Post-immunotherapy CTLA-4 Ig treatment improves antitumor efficacy.

Immune checkpoint therapies (ICT) improve overall survival of patients with cancer but may cause immune-related adverse events (irAEs) such as myocarditis. Cytotoxic T lymphocyte-associated antigen 4 immunoglobulin fusion protein (CTLA-4 Ig), an inhibitor of T cell costimulation through CD28, reverses irAEs in animal models. However, concerns exist about potentially compromising antitumor response of ICT. In mouse tumor models, we administered CTLA-4 Ig 1) concomitantly with ICT or 2) after ICT completion. Concomitant treatment reduced antitumor efficacy, while post-ICT administration improved efficacy without affecting frequency and function of CD8 T cells. The improved response was independent of the ICT used, whether CTLA-4 or PD-1 blockade. The frequency of Tregs was significantly decreased with CTLA-4 Ig. The resulting increased CD8/Treg ratio potentially underlies the enhanced efficacy of ICT followed by CTLA-4 Ig. This paradoxical mechanism shows that a CTLA-4 Ig regimen shown to reduce irAE severity does not compromise antitumor efficacy.

Coverage of HIV pre-exposure prophylaxis (PrEP) within the active duty U.S. military, 2023.

Estimates of HIV pre-exposure prophylaxis (PrEP) coverage in the U.S. military, defined as the proportion of the persons taking HIV PrEP out of the estimated number of persons who had indications for it, have never been published. The objective of this study was to provide an estimate of HIV PrEP coverage comparable to U.S. civilian estimates. The population with indications for HIV PrEP was obtained from the Department of Defense 2018 Health Related Behaviors Survey, a stratified random sample of members of all military service branches. The military PrEP coverage estimate of 31.6% in 2023 was lower than the national U.S. estimate of 36.0% in 2022. Among the military population of men who have sex with men (MSM), an estimated 24.6% of service members had indications for PrEP, similar to the national estimate of 24.7%. MSM comprised 66% of all military service members with HIV PrEP indications, compared to 40% in the U.S. general population. The U.S. military should continue deliberate, sustained, and effective actions to address sexual health inequities among MSM, aligned and coordinated with societal efforts including improved coverage of HIV PrEP to prevent HIV transmission.

Tobacco and nicotine use among active component U.S. military service members: a comparison of 2018 estimates from the Health Related Behaviors Survey and the Periodic Health Assessment.

This study compared estimates of the prevalence of and risk factors for tobacco and nicotine use obtained from the 2018 Health Related Behaviors Survey (HRBS) and Periodic Health Assessment (PHA) survey. The HRBS and the PHA are important Department of Defense sources of data on health behavior collected from U.S. military service members. While their collection methods differ, some survey questions are similar, which provides an opportunity to compare survey estimates. Active duty service members consistently reported a much lower prevalence of all types of tobacco and nicotine use on the PHA compared to the HRBS: cigarettes (11.1% vs. 18.4%), e-cigarettes (7.3% vs. 16.2%), chewing tobacco (9.7% vs. 13.4%), any tobacco or nicotine use (25.3% vs. 37.8%), and use of 2 or more tobacco or nicotine products (5.8% vs. 17.4%). Associations between tobacco and nicotine use as well as demographic and other behavioral variables were fairly similar, including age, sex, education, race and ethnicity, rank, and alcohol use. The associations with service branch, body mass index, and sleep were inconsistent. This results of this study suggest that the PHA can provide timely information on trends in military tobacco and nicotine use over time, but much higher estimates from the confidential, voluntary HRBS reported in this study suggest that the command-directed PHA may substantially underestimate the prevalence of all types of tobacco and nicotine use.

The Relationship Between Physical Activity Profiles and Cardiovascular Disease Risk Factors: Results of a Cross-Sectional Survey of Active Duty U.S. Service Members.

INTRODUCTION: This study aimed to identify subgroups of active duty U.S. service members (ADSMs) based on physical activity levels and their association with cardiovascular disease (CVD) risk factors. Our secondary aim was to assess how these profiles vary across sociodemographic factors. METHODS: A cross-sectional survey of ADSMs, yielding a 9.6% response rate and 17,166 usable surveys, was conducted by the DoD and RAND Corporation in 2018 using stratified random sampling. In this secondary analysis, latent subgroups of ADSMs were determined based on physical activity levels and a weighted multinomial logistic regression was used to examine associations. RESULTS: Three latent subgroups were identified as "High Activity" (17.1%), "Moderate Activity" (45.3%), and "Low Active" (37.6%). Older age, female, White (as compared to Hispanic), cohabiting, Air Force, Navy, and Coast Guard were associated with increased odds of "Low Active" membership. Compared to the "Low Active" class, the "High Active" class showed lower odds of hyperlipidemia (aOR = 0.62, 95% CI: 0.38, 0.99), hypertension (aOR = 0.69, 95% CI: 0.48, 0.98), and multimorbidity (aOR = 0.55, 95% CI: 0.38, 0.80). Compared to the "Low Active" class, the "Moderate Active" class showed lower odds of hyperlipidemia (aOR = 0.62, 95% CI: 0.47, 0.81) and multimorbidity (aOR = 0.66, 95% CI: 0.53, 0.83). Similar patterns of associations were seen in ADSMs who met the objectives for Healthy People 2030 (HP2030) standards. CONCLUSIONS: The study emphasizes the importance of combining physical activity and strength training to reduce CVD risk factors, supporting the implementation of tailored physical activity programs within the military to align fitness standards.

Smoking and multiple sclerosis risk in black people: A nested case-control study.

BACKGROUND: Smoking is a well-established risk factor for MS; however, it is not known whether its effect on disease risk varies by race/ethnicity. METHODS: We conducted a nested case-control study among US military personnel who have serum samples stored at the Department of Defense Serum Repository. We measured serum cotinine levels, a marker of tobacco smoke exposure, in 157 Black and 23 White individuals who developed MS during follow-up. Controls were randomly selected and matched to each case by age, sex, race/ethnicity, dates of sample collection, and branch of military service. RESULTS: Smoking was not associated with an increased risk of MS in Black people (RR: 1.08, 95 % CI: 0.63-1.85). The results remained similar in analyses restricted to smoking status at baseline, to samples collected 5 years before symptom onset, and using different cut-off levels in cotinine to define smoking status. Smoking was not statistically significantly associated with MS risk in White people, but the point estimate was similar to what has previously been reported in other studies (RR: 1.85, 95 % CI: 0.56-6.16). CONCLUSIONS: Smoking was not associated with MS risk in Black people. Given the consistent association between smoking and MS risk in predominantly White populations, this may suggest that the association between smoking and MS varies by race/ethnicity.

Serologic Response to the Epstein-Barr Virus Peptidome and the Risk for Multiple Sclerosis.

Importance: It remains unclear why only a small proportion of individuals infected with the Epstein-Barr virus (EBV) develop multiple sclerosis (MS) and what the underlying mechanisms are. Objective: To assess the serologic response to all EBV peptides before the first symptoms of MS occur, determine whether the disease is associated with a distinct immune response to EBV, and evaluate whether specific EBV epitopes drive this response. Design, Setting, and Participants: In this prospective, nested case-control study, individuals were selected among US military personnel with serum samples stored in the US Department of Defense Serum Repository. Individuals with MS had serum collected at a median 1 year before onset (reported to the military in 2000-2011) and were matched to controls for age, sex, race and ethnicity, blood collection, and military branch. No individuals were excluded. The data were analyzed between September 1, 2022, and August 31, 2023. Exposure: Antibodies (enrichment z scores) to the human virome measured using VirScan (phage-displayed immunoprecipitation and sequencing). Main Outcome and Measure: Rate ratios (RRs) for MS for antibodies to 2263 EBV peptides (the EBV peptidome) were estimated using conditional logistic regression, adjusting for total anti-EBV nuclear antigen 1 (EBNA-1) antibodies, which have consistently been associated with a higher MS risk. The role of antibodies against other viral peptides was also explored. Results: A total of 30 individuals with MS were matched with 30 controls. Mean (SD) age at sample collection was 27.8 (6.5) years; 46 of 60 participants (76.7%) were male. The antibody response to the EBV peptidome was stronger in individuals with MS, but without a discernible pattern. The antibody responses to 66 EBV peptides, the majority mapping to EBNA antigens, were significantly higher in preonset sera from individuals with MS (RR of highest vs lowest tertile of antibody enrichment, 33.4; 95% CI, 2.5-448.4; P for trend = .008). Higher total anti-EBNA-1 antibodies were also associated with an elevated MS risk (top vs bottom tertile: RR, 27.6; 95% CI, 2.3-327.6; P for trend = .008). After adjusting for total anti-EBNA-1 antibodies, risk estimates from most EBV peptides analyses were attenuated, with 4 remaining significantly associated with MS, the strongest within EBNA-6/EBNA-3C, while the association between total anti-EBNA-1 antibodies and MS persisted. Conclusion and Relevance: These findings suggest that antibody response to EBNA-1 may be the strongest serologic risk factor for MS. No single EBV peptide stood out as being selectively targeted in individuals with MS but not controls. Larger investigations are needed to explore possible heterogeneity of anti-EBV humoral immunity in MS.

Perceived Health Status and Medical Conditions Among US Active-Duty Service Members.

Purpose: This paper investigates the association between self-reported perceived health status and doctor-informed medical conditions among US active duty service members (ADSM). Methods: Data are from the 2018 Health-Related Behaviors Survey - a cross-sectional survey weighted to represent the US military (N = 17166). Perceived good health status was defined as having a response choice of "good", "very good", or "excellent" to the question: Would you say your overall physical health is ___? Medical conditions were based on self-reported presence of nine clinical conditions. Analysis included weighted prevalence and log-binomial regression models to explore relationships between ADSM characteristics with perceived good health status as well as concordance between perceived status and medical conditions. Results: ADSM rated their health to be excellent (14.6%), very good (37.7%), good (36.2%), fair (9.7%) and poor (1.7%). About 88.5% perceived a good (to excellent) health status. Perceived good health status was negatively associated with the number of medical conditions present (adjusted odds ratio (aOR): ranging from 0.78 to 0.92) as well as several health behaviors (aOR): ranging from 0.86 to 0.98) and other sociodemographic factors. Among all ADSMs, 51% perceived good health in the absence of medical conditions, while 8% perceived poor health status in the presence of medical conditions. Concordance between perceived health status and medical conditions was significantly lower among ADSM who were older (aOR: 0.61; 95% CI: 0.54-0.69), with dependent children (aOR: 0.89; 95% CI: 0.84-0.95), or had been deployed (aOR: 0.89, 95% CI: 0.84-0.95). Conclusion: The prevalence of perceived good health status among ADSMs was consistent with those documented in the general US population. The interrelationships between ADSM's perceptions, medical conditions and sociodemographic characteristics may have implications for their health literacy and utilization of health services. Study findings suggest that interventions promoting healthy behaviors, health literacy and treatment-seeking may influence perceived health status and mitigate medical conditions among ADSM, thus improving the US Military readiness, resilience and mission success.