Disclaimer

U.S. Military HIV Natural History Study Cohort

Contact details:

Brian K. Agan, MD
301 295-0597
bagan@idcrp.org
fax: 301 295-1812
USU/IDCRP, Bldg 28, Room 201
4301 Jones Bridge Road
Bethesda, MD 20814 USA

Cohort description:

The U.S. Military (DoD) HIV Natural History Study (NHS) has enrolled over 5000 beneficiaries into an ongoing, continuous enrollment, prospective multicenter observational study cohort since 1986 with some Service-specific participants since 1984. The study is conducted through the Uniformed Services University of the Health Sciences (USU) Infectious Disease Clinical Research Program (IDCRP) at seven Military Treatment Facilities (MTF) throughout the United States with the objective of producing a data and tissue repository that can be used for future HIV-related studies. Funding is provided through the National Institute of Allergy and Infectious Diseases (NIAID). To date, over 300 peer-reviewed publications have been produced as a direct result of this study.

Participants are routinely evaluated every six months using standardized physician and coordinator interviews and questionnaires to obtain information regarding demographics, medical history including detailed HIV-related information and coinfections, medications, adherence, immunizations, quality of life, depression, hospitalizations, and other health-related data. The study protocol has been reviewed and approved by a central and by site institutional review boards and all participants provide voluntary informed consent.

Blood is drawn at each study visit for routine laboratory evaluation including CD4, HIV viral load, chemistry, hematology, and serology testing, and urinalysis is performed. Aliquots of PBMC, serum, and plasma are stored in a tissue repository for future use including genetic studies. Due to the military environment, HIV risk factors have not been directly captured, but previous anonymous studies have demonstrated that intravenous drug use is rare, accounting for <3% of HIV cases. HAART use is prevalent with over 80% of those seen in the past year having ever been on treatment.

Also called the Tri-Service AIDS Clinical Consortium (TACC) NHS cohort, this study population possesses unique strengths. Since 1985 applicants for U.S. military service have been tested for HIV. Following enlistment, military members are screened for HIV every one to five years and positive tests are repeated and confirmed. As a result, over 55% of the cohort has a documented negative followed by a documented positive HIV test (i.e. documented seroconversion) and since 1995 over 90% of subjects have documented seroconversion with a median seroconversion window of 16 months.

As military beneficiaries, all study subjects have open access to the military healthcare system including regular clinical follow-up and free medications. Those on active duty (87% at HIV+ date) have at least a high school level of education and relatively stable socioeconomic environment. Due to the drug testing program for active duty members, substance abuse is uncommon. The DoD HIV Natural History Study cohort is racially/ethnically diverse with approximately 45% African American, 44% European American, 8% Hispanic, and 3% Other by self report.

In addition to study visit-related data sources, the single-payer nature of the DoD healthcare system allows direct capture and collection of clinical and administrative data from databases including laboratory, pharmacy, clinic and hospital discharge, personnel, and health surveillance. Death information is actively sought using health clinic contacts as well as through routine searching of multiple administrative databases including NDI+, SSDI, VA, and others.

Collaborations are welcomed and more information is available. Please contact the principal investigator, Brian Agan, MD at 301-295-0597 or bagan@idcrp.org.

Cohort Enrollment Dates:
1984-present (continuous enrollment)

Address:

Attn: Brian Agan
USU/IDCRP, Bldg 28, Room 201
4301 Jones Bridge Road
Bethesda, MD 20814 USA

Data Collection:

Research Interests:

The U.S. Military HIV NHS cohort is open to and encourages new collaborations. The IDCRP HIV Working Group has an active research portfolio with several areas of focus currently including:

1. HAART (outcomes, complications, adherence)
2. HIV/STI epidemiology (and prevention)
3. HIV outcomes
4. Serious AIDS and non-AIDS events including cancer and renal disease
5. Host genetics
6. Neurocognitive effects of HIV infection and mitigation/early predictors of these
7. Vaccine effectiveness, response, genetics, and management strategies
8. Co-infections

Types of Data collected:

• Demographic
  • Including military service and non-subtype B screening
• Medical (prospective and retrospective)
  • Medical history including all hospitalizations and OI occurrences
    • Diagnoses are captured and verified through a variety of means including patient report, clinician notes, pathology, laboratory, radiology, etc.
  • Smoking, alcohol use
  • Circumcision status
  • Medications with start/stop dates
    • Information regarding all medications prescribed to subjects is directly captured from DoD systems and confirmed through coordinator interview. The DoD is a single healthcare payer system, so data are quite complete.
    • Medication adherence is assessed both by questionnaire and by use of administrative pharmacy database surrogates (medication possession)
  • Vital signs, Ht, Wt
  • Laboratory including CD4, VL, Chemistry, CBC, LFT, STI scrn, Serologies, UA
    • Laboratory data are extensive and have been collected serially since the beginning of the study. Direct electronic data capture from clinical databases in this single payer healthcare system results in high quality, very complete datasets. Repository specimens can be used to fill missing data points or for tests that were not routinely conducted.
  • Family medical history
  • Quality of life (36 Item Health Survey)
  • CES-D (Depression Scale)
  • Repository specimens (cells, plasma, serum)
  • Data generated through substudies are returned to the NHS database for use in future studies

Data collection interval:

Participants are seen biannually for full visits including laboratory testing and repository specimen collection. Interim laboratory and clinical data are captured both retrospectively via chart review/interviews and also through electronic means. New laboratory data generated from substudies are returned to the database at least annually.

Data collection methodology:

Physician and Coordinator in-person interviews; Medical record review; Participant questionnaires; Electronic data capture from military health systems

Data Quality:

Data are checked and validated during collection, entry, processing, and post-hoc. Additionally routine monitoring is conducted both to check CRFs against source documents as well as to foster standardization. A QA/QC program is also used to document data quality. Direct capture of data from electronic sources provides opportunity for validation of manual entry processes and also provides very complete historical datasets as this is a single payer system with high utilization.

Population Characteristics:

Inclusion criteria:

≥18 y/o, U.S. Military beneficiary (eligible for care in DoD MTF), HIV infected, Willing and able to provide informed consent.

Number of patients enrolled to date:

5042 total, 2875 documented seroconverters, 2167 seroprevalent, 1620 deceased, 1493 active

Gender: 4577 male, 464 female

Race/Ethnicity: 2190 (43.5%) Caucasian, 2243 (44.5%) African American, 420 (8.3%) Hispanic, 184 (3.7%) Other

Mean age at enrollment: 31.7 years

Other Information:

Principal investigator:

Brian Agan, MD; Uniformed Services University of the Health Sciences, Bethesda, MD

Primary collaborators:

• CDR Braden Hale, MD and Nancy Crum-Cianflone, MD, MPH (NMCSD)
• LCDR Timothy Whitman, MD and Anuradha Ganesan, MD, MPH (NNMC)
• COL Glenn Wortmann, MD and Amy Weintrob, MD (WRAMC)
• LCDR Vincent Barthel, MD (NMCP)
• Maj Vincent Marconi, MD and Michael Landrum, MD (BAMC/WHMC)
• LTC Tomas Ferguson, MD (TAMC)
• Alan Lifson, MD, MPH; Lynn Eberly, PhD; Kathy Huppler Hullsiek, PhD; Greg Grandits, MS (University of Minnesota)
• COL Nelson Michael, MD, PhD (WRAIR)

Participating organisations:

• Uniformed Services University of the Health Sciences (Management, Regulatory Oversight)
• Walter Reed Army Institute of Research (WRAIR) (Data Management, Laboratory Testing, Specimen Repository)
• University of Minnesota (Data Analysis Center)
• NIAID Regulatory Compliance and Human Subjects Protection Branch (Monitoring)
• Henry M. Jackson Foundation for the Advancement of Military Medicine (Support)

Study Sites:

• Brooke Army Medical Center (BAMC), San Antonio, TX
• National Naval Medical Center (NNMC), Bethesda, MD
• Naval Medical Center Portsmouth (NMCP), Portsmouth, VA
• Naval Medical Center San Diego (NMCSD), San Diego, CA
• Tripler Army Medical Center (TAMC), Honolulu, HI
• Walter Reed Army Medical Center (WRAMC), Washington, DC
• Wilford Hall U.S. Air Force Medical Center (WHMC), San Antonio, TX

Funding sources:

Support is provided by the Infectious Disease Clinical Research Program (IDCRP) of the Uniformed Services University of the Health Sciences (USUHS). The IDCRP is a DoD tri-service program executed through USUHS and the Henry M. Jackson Foundation for the Advancement of Military Medicine (HJF), in collaboration with HHS/NIH/NIAID/DCR through Interagency Agreement HU0001-05-2-0011.

Recent Publications:

Crum-Cianflone N. Hullsiek KH. Marconi V. Weintrob A. Ganesan A. Barthel RV. Fraser S. Agan BK. Wegner S. Trends in the incidence of cancers among HIV-infected persons and the impact of antiretroviral therapy: a 20-year cohort study. AIDS 23(1):41-50, 2009 Jan 2.

Kulkarni H, Marconi VC, Agan BK, McArthur C, Crawford G, Clark RA, Dolan MJ, Ahuja SK. Role of CCL3L1-CCR5 Genotypes in the Epidemic Spread of HIV-1 and Evaluation of Vaccine Efficacy. PLoS ONE 3(11): e3671. 7 Nov 2008.

Weintrob AC. Fieberg AM. Agan BK. Ganesan A. Crum-Cianflone NF. Marconi VC. Roediger M. Fraser SL. Wegner SA. Wortmann GW. Increasing Age at HIV Seroconversion From 18 to 40 years is associated with favorable virologic and immunologic responses to HAART. Journal of Acquired Immune Deficiency Syndromes: JAIDS 49(1):40-7, 2008 Sep 1.