Since 1985, >10,000 active-duty service members have been infected with HIV; however, the number of personnel able to remain on active duty is growing due to earlier diagnosis and successful treatment with antiretroviral therapy. Still, non-AIDS complications, such as neurocognitive impairment, cardiovascular disease, and cancer are becoming more frequent at a younger age, constituting a substantial threat to long-term health. With approximately 350 new active-duty HIV diagnoses yearly, despite ongoing prevention efforts, the lifetime healthcare burden to the Departments of Defense (DoD) and Veterans Affairs (VA) is substantial and growing. The IDCRP HIV Research Area seeks to advance HIV care and treatment to maintain health, function, and readiness.
Following introduction of antiretroviral therapy (ART), viral suppression has vastly improved and, as such, death and AIDS have become rare events within the Military Health System (MHS). Nevertheless, non-AIDS complications, sexually-transmitted infections (STIs), and mental health diagnoses remain a source of morbidity among HIV+ service members and beneficiaries. The overarching vision of the HIV Research Area is to inform military HIV policy and clinical practice guidelines and improve the longterm health, function, and readiness of HIV+ active-duty service members, benefiting not only DoD beneficiaries, but also civilian populations.
The U.S. Military HIV Natural History Study (NHS), led by Dr. Brian Agan (pictured on the left), remains the centerpiece of the HIV Research Area with >6,300 HIV+ active-duty service members and DoD beneficiaries enrolled. During 2019, NHS data were utilized to examine various comorbidities related to HIV infection and ART, including cardiovascular disease, diabetes, eye disease, mental health disorders, and STIs. Analyses found that ART reduced the incidence of eye disease in HIV+ individuals and that disease likely resulted from comorbidities, rather than HIV. Coinfections have also been a research focus, and an elevated incidence of shingles was identified in HIV+ individuals, even those with successful ART. Based on these findings, a randomized controlled trial to evaluate the safety and immunogenicity of the Shingrix® vaccine in HIV-negative and HIV+ populations is being developed.
As active-duty populations are routinely screened for HIV, resulting in early diagnosis and prompt referrals to care when tests are positive, the cascade of care framework (diagnosis, ART adherence, and viral suppression) can be effectively studied in this population. Research into the cascade of care interconnects with the U.S. Health and Human Services plan to end the HIV epidemic in the United States within 10 years. The NHS population has demonstrated a high-level attainment of the three goals with a large proportion reaching their full cascade of care.
Another major protocol is the DoD HIV Virtual Cohort Study (VCS), also led by Dr. Agan, which is a retrospective study of HIV+ subjects matched to a representative sample of HIV-negative individuals to assess the relationship between HIV and the development of serious non-AIDS events and identify potentially modifiable risk factors. Presently, data have been obtained from the MHS Data Repository and analysis is underway.
HIV-associated neurocognitive disorder (HAND) is a serious non-AIDs comorbidity and remains the primary reason why HIV+ service members are assigned limited duty status. Thus, improved diagnostic methods for the disorder may impact military policy and allow active-duty personnel with HIV to expand job functions and increase rank. Through the HIV-Associated Neurocognitive Disorders (ALLHANDS) protocol, the functional consequences of HAND in a high demand setting are being evaluated. Presently, data collection using the NIH Toolbox is underway and expected to provide new insights into prospective HAND screening. As the diagnosis of HAND is unclear and neuropsychiatric testing alone is inadequate, studies to utilize biomarkers to more objectively identify a population with HAND are being developed in collaboration with the National Institute of Neurological Disorders and Stroke and the National Institute of Mental Health.
A randomized controlled trial, led by Dr. Anuradha Ganesan, to evaluate use of rifaximin to modulate chronic immune activation in HIV+ subjects was completed. Although short-term rifaximin use did not alter CD14 levels or T-cell activation, further analysis is needed to determine if ART interfered with the impact of rifaximin on gut bacterial flora. Regarding the Strategic Timing of Anti-Retroviral Therapy (START) protocol, long-term follow-up through review of electronic medical records is underway. Lastly, through the CD4 Zeta protocol, led by COL (Ret.) Naomi Aronson, analysis is underway to examine the HIV reservoir and persistence of the gene therapy modified cells.
IDCRP will continue to study the quality and cost of DoD HIV care among active-duty personnel, emphasizing additional performance measures and evaluating the impact of Service differences in HIV policy on these outcomes. Discussions are also underway to collaborate with the VA to expand understanding of predictors of long-term HIV outcomes, which would enable prospective trials of early interventions to prevent or minimize harm.
Military Impact
The HIV Research Area continues to support the MHS by examining the continuum of HIV care in the DoD and assessing serious outcomes of HIV infection, including HAND. Building on our efforts in 2018 to convene a DoD HIV Quality of Care Interest Group comprised of Service Leaders for HIV and IDCRP investigators, initial analyses to understand the cascade of care among DoD HIV+ active duty and NHS subjects were recently completed. We also provided subject matter expertise to the Defense Health Agency for their development of the active-duty HIV viral suppression measure (now available on CarePoint) in response to the Congressional National Defense Authorization Act of 2017. We are exploring the impact of mild and asymptomatic forms of HAND on functional performance, an outcome of significant interest to military duties. Lastly, our study of STIs among HIV+ subjects and our NHS risk behavior questionnaire continues to generate data that may inform policy to improve prevention efforts, diagnosis, and treatment of these infections.
Highlights and Key Findings
- In a collaborative study with the Military HIV Research Program and National Institute of Allergy and Infectious Diseases, immune reconstitution inflammatory syndrome (IRIS) occurred in 19% of HIV+ individuals who started ART with a CD4 count <100 cells/μL. Within 6 months, 6.5% died and IRIS was significantly associated with an increased risk of death.
- A low incidence of complications (7.6%) was reported following refractive eye surgery in HIV+ patients. In the unadjusted model, AIDS was identified as a risk factor for complications, indicating that ophthalmologists should consider ART status, history of AIDS, and viral load before performing the surgery.
- In a population of active-duty and retired male service members with HIV, 19% were diagnosed with neurocognitive impairment. Assessment of mental health disorders identified lifetime history of posttraumatic stress disorders as an independent predictor of neurocognitive impairment.
Partners and Collaborators
The IDCRP HIV research program is primarily funded by the National Institute of Allergy and Infectious Diseases (NIAID). The program is complementary to other DoD HIV research and surveillance efforts.
- Department of Defense HIV/AIDS Prevention Program
- Division of AIDS (DAIDS), NIAID, NIH
- Henry M. Jackson Foundation for the Advancement of Military Medicine (HJF)
- International Network for Strategic Initatives in Global HIV Trials (INSIGHT)
- National Institute of Allergy and Infectious Diseases (NIAID)
- National Institutes of Health (NIH)
- NIH AIDS Information
- Uniformed Services University of the Health Sciences (USU)
- U.S. Department of Defense Global Emerging Infections Surveillance and Response System (DoD-GEIS)
- Walter Reed Army Institute of Research (WRAIR)