Self-Perception of Risk for HIV Acquisition and Calculated Risk for HIV Acquisition Among Active Duty Air Force Members With Newly Diagnosed HIV Infection.

INTRODUCTION: There have been nearly 1,600 new diagnoses of Human Immunodeficiency Virus (HIV) across the US Armed Forces between 2017 and 2022. While treatment has improved overall survival, self-perception of acquiring HIV may not align with actual risk of acquiring HIV, thus slowing diagnosis and treatment. We aim to evaluate self-perceived risk (SPR) versus calculated risk (CR) of HIV infection in US Air Force (USAF) members with incident HIV diagnosis. METHODS: All USAF members with new HIV diagnosis evaluated at a specialty care military medical center between January 2015 and March 2020 with case report forms were included (n = 142). SPR was compared to CR using the Denver HIV Risk Score (DHRS). The study was approved by the Army Public Health Center's Public Health Review Board (#14-311) and the Walter Reed Army Institute of Research Human Subjects Protection Branch (#1861E). RESULTS: Patients were predominantly male (98%), with a median age of 26 (IQR 22-30) years, and the majority (85%) reported same-sex partners. Most patients reported a low SPR (n = 78; 55%). A higher proportion of low SPR patients were married or partnered than high SPR patients (29% versus 14%; P = 0.04). Both groups had median DHRS scores in the highest risk category with similar results by reason for HIV screening. CONCLUSION: The majority of USAF members with incident HIV infection reported a low SPR despite risk factors and CRs identical to high SPR patients. In order to inform HIV prevention strategies in the military, further efforts are needed to educate the military population and providers about HIV risk perception.

Racial and Ethnic Disparities in COVID-19 Treatments in the United States.

INTRODUCTION: Racial and ethnic disparities in patient outcomes following COVID-19 exist, in part, due to factors involving healthcare delivery. The aim of the study was to characterize disparities in the administration of evidence-based COVID-19 treatments among patients hospitalized for COVID-19. METHODS: Using a large, US hospital database, initiation of COVID-19 treatments was compared among patients hospitalized for COVID-19 between May 2020 and April 2022 according to patient race and ethnicity. Multivariate logistic regression models were used to examine the effect of race and ethnicity on the likelihood of receiving COVID-19 treatments, stratified by baseline supplemental oxygen requirement. RESULTS: The identified population comprised 317,918 White, 76,715 Black, 9297 Asian, and 50,821 patients of other or unknown race. There were 329,940 non-Hispanic, 74,199 Hispanic, and 50,622 patients of unknown ethnicity. White patients were more likely to receive COVID-19 treatments, and specifically corticosteroids, compared to Black, Asian, and other patients (COVID-19 treatment: 87% vs. 81% vs. 85% vs. 84%, corticosteroids: 85% vs. 79% vs. 82% vs. 82%). After covariate adjustment, White patients were significantly more likely to receive COVID-19 treatments than Black patients across all levels of supplemental oxygen requirement. No clear trend in COVID-19 treatments according to ethnicity (Hispanic vs. non-Hispanic) was observed. CONCLUSION: There were important racial disparities in inpatient COVID-19 treatment initiation, including the undertreatment of Black patients and overtreatment of White patients. Our new findings reveal the actual magnitude of this issue in routine clinical practice to clinicians, policymakers, and guideline developers. This is crucial to ensuring equitable and appropriate access to evidence-based therapies.

Long-term outcomes after new onset seizure in children living with HIV: A cohort study.

OBJECTIVE: To determine the long-term outcomes, including mortality and recurrent seizures, among children living with HIV (CLWH) who present with new onset seizure. METHODS: Zambian CLWH and new onset seizure were enrolled prospectively to determine the risk of and risk factors for recurrent seizures. Demographic data, clinical profiles, index seizure etiology, and 30-day mortality outcomes were previously reported. After discharge, children were followed quarterly to identify recurrent seizures and death. Given the high risk of early death, risk factors for recurrent seizure were evaluated using a model that adjusted for mortality. RESULTS: Among 73 children enrolled, 28 died (38%), 22 within 30-days of the index seizure. Median follow-up was 533 days (IQR 18-957) with 5% (4/73) lost to follow-up. Seizure recurrence was 19% among the entire cohort. Among children surviving at least 30-days after the index seizure, 27% had a recurrent seizure. Median time from index seizure to recurrent seizure was 161 days (IQR 86-269). Central nervous system opportunistic infection (CNS OI), as the cause for the index seizure was protective against recurrent seizures and higher functional status was a risk factor for seizure recurrence. SIGNIFICANCE: Among CLWH presenting with new onset seizure, mortality risks remain elevated beyond the acute illness period. Recurrent seizures are common and are more likely in children with higher level of functioning even after adjusting for the outcome of death. Newer antiseizure medications appropriate for co-usage with antiretroviral therapies are needed for the care of these children. CNS OI may represent a potentially reversible provocation for the index seizure, while seizures in high functioning CLWH without a CNS OI may be the result of a prior brain injury or susceptibility to seizures unrelated to HIV and thus represent an ongoing predisposition to seizures. PLAIN LANGUAGE SUMMARY: This study followed CLWH who experienced a new onset seizure to find out how many go on to have more seizures and identify any patient characteristics associated with having more seizures. The study found that mortality rates continue to be high beyond the acute clinical presentation with new onset seizure. Children with a CNS OI causing the new onset seizure had a lower risk of later seizures, possibly because the trigger for the seizure can be treated. In contrast, high functioning children without a CNS OI were at higher risk of future seizures.

Early Initiation of Antiretroviral Therapy is Protective Against Seizures in Children With HIV in Zambia: A Prospective Case-Control Study.

BACKGROUND: Seizures are relatively common among children with HIV in low- and middle-income countries and are associated with significant morbidity and mortality. Early treatment with antiretroviral therapy (ART) may reduce this risk by decreasing rates of central nervous system infections and HIV encephalopathy. METHODS: We conducted a prospective, unmatched case-control study. We enrolled children with new-onset seizure from University Teaching Hospital in Lusaka, Zambia and 2 regional hospitals in rural Zambia. Controls were children with HIV and no history of seizures. Recruitment took place from 2016 to 2019. Early treatment was defined as initiation of ART before 12 months of age, at a CD4 percentage >15% in children aged 12-60 months or a CD4 count >350 cells/mm 3 for children aged 60 months or older. Logistic regression models were used to evaluate the association between potential risk factors and seizures. RESULTS: We identified 73 children with new-onset seizure and compared them with 254 control children with HIV but no seizures. Early treatment with ART was associated with a significant reduction in the odds of seizures [odds ratio (OR) 0.04, 95% confidence interval: 0.02 to 0.09; P < 0.001]. Having an undetectable viral load at the time of enrollment was strongly protective against seizures (OR 0.03, P < 0.001), whereas history of World Health Organization Stage 4 disease (OR 2.2, P = 0.05) or CD4 count <200 cells/mm 3 (OR 3.6, P < 0.001) increased risk of seizures. CONCLUSIONS: Early initiation of ART and successful viral suppression would likely reduce much of the excess seizure burden in children with HIV.

Mandated checkups, knowledge of own health status, and chronic care utilization: The effect of HIV medical evaluation mandates on healthcare quality and expenditure in a US-single payer system.

In an effort to improve military readiness, in 2014 the US Air Force reduced the frequency of mandated HIV medical evaluation visits from every 6 months to every 12 months. We employ this natural experiment using data for 2676 active-duty Military Health System beneficiaries living with HIV with a difference-in-differences empirical strategy using the Army, Navy, and Marines as a control group to estimate the causal effect of reducing the frequency of mandated evaluation visits on the quality and cost of medical care for active-duty military members living with HIV. We find that reducing the frequency of mandated HIV medical evaluation visits reduced the likelihood of regular HIV visits by 23 percentage points but did not affect the likelihood of receiving other preventive care, adhering to HIV therapy, or maintaining viral testing and suppression. The study finds evidence that the recommended level of regular HIV visits may be higher than necessary. The reduction in regular HIV visits was not associated with a similar reduction in the studied quality of care measures, therefore, the effect of alleviating the mandate was overall positive in terms of reducing healthcare utilization without adversely affecting preventive care, HIV therapy, or viral testing and suppression.

Evolution of HIV-1 envelope towards reduced neutralization sensitivity, as demonstrated by contemporary HIV-1 subtype B from the United States.

Subtype B HIV-1 has been the primary driver of the HIV-1 epidemic in the United States (U.S.) for over forty years and is also a prominent subtype in the Americas, Europe, Australia, the Middle East and North Africa. In this study, the neutralization profiles of contemporary subtype B Envs from the U.S. were assessed to characterize changes in neutralization sensitivities over time. We generated a panel of 30 contemporary pseudoviruses (PSVs) and demonstrated continued diversification of subtype B Env from the 1980s up to 2018. Neutralization sensitivities of the contemporary subtype B PSVs were characterized using 31 neutralizing antibodies (NAbs) and were compared with strains from earlier in the HIV-1 pandemic. A significant reduction in Env neutralization sensitivity was observed for 27 out of 31 NAbs for the contemporary as compared to earlier-decade subtype B PSVs. A decline in neutralization sensitivity was observed across all Env domains; the NAbs that were most potent early in the pandemic suffered the greatest decline in potency over time. A meta-analysis demonstrated this trend across multiple subtypes. As HIV-1 Env diversification continues, changes in Env antigenicity and neutralization sensitivity should continue to be evaluated to inform the development of improved vaccine and antibody products to prevent and treat HIV-1.

Risk of sexually transmitted infections among U.S. military service members in the setting of HIV pre-exposure prophylaxis use.

BACKGROUND: The evidence for an increased incidence of sexually transmitted infections (STIs) among patients utilizing HIV pre-exposure prophylaxis (PrEP) has been inconsistent. We assessed the risk of incident STI while on PrEP compared to periods off PrEP among military service members starting PrEP. METHODS: Incidence rates of chlamydia, gonorrhea, syphilis, hepatitis C virus, and HIV were determined among military service members without HIV prescribed daily oral tenofovir disoproxil fumarate and emtricitabine for HIV PrEP from February 1, 2014 through June 10, 2016. Hazard ratios for incident STIs were calculated using an Anderson-Gill recurrent event proportional hazard regression model. RESULTS: Among 755 male service members, 477 (63%) were diagnosed with incident STIs (overall incidence 21.4 per 100 person-years). Male service members had a significantly lower risk of any STIs (adjusted hazard ratio (aHR) 0.21, 95% CI 0.11-0.40) while using PrEP compared to periods off PrEP after adjustment for socio-demographic characteristics, reasons for initiating PrEP, surveillance period prior to PrEP initiation, and the effect of PrEP on site and type of infection in multivariate analysis. However, when stratifying for anatomical site and type of infection, the risk of extragenital gonorrhea infection (pharyngeal NG: aHR 1.84, 95% CI 0.82-4.13, p = 0.30; rectal NG: aHR 1.23, 95% CI 0.60-2.51, p = 1.00) and extragenital CT infection (pharyngeal CT: aHR 2.30, 95% CI 0.46-11.46, p = 0.81; rectal CT: aHR 1.36, 95% CI 0.81-2.31, p = 0.66) was greater on PrEP compared to off PrEP although these values did not reach statistical significance. CONCLUSIONS: The data suggest entry into PrEP care reduced the overall risk of STIs following adjustment for anatomical site of STI and treatment. Service members engaged in PrEP services also receive more STI prevention counseling, which might contribute to decreases in STI risk while on PrEP.

Epidemiology, clinical characteristics, and outcomes of nontuberculous mycobacterial skin, soft tissue, and bone infections from a single center over a 10-year period.

Introduction: Non-tuberculous mycobacteria (NTM) cause a wide variety of clinical syndromes. Data guiding diagnosis and treatment of NTM skin and soft tissue infections (SSTI) and bone infections are limited. We sought to better understand SSTI and bone infections caused by NTM. Methods: All NTM clinical isolates recovered at Brooke Army Medical Center from 2012 to 2022 were screened; SSTI and bone isolates were included. Electronic health records were reviewed for epidemiologic, microbiologic, and clinical data. Infections were defined as recovery of one or more NTM isolate from skin, soft tissue, or bone cultures with a corresponding clinical syndrome. Results: Forty isolates of skin, soft tissue, or bone origin from 29 patients were analyzed. Twenty (69 %) patients, majority female (14/20, 70 %), had infecting isolates, most commonly secondary to surgery (35 %) or trauma (35 %). Six of 20 (30 %) had bone infections. Time from symptom onset to isolate recovery was a median 61 days (IQR 43-95). Eight (40 %) had combined medical/surgical therapy, 8 (40 %) had surgery alone, and 4 (20 %) had medical therapy alone. M. abscessus was more frequently isolated from patients with true infections. Conclusions: Data supporting diagnosis and treatment decisions in NTM SSTI/bone infections is sparse. In this study the majority of NTM isolated were true infections. We confirm that surgery and trauma are the most common routes of exposure. The delay between symptom onset and directed therapy and the wide variety of treatment regimens highlight a need for additional studies delineating criteria for diagnosis and treatment.

Evaluation of a two step testing algorithm to improve diagnostic accuracy and stewardship of Clostridioides difficile infections.

In response to national guidelines, we implemented a two-step testing algorithm for Clostridioides difficile in an effort to improve diagnostic accuracy. Following implementation, we analyzed treatment frequency between discordant and concordant patients. We found that the majority of discordant cases were treated with no significant differences in patient characteristics or outcomes between the concordant and discordant groups. Additionally, there were no differences in outcomes when discordant patients were further stratified by treatment status. Given little added diagnostic accuracy with the addition of EIA toxin testing, our facility resumed diagnosis by PCR testing alone. Further studies are needed to investigate alternative processes for improvement in diagnostic accuracy aside from toxin EIA testing including stool submission criteria and educational programs.

Humoral immune responses associated with control of SARS-CoV-2 breakthrough infections in a vaccinated US military population.

BACKGROUND: COVID-19 vaccines have been critical for protection against severe disease following infection with severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) but gaps remain in our understanding of the immune responses that contribute to controlling subclinical and mild infections. METHODS: Vaccinated, active-duty US military service members were enrolled in a non-interventional, minimal-risk, observational study starting in May, 2021. Clinical data, serum, and saliva samples were collected from study participants and were used to characterise the humoral immune responses to vaccination and to assess its impact on clinical and subclinical infections, as well as virologic outcomes of breakthrough infections (BTI) including viral load and infection duration. FINDINGS: The majority of VIRAMP participants had received the Pfizer COVID-19 vaccine and by January, 2022, N = 149 had a BTI. The median BTI duration (PCR+ days) was 4 days and the interquartile range was 1-8 days. Participants that were nucleocapsid seropositive prior to their BTI had significantly higher levels of binding and functional antibodies to the spike protein, shorter median duration of infections, and lower median peak viral loads compared to seronegative participants. Furthermore, levels of neutralising antibody, ACE2 blocking activity, and spike-specific IgA measured prior to BTI also correlated with the duration of infection. INTERPRETATION: We extended previous findings and demonstrate that a subset of vaccine-induced humoral immune responses, along with nucleocapsid serostatus are associated with control of SARS-CoV-2 breakthrough infections in the upper airways. FUNDING: This work was funded by the DoD Joint Program Executive Office for Chemical, Biological, Radiological and Nuclear Defense (JPEO-CBRND) in collaboration with the Defense Health Agency (DHA) COVID-19 funding initiative for the VIRAMP study.

Follow-up of Military Blood Donors Who Test Positive for Syphilis.

BACKGROUND: Several large studies have demonstrated that syphilis carries a risk of future sexually transmitted infections (STI), such as human immunodeficiency virus. There are limited data on outcomes of syphilis infections that occur in populations that undergo universal syphilis screening, such as blood donors. Military trainees who donate blood can be followed through their military career to determine the future risk of STIs. METHODS: Blood donor data were gathered from the Armed Services Blood Bank Center-San Antonio for those with positive Treponema pallidum antibodies between 2014 and 2021. The medical chart of each case was compared with 6 sex- and military accession date-matched controls with negative T. pallidum antibodies to determine the risk of STI in the 3 years after donation. RESULTS: A total of 63,375 individuals donated blood during the study period. A total of 23 military trainees (0.36 per 1000 donors) had positive T. pallidum antibodies. A minority (n = 7; 30%) of cases were treated for early syphilis. Only 6 cases (26%) received a follow-up nontreponemal test within 1 year. Donors who tested positive had a significantly higher risk of developing an STI within 3 years after blood donation compared with blood donors who tested negative (relative risk, 3.8; 95% confidence interval, 1.3-10.5; P = 0.01) including gonorrhea (9% vs. 0%, P = 0.02) and syphilis (9% vs. 0%, P = 0.02). CONCLUSIONS: This study shows the presence of T. pallidum antibodies in blood donors was associated with an increased risk of future STIs. These cases support the need for close follow-up and broad STI testing in blood donors with positive T. pallidum antibodies.

Breath Biomarkers of Influenza Infection.

Background: Volatile organic compounds (VOCs) are produced systemically due to varied physiological states such as oxidative stress and are excreted through the lungs. Benchtop and preliminary clinical data suggest that breath testing may be a useful diagnostic modality for viral respiratory tract infections. Methods: Patients with influenza-like illness (ILI) presenting to a single clinic in San Antonio, Texas, from 3/2017 to 3/2019 submitted a 2-minute breath sample in addition to a nasopharyngeal swab collected for polymerase chain reaction (PCR) assay for respiratory pathogens. VOCs were assayed with gas chromatography-mass spectrometry (GC-MS), and data were analyzed to identify breath VOC biomarkers that discriminated between ILI patients with and without a polymerase chain reaction (PCR) assay that was positive for influenza. Results: Demographic, clinical, PCR, and breath data were available for 237 episodes of ILI, among which 32 episodes (13.5%) were PCR positive for influenza. Twenty candidate VOCs identified patients with influenza with greater than random accuracy. A predictive algorithm using 4 candidate biomarkers identified this group with 78% accuracy (74% sensitivity, 70% specificity). Based on their mass spectra, most of these biomarkers were n-alkane derivatives, consistent with products of oxidative stress. Conclusions: A breath test for VOC biomarkers accurately identified ILI patients with PCR-proven influenza. These findings bolster those of others that a rapid, accurate, universal point-of-care influenza diagnostic test based on assay of exhaled-breath VOCs may be feasible. The next step will be a study of patients with ILI using a simplified method of breath collection that would facilitate translation for use in clinical practice.

Provider uptake of extragenital screening for gonorrhea and chlamydia in a cohort of Air Force members with incident HIV diagnosis.

The prevalence of Neisseria gonorrhea (GC) and Chlamydia trachomatis (CT) is higher at extragenital anatomic sites among men who have sex with men (MSM) with HIV infection. Although national guidelines recommend that all MSM with HIV infection undergo screening for extragenital sexually transmitted infections (EG-STIs), uptake is low in many primary care settings. We evaluated EG-STI screening by primary care providers (PCPs) for US Air Force (USAF) members with incident HIV infection. All USAF members with incident HIV infection who received initial HIV specialty care with Infectious Disease (ID) providers at Brooke Army Medical Center from 2016 to 2018 (n = 98) were included. A retrospective chart review was conducted to evaluate STI screening performed by PCPs within 1 week of HIV diagnosis compared to screening at entry into ID care. Demographic, clinical, laboratory and behavioral risk data were collected. STI screening included GC/CT EG-STIs, urethral GC/CT, syphilis, and hepatitis B and C. Patients were predominantly male (98%) with a median age of 26 (IQR 23, 32) years at HIV diagnosis. A previous history of STIs was reported in 53 (54%) patients and the majority of males self-identified as MSM (66%) or bisexual (23%). The median time from HIV diagnosis to ID evaluation was 26 days (IQR 9, 33). PCPs performed any STI screening in 61 (62%) patients. EG-STI screening was conducted in 3 (3%) patients overall and in (3%) MSM/bisexuals. A total of 31 (32%) patients had missed STIs; the majority due to EG-STIs of the rectum (59%) and pharynx (19%). All EG-STIs would have been missed by urethral GC/CT screening alone. EG-STI screening uptake was low among PCPs evaluating USAF members with incident HIV infection. Underutilization of EG-STI screening can result in missed infections and forward transmission of GC/CT. Barriers to low uptake need to be explored.

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.

Clinical characteristics and outcomes after new-onset seizure among Zambian children with HIV during the antiretroviral therapy era.

OBJECTIVE: This study describes clinical profiles including human immunodeficiency virus (HIV) disease history and seizure etiology among children living with HIV presenting with new-onset seizure during the era of antiretroviral therapy (ART) in Zambia. 30-day mortality and cause of death are also reported. METHODS: Children living with HIV (CLWHIV) with new-onset seizures were prospectively evaluated at one large urban teaching hospital and two non-urban healthcare facilities. Interviews with family members, review of medical records, and where needed, verbal autopsies were undertaken. Two clinicians who were not responsible for the patients' care independently reviewed all records and assigned seizure etiology and cause of death with adjudication as needed. RESULTS: From April 2016 to June 2019, 73 children (49 urban, 24 rural) were identified. Median age was 6 years (IQR 2.2-10.0) and 39 (53%) were male children. Seizures were focal in 36 (49%) and were often severe, with 37% presenting with multiple recurrent seizures in the 24 hours before admission or in status epilepticus. Although 36 (49%) were on ART at enrollment, only 7 of 36 (19%) were virally suppressed. Seizure etiologies were infectious in over half (54%), with HIV encephalitis, bacterial meningitis, and tuberculous meningitis being the most common. Metabolic causes (19%) included renal failure and hypoglycemia. Structural lesions identified on imaging accounted for 10% of etiologies and included stroke and non-accidental trauma. No etiology could be identified in 12 (16%) children, most of whom died before the completion of clinical investigations. Twenty-two (30%) children died within 30 days of the index seizure. SIGNIFICANCE: Despite widespread ART roll out in Zambia, new-onset seizure in CLWHIV occurs in the setting of advanced, active HIV disease. Seizure severity/burden is high as is early mortality. Enhanced programs to assure early ART initiation, improve adherence, and address ART failure are needed to reduce the burden of neurological injury and premature death in CLWHIV.

Clinical factors and outcomes associated with immune non-response among virally suppressed adults with HIV from Africa and the United States.

A significant minority of people living with HIV (PLWH) achieve viral suppression (VS) on antiretroviral therapy (ART) but do not regain healthy CD4 counts. Clinical factors affecting this immune non-response (INR) and its effect on incident serious non-AIDS events (SNAEs) have been challenging to understand due to confounders that are difficult to control in many study settings. The U.S. Military HIV Natural History Study (NHS) and African Cohort Study (AFRICOS). PLWH with sustained VS (< 400 copies/ml for at least two years) were evaluated for INR (CD4 < 350 cells/µl at the time of sustained VS). Logistic regression estimated adjusted odds ratios (aORs) and 95% confidence intervals (CIs) for factors associated with INR. Cox proportional hazards regression produced adjusted hazard ratios (aHRs) for factors associated with incident SNAE after sustained VS. INR prevalence was 10.8% and 25.8% in NHS and AFRICOS, respectively. Higher CD4 nadir was associated with decreased odds of INR (aOR = 0.34 [95% CI 0.29, 0.40] and aOR = 0.48 [95% CI 0.40, 0.57] per 100 cells/µl in NHS and AFRICOS, respectively). After adjustment, INR was associated with a 61% increase in relative risk of SNAE [95% CI 1.12, 2.33]. Probability of "SNAE-free" survival at 15 years since sustained VS was approximately 20% lower comparing those with and without INR; nearly equal to the differences observed by 15-year age groups. CD4 monitoring before and after VS is achieved can help identify PLWH at risk for INR. INR may be a useful clinical indicator of future risk for SNAEs.

Large-scale provocation studies identify maladaptive responses to ubiquitous aeroallergens as a correlate of severe allergic rhinoconjunctivitis and asthma.

BACKGROUND: Allergic asthma (AA) and allergic rhinoconjunctivitis (ARC) are common comorbid environmentally triggered diseases. We hypothesized that severe AA/ARC reflects a maladaptive or unrestrained response to ubiquitous aeroallergens. METHODS: We performed provocation studies wherein six separate cohorts of persons (total n = 217) with ARC, with or without AA, were challenged once or more with fixed concentrations of seasonal or perennial aeroallergens in an aeroallergen challenge chamber (ACC). RESULTS: Aeroallergen challenges elicited fully or partially restrained vs. unrestrained evoked symptom responsiveness, corresponding to the resilient and adaptive vs. maladaptive AA/ARC phenotypes, respectively. The maladaptive phenotype was evoked more commonly during challenge with a non-endemic versus endemic seasonal aeroallergen. In an AA cohort, symptom responses evoked after house dust mite (HDM) challenges vs. recorded in the natural environment were more accurate and precise predictors of asthma severity and control, lung function (FEV1), and mechanistic correlates of maladaptation. Correlates included elevated levels of peripheral blood CD4+ and CD8+ T-cells, eosinophils, and T-cell activation, as well as gene expression proxies for ineffectual epithelial injury/repair responses. Evoked symptom severity after HDM challenge appeared to be more closely related to levels of CD4+ and CD8+ T-cells than eosinophils, neutrophils, or HDM-specific IgE. CONCLUSIONS: Provocation studies support the concept that resilience, adaptation, and maladaptation to environmental disease triggers calibrate AA/ARC severity. Despite the ubiquity of aeroallergens, in response to these disease triggers in controlled settings (ie, ACC), most atopic persons manifest the resilient or adaptive phenotype. Thus, ARC/AA disease progression may reflect the failure to preserve the resilient or adaptive phenotype. The triangulation of CD8+ T-cell activation, airway epithelial injury/repair processes and maladaptation in mediating AA disease severity needs more investigation.

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.

Rates of nosocomial infection associated with interhospital transfer of patients receiving extracorporeal membrane oxygenation.

OBJECTIVES: Critically ill patients requiring extracorporeal membrane oxygenation (ECMO) frequently require interhospital transfer to a center that has ECMO capabilities. Patients receiving ECMO were evaluated to determine whether interhospital transfer was a risk factor for subsequent development of a nosocomial infection. DESIGN: Retrospective cohort study. SETTING: A 425-bed academic tertiary-care hospital. PATIENTS: All adult patients who received ECMO for >48 hours between May 2012 and May 2020. METHODS: The rate of nosocomial infections for patients receiving ECMO was compared between patients who were cannulated at the ECMO center and patients who were cannulated at a hospital without ECMO capabilities and transported to the ECMO center for further care. Additionally, time to infection, organisms responsible for infection, and site of infection were compared. RESULTS: In total, 123 patients were included in analysis. For the primary outcome of nosocomial infection, there was no difference in number of infections per 1,000 ECMO days (25.4 vs 29.4; P = .03) by univariate analysis. By Cox proportional hazard analysis, transport was not significantly associated with increased infections (hazard ratio, 1.7; 95% confidence interval, 0.8-4.2; P = .20). CONCLUSION: In this study, we did not identify an increased risk of nosocomial infection during subsequent hospitalization. Further studies are needed to identify sources of nosocomial infection in this high-risk population.

Immunologic resilience and COVID-19 survival advantage.

BACKGROUND: The risk of severe coronavirus disease 2019 (COVID-19) varies significantly among persons of similar age and is higher in males. Age-independent, sex-biased differences in susceptibility to severe COVID-19 may be ascribable to deficits in a sexually dimorphic protective attribute that we termed immunologic resilience (IR). OBJECTIVE: We sought to examine whether deficits in IR that antedate or are induced by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection independently predict COVID-19 mortality. METHODS: IR levels were quantified with 2 novel metrics: immune health grades (IHG-I [best] to IHG-IV) to gauge CD8+ and CD4+ T-cell count equilibrium, and blood gene expression signatures. IR metrics were examined in a prospective COVID-19 cohort (n = 522); primary outcome was 30-day mortality. Associations of IR metrics with outcomes in non-COVID-19 cohorts (n = 13,461) provided the framework for linking pre-COVID-19 IR status to IR during COVID-19, as well as to COVID-19 outcomes. RESULTS: IHG-I, tracking high-grade equilibrium between CD8+ and CD4+ T-cell counts, was the most common grade (73%) among healthy adults, particularly in females. SARS-CoV-2 infection was associated with underrepresentation of IHG-I (21%) versus overrepresentation (77%) of IHG-II or IHG-IV, especially in males versus females (P < .01). Presentation with IHG-I was associated with 88% lower mortality, after controlling for age and sex; reduced risk of hospitalization and respiratory failure; lower plasma IL-6 levels; rapid clearance of nasopharyngeal SARS-CoV-2 burden; and gene expression signatures correlating with survival that signify immunocompetence and controlled inflammation. In non-COVID-19 cohorts, IR-preserving metrics were associated with resistance to progressive influenza or HIV infection, as well as lower 9-year mortality in the Framingham Heart Study, especially in females. CONCLUSIONS: Preservation of immunocompetence with controlled inflammation during antigenic challenges is a hallmark of IR and associates with longevity and AIDS resistance. Independent of age, a male-biased proclivity to degrade IR before and/or during SARS-CoV-2 infection predisposes to severe COVID-19.