Attachment 1 - Protocols and Objectives.docx

Attachment 1 – Protocols and Objectives

PROTOCOL #1 - IDCRP-000 NHS. A Retrospective and Prospective Observational Study of the Natural History of HIV Infection in Active-Duty U.S. Military Personnel and Department of Defense Beneficiaries, RV168. This study continues a long-term HIV Natural History study of U.S. Military and DoD beneficiaries that began in 1986. It is a longitudinal epidemiological, observational, open cohort study collecting retrospective and prospective data in the U.S. Military active duty and Department of Defense (DoD) health care beneficiary HIV infected population. Study subjects in this protocol are followed with study visits every six months after enrollment. The study staff collect data from written and electronic medical records. Data is also electronically captured from database sources. Samples of blood are obtained at each visit, fractionated, and stored at the U.S Military Natural History Study Repository (NHSR) for future HIV research. The study includes mechanisms for retrieval of data and samples by qualified investigators for future research.

Protocol 1 Actions:

1. Complete 100% of the enrollment and follow-up targets with approximately 1300 yearly data and specimen collections.

2. Execute queries, CHCS and MDR data extraction, cleaning, and processing to support these subject-level data and specimen collections.

3. Ongoing data analysis and review of findings.

4. Complete data analysis and submit manuscripts.

5. Prepare and gain approval for an HIV repository protocol to consolidate completed protocols and substudies.

6. Establish overlap cohort collaborative (existing data) protocol with VACS and complete analysis and submit abstracts and manuscripts.

PROTOCOL #2 - IDCRP-078 ALLHANDS. Evaluation of HIV-associated Neurocognitive Disorders (HAND) Among Military HIV-infected Subjects. This protocol is conducted in conjunction with a parallel NIH protocol (NIH Protocol Number: 13-N-0149, “Screening and Recruitment for HIV-associated Neurocognitive Disorders (HAND) Studies and An Evaluation of HIV-associated Neurocognitive Disorders in Virologically Controlled Patients with CD4 Nadir of < 200 cells/mm3”), upon which it is based, however, the military population and setting offer unique differences that can be leveraged to better understand HAND. ALLHANDS is an observational study (n=250) that characterizes longitudinal neurocognitive function among military HIV infected individuals (n=200) including the natural course of HAND and compares them to an HIV uninfected control group (n=50). A repository of cryopreserved biological samples is under development to be used for validation of candidate biomarkers in future studies. Collection and analysis of these data will not only enhance understanding of the central nervous system (CNS) as a potential HIV reservoir in virally controlled individuals, but will further define the associations among CNS imaging, biomarkers, and neurocognitive function in an aging HIV-infected population.

Protocol 2 Actions:

1. Complete 100% of approximately 250 visits.

2. Execute queries, CHCS and MDR data extraction, cleaning, and processing to support these subject-level data and specimen collections.

3. Ongoing data analysis and review of findings.

4. Complete data analysis and submit manuscripts.

PROTOCOL #3 - IDCRP-091. A Cohort Study of Clinical Outcomes among Military HIV+ Beneficiaries and Stratified HIV- Controls (VCS). This study compliments the HIV Natural History study by providing a similar (de-identified) population with matched HIV negative controls; it seeks to assess the development of non-AIDS comorbidities among active-duty military members and Department of Defense (DoD) beneficiaries infected with HIV, as compared to a similar cohort of uninfected individuals, in order to better understand the association between HIV and the increased burden of these illnesses. Specifically, we will test the hypothesis that HIV is associated with an increased prevalence and incidence of: 1) the number of non-AIDS co-morbidities in aggregate (1st, 2nd, 3rd, etc. with those listed as primary outcomes taken together), which will occur at an earlier age among HIV+; and 2) some specific individual comorbidities among the primary endpoints. Data and specimens from the HIV Natural History Study are analyzed under the auspices of a number of analysis ‘sub-study’ protocols. These regulatory vehicles enable non-human subjects research collaborations with extramural researchers. Likewise, NHS-related analyses incorporating data and/or specimens from extramural collaborators are also employed to simplify the regulatory process.

Protocol 3 Actions:

1. Ongoing data analysis and review of findings.

2. Extract and process additional case and control cohort data.

3. Estimate up to 130,000 de-identified individuals’ records, hundreds of data fields / record.

4. Estimate 10-20 discrete analyses.

5. Complete data analysis and submit manuscripts.

PROTOCOL #4 - IDCRP Concept (C0176). Leptospirosis risk associated with jungle warfare/operations training. Leptospirosis is a worldwide bacterial zoonotic disease that affects humans and one of the most common life-threatening tropical infectious diseases in returning Western travelers. Military population, especially those involved in jungle operations, are considered high-risk for leptospirosis exposure and infection. Outbreaks among military training populations, particularly in jungle operations settings, have been as high as 20-35%. This 2-year observational cohort study will estimate the incidence, clinical and mission impact of leptospirosis during US military jungle wartime/operations training (JWT) at the two primary training locations (Okinawa for USMC and Schofield Barracks, HI for USA). USMC and USA trainee and instructor staff cohort study, at DoD's lead Jungle Warfare Training Centers in Okinawa and Hawaii, to define disease burden (asymptomatic seroconversion and symptomatic leptospirosis rates) and operational impact. Mitigation approaches, including antibiotic prophylaxis, will be evaluated for risk assessment coupled with environmental factors to inform DoD Clinical Practice Guidelines (CPG). Emergent antimicrobial resistance which may impact prevention strategy will be evaluated through environmental (soil and water sampling) leptospire isolates. In addition to generating evidence for prevention of Leptospirosis in JWTC training CPG, knowledge gaps will be identified for future studies in disease modeling and prevention trials.

Protocol 4 Actions:

1. Develop and secure approval of study protocol.

2. Enroll approximately 1100 ACSM at 2 locations.

3. Collect blood specimens at 3 time points, collect data from subjects at 3 visits.

4. Abstract data from MHS Data Repository.

5. Staffing at 2 OCONUS study sites.

6. Travel for study team.

7. Ongoing data analysis and submission of manuscripts, technical reports; estimate 5 – 10 discrete analytic products.

PROTOCOL #5 - IDCRP-037 (TravMil). Deployment and Travel Related Infectious Disease Risk Assessment, Outcomes, and Prevention Strategies among Department of Defense Beneficiaries. Military deployment infection threat assessment and mitigation: IDCRP has supported long-standing prospective research assessing military travel infection risks and outcomes which has included well-characterized clinical data and specimens for over a decade. The rich repository has supported several analyses and publications informing Force Health Protection. Ongoing analyses, as well as continued opportunities for deployment-related targeted surveillance require sustainable resources.

Protocol 5 Actions:

1. Ongoing data analysis and review of findings.

2. Assemble and analyze datasets from multiple prior studies with hundreds of data elements.

3. Complete data analysis and submit manuscripts; estimate 10 – 20 discrete analysis products.

4. Develop surveys and protocol documents in support of follow-on studies in development MARSID and MILOPSID.

5. IRB approval for MARSID and MILOPSID.

6. Site setup and activation for MARSID and MILOPSID.

PROTOCOL #6 - IDCRP-079. Clinical Illness and Immunologic responses in Natural and Experimental Campylobacter jejuni Infection. This study analyzes prior experimental and field studies (natural infection) of campylobacteriosis, a priority infection threat for deployed military service members, to expand understanding of C. jejuni clinical illness spectrum utilizing scoring algorithms in relation to infectious dose, strain exposure, gut microbiome, and host immunity in support of mitigation approaches. Comparative analyses will utilize the well-characterized controlled human infection (CHIM) model data to extrapolate to field conditions thereby supporting application of advanced laboratory analyses such as gut microbiome findings and immune proteomic data. These results will support DoD efforts to develop prevention approaches for deployed personnel.

Protocol 6 Actions:

1. Ongoing data analysis and review of findings.

2. Assemble and analyze datasets from multiple prior studies with hundreds of data elements.

3. Complete data analysis and submit manuscripts; estimate 10 – 20 discrete analysis products.