Precision symptom phenotyping identifies early clinical and proteomic predictors of distinct COVID-19 sequelae.

BACKGROUND: Post-COVID conditions (PCC) are difficult to characterize, diagnose, predict, and treat due to overlapping symptoms and poorly understood pathology. Identifying inflammatory profiles may improve clinical prognostication and trial endpoints. METHODS: 1,988 SARS-CoV-2 positive U.S. Military Health System beneficiaries with quantitative post-COVID symptom scores were included in this analysis. Among participants who reported moderate-to-severe symptoms on surveys collected 6-months post-SARS-CoV-2 infection, principal component analysis (PCA) followed by K-means clustering identified distinct clusters of symptoms. RESULTS: Three symptom-based clusters were identified: a sensory cluster (loss of smell and/or taste), a fatigue/difficulty thinking cluster, and a difficulty breathing/exercise intolerance cluster. Individuals within the sensory cluster were all outpatients during their initial COVID-19 presentation. The difficulty breathing cluster had a higher likelihood of obesity and COVID-19 hospitalization compared to those with no/mild symptoms at 6-months post-infection. Multinomial regression linked early post-infection D-dimer and IL-1RA elevation to fatigue/difficulty thinking, and elevated ICAM-1 concentrations to sensory symptoms. CONCLUSIONS: We identified three distinct symptom-based PCC phenotypes with specific clinical risk factors and early post-infection inflammatory predictors. With further validation and characterization, this framework may allow more precise classification of PCC cases and potentially improve the diagnosis, prognostication, and treatment of PCC.

Statin usage and cardiovascular risk among people living with HIV in the U.S. Military HIV Natural History Study.

OBJECTIVES: Using the American College of Cardiology/American Heart Association 2013 atherosclerotic cardiovascular disease (ASCVD) management guidelines, we conducted a retrospective cross-sectional analysis of people living with HIV in the US Military HIV Natural History Study to determine whether individuals were receiving statins when indicated. METHODS: Prescription data was taken from Military Health System data. Statin eligibility was defined by ASCVD guidelines. We used the 10-year ASCVD pooled cohorts' equation to evaluate risk for each participant. RESULTS: Across all categories, 31.9% (n = 390) of individuals met criteria for statin use, and when adding these subjects to the number of those already receiving statins (n = 96), 62.1% of all eligible subjects (n = 302/486) were actually receiving statin therapy. In multivariable analysis, individuals of African American race [odds ratio (OR) = 0.48, 95% confidence interval (CI): 0.31-0.73] or Hispanic ethnicity (OR = 0.42, 95% CI: 0.19-0.94) were less likely to receive statin prescriptions than white individuals. Individuals with a higher CD4 count (OR = 1.12, 95% CI: 1.05-1.20 per 100 cells/µL]) were significantly more likely to receive a statin prescription. CONCLUSIONS: These data highlight discrepancies between ASCVD guidelines and primary care management of people living with HIV (PLWH) in the military health system, along with important racial differences. Targeted interventions are critical to identify and treat appropriate candidates for statin therapy among PLWH in the military and other settings.

Comparison of A(H3N2) Neutralizing Antibody Responses Elicited by 2018-2019 Season Quadrivalent Influenza Vaccines Derived from Eggs, Cells, and Recombinant Hemagglutinin.

BACKGROUND: Low vaccine effectiveness against A(H3N2) influenza in seasons with little antigenic drift has been attributed to substitutions in hemagglutinin (HA) acquired during vaccine virus propagation in eggs. Clinical trials comparing recombinant HA vaccine (rHA) and cell-derived inactivated influenza vaccine (IIV) to egg-derived IIVs provide opportunities to assess how egg-adaptive substitutions influence HA immunogenicity. METHODS: Neutralization titers in pre- and postimmunization sera from 133 adults immunized with 1 of 3 types of influenza vaccines in a randomized, open-label trial during the 2018-2019 influenza season were measured against egg- and cell-derived A/Singapore/INFIMH-16-0019/2016-like and circulating A(H3N2) influenza viruses using HA pseudoviruses. RESULTS: All vaccines elicited neutralizing antibodies to all H3 vaccine antigens, but the rHA vaccine elicited the highest titers and seroconversion rates against all strains tested. Egg- and cell-derived IIVs elicited responses similar to each other. Preimmunization titers against H3 HA pseudoviruses containing egg-adaptive substitutions T160K and L194P were high, but lower against H3 HA pseudoviruses without those substitutions. All vaccines boosted neutralization titers against HA pseudoviruses with egg-adaptive substitutions, but poorly neutralized wild-type 2019-2020 A/Kansas/14/2017 (H3N2) HA pseudoviruses. CONCLUSION: Egg- and cell-derived 2018-2019 season influenza vaccines elicited similar neutralization titers and response rates, indicating that the cell-derived vaccine did not improve immunogenicity against the A(H3N2) viruses. The higher responses after rHA vaccination may be due to its higher HA content. All vaccines boosted titers to HA with egg-adaptive substitutions, suggesting boosting from past antigens or better exposure of HA epitopes. Studies comparing immunogenicity and effectiveness of different influenza vaccines across many seasons are needed.

Association between depression and HIV treatment outcomes in a US military population with HIV infection.

BACKGROUND: Depression is common among HIV-infected individuals and may contribute to suboptimal adherence to antiretroviral therapy (ART) and subsequent inability to attain viral load (VL) suppression. We evaluated associations between depression, self-reported adherence, and longitudinal HIV treatment outcomes in US Military HIV Natural History Study (NHS) participants with and without depression. METHODS: Male NHS participants with available ICD-9 data for mental health diagnoses, Center for Epidemiological Studies Depression (CES-D) measures, and self-reported adherence (SRA) were included. ART use was defined as ART initiation between 2006 and 2010, with follow-up through 2015. SRA was defined as taking 95% of ART doses and continuous ART was defined as longitudinal ART use with gaps < 30 days. Continuous VL suppression was defined as maintaining VLs < 200 c/mL on ART. To analyse the association between depression and HIV treatment outcomes, latent class analysis was used to create classes of depression trajectories: low depression (LD), recent onset depression (ROD) and high Depression (HD). RESULTS: Participants had a mean age of 32 (± 8.3) years at HIV diagnosis, and similar proportions were Caucasian (44.3%) or African American (40.8%). Overall, older participants at HIV diagnosis had greater odds of having 95% self-reported adherence (OR 1.06, 95% CI 1.02-1.12), and African Americans had lower odds (OR 0.41, 95% CI 0.22-0.76) compared to Caucasians (OR 1.49, 95% CI 0.52-4.28). However, there was no difference in SRA by depression trajectory. Participants with HD had an increased odds of taking ART continuously (OR 1.75, 95% CI 0.99-3.09), and those with ROD had significantly higher odds of virologic failure (OR 0.58, 95% CI 0.38-0.91). CONCLUSIONS: Although there was no observed association between depression and SRA, participants with ROD had lower odds of attaining the HIV treatment goal of VL suppression. Continued efforts to identify and aggressively manage mental health disorders is important to success along the HIV care continuum.

Persistent Low-level Viremia While on Antiretroviral Therapy Is an Independent Risk Factor for Virologic Failure.

BACKGROUND: Whether persistent low-level viremia (pLLV) predicts virologic failure (VF) is unclear. We used data from the US Military HIV Natural History Study (NHS), to examine the association of pLLV and VF. METHODS: NHS subjects who initiated combination antiretroviral therapy (ART) after 1996 were included if they had 2 or more VLs measured with a lower limit of detection of ≤50 copies/mL. VF was defined as a confirmed VL ≥200 copies/mL or any VL >1000 copies/mL. Participants were categorized into mutually exclusive virologic categories: intermittent LLV (iLLV) (VL of 50-199 copies/mL on <25% of measurements), pLLV (VL of 50-199 copies/mL on ≥25% of measurements), high-level viremia (hLV) (VL of 200-1000 copies/mL), and continuous suppression (all VL <50 copies/mL). Cox proportional hazards models were used to evaluate the association between VF and LLV; hazard ratios and 95% confidence interval (CI) are presented. RESULTS: Two thousand six subjects (median age 29.2 years, 93% male, 41% black) were included; 383 subjects (19%) experienced VF. After adjusting for demographics, VL, CD4 counts, ART regimen, prior use of mono or dual antiretrovirals, and time to ART start, pLLV (3.46 [2.42-4.93]), and hLV (2.29 [1.78-2.96]) were associated with VF. Other factors associated with VF include black ethnicity (1.33 [1.06-1.68]) and antiretroviral use prior to ART (1.79 [1.34-2.38]). Older age at ART initiation (0.71 [0.61-0.82]) and non-nucleoside reverse transcriptase inhibitor (0.68 [0.51-0.90]) or integrase strand transfer inhibitor use (0.26 [0.13-0.53]) were protective. CONCLUSION: Our data add to the body of evidence that suggests persistent LLV is associated with deleterious virologic consequences.

Herpes Zoster Rates Continue to Decline in People Living With Human Immunodeficiency Virus but Remain Higher Than Rates Reported in the General US Population.

In the antiretroviral therapy era, herpes zoster incidence continued to decline in people living with HIV (PLWH). However, at 0.9 cases/100 person-years, rates in PLWH are substantially higher than the general US population; emphasizing the needs for studies of the subunit vaccine in PLWH.

Development of the Flu-PRO: a patient-reported outcome (PRO) instrument to evaluate symptoms of influenza.

BACKGROUND: To develop content validity of a comprehensive patient-reported outcome (PRO) measure following current best scientific methodology to standardize assessment of influenza (flu) symptoms in clinical research. METHODS: Stage I (Concept Elicitation): 1:1 telephone interviews with influenza-positive adults (≥18 years) in the US and Mexico within 7 days of diagnosis. Participants described symptom type, character, severity, and duration. Content analysis identified themes and developed the draft Flu-PRO instrument. Stage II (Cognitive Interviewing): The Flu-PRO was administered to a unique set of influenza-positive adults within 14 days of diagnosis; telephone interviews addressed completeness, respondent interpretation of items and ease of use. RESULTS: Samples: Stage I: N = 46 adults (16 US, 30 Mexico); mean (SD) age: 38 (19), 39 (14) years; % female: 56%, 73%; race: 69% White, 97% Mestizo. Stage II: N = 34 adults (12 US, 22 Mexico); age: 37 (14), 39 (11) years; % female: 50%, 50%; race: 58% White, 100% Mestizo. SYMPTOMS: Symptoms identified by >50%: coughing, weak or tired, throat symptoms, congestion, headache, weakness, sweating, chills, general discomfort, runny nose, chest (trouble breathing), difficulty sleeping, and body aches or pains. No new content was uncovered during Stage II; participants easily understood the instrument. CONCLUSIONS: Results show the 37-item Flu-PRO is a content valid measure of influenza symptoms in adults with a confirmed diagnosis of influenza. Research is underway to evaluate the suitability of the instrument for children and adolescents. This work can form the basis for future quantitative tests of reliability, validity, and responsiveness to evaluate the measurement properties of Flu-PRO for use in clinical trials and epidemiology studies.

An In Vitro Model of the Blood-Brain Barrier for the Investigation and Isolation of the Key Drivers of Barriergenesis.

The blood-brain barrier (BBB) tightly regulates substance transport between the bloodstream and the brain. Models for the study of the physiological processes affecting the BBB, as well as predicting the permeability of therapeutic substances for neurological and neurovascular pathologies, are highly desirable. Existing models, such as Transwell utilizing-models, do not mimic the extracellular environment of the BBB with their stiff, semipermeable, non-biodegradable membranes. To help overcome this, we engineered electrospun membranes from poly L-lactic acid in combination with a nanometric coating of poly(ethyl acrylate) (PEA) that drives fibrillogenesis of fibronectin, facilitating the synergistic presentation of both growth factors and integrin binding sites. Compared to commercial semi-porous membranes, these membranes significantly improve the expression of BBB-related proteins in brain endothelial cells. PEA-coated membranes in combination with different growth factors and extracellular protein coatings reveal nerve growth factor (NGF) and fibroblast growth factor (FGF-2) caused formation of better barriers in vitro. This BBB model offers a robust platform for studying key biochemical factors influencing barrier formation that marries the simplicity of the Transwell model with the highly tunable electrospun PEA-fibronectin membranes. This enables the generation of high-throughput drug permeability models without the need of complicated co-culture conditions.

Decreased Self-reported Physical Fitness Following SARS-CoV-2 Infection and the Impact of Vaccine Boosters in a Cohort Study.

Background: The long-term effects of coronavirus disease 2019 (COVID-19) on physical fitness are unclear, and the impact of vaccination on that relationship is uncertain. Methods: We compared survey responses in a 1-year study of US military service members with (n = 1923) and without (n = 1591) a history of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection. We fit Poisson regression models to estimate the association between history of SARS-CoV-2 infection and fitness impairment, adjusting for time since infection, demographics, and baseline health. Results: The participants in this analysis were primarily young adults aged 18-39 years (75%), and 71.5% were male. Participants with a history of SARS-CoV-2 infection were more likely to report difficulty exercising (38.7% vs 18.4%; P < .01), difficulty performing daily activities (30.4% vs 12.7%; P < .01), and decreased fitness test (FT) scores (42.7% vs 26.2%; P < .01) than those without a history of infection. SARS-CoV-2-infected participants were at higher risk of these outcomes after adjusting for other factors (unvaccinated: exercising: adjusted risk ratio [aRR], 3.99; 95% CI, 3.36-4.73; activities: aRR, 5.02; 95% CI, 4.09-6.16; FT affected: aRR, 2.55; 95% CI, 2.19-2.98). Among SARS-CoV-2-positive participants, full vaccination before infection was associated with a lower risk of post-COVID-19 fitness impairment (fully vaccinated: exercise: aRR, 0.81; 95% CI, 0.70-0.95; activities: aRR, 0.76; 95% CI, 0.64-0.91; FT: aRR, 0.87; 95% CI, 0.76-1.00; boosted: exercise: aRR, 0.62; 95% CI, 0.51-0.74; activities: aRR, 0.52; 95% CI, 0.41-0.65; FT: aRR, 0.59; 95% CI, 0.49-0.70). Conclusions: In this study of generally young, healthy military service members, SARS-CoV-2 infection was associated with lower self-reported fitness and exercise capacity; vaccination and boosting were associated with lower risk of self-reported fitness loss.

Patients with HIV-associated cancers have evidence of increased T cell dysfunction and exhaustion prior to cancer diagnosis.

BACKGROUND: People living with HIV (PLWH) have increased risk of developing cancers after controlling traditional risk factors and viral suppression. This study explores whether T cells can serve as a marker of risk for cancer among HIV-infected virally suppressed patients. METHODS: A nested case control study design was pursued with 17 cancer cases and 73 controls (PLWH without cancer)ouidentified among the US Military HIV Natural History Study cohort, and were matched for CD4 + count, duration of HIV infection, and viral suppression. Cells were obtained from PLWH on an average of 12 months prior to clinical cancer diagnosis. Expression of inhibitory receptors (PD-1, CD160, CD244, Lag-3, and TIGIT), and transcription factors (T-bet, Eomesodermin, TCF-1, and (TOX) was measured on CD8 +T cells from that early time point. RESULTS: We found that cases have increased expression of PD-1 +CD160+CD244+ ('triple positive') on total and effector CD8 + compared with controls (p=0.02). Furthermore, CD8 +T cells that were both PD-1 +CD160+CD244+ and T-betdimEomeshi were significantly elevated in cases at time point before cancer detection, compared with controls without cancer (p=0.008). This was driven by the finding that transcriptional factor profile of cells was altered in cancers compared with controls. Triple-positive cells were noted to retain the ability for cytotoxicity and cytokine secretion mediated by expression of CD160 and PD-1, respectively. However, triple-positive cells demonstrated high expression of TOX-1, a transcription factor associated with T cell exhaustion. CONCLUSION: In conclusion, we have found a subset of dysfunctional CD8 +T cells, PD-1 +CD160+CD244+T-betdimEomeshi, that is elevated 12 months before cancer diagnosis, suggesting that peripheral T cell alterations may serve as a biomarker of increased cancer risk among PLWH.

Retrospective Review of a Novel Virtual Medical Soldier Readiness Processing Process in Response to the COVID-19 Pandemic.

INTRODUCTION: Medical solider readiness processing (SRP) needed to continue during the COVID-19 pandemic. We developed a rapid practice improvement project to allow for a hybrid virtual medical SRP/in-person medical SRP to decrease exposure risk. A retrospective review comparing this virtual SRP to a historical in-person SRP cohort to the same combatant command was then performed. PROCEDURES: A virtual medical SRP was completed for 204 soldiers in preparation for deployment within 24 hours of receiving the deployment roster. Each soldier had their MEDPROS data sheet printed and reviewed for deficiencies. Soldiers were then divided into two groups. Group 1 required hybrid SRP with need for in-person labs or vaccinations. Group 2 had no deficiencies noted on MEDPROS review, and the entire medical SRP was done virtually. Pre-deployment health assessment (pre-DHA) was completed over the phone for both groups. The provider then determined whether the soldier was a GO or NO GO, and this information was passed to the unit's medical staff. Comparative data analysis was performed using t-tests assuming unequal variances and chi-square tests. INFORMATION FOUND: A total of 204 soldiers were expected to complete the virtual SRP process. Of those 204, 191 MEDPROS records were reviewed (93%). Seventy-seven of the 191 soldiers (40%) required level one labs and immunizations, had not completed their pre-DHA, or had a combination of these factors. One hundred and fourteen soldiers (60%) had these items completed and were given virtual appointments in GENESIS. One hundred and six of the 114 (95%) soldiers were able to complete their medical SRP virtually. Eighty-six soldiers (80%) of this cohort were a GO for deployment at the end of their virtual SRP visit.The novel virtual SRP process was comparable to the historic in-person SRP as evidenced by no statistically significant difference in terms of the number of providers required and the number of soldiers that was seen by any one provider. The groups did show statistically significant differences based on age, gender, and GOs/NO GOs. CONCLUSION: This is the first proof of concept of a virtual medical SRP on literature review. A virtual SRP process that combines a pre-visit record review with a virtual pre-DHA is a viable process for SRP. The ability to utilize providers outside of a confined location or post may allow for optimized utilization of this scarce resource and result in cost savings to the Army. The recreation of this virtual medical SRP within other Army installations may allow for the improvement and standardization of the medical SRP process as a whole.

Risk Factors Associated With Chronic Liver Enzyme Elevation in Persons With HIV Without Hepatitis B or C Coinfection in the Combination Antiretroviral Therapy Era.

BACKGROUND: As morbidity due to viral coinfections declines among HIV-infected persons, changes in liver-related morbidity are anticipated. We examined data from the US Military HIV Natural History Study (NHS), a cohort of military beneficiaries, to evaluate incidence and risk factors associated with chronic liver enzyme elevation (cLEE) in HIV-monoinfected patients in the combination antiretroviral therapy (cART) era. METHODS: Participants who were hepatitis B virus and hepatitis C virus seronegative with follow-up after 1996 were included. We defined chronic liver enzyme elevation (cLEE) as alanine aminotransferase elevations ≥1.25 times the upper limit of normal on at least 2 visits, for a duration of ≥6 months within 2 years. We used multivariate Cox proportional hazards models to examine risk factors for cLEE. RESULTS: Of 2779 participants, 309 (11%) met criteria for cLEE for an incidence of 1.28/100 PYFU (1.28-1.29/100 PYFU). In an adjusted model, cLEE was associated with Hispanic/other ethnicity (reference Caucasian: hazard ratio [HR], 1.744; 95% CI, 1.270-2.395), non-nucleoside reverse transcriptase inhibitor-based cART (reference boosted protease inhibitors: HR, 2.232; 95% CI, 1.378-3.616), being cART naïve (HR, 6.046; 95% CI, 3.686-9.915), or having cART interruptions (HR, 8.671; 95% CI, 4.651-16.164). African American race (HR, 0.669; 95% CI, 0.510-0.877) and integrase strand transfer inhibitor (INSTI)-based cART (HR, 0.222; 95% CI, 0.104-0.474) were protective. CONCLUSIONS: Our findings demonstrate that initiation and continued use of cART are protective against cLEE and support the hypothesis that HIV infection directly impacts the liver. INSTI-based regimens were protective and could be considered in persons with cLEE.

Effects of human immunodeficiency virus status on symptom severity in influenza-like illness in an otherwise healthy adult outpatient cohort.

The impact of HIV on influenza-like illness (ILI) has been incompletely described in the era of combination antiretroviral therapy, particularly in the post-H1N1 pandemic period. This analysis informs on ILI in an otherwise healthy, predominantly outpatient cohort of adults with HIV in the USA. From September 2010 to March 2015, this multisite observational cohort study enrolled otherwise healthy adults presenting to a participating US military medical center with ILI, a subset of whom were HIV positive. Demographics, clinical data, and self-reported symptom severity were ascertained, and enrollees completed a daily symptom diary for up to 10 days. 510 men were included in the analysis; 50 (9.8%) were HIV positive. Subjects with HIV were older and less likely to be on active duty. Rhinovirus and influenza A were the most commonly identified pathogens. Moderate-severe diarrhea (p<0.001) and fatigue (p=0.01) were more frequently reported by HIV-positive men. HIV positivity was associated with higher gastrointestinal scores, but not other measures of ILI symptom severity, after controlling for age, race, military status, and influenza season. Few were hospitalized. HIV-positive subjects had more influenza B (p=0.04) and were more likely to receive antivirals (32% vs 6%, p<0.01). Antiviral use was not significantly associated with symptom scores when accounting for potential confounders. In this predominantly outpatient cohort of adult men, HIV had minimal impact on ILI symptom severity. Despite similar illness severity, a higher percentage of subjects with HIV reported undergoing antiviral treatment for ILI, likely reflecting differences in prescribing practices.Trial registration number: NCT01021098.

Post-artemisinin delayed hemolysis after oral therapy for P. falciparum infection.

A documented side-effect of artemisinin therapy is post-artemisinin delayed hemolysis (PADH), primarily occurring after parenteral treatment for severe P. falciparum infections. PADH has been infrequently reported after oral therapy and is rarely severe enough to require hospitalization and blood transfusions. A 24 year old man was diagnosed with P. falciparum, prompting initiation of oral artemether-lumefantrine (AL). Further work-up demonstrated that he met WHO criteria for severe malaria infection on the basis of high parasitemia and his regimen was switched to intravenous quinidine and oral doxycycline. He was transitioned back to AL after 4 days and was discharged on hospital day six. Five days later, he was readmitted for hemolytic anemia. His peripheral blood was absent of malaria parasites and he was diagnosed with PADH, ultimately requiring multiple blood transfusions. Severe hemolytic anemia requiring blood transfusions after oral artemisinin therapy is rare and may be associated with higher parasite loads. This case demonstrates the importance of close reassessment and consideration of PADH in patients treated with oral therapies, particularly in the setting of severe malarial infections.

Sexual Risk Behaviors Associated with Sexually Transmitted Infections in a US Military Population Living with HIV After the Repeal of "Don't Ask, Don't Tell".

Risk behaviors associated with sexually transmitted infections (STIs) among people living with HIV (PLWH) have not been well characterized in the US military. We identified risk behaviors associated with a new STI in this population after the repeal of "Don't Ask, Don't Tell." US Military HIV Natural History Study participants who completed the risk behavior questionnaire (RBQ) between 2014 and 2017 and had at least 1 year of follow-up were included (n = 1589). Logistic regression identified behaviors associated with incident STI in the year following RBQ completion. Overall, 18.9% acquired an STI and 52.7% reported condom use at last sexual encounter. Compared with those with no new sex partners, participants with between one and four or five or more new partners were 1.71 [1.25-2.35] and 6.12 [3.47-10.79] times more likely to get an STI, respectively. Individuals reporting low or medium/high perceived risk of STI were 1.83 [1.23-2.72] and 2.65 [1.70-4.15] times more likely to acquire a new STI than those reporting no perceived risk, respectively. Participants who preferred not to answer about sexual preference, number of new partners, or perceived STI risk were also more likely to acquire a new STI. Our study illustrates that despite regular access to health care and accurate perceptions of risk, rates of STI among PLWH remain high in the US military setting, as in others. Given the potential individual and public health consequences of STI coinfection after HIV, more work is needed to assess interventions aimed at sexual behavior change for PLWH.

HIV Care Continuum and Meeting 90-90-90 Targets: Cascade of Care Analyses of a U.S. Military Cohort.

INTRODUCTION: The new initiative by the Department of Health and Human Services (DHHS) aims to decrease new HIV infections in the U.S. by 75% within 5 years and 90% within 10 years. Our objective was to evaluate whether the U.S. military provides a good example of the benefits of such policies. MATERIALS AND METHODS: We conducted an analysis of a cohort of 1,405 active duty military personnel with HIV enrolled in the Natural History Study who were diagnosed between 2003 and 2015 at six U.S. military medical centers. The study was approved by institutional review boards at the Uniformed Services University of the Health Sciences and each of the sites. We evaluated the impact of Department of Defense (DoD) HIV care policies, including screening, linkage to care, treatment eligibility, and combined antiretroviral therapy (cART) initiation on achieving viral suppression (VS) within 3 years of diagnosis. As a secondary outcome, we evaluated the DoD's achievement of UNAIDS 90-90-90 targets. RESULTS: Nearly all (99%) were linked to care within 60 days. Among patients diagnosed in 2003-2009, 77.5% (95% confidence intervals (CI) 73.9-80.6%) became eligible for cART within 3 years of diagnosis, 70.6% (95% CI 66.6-74.1%) overall initiated cART, and 64.2% (95% CI 60.1-68.0%) overall achieved VS. Among patients diagnosed in 2010-2015, 98.7% (95% CI 96.7-99.5%) became eligible for cART within 3 years of diagnosis, 98.5% (95% CI 96.4-99.4%) overall initiated cART, and 89.8% (95% CI 86.0-92.5%) overall achieved VS. CONCLUSIONS: U.S. military HIV policies have been highly successful in achieving VS goals, exceeding the UNAIDS 90-90-90 targets. In spite of limitations, including generalizability, this example demonstrates the feasibility of the DHHS initiative to decrease new infections through testing, early treatment, and retention in care.

Comparable Disease Severity by Influenza Virus Subtype in the Acute Respiratory Infection Consortium Natural History Study.

INTRODUCTION: Since the influenza A/H1N1 pandemic of 2009 to 2010, numerous studies have described the clinical course and outcome of the different subtypes of influenza (A/H1N1, A/H3N2, and B). A recent systematic literature review concluded that there were no appreciable differences in either clinical presentation or disease severity among these subtypes, but study parameters limit the applicability of these results to military populations. We sought to evaluate differences in disease severity among influenza subtypes in a cohort of healthy, primarily outpatient adult U.S. Department of Defense beneficiaries. MATERIALS AND METHODS: From 2009 to 2014, we enrolled otherwise healthy adults age 18 to 65 years with influenza-like illness in an observational cohort study based in 5 U.S. military medical centers. Serial nasopharyngeal swabs were collected for determination of etiology and viral shedding by polymerase chain reaction. The presence and severity of symptoms was assessed by interview and patient diary. RESULTS: Over a 5-year period, a total of 157 adults with laboratory-confirmed influenza and influenza subtype were enrolled. Of these, 69 (44%) were positive for influenza A(H1N1), 69 (44%) for influenza A(H3N2), and 19 (12%) for influenza B. About 61% were male, 64% were active duty military personnel, and 72% had received influenza vaccine in the past 8 months. Almost 10% were hospitalized with influenza. Seasonal influenza virus distribution among enrollees mirrored that of nationwide trends each year of study. Individuals with A/H1N1 had upper respiratory composite scores that were lower than those with A/H3N2. Multivariate models indicated that individuals with A(H1N1) and B had increased lower respiratory symptom scores when compared to influenza A(H3N2) (A[H1N1]: 1.51 [95% CI 0.47, 2.55]; B: 1.46 [95% CI 0.09, 2.83]), whereas no other differences in symptom severity scores among influenza A(H1N1), influenza A(H3N2), and influenza B infection were observed. Overall, influenza season (maximum in 2012-2013 season) and female sex of the participant were found to be associated with increased influenza symptom severity. CONCLUSIONS: Our study of influenza in a cohort of otherwise healthy, outpatient adult Department of Defense beneficiaries over 5 influenza seasons revealed few differences between influenza A(H1N1), influenza A(H3N2), and influenza B infection with respect to self-reported disease severity or clinical outcomes. This study highlights the importance of routine, active, and laboratory-based surveillance to monitor ongoing trends and severity of influenza in various populations to inform prevention measures.

Late-onset ulnar neuritis following treatment of lepromatous leprosy infection.

Neuritis is a frequent complication of Myocobacteria leprae infection and treatment due to the variety of mechanisms through which it can occur. Not only can mycobacterial invasion into peripheral nerves directly cause damage and inflammation, but immune-mediated inflammatory episodes (termed leprosy reactions) can also manifest as neuritis at any point during infection. Treatment of leprosy reactions with thalidomide can also lead to neuritis due to an adverse drug effect. Neuritis can emerge years after initial diagnosis and treatment, although it is most frequently found at time of diagnosis or early into the treatment course. Treatment of neuritis is dependent on high-dose corticosteroid therapy as well as therapy for suspected underlying etiology. Here, we present a case of ulnar neuritis presenting in a patient with lepromatous leprosy four years after treatment of initial infection, with subsequent improvement after corticosteroid burst while maintained on thalidomide therapy.

Age, Race, and At-Risk Drinking in an HIV-infected U.S. Military Cohort.

INTRODUCTION: There is a high prevalence of at-risk drinking in the U.S. military. Among HIV-infected individuals, alcohol abuse confers additional risk for adverse health outcomes. In the military, however, the characteristics of HIV-infected individuals who engage in high-risk drinking are not well defined. The purpose of this study was to assess risk factors associated with at-risk drinking in an HIV-positive longitudinal cohort of DoD beneficiaries. MATERIALS AND METHODS: Annual prevalence of at-risk drinking was calculated for members of the U.S. Military HIV Natural History Study who initiated highly active antiretroviral therapy (HAART) during or after January 2006 through May 2014; each participant completed at least one self-reported alcohol survey within a year of HAART initiation. Univariate and multivariable logistic regression was used to analyze factors associated with at-risk drinking. RESULTS: Sixty-six percent of subjects (495/752) reported at-risk drinking on at least one survey after HAART initiation. At-risk drinkers were more likely to be Active Duty compared to Retired (OR 0.65 95% CI [0.46, 0.92]). In multivariate models, Caucasian race (OR 3.30 95% CI [2.31, 4.71]); Hispanic/other race (OR 2.17 95% CI [1.51, 3.14]) and younger age (OR 0.61 per 10 years older, [95%CI 0.49, 0.75]) were significantly associated with at-risk drinking. Single relationship status (OR 1.51 95% CI [1.08, 2.13]) was also associated with at-risk drinking. CONCLUSIONS: Consistent with general alcohol consumption patterns in the military, we found a high prevalence of at-risk drinking among individuals with HIV infection, which was associated most closely with young, non-African Americans. Targeting interventions toward this group will be important to reduce at-risk drinking and its potential for HIV-related complications.

Refractive surgery in the HIV-positive U.S. Military Natural History Study Cohort: complications and risk factors.

PURPOSE: This study sought to assess the frequency of refractive surgery complications in HIV+ individuals and related risk factors. SETTINGS: Multiple centers in the United States. DESIGN: Prospective observational cohort study. METHODS: The U.S. Military HIV Natural History Study is a prospective observational cohort study of HIV+ service members and beneficiaries. Participants were selected who had Current Procedural Terminology codes for laser in situ keratomileusis (LASIK), photorefractive keratectomy (PRK), and other refractive surgeries. The frequency of complications was determined using International Classification of Diseases-9 codes. Covariates included age, sex, antiretroviral therapy, time since HIV diagnosis, history of AIDS, and CD4 (T lymphocytes) count and viral load. Statistical analysis was completed using univariate (χ2 and Wilcoxon-Mann-Whitney tests) and multivariate analyses. RESULTS: Seventy-nine of 2073 participants had refractive surgery. Fifty-three patients underwent PRK, 23 LASIK, 2 radial keratotomy (RK), and 1 astigmatic correction. Complications occurred in 6 (7.6%) of 79 participants, including 5 patients who underwent PRK and 1 after RK, occurring between 8 and 217 days after surgery. Five ulcers and 1 unspecified keratitis were noted. In the univariate analysis, type of surgery (P = .02) and history of AIDS (P = .02) were risk factors for complications. In logistic regression analysis, no variables were found to be risk factors for complications. CONCLUSION: Complications were infrequent among HIV+ participants after refractive surgery. Point estimates suggest that PRK might have more complications than LASIK and that advanced HIV, reflected by previous AIDS, might be associated with an increased risk for complications. Further study will be required to confirm these findings.