Early diagnosis and rapid viral suppression have been accomplished for active-duty service members (ADSM) with HIV within the Military Health System (MHS). Nevertheless, the development of non-AIDS complications (e.g., neurocognitive impairment) remains a challenge. As rates of sexually-transmitted infections (STIs) are high among ADSM, further assessment of effective countermeasures are needed.
With the goal to eliminate the occurrence and prevent adverse effects of STIs among ADSMs and MHS beneficiaries, the HIV/STI Research Area conducts research to characterize high-priority STIs, support development of STI biomedical countermeasures, assess care practice patterns and utilization, and evaluate STI prevention and treatment strategies to inform military policy.
In support of identifying effective STI countermeasures, a Phase II randomized, placebo-controlled, observer-blinded clinical trial of the group B Meningococcal (Bexerso®) Vaccine for Gonococcal Infection (MAGI Trial) is evaluating the effectiveness of the Bexsero® vaccine as a potential prevention strategy against Neisseria gonorrhoeae (gonococcus, GC) in high-risk populations. Led in the DoD by COL Eric Garges, this trial, sponsored by the National Institute of Allergy and Infectious Diseases (NIAID) Division of Microbiology and Infectious Diseases, is a collaboration including the University of Alabama at Birmingham and GlaxoSmithKline plc, and findings will help to inform clinical practice in the MHS. During 2024, enrollment was completed at Walter Reed National Military Medical Center, two sites in Thailand associated with the U.S. Military HIV Research Program, and the civilian academic sites, and one-year follow-up is targeted for completion in 2025. Collaborative efforts with multiple USU departments to support the pre-clinical evaluation of a combined GC/Chlamydia trachomatis (CT) vaccine also continued.
Led by Dr. Brian Agan with longstanding support from the NIAID Division of Clinical Research, the U.S. Military HIV Natural History Study (NHS) has collected clinical data and blood specimens from >6,500 HIV+ ADSMs and MHS beneficiaries. During 2024, following on from the assessment of cardiovascular disease genetics in collaboration with the University of California San Francisco (UCSF) and Emory University, the association of acquired DNA mutations with risk of cardiovascular disease was assessed (UCSF and Vanderbilt University collaboration). Specimens from HIV NHS are also being used to examine the HIV reservoir. As part of a collaboration with the NIAID Vaccine Research Center, as well as the U.S. Military HIV Research Program, the initial screening of broadly neutralizing antibody responses among HIV NHS participants was completed with comprehensive characterization planned for 2025. Specimens and data were also shared with collaborators at the University of Minnesota (UMN) to validate results of their losartan clinical trial.
Through collaboration with the Department of Veterans Affairs (VA) Veterans Aging Cohort Study, a new study to evaluate quality and costs of DoD and VA HIV healthcare was funded and has been initiated. Furthermore, a new DoD-VA overlap cohort protocol (HIV-PROLONG) has been developed and is undergoing regulatory review. The goal of the retrospective HIV-PROLONG study is to further characterize HIV-associated comorbidities, long-term treatment outcomes, immune responses, co-infections, STIs, healthcare utilization, and quality of healthcare to support HIV cure.
With recent judicial ruling and interim guidance opening a pathway for individuals with well-controlled HIV to potentially join the military, understanding the impact of HIV-associated neurocognitive disorders (HAND) is a priority. Through the ALLHANDS study, led by Dr. Agan, the functional consequences of HAND among people with HIV (PWH), including ADSMs, in high-demand military settings are being assessed. Presently, HAND biotypes are being examined in collaboration with the National Institute of Neurological Disorders and Stroke, National Institute of Mental Health, and five other institutes through the National Institutes of Health.
During 2024, revisions to the GC Resistance Study to expand surveillance efforts and clinical outcome evaluation to include CT and Mycoplasma genitalium was approved. Led by CDR Mark Simons, the revised protocol also includes assessment of antimicrobial resistance (AMR) and the impact of high-priority STIs on operational readiness and patient-reported outcomes. Moreover, the USU GC Reference Laboratory and Repository, led by Dr Ann Jerse (USU) and coordinated by the IDCRP (funded by DoD Global Emerging Infections Surveillance [GEIS] program), continued to examine AMR among surveillance GC isolates received from overseas military sites (e.g., Kenya and Republic of Georgia) and identified resistance levels that warrant ongoing monitoring.
For 2025, a new study will assess the reactogenicity of the recombinant zoster vaccine (RZV, Shingrix®) among PWH <50 years of age. Funded by the Defense Health Agency (DHA) Immunization Healthcare Division, the findings will identify potential vaccine safety concerns and support DoD clinical practice in response to recommendations by the Advisory Committee on Immunization Practices. A new study in collaboration with UMN is also being developed to use HIV NHS specimens to study deficiencies in the hepatitis B vaccine response among PWH.
Military Impact
Initiatives through the HIV/STI Research Area remain responsive to clinical HIV and STI-related research priorities of the DHA, including GEIS, the Tri-Service Infectious Diseases Working Group, and DHA Military Infectious Diseases. With the Virginia judicial decision that individuals with well-treated HIV should be allowed to join the military, information was provided to the Office of the Assistant Secretary of Defense for Health Affairs to inform a re-evaluation of DoD HIV policies. Findings from the MAGI clinical trial of the Bexsero® vaccine to reduce GC risk, as well as the forthcoming evaluation of the RZV vaccine, may also be used to inform military practice. Findings from HIV NHS have addressed DHA research priorities related to ADSM HIV care, treatment, and outcomes, and ALLHANDS findings on the impact and predictors of HAND among ADSMs with HIV may inform military policy. Surveillance and AMR findings from the GC Resistance Study and the GC Repository continue to be provided to GEIS to inform operational planning and COL Garges serves on the GEIS AMR Working Group.