a prescription medication will reduce hazardous alcohol consumption and its consequences in HIV-infected women. The central hypothesis is that women who receive active medication (vs. placebo medication) will decrease their alcohol consumption and have improved health outcomes. The specific aims are to determine whether a drinking-reduction medication (naltrexone or topiramate), provided to HIV-infected women with hazardous drinking (>7 drinks/wk or >4 drinks/occasion) will result in reduced alcohol consumption and improved HIV-related outcomes (antiretroviral medication adherence, reduced HIV disease progression, and reduced risky sexual behavior).This study represents the clinical trial component of our Consortiums for HIV/AIDS and Alcohol-Related Outcomes Research Trials (CHAART), a series of three inter-related projects surrounding a central Core. We propose a randomized controlled trial involving 240 HIV-infected women with hazardous drinking recruited from outpatient clinics and research settings in Miami, FL. Women will be randomized to receive medication or placebo for 4 months; main outcomes will be assessed at 2-months, 4-months, and 7-months. The research involves collaboration with investigators in the Women’s Interagency HIV Study (WIHS). The study will build upon a currently-established pilot study in which we have established the study procedures, identified key measures, and developed the research infrastructure needed to fully implement this multi-site, randomized clinical trial. The proposed work is innovative because pharmacologic treatment for alcohol has not been evaluated in HIV-infected women outside of substance abuse treatment settings, and alcohol medication will be chosen based on an individual assessment. The expected outcome supporting the effectiveness of this treatment would transform the approach to clinical management of hazardous drinking in clinics serving HIV-infected women, and could readily be adapted to women with other chronic disease.

Immune Dys-regulation in HIV-infected Women with Heavy Alcohol Consumption
U01AA020800 (September 10, 2011 – August 31, 2016)
PI: Desai, Co-I: Cook

Alcohol consumption is common in HIV infected individuals and heavy alcohol consumption has been associated with accelerated HIV disease progression and poor health outcomes. This proposal will investigate mechanism underlying CD4 T cell decline and HIV disease progression in HIV infected women who engage in heavy alcohol consumption. One mechanism by which alcohol may cause immune dysfunction is by inducing microbial translocation. We will examine whether chronic cumulative exposure (amount x duration) over 10 years of observation period is associated with more rapid CD4 T cell decline and immune dysfunctionality namely exacerbation in levels of immune activation, inflammation and immune senescence leading to early advent of AIDS and Non AIDS co-morbidities. We will test our hypothesis that heavy alcohol consumption, defined using NIAAA criteria for hazardous drinking (for women, >7drinks/week or >3 drinks per occasion), disrupts the gut barrier causing microbial translocation which enhances systemic immune activation, inflammation and senescence; all events that contribute to CD4 T-cell decline and HIV disease progression. We will conduct this study retrospectively in bioreposited specimens from the longitudinal cohort, the Women’s Interagency HIV Study. As a secondary aim linked to the other UO-1 in this consortium; a randomized clinical trial on alcohol reduction medication naltrexone, we will examine in subset of HIV infected heavy drinkers, whether alcohol reduction medication, naltrexone improves alcohol related immune dysregulation. We will create a repository and database of immune markers (translocation, immune activation, inflammation, and immune senescence) in HIV infected women who engage in hazardous drinking; which can be used for future translational studies related to alcohol and HIV interaction: observational or mechanistic. This project has a cross discipline expertise, from leading clinicians in the HIV/AIDS field, behavioral scientists, epidemiologist, and immunologist for successful implementation of the aims and objectives of this study.

Rural South Public Health Training Center
UB6HP22825 (2011 – 2015)
PI: Peoples-Sheps, Co-I: Cook

The Rural South Public Health Training Center, proposed by the University of Florida (UF) College of Public Health and Health Professions in partnership with the Florida Agricultural and Mechanical University (FAMU) Institute of Public Health, has been established to serve the medically under-served counties of Florida, especially those in rural regions of the state.  The goals of the center are to provide competency-based training for the public health workforce, especially those workers in under-served areas of the state, and to enhance public health services and decrease disparities in access to services in medically under-served areas.  The center will identify the needs of the workforce and of residents in medically under-served areas and tailor training and services based on those needs, with a special emphasis on needs related to HIV/AIDS
To help address the looming public health work force crisis in Florida, the center will provide advanced training for public health professionals with the goal of improving the skills of current public health workers.  Since travel, even within Florida, has been greatly curtailed in the past few years, the center will focus its efforts on providing online training to increase the accessibility and convenience of the programs being offered.  Free distance courses will allow public health workers to stay current in their fields and to increase the breadth of their knowledge without having to use professional or personal resources for travel.  The objective of these distance courses is to provide continuing education credits for public health workers which can be completed at home, free of charge.  For public health professionals with a Bachelor’s degree who are interested in more intensive training, the Rural South Public Health Training Center will offer an online MPH certificate in Public Health Foundations and Prevention and Management of HIV.

MIAMI WOMENS INTERAGENCY HIV STUDY WIHS
1U01AI103397-01 (January 1, 2013 – December 31, 2017)
Co-PI: Cook

A growing proportion of U.S. women with HIV infection are from the Southeastern United States. Compared to all other states in the Southern region of the U.S., Florida has the highest number of HIV-infected individuals and the highest rates of HIV transmission. Miami-Dade County has one of the highest rates of new infections among women and the prevalence of HIV among women was among the highest in a national study of 21 epicenter cities in the U.S. Heterosexual transmission and intravenous drug use were the major risk factors for infection. Compounding these issues, Miami-Dade County ranks high among U.S. areas in measures of social and economic distress. The Women’s Interagency HIV Study (WIHS) seeks to expand its efforts to better understand the current epidemiology of HIV infection in women with the identification of new sites from the Southern region of the U.S. The Miami WIHS is well positioned to engage women with HIV infection and at risk for HIV infection that are representative of this region and the changing demographics of the HIV epidemic, as well as addressing important current treatment outcomes and the impact of disassociation from care among hard-to-reach populations (e.g. substance abusing individuals). Miami sits at the portal to the Caribbean and Central and South America and, as a result of the high rates of immigration from these regions; the women infected with HIV belong to a wide, diverse population. In addition, the HIV-infected population of women in Miami spans generational boundaries from pediatrics through to the elder. This project is a multiple PI project between the University of Miami Miller School of Medicine and the Columbia University Mailman School of Public Health with collaboration from the University of Florida. We will seek to enroll a diverse cohort of 300 youth, young adult and adult women, including women who are at-risk for HIV, those with limited disease progression, those with newly recognized infection, who are antiretroviral treatment na¿ve and antiretroviral treatment experienced participants, and who are in care, intermittently in care and not in care. A highly experienced and diverse team of researchers has been assembled to ensure the success of this program, including clinical, basic and behavioral/social scientists, with strong ties to th community. The specific aims outlined respond directly to the overall WIHS scientific goals and advance and expand the WIHS basic, clinical and epidemiologic/behavioral/social science research agenda. The proposed scientific agenda taps into the experience and expertise of the Miami WIHS researchers to examine critically important and scientifically rigorous research questions. The proposed research projects will examine the impact of aging on immune functionality; reproductive decision making among young adult and adult women living with HIV/AIDS; increasing viral diversity and the impact of HIV-1 non-B subtype infections on the clinical course of HIV and response to therapy; and the interplay of crack cocaine use and associated co-occurring epidemics (mental health, poverty, unemployment and interpersonal violence with uptake of optimal antiretroviral therapy and engagement and retention in care. By coupling the diverse population base of HIV-infected and at risk women with the recognized strengths in HIV/AIDS research, the Miami WIHS is perfectly situated to advance the overall WIHS scientific agenda of defining clinical outcomes among women across their lifespan, including the uptake of antiretroviral therapy; use and retention of HIV primary care and other ancillary services; treatment outcomes on viral suppression, immune recovery and normalization of the effects of HIV, and disease pathogenesis, as well as, promoting and advancing local scientific research goals.

Completed Grants

Quadravalent HPV vaccination and oral HPV infection in college women.
Merck, Inc (2010-2012)
PI: Cook

This study was designed to determine the prevalence of oral humanpapillomavirus infections in college women, to determine risk factors associated with transmission, and to identify the persistence of oral HPV infections over a 12-month follow-up.  1030 women were recruited from the University of Florida Student HealthCare Center; each provided an oral sample for HPV testing and completed a questionnaire using a netbook.  Many UF graduate and undergraduate students also participated on the research team involving data collection and analysis.  Additional co-investigators on the study include Drs. Phil Barkley, Virginia Dodd, Anna Guiliano, as well as investigators and staff involved in clinical laboratories at the University of Florida Emerging Pathogens Institute and the Moffitt Cancer Center.  The study findings will be presented at the 2012 Annual Meeting of the American Public Health Association.

Geo-Spatial and Longitudinal Trends in Plasmodium falciparum Resistance in Haiti
DOD (2010-2012)
PI: Okech, Co-I: Cook

This study is led by Dr. Okech, and is designed to study factors associated with resistance to antimalarial drug therapy in persons attending health clinics in Haiti.  Persons with symptoms of malaria will be recruited and followed to determine their outcomes related to malaria and response to treatment

Pharmacotherapy to reduce hazardous drinking in HIV-infected women
R01AA018934 (September 30, 2009 – June 30, 2012)
PI: Cook

Approximately 15% to 20% of U.S. women consume alcohol at hazardous levels each year; however women with HIV infection face additional health consequences. In women with HIV infection, hazardous drinking has been associated with nonadherence to medications, risky sexual behavior, and increased disease progression. Despite the documented prevalence and health consequences, there are no data on acceptability or effectiveness of pharmacologic treatment for hazardous drinking in women seen in HIV clinic settings. Thus, there is a critical need to evaluate a treatment program in this population. The primary objective of this application is to evaluate the acceptability and effectiveness of a treatment program that involves oral naltrexone and an accompanying medical management program designed to maximize adherence. The project specific aims are: (1) determine whether an alcohol treatment intervention involving naltrexone can reduce hazardous drinking in HIV-infected women, and (2) determine whether an alcohol treatment program involving naltrexone can improve clinical and behavioral outcomes in HIV-infected women. Our central hypotheses are that women randomized to the treatment program will have decreased rates of hazardous drinking and improved HIV-related outcomes such as medication adherence, disease progression, and risky sexual behavior. The study design is a randomized controlled trial involving HIV-infected women with hazardous drinking, recruited from HIV clinics in Chicago and northern Florida. Women will be randomized to either an intervention group, who will receive naltrexone for 4 months, or a control group that will placebo. The primary study endpoints will be assessed at 2, 4 and 7-months after enrollment. The proposed work is innovative because: (1) we will target a broad spectrum of hazardous drinking, (2) pharmacologic treatment for alcohol has not been evaluated in HIV-infected women, (3) we will use computers to facilitate assessment and feedback, and (4) we will assess the impact of the alcohol intervention on HIV-related outcomes. The proposed research is significant because the therapy will be offered within HIV clinic settings to a group of persons that is significantly undertreated. In addition to determining the effectiveness of the alcohol treatment intervention, we will also identify key barriers and facilitators associated with adherence to pharmacologic treatment for alcohol in women with hazardous drinking. If our hypotheses are confirmed, the study findings would transform the approach to hazardous drinking within clinics serving HIV-infected women, and could easily be adapted to women with other types of chronic diseases. PUBLIC HEALTH RELEVANCE: This clinical trial of treatment for hazardous drinking in HIV-infected women has significant public health relevance. First, we will demonstrate the ability to improve outcomes related to hazardous drinking efficiently within HIV clinic settings. Second, we will identify factors related to the acceptability and feasibility of pharmacologic treatment in a group of women at increased risk for alcohol-related health outcomes.

Home Screening for Bacterial Vaginosis to Prevent STD: A study of the STI Clinical Trials Group
NIAID HHSN2662 (2007-2010)
Protocol Chair (2007-2009): Cook

Bacterial vaginosis (BV) is characterized by an imbalance in the normal vaginal bacterial flora. In the United States (US), BV is very common, and the most common cause of vaginitis, affecting approximately 1 in 10 sexually active young women. Because BV is so common, interventions targeting BV could have a tremendous public health impact. This is a phase III randomized controlled trial, in which the primary objective is to determine whether regular screening (every two months) and treatment for asymptomatic BV can reduce the one-year incidence of chlamydial and gonococcal infections, compared to a control group of women who receive regular monitoring (every two months) for BV but no treatment. The secondary study objective is to determine demographic and behavioral factors associated with the acquisition of BV, its persistence among women who are not treated for this condition, its spontaneous resolution, and its recurrence in women who are treated for this condition. This study protocol will enroll 1500 sexually active females, aged 15 – 25 years, from 6 US cities involved in the Sexually Transmitted Infections Clinical Trials Group network (Birmingham, Durham, Raleigh, Pittsburgh, Baltimore and San Francisco). To be eligible, women must have 2 or more risk factors for sexually transmitted diseases (STDs) and must have clinical evidence of asymptomatic BV at enrollment. For the purposes of this study, women with a vaginal pH>4.5 with >20 percent clue cells detected by microscopy to have asymptomatic BV. In addition, women must deny the presence of unusual or abnormal vaginal discharge or odor. Subjects will receive bi-monthly (every two months) home self-testing kits for BV using a vaginal swab. If BV is detected by self-test, the subjects in the intervention group will receive antibiotic treatment consisting of metronidazole 500mg twice daily for 7 days. Subjects will be randomized to either an intervention group (screening and treatment for BV) or a control group (monitoring for BV without treatment). Subjects in both the intervention group and the control group will complete bi-monthly (every 2 months) follow-up assessments for BV at months 2, 4, 6, 8, 10, and 12 (the final follow-up). In addition, subjects will provide sample collections for Chlamydia trachomatis and Neisseria gonorrhoeae at 4, 8, and 12 months after study entry.

Evaluation of Florida Medicaid Programs for Fiscal Year 2006 Amendment: Evaluation of Florida Medicaid Programs for Fiscal Year 2009-10
Florida Agency for Health Care Administration (2007 – 2010)
Co-I: Cook

This grant provides support for the overall structure and research conducted as part of the Florida Center for Medicaid and the Uninsured, and that is funded by the Florida Agency for Health Care Administration.  As part of the grant, the Center coordinates an annual meeting to present ongoing research involving Florida Medicaid.  In addition, the Center helps to coordinate the function and reporting regarding specific research projects, most of which involve principal investigators at the University of Florida.

Molecular epidemiology and anthropological determinants of HIV-1 emerging epidemic in Southern Morocco
University of Florida Center for AIDS Research and University of Florida Emerging Pathogens Institute (2009)
Co-PI: Cook

The purpose of this grant was to establish a research collaboration between the University of Florida and the National Institute of Hygiene in Morocco.  As part of the collaboration, our research group focused on examining the distribution of HIV-1 subtype infections across Morocco, and conducted an analysis of behavioral and geographic factors associated with HIV-1 subtype distribution in Agadir, Morocco.

Seeking out sex online: A novel 3-campus research study of HIV and other sexual health risks among young people
University of Florida Center for AIDS Research (2009)
PI: Buhi, Co-I: Cook

This study, led by Dr. Eric Buhi at the University of South Florida, sought to determine whether the types of sexual partners and activities among persons met via “online” settings (like Facebook) were different from the types of partners and activities among persons met in real life settings.  Data were obtained by online surveys of students at the University of Florida and the University of South Florida.

Reducing alcohol and drug use in American youth through Interactive Digital Media
University of Florida Opportunity Fund Award (2008 – 2009)
Co-PI: Cook

This study, co-led by Dr. Cook and James Oliverio of the University of Florida Digital Worlds Institute, sought to obtain pilot data to support a larger intervention study. Specifically, we sought to determine whether persons attending public health HIV/STD clinics in Florida would be willing to participate in research or clinical activities that include digital media.  We conducted a survey of over 300 persons at the STD clinics at the Alachua County Health Department and the Marion County Health Department.  In addition, the Digital Worlds team created a prototype intervention intended to reduce alcohol and drug use in young persons at risk for HIV/STD.  This work is still being considered for a new grant application at NIH.

Medicaid and HPV infection in Florida
Merck, Inc (2008 – 2009)
PI: Cook

The purpose of this study was to identify the proportion of women, enrolled in Florida Medicaid, who received HPV vaccination during the first 5 years after vaccine availability.  We also sought to determine factors associated with HPV vaccine uptake.  As part of this work, we are also working to determine the costs related to genital warts among persons enrolled in Florida Medicaid during this same time period.  These analyses involve collaboration with the Florida Center for Medicaid and the Uninsured, and with several additional investigators at the University of Florida.

Direct Epitope Identification and Testing
NIAID HHSN226200400027C (2005-2009)
PI: Hildebrandt, Co-I: Cook

The Large Scale Antibody and T Cell Epitope Discovery Program supports the large scale discovery of novel B and T cell epitopes that utilize recent technological advances such as, but not limited to: computer-based epitope prediction algorithms; genome-wide scanning; structural genomic; high pressure liquid chromatography; mass spectrometry; phage-display libraries; and combinatorial synthetic peptide library screens. In addition, NIAID seeks to develop new or improved high throughput screening methods for epitope discovery, with a strong interest in antibody epitope screening methods. This program emphasizes epitope discovery for category A-C bioterrorism agents and emerging/re-emerging infectious diseases.

Multicenter AIDS Cohort Study
NIAID U01AI35041 (May 3, 2004 – April 30, 2009)
PI: Rinaldo, Co-I: Cook

The current priority of the MACS is to enhance our epidemiologic and pathogenesis information in relation to treatment intervention. We need to describe the long-term patterns of therapy use that are consequential in terms of treatment efficacy. Our specific aims emphasize COHORT retention and maintenance, biological specimen procurement and central lipid/insulin/glucose testing for dyslipidemia, diabetes, lipodystrophy and cardiovascular disease for the MACS. These are: (1) To characterize the evolving natural history of treated HIV infection and identify the determinants and trends of long-term HIV-related outcomes in the era of HAART. We will determine the effect of anti-retroviral therapies on disease incidence, surrogate markers and survival expectation. This includes special emphasis on our recently expanded COHORT of young, African-American MSM, who were underrepresented in the original MACS COHORT, yet maintain an inordinately greater prevalence of HIV infection in the USA. (2) To maintain the longitudinally collected epidemiological data and biological specimen repository framework of the Pittsburgh MACS as a platform to facilitate natural history and pathogenesis studies. (3) To perform the required clinical and laboratory testing of HIV seropositive and seronegative MSM in the Pittsburgh MACS. (4) To perform cardiovascular testing (Electron Beam Computed Tomography [EBCT], carotid intima media thickness [IMT], and EKG testing) on a sub-sample of the MACS to address key questions related to risk of cardiovascular disease among HAART recipients. We believe that through these aims, as well as through substudies on the immunopathogenesis of HIV infection that are closely linked to the Pittsburgh MACS, we will significantly contribute to the scientific agenda and goals of the MACS.

High throughput sequencing of microbial communities from fecal and vaginal samples in a study of bacterial vaginosis
University of Florida EPI-ICBR Seed Initiative (2008)
PI: Cook

Dr. Cook and Dr. Volker Mai co-led a study designed to identify the best methods of sample collection for self-swabs of vaginal microbiota, and to determine whether the microbiota appears to vary across the menstrual cycle.

Alcohol Intervention for the Chicago Consortium Women’s Interagency HIV Study
Hektoen Institute (2006)
PI: Cook

This small study helped to support two focus groups in Chicago, IL, designed to understand reasons that women with HIV infection drink alcohol, and whether they would be receptive to different types of intervention options related to their drinking.  The study collaborators included Mardge Cohen and Kathleen Weber from the Chicago WIHS consortium.

Alcohol Associated Outcomes in HIV+/- Aging Veterans
R01AA013566/U01AA013566 (September 30, 2001 – August 31, 2006)
PI: Justice, Co-I: Cook

Alcohol consumption likely plays a pivotal, but largely ill-defined role in HIV infection, disease progression, comorbid conditions and adverse events from treatment (drug toxicity). This may be especially true among the nation’s veterans. In preliminary work with HIV positive veterans, 33% report binge drinking, 21% report hazardous drinking and 32% have diagnosis of alcohol addiction or dependence. The Veterans Aging Cohort Study (VACS 5) is a five-site (Houston, New York, Bronx, Atlanta, and Los Angeles) observational study of veterans with and without HIV infection (n=4010). The study includes age/race/gender/site-matched veterans from general medical clinics to better differentiate effects of HIV and its treatment from those of comorbid conditions. Data sources include laboratory, pathology, pharmacy, diagnostic data, patient and provider surveys, and blood and plasma banking. Our long-range goal is to design, implement, and evaluate interventions that improve outcomes for people aging with HIV infection complicated by comorbid conditions including alcohol and other substance use, medical conditions, neuropsychiatric and cognitive disease, and homelessness. Targeted interventions for future studies include electronic medical record reminders and nurse-delivered brief motivational interventions. In order to be effective, these interventions require detailed information concerning specific health risks for individual patients. VACS 5 has received funding from the National Institute on Aging and the National Institute for Mental Health to conduct a 6-month feasibility study to begin August 2001 (VACS 5- Feasibility). These funds will allow us to complete half of our targeted enrollment and provide for no follow-up. Because of the substantial prevalence of alcohol use and abuse among our patients, we propose to extend VACS 5-Feasibility for 5 years to study the role of alcohol in determining patient outcomes in HIV infection. Specific aims address: 1) the influence of alcohol on adherence, CD4 cell count, viral load, Hepatitis C viral load, liver function, and complete blood counts; 2) the influence of alcohol on HIV disease progression and comorbid disease occurrence, symptom burden and quality of life, and survival and 3) provider and patient awareness and attitudes toward alcohol consumption. In addition to the standard data collection of VACS 5, a 30-day Time Line Follow Back will be self completed by all patients and validated by interview in a subset, and additional liver function tests will be analyzed on banked specimens (CDT, GGT, ALT, and AST). Four alcohol focus groups will be conducted at each site: 1) HIV positive patients who consume alcohol; 2) HIV negative patients who consume alcohol; 3) clinicians from HIV clinic; 4) clinicians from the general medical clinic. After completing baseline enrollment, follow up will occur at 6-month intervals and new patients will be enrolled as they present for care.

Home Screening for Chlamydia Surveillance
R01HS010592 (July 25, 2000 – June 30, 2006)
PI: Ness, Co-PI: Cook

Bacterial sexually transmittd diseases (STD’s), the most common of which is C. trachomatis, are major causes of reproductive morbidity among women in the U.S.. Advances in technology for detecting STD’s offer the novel opportunity for home-based self- screening. However, whether such a strategy could enhance adherence with screening has not been examined in this country. We propose a randomized clinical trial to evaluate the effectiveness of home-testing versus return clinic visits for screening of STD’s among high risk women. Women aged 14-29 with documented C. trachomatis cervicitis will be enrolled from family planning services, STD clinics, adolescent clinics and gynecology clinics in Pennsylvania and South Carolina. Baseline characteristics including risk factors for STDs and attitudes about screening will be collected. Women will be randomly assigned in equal numbers to 1) home samplings vs. 2) return visits for screening. At 6, 12, and 18 months, the two groups will then receive either 1) self-sampling vaginal swabs that they can elect to be mailed home or picked-up or 2) post-card reminders to return to the enrollment site for screening. Swabs will be tested at a central laboratory for C. trachomatis and N. gonorrhoeae by DNA amplification. All women with STD’s detected will bu urged to return for treatment, and all obtained treatment will be recorded. Main analyses will compare between home screening and return visit groups: 1) proportion of screening tests completed; 2) proportion of women with C. trachomatis infections detected by screening. Secondary analyses will include: 1) proportion of women with N. gonorrhoeae detected by screening; 2) proportion of detected chlamydia/gonococcal infections treated; 3) attitudes towards screening. At two years after enrollment, we will recontact all study participants (both those who complied with screening and those that did not). All participants will be interviewed by telephone and asked to complete a self-collected vaginal swab for C. trachomatis and N. gonorrhoeae infections. Based on these end-of-study data, secondary analyses will compare between study group: 1) the proportion of women with C. trachomatis after the screening period; 2) the proportion of women who sought care for PID during the study. This study will determine whether a home screening strategy for bacterial STD’s would enhance compliance with screening recommendations; such a strategy could contribute to elimination of STD’s at reduced societal cost.

Herpes and Stigma
U01AI47638 (September 30, 1999 – August 31, 2004)
PI: Fischhoff, Co-I: Cook

This Sexually Transmitted Diseases Cooperative Research Center will emphasize prevention of selected STDs and the consequences of STDs. In particular we are stressing STDs which have significant adverse impact on the health of women. With this approach we will identify ways in which the burden of complications associated with STDs that disproportionately result in adverse affects on the reproductive health of women can be reduced. To achieve this goal we will be taking several approaches. Two intervention studies, an indirect and direct approach, will be undertaken to prevent acquisition of bacterial vaginosis (BV), chlamydia and herpes and thereby the complications associated with these STDs. In a biologic intervention approach use of a Lactobacillus capsule will be assessed in a double blinded placebo-controlled trial to prevent infection with BV, C. trachomatis, and other genital infections. By studying the stigma associated with herpes and developing an intervention designed to produce more rational herpes-related decision making we are attempting to prevent acquisition of HSV. Determining the antimicrobial protective function of secretory leukocyte protease inhibitor (SLPI) will add to our understanding of the biologic interaction between T. vaginalis and HIV and other STDs; it also may lead to innovative vaginal microbicidal strategies. Determining the molecular mechanisms of gonococcal iron acquisition and the expression and Immunogenicity of iron acquisition will provide information relevant to developing gonococcal vaccines based on the human transferrin- binding protein complex and pathogen-targeted antimicrobial interventions targeting the iron-acquisition mechanism of N. gonorrhoeae. Studies to measure expression of the HPV genes E1, E2, E7 and E7 will expand our knowledge of HPV progression, thus allowing development of strategies to prevent cervical cancer. Determining the role of BV in spontaneous abortion will allow establishment of interventions to decrease the fetal loss associated with second trimester spontaneous abortion. This STD CRC proposal integrates clinical, epidemiological, behavioral and fundamental research into a collaborative effort by investigators from Ob/Gyn, Medicine, Infectious Diseases, Microbiology, Molecular Biology, Immunology, Behavioral Sciences and Epidemiology that addresses the disproportionate burden of the STD epidemic that affects women.

Alcohol Use Disorders and STDs among Youth
K23AA00303 (September 28, 1999 – August 31, 2003)
PI: Cook

The overarching goal of this proposal is to provide support for the career development activities that will enable the candidate to become an independent investigator in the field of alcohol research, particularly in the area of detection and prevention of alcohol problems and their intersection with infectious diseases. Whereas alcohol problems and infectious diseases represent significant health problems for adolescents and young adults, a majority of youth do not receive recommended assessment and prevention services for these health issues. The specific aims of the research proposal are 1) to identify the extent to which alcohol use behaviors and alcohol use disorders (AUD) are associated with acquisition of Infectious diseases; 2) to determine the extent to which alcohol use behavior and AUD interferes with timely utilization of diagnostic and treatment services for infectious diseases; and 3) to determine the effect of alcohol use behavior and AUD on utilization of health services. These issues will be examined through a cross-sectional study of 488 adolescents and young adults (age 15-24) who will be tested for infectious diseases, and will complete a detailed assessment of alcohol consumption behaviors, demographics, and health care utilization patterns. The findings will identify barriers to the timely receipt of assessment, prevention and treatment services for alcohol problems, and will provide targets for future interventions to improve delivery of these health services. The proposal also includes a career development plan to obtain additional knowledge, skills and experience in assessment and diagnosis of alcohol problems, an understanding of client characteristics that affect health service utilization, and health system organization characteristics that influence delivery of health services. The career development plan and supervised research experience will provide the candidate with the training necessary to become an independent clinical investigator in the area of alcohol research and infectious diseases within the health services delivery system.

Microbicidal Lactobacilli for Prevention of Genital Infections
U01AI47785 (September 1, 2002 – August 31, 2003)
PI: Hillier, Co-I: Cook

Lactobacilli function as microbicides in the human vagina through production of H2O2, acids and other products which inhibit the survival and/or growth of genital pathogens. The goal of the proposed project is to evaluate the efficacy of a Lactobacillus capsule in colonizing the vagina and decreasing acquisition of bacterial vaginosis. A vaginal capsule containing Lactobacillus crispatus has been developed and shown to colonize women during a phase II study. The proposed study is a double-blind, placebo-controlled trial of a Lactobacillus crispatus capsule in women attending an Adolescent Medicine Clinic (n=200), the Allegheny Country Health Department (n=250) or the University of Pittsburgh Student Health Clinic (n=250). Women will be followed at 3 month intervals for 1 year. The presence of genital tract injection and vaginal lactobacilli will be determined at baseline and each follow-up visit. The hypothesis is that monthly use of exogenous lactobacilli intravaginally will decrease acquisition of bacterial vaginosis. The specific aims are 1) to assess the relationship between genital infection and lack of lactobacilli in a population of women of reproductive age; 2) to assess the effect of the Lactobacillus capsule on the vaginal ecosystem (vaginal pH, lactobacilli, other microorganisms); 3) to determine whether women randomized to receive the Lactobacillus capsule have decreased acquisition of bacterial vaginosis compared to placebo-treated women after accounting for potentially confounding behaviors; 4) to evaluate thje effect of the Lactobacillus capsule on acquisition of other injections including chlamydia, trichomoniasis, vulvovaginal candidiasis, urinary tract infections and pelvic inflammatory disease; 5) assess the immunologic response to Lactobacillus crispatus among women assigned to the microbiologic factors associated with loss or acquisition of H2O2-producing and H2O2-negative lactobacilli. This project will yield new information on lactobacilli as endogenous microbicides and suggest new strategies for prevention of STD’s and their sequelae.

Sexually transmitted diseases among young women seeking HIV testing in Rio de Janeiro
University of Pittsburgh Center for Latin American Studies (2002 – 2003)
PI: Cook

This study involved an international collaboration between HIV researchers in the US and Brazil.  The study sought to determine the prevalence of chlamydia, gonorrhea, syphilis, and HIV among persons seeking an HIV test in a public HIV clinic in Rio de Janeiro.  We also sought to identify risk factors associated with the prevalence of STDs and HIV.

Chlamydia Screening in Gay and Bisexual Men
Roche Diagnostics (1998 – 1999)
PI: Cook

The purpose of the study was to determine the prevalence of chlamydial and gonoccal infections from urethral, anal, and oral samples obtained from participants in the Multicenter AIDS Cohort study.  The goal of the research was to help establish guidelines for screening in men who have sex with men.