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Background Inappropriate antibiotic use in acute respiratory infections (ARIs) is a major public health concern; however, data for people with human immunodeficiency virus (PWH) are limited. Methods The HIV Virtual Cohort Study is a retrospective cohort of adult Department of Defense beneficiaries. Male PWH cases (n = 2413) were matched 1:2 to controls without HIV (n = 4826) by age, gender, race/ethnicity, and beneficiary status. Acute respiratory infection encounters between 2016 and 2020 and corresponding antibiotic prescriptions were characterized as always, sometimes, or never appropriate based on International Classification of Diseases, Tenth Revision coding. Incidence of ARI encounters and antibiotic appropriateness were compared between PWH and controls. Subgroup analyses were assessed by CD4 count and viral load suppression on antiretroviral therapy. Results Mean rates of ARI encounters were similar for PWH (1066 per 1000 person-years) and controls (1010 per 1000 person-years); however, the rate was double among PWH without viral load (VL) suppression (2018 per 1000 person-years). Antibiotics were prescribed in 26% of encounters among PWH compared to 34% for controls (P ≤.01); antibiotic use was "never" appropriate in 38% of encounters with PWH and 36% in controls. Compared to controls, PWH received more sulfonamides (5.5% vs 2.7%; P =.001), and variation existed among HIV subgroups in the prescription of sulfonamides, fluoroquinolones, and β-lactams. Discussion Acute respiratory infection encounters were similar for PWH and those without HIV; however, PWH with lower CD4 counts and/or nonsuppressed VL had more frequent ARI visits. Inappropriate antibiotic use for ARIs was high in both populations, and focused interventions to improve antibiotic appropriateness for prescribers caring for PWH should be pursued. [ABSTRACT FROM AUTHOR]

This study investigates the role of environmental policies and regulations in mitigating climate change by promoting clean innovations and discouraging dirty ones. Utilizing nonparametric copula and quantile estimation techniques, along with carefully constructed innovation variables based on patents from 2000 to 2021 across 34 countries, the research examines the effects of policy interventions and external events on energy-related innovations. Findings reveal that climate policy interventions effectively promote clean innovation, particularly at higher levels, and discourage dirty innovations. Therefore, climate change policies and regulations are crucial in achieving net-zero carbon emission targets.

US military personnel are routinely screened for HIV infection. Herpes simplex virus type 2 (HSV-2) is a risk factor for HIV acquisition. To determine the association between HSV-2 and HIV, a matched case-control study was conducted among US Army and Air Force servicemembers with incident HIV infections (cases) randomly matched with two HIV-uninfected servicemembers (controls) between 2000 and 2004. HSV-2 prevalence was significantly higher among cases (30.3%, 138/456) than among controls (9.7%, 88/912, P < 0.001). HSV-2 was strongly associated with HIV in univariate (odds ratio [OR] = 4.2, 95% confidence interval [CI] = 3.1-5.8) and multiple analyses (adjusted [OR] = 3.9, 95% CI = 2.8-5.6). The population attributable risk percentage of HIV infection due to HSV-2 was 23%. Identifying HSV-2 infections may afford the opportunity to provide targeted behavioural interventions that could decrease the incidence of HIV infections in the US military population; further studies are needed. [ABSTRACT FROM AUTHOR]

Abstract Background Although highly active antiretroviral therapy (HAART) has improved HIV survival, some patients receiving therapy are still dying. This analysis was conducted to identify factors associated with increased risk of post-HAART mortality. Methods We evaluated baseline (prior to HAART initiation) clinical, demographic and laboratory factors (including CD4+ count and HIV RNA level) for associations with subsequent mortality in 1,600 patients who began HAART in a prospective observational cohort of HIV-infected U.S. military personnel. Results Cumulative mortality was 5%, 10% and 18% at 4, 8 and 12 years post-HAART. Mortality was highest (6.23 deaths/100 person-years [PY]) in those with ≤ 50 CD4+ cells/mm3 before HAART initiation, and became progressively lower as CD4+ counts increased (0.70/100 PY with ≥ 500 CD4+ cells/mm3). In multivariate analysis, factors significantly (p < 0.05) associated with post-HAART mortality included: increasing age among those ≥ 40 years (Hazard ratio [HR] = 1.32 per 5 year increase), clinical AIDS events before HAART (HR = 1.93), ≤ 50 CD4+ cells/mm3 (vs. CD4+ ≥ 500, HR = 2.97), greater HIV RNA level (HR = 1.36 per one log10 increase), hepatitis C antibody or chronic hepatitis B (HR = 1.96), and HIV diagnosis before 1996 (HR = 2.44). Baseline CD4+ = 51-200 cells (HR = 1.74, p = 0.06), and hemoglobin < 12 gm/dL for women or < 13.5 for men (HR = 1.36, p = 0.07) were borderline significant. Conclusions Although treatment has improved HIV survival, defining those at greatest risk for death after HAART initiation, including demographic, clinical and laboratory correlates of poorer prognoses, can help identify a subset of patients for whom more intensive monitoring, counseling, and care interventions may improve clinical outcomes and post-HAART survival.

Abstract Background Among HIV-infected persons initiating highly active antiretroviral therapy (HAART), early CD4+ lymphocyte count increases are well described. However, whether CD4+ levels continue to increase or plateau after 4-6 years is controversial. Methods To address this question and identify other determinants of CD4+ response, we analyzed data for 1,846 persons from a prospective HIV military cohort study who initiated HAART, who had post-HAART CD4+ measurements, and for whom HIV seroconversion (SC) date was estimated. Results CD4+ count at HAART initiation was ≤ 200 cells/mm3 for 23%, 201-349 for 31%, 350-499 for 27%, and ≥500 for 19%. The first 6 months post-HAART, the greatest CD4+ increases (93-151 cells) occurred, with lesser increases (22-36 cells/year) through the first four years. Although CD4+ changes for the entire cohort were relatively flat thereafter, HIV viral load (VL) suppressors showed continued increases of 12-16 cells/year. In multivariate analysis adjusting for baseline CD4+ and post-HAART time interval, CD4+ responses were poorer in those with: longer time from HIV SC to HAART start, lower pre-HAART CD4+ nadir, higher pre-HAART VL, and clinical AIDS before HAART (P < 0.05). Conclusions Small but positive long-term increases in CD4+ count in virally suppressed patients were observed. CD4+ response to HAART is influenced by multiple factors including duration of preceding HIV infection, and optimized if treatment is started with virally suppressive therapy as early as possible.

Abstract Background To examine the outcomes of highly-active antiretroviral therapy (HAART) for individuals with free access to healthcare, we evaluated 2327 patients in a cohort study composed of military personnel and beneficiaries with HIV infection who initiated HAART from 1996 to the end of 2007. Methods Outcomes analyzed were virologic suppression (VS) and failure (VF), CD4 count changes, AIDS and death. VF was defined as never suppressing or having at least one rebound event. Multivariate (MV) analyses stratified by the HAART initiation year (before or after 2000) were performed to identify risk factors associated with these outcomes. Results Among patients who started HAART after 2000, 81% had VS at 1 year (N = 1,759), 85% at 5 years (N = 1,061), and 82% at 8 years (N = 735). Five years post-HAART, the median CD4 increase was 247 cells/ml and 34% experienced VF. AIDS and mortality rates at 5 years were 2% and 0.3%, respectively. In a MV model adjusted for known risk factors associated with treatment response, being on active duty (versus retired) at HAART initiation was associated with a decreased risk of AIDS (HR = 0.6, 95% CI 0.4-1.0) and mortality (0.6, 0.3-0.9), an increased probability of CD4 increase ≥ 50% (1.2, 1.0-1.4), but was not significant for VF. Conclusions In this observational cohort, VS rates approach those described in clinical trials. Initiating HAART on active duty was associated with even better outcomes. These findings support the notion that free access to healthcare likely improves the response to HAART thereby reducing HIV-related morbidity and mortality.

Lethal COVID-19 outcomes are attributed to classic cytokine storm. We revisit this using RNA sequencing of nasopharyngeal and 40 autopsy samples from patients dying of SARS-CoV-2. Subsets of the 100 top-upregulated genes in nasal swabs are upregulated in the heart, lung, kidney, and liver, but not mediastinal lymph nodes. Twenty-two of these are "noncanonical" immune genes, which we link to components of the renin-angiotensin-activation-system that manifest as increased fibrin deposition, leaky vessels, thrombotic tendency, PANoptosis, and mitochondrial dysfunction. Immunohistochemistry of mediastinal lymph nodes reveals altered architecture, excess collagen deposition, and pathogenic fibroblast infiltration. Many of the above findings are paralleled in animal models of SARS-CoV-2 infection and human peripheral blood mononuclear and whole blood samples from individuals with early and later SARS-CoV-2 variants. We then redefine cytokine storm in lethal COVID-19 as driven by upstream immune gene and mitochondrial signaling producing downstream RAAS (renin-angiotensin-aldosterone system) overactivation and organ damage, including compromised mediastinal lymph node function., Competing Interests: Competing interests statement:R.E.S. is on the scientific advisory of Miromatrix, Inc. and Lime Therapeutics and is a consultant for Alnylam, Inc. D.C.W. is on the scientific advisory boards of Pano Therapeutics, Inc., and Medical Excellent Capital.

Antigenic assessments of SARS-CoV-2 variants inform decisions to update COVID-19 vaccines. Primary infection sera are often used for assessments, but such sera are rare due to population immunity from SARS-CoV-2 infections and COVID-19 vaccinations. Here, we show that neutralization titers and breadth of matched human and hamster pre-Omicron variant primary infection sera correlate well and generate similar antigenic maps. The hamster antigenic map shows modest antigenic drift among XBB sub-lineage variants, with JN.1 and BA.4/BA.5 variants within the XBB cluster, but with fivefold to sixfold antigenic differences between these variants and XBB.1.5. Compared to sera following only ancestral or bivalent COVID-19 vaccinations, or with post-vaccination infections, XBB.1.5 booster sera had the broadest neutralization against XBB sub-lineage variants, although a fivefold titer difference was still observed between JN.1 and XBB.1.5 variants. These findings suggest that antibody coverage of antigenically divergent JN.1 could be improved with a matched vaccine antigen.IMPORTANCEUpdates to COVID-19 vaccine antigens depend on assessing how much vaccine antigens differ antigenically from newer SARS-CoV-2 variants. Human sera from single variant infections are ideal for discriminating antigenic differences among variants, but such primary infection sera are now rare due to high population immunity. It remains unclear whether sera from experimentally infected animals could substitute for human sera for antigenic assessments. This report shows that neutralization titers of variant-matched human and hamster primary infection sera correlate well and recognize variants similarly, indicating that hamster sera can be a proxy for human sera for antigenic assessments. We further show that human sera following an XBB.1.5 booster vaccine broadly neutralized XBB sub-lineage variants but titers were fivefold lower against the more recent JN.1 variant. These findings support updating the current COVID-19 vaccine variant composition and developing a framework for assessing antigenic differences in future variants using hamster primary infection sera., Competing Interests: The authors declare no conflict of interest.

Use of HIV pre-exposure prophylaxis (PrEP) among U.S. military service members at high risk for HIV infection remains suboptimal, resulting in preventable new HIV infections and decreased medical readiness among service members. PrEP coverage should be increased to the greatest extent possible to prevent HIV infection and support the Military Health System (MHS) quadruple aim. This policy analysis employed the Centers for Disease Control and Prevention (CDC)'s Policy Analytical Framework to develop several policy options based upon the evidence summary and interventions described. Evaluation criteria based on the CDC's Policy Analytical Framework incorporated all elements of the Military Health System (MHS)'s quadruple aim, including impact on population health and readiness, impact on the experience of care, and value in terms of cost-effectiveness. An additional criterion of feasibility was also added to account for cultural, societal, and political factors influencing this policy decision. This policy analysis suggests that HIV PrEP coverage in the MHS remains suboptimal, while several available interventions could result in substantial increases in PrEP coverage that would, in turn, result in further reductions in new service member HIV infections and increased medical readiness.

Sustainable development addresses global challenges by promoting practices that balance economic, social, and environmental considerations. Key factors include the shifting to green energy and the integrating of green technology in the sustainable development process. This study investigates the heterogenous effects of green technology development, green energy, R&D expenditures, FDI, economic growth, and urbanization on CO 2 emissions in 25 European Union (EU) countries using panel quantile regression over the period 2000-2021. The results, based on panel quantile regression, indicate that green energy decreases CO 2 emissions from the 10th to the 90th quantiles, while green technology development increases CO 2 emissions at the lower quantiles (10th to 60th) and then turns negative. The robustness of the fixed effect model also confirms the findings of the study. Additionally, panel causality tests indicate no causal link between green technology development and CO 2 emissions, but there is bidirectional causality between green energy and CO 2 emissions. Therefore, the findings highlight that policymakers should thoroughly evaluate measures and strategies to encourage the development of green technologies and green energy sources to reduce high levels of CO 2 emissions. One strategy is to provide financial aid and support technological advances to produce green energy at reduced costs., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 Elsevier Ltd. All rights reserved.)

Objective: To investigate the relationship between neurocognitive deficits and structural changes on brain magnetic resonance imaging in people living with HIV (PLWH) with good virological control on combination antiretroviral therapy, compared with socioeconomically matched control participants recruited from the same communities., Methods: Brain magnetic resonance imaging scans, and clinical and neuropsychological data were obtained from virologically controlled PLWH (viral load of <50 c/mL and at least 1 year of combination antiretroviral therapy) and socioeconomically matched control participants. Magnetic resonance imaging was carried out on 3 T scanner with 8-channel head coils and segmented using Classification using Derivative-based Features. Multiple regression analysis was performed to examine the association between brain volume and various clinical and neuropsychiatric parameters adjusting for age, race, and sex. To evaluate longitudinal changes in brain volumes, a random coefficient model was used to evaluate the changes over time (age) adjusting for sex and race., Results: The cross-sectional study included 164 PLWH and 51 controls, and the longitudinal study included 68 PLWH and 20 controls with 2 or more visits (mean 2.2 years, range 0.8-5.1 years). Gray matter (GM) atrophy rate was significantly higher in PLWH compared with control participants, and importantly, the GM and global atrophy was associated with the various neuropsychological domain scores. Higher volume of white matter hyperintensities were associated with increased atherosclerotic cardiovascular disease risk score, and decreased executive functioning and memory domain scores in PLWH., Interpretation: These findings suggest ongoing neurological damage even in virologically controlled participants, with significant implications for clinical management of PLWH. ANN NEUROL 2024;95:941-950., (Published 2024. This article is a U.S. Government work and is in the public domain in the USA. Annals of Neurology published by Wiley Periodicals LLC on behalf of American Neurological Association.)

Background: There is limited information on the functional consequences of coronavirus disease 2019 (COVID-19) vaccine side effects. To support patient counseling and public health messaging, we describe the risk and correlates of COVID-19 vaccine side effects sufficient to prevent work or usual activities and/or lead to medical care ("severe" side effects)., Methods: The EPICC study is a longitudinal cohort study of Military Healthcare System beneficiaries including active duty service members, dependents, and retirees. We studied 2789 adults who were vaccinated between December 2020 and December 2021., Results: Severe side effects were most common with the Ad26.COV2.S (Janssen/Johnson and Johnson) vaccine, followed by mRNA-1273 (Moderna) then BNT162b2 (Pfizer/BioNTech). Severe side effects were more common after the second than first dose (11% vs 4%; P  < .001). First (but not second) dose side effects were more common in those with vs without prior severe acute respiratory syndrome coronavirus 2 infection (9% vs 2%; adjusted odds ratio [aOR], 5.84; 95% CI, 3.8-9.1), particularly if the prior illness was severe or critical (13% vs 2%; aOR, 10.57; 95% CI, 5.5-20.1) or resulted in inpatient care (17% vs 2%; aOR, 19.3; 95% CI, 5.1-72.5). Side effects were more common in women than men but not otherwise related to demographic factors., Conclusions: Vaccine side effects sufficient to prevent usual activities were more common after the second than first dose and varied by vaccine type. First dose side effects were more likely in those with a history of COVID-19-particularly if that prior illness was severe or associated with inpatient care. These findings may assist clinicians and patients by providing a real-world evaluation of the likelihood of experiencing impactful postvaccine symptoms., (Published by Oxford University Press on behalf of Infectious Diseases Society of America 2022.This work is written by (a) US Government employee(s) and is in the public domain in the US.)

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-bet dim Eomes hi 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-bet dim Eomes hi , 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., Competing Interests: Competing interests: None declared., (© Author(s) (or their employer(s)) 2022. Re-use permitted under CC BY-NC. No commercial re-use. See rights and permissions. Published by BMJ.)

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., Competing Interests: Competing interests: None declared., (© American Federation for Medical Research 2021. Re-use permitted under CC BY-NC. No commercial re-use. Published by BMJ.)

Objectives: HIV infection is associated with increased risk of erectile dysfunction (ED); however, factors associated with ED remain unclear. We evaluated the prevalence of ED among men living with HIV and factors associated with ED diagnosis in the US Military HIV Natural History Study (NHS)., Methods: A retrospective cohort study evaluated participants in the NHS, a cohort of HIV-positive active duty members and beneficiaries with HIV infection. Men with a diagnosis of ED after HIV diagnosis were included. Cohort controls without ED diagnosis were matched 2:1 by age at HIV diagnosis and duration of follow-up. Multivariate logistic regression models were used to identify factors associated with ED., Results: A total of 543 of 5682 male participants (9.6% prevalence) had a diagnosis of ED, of whom 488 were included in the analysis. The median (interquartile range, IQR) age at ED diagnosis was 43 (37.0-49.0) years and the time from HIV diagnosis to antiretroviral therapy (ART) start was longer for cases (5.0 years, IQR: 2.0-9.0) than for controls (3.0 years, 1.0-6.0; P < 0.01). Cases had higher proportions of multiple comorbid conditions, including depression (33.4% vs. 21.7%), tobacco use (19.7% vs. 9.0%) and sleep apnoea (14.8% vs. 4.2%) compared with controls (P < 0.01 for all). Logistic regression showed increased odds of ED for delayed ART initiation > 4 years [odds ratio (OR) = 2.05, 95% confidence interval (CI): 1.56-2.71], protease inhibitor use ≥ 1 year (OR = 1.81, 95% CI: 1.38-2.38) and sleep apnoea (OR = 2.60, 95% CI: 1.68-4.01)., Conclusions: Erectile dysfunction was common in men with HIV and associated factors included both HIV-related and traditional factors., (© 2021 British HIV Association. This article is a U.S. Government work and is in the public domain in the USA.)

Objectives: With the goal of facilitating the use of HIV-TRePS to optimize therapy in settings with limited healthcare resources, we aimed to develop computational models to predict treatment responses accurately in the absence of commonly used baseline data., Methods: Twelve sets of random forest models were trained using very large, global datasets to predict either the probability of virological response (classifier models) or the absolute change in viral load in response to a new regimen (absolute models) following virological failure. Two 'standard' models were developed with all baseline variables present and 10 others developed without HIV genotype, time on therapy, CD4 count or any combination of the above., Results: The standard classifier models achieved an AUC of 0.89 in cross-validation and independent testing. Models with missing variables achieved AUC values of 0.78-0.90. The standard absolute models made predictions that correlated significantly with observed changes in viral load with a mean absolute error of 0.65 log10 copies HIV RNA/mL in cross-validation and 0.69 log10 copies HIV RNA/mL in independent testing. Models with missing variables achieved values of 0.65-0.75 log10 copies HIV RNA/mL. All models identified alternative regimens that were predicted to be effective for the vast majority of cases where the new regimen prescribed in the clinic failed. All models were significantly better predictors of treatment response than genotyping with rules-based interpretation., Conclusions: These latest models that predict treatment responses accurately, even when a number of baseline variables are not available, are a major advance with greatly enhanced potential benefit, particularly in resource-limited settings. The only obstacle to realizing this potential is the willingness of healthcare professions to use the system., (© The Author(s) 2021. Published by Oxford University Press on behalf of the British Society for Antimicrobial Chemotherapy. All rights reserved. For permissions, please email: journals.permissions@oup.com.)

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.

Background: Patients living with human immunodeficiency virus (PLWH) with low CD4 counts are at high risk for immune reconstitution inflammatory syndrome (IRIS) and death at antiretroviral therapy (ART) initiation., Methods: We investigated the clinical impact of IRIS in PLWH and CD4 counts <100 cells/μL starting ART in an international, prospective study in the United States, Thailand, and Kenya. An independent review committee adjudicated IRIS events. We assessed associations between baseline biomarkers, IRIS, immune recovery at week 48, and death by week 48 with Cox models., Results: We enrolled 506 participants (39.3% were women). Median age was 37 years, and CD4 count was 29 cells/μL. Within 6 months of ART, 97 (19.2%) participants developed IRIS and 31 (6.5%) died. Participants with lower hemoglobin at baseline were at higher IRIS risk (hazard ratio [HR], 1.2; P = .004). IRIS was independently associated with increased risk of death after adjustment for known risk factors (HR, 3.2; P = .031). Being female (P = .004) and having a lower body mass index (BMI; P = .003), higher white blood cell count (P = .005), and higher D-dimer levels (P = .044) were also significantly associated with increased risk of death. Decision-tree analysis identified hemoglobin <8.5 g/dL as predictive of IRIS and C-reactive protein (CRP) >106 μg/mL and BMI <15.6 kg/m2 as predictive of death., Conclusions: For PLWH with severe immunosuppression initiating ART, baseline low BMI and hemoglobin and high CRP and D-dimer levels may be clinically useful predictors of IRIS and death risk., (Published by Oxford University Press for the Infectious Diseases Society of America 2019.)

Introduction: Sexually transmitted infections (STIs) continue to plague militaries and defense forces. While the historical recognition of the impact of STIs on operations is evident, contemporary surveillance and research activities are limited. As Neisseria gonorrhoeae and other sexually transmitted pathogens become increasingly resistant to antibiotics, the role of the Department of Defense (DoD) in disease surveillance and clinical research is essential to military Force Health Protection., Methods: The Infectious Disease Clinical Research Program (IDCRP) of the Uniformed Services University of the Health Sciences partnered with the DoD Global Emerging Infections Surveillance (GEIS) program to monitor the distribution of gonorrhea antimicrobial resistance (AMR) both domestically and abroad. The DoD gonococcal reference laboratory and repository was established in 2011 as a resource for confirmatory testing and advanced characterization of isolates collected from sites across the continental United States (CONUS) and GEIS-funded sites outside the continental United States (OCONUS). The IDCRP is currently implementing surveillance efforts at CONUS military clinics, including Madigan Army Medical Center, Naval Medical Center Camp Lejeune, Naval Medical Center Portsmouth, Naval Medical Center San Diego, and San Antonio Military Medical Center (efforts were also previously at Womack Army Medical Center). The reference laboratory and repository receives specimens from OCONUS collaborators, including Armed Forces Research Institute of Medical Sciences (AFRIMS; Bangkok, Thailand), Naval Medical Research Unit No. 3 (NAMRU-3), Ghana Detachment (Accra, Ghana), Naval Medical Research Unit No. 6 (NAMRU-6; Lima, Peru), U.S. Army Medical Research Unit - Georgia (USAMRD-G; Tbilisi, Republic of Georgia), and U.S. Army Medical Research Directorate - Kenya (USAMRD-K; Nairobi, Kenya). The gonococcal surveillance program, to include findings, as well as associated clinical research efforts are described., Results: Among N. gonorrhoeae isolates tested within the United States, 8% were resistant to tetracycline, 2% were resistant to penicillin, and 30% were resistant to ciprofloxacin. To date, only one of the 61 isolates has demonstrated some resistance (MIC=1 μg/ml) to azithromycin. No resistance to cephalosporins has been detected; however, reduced susceptibility (MIC=0.06-0.125 μg/ml) has been observed in 13% of isolates. Resistance is commonly observed in N. gonorrhoeae isolates submitted from OCONUS clinical sites, particularly with respect to tetracycline, penicillin, and ciprofloxacin. While no azithromycin-resistant isolates have been identified from OCONUS sites, reduced susceptibility (MIC=0.125-0.5 μg/ml) to azithromycin was observed in 23% of isolates., Conclusion: Continued monitoring of circulating resistance patterns on a global scale is critical for ensuring appropriate treatments are prescribed for service members that may be infected in the U.S. or while deployed. Domestic surveillance for gonococcal AMR within the Military Health System has indicated that resistance patterns, while variable, are not dramatically different from what is seen in U.S. civilian data. Global patterns of gonococcal AMR have been described through the establishment of a central DoD gonococcal reference laboratory and repository. This repository of global isolates provides a platform for further research and development into biomedical countermeasures against gonococcal infections., (Published by Oxford University Press on behalf of the Association of Military Surgeons of the United States 2019. This work is written by (a) US Government employee(s) and is in the public domain in the US.)

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., (© The Author(s) 2018. Published by Oxford University Press for the Infectious Diseases Society of America. All rights reserved. For permissions, e-mail: journals.permissions@oup.com.)

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., (Published by Oxford University Press on behalf of Association of Military Surgeons of the United States 2018.)

The purpose of this study was to assess humoral antibody responses as a function of disease progression (DP) in a well-defined HIV + cohort. We quantified antibodies to HIV-1 gp120, Gag, and CD4 receptor by enzyme-linked immunosorbent assay in sera from a cohort of 97 HIV + subjects at defined stages of DP. We also measured antibody-dependent cellular cytotoxicity (ADCC) as a function of the clinical status of the patients. We purified antibodies to CD4 and gp120 and assessed them for specificity, ability to block gp120 binding to target cells, ability to block virus infection, and ability to facilitate ADCC. All of the HIV + patient samples were positive for antibodies to HIV gp120 and p24 and 80% showed evidence of hypergammaglobulinemia. Approximately 10% of cohort members were positive for antibodies to CD4, but we noted no significant correlation relevant to DP. There were statistically significant differences between the groups concerning the level of humoral response to gp120 and Gag. However, we observed no distinction in ability of anti-gp120 antibodies purified from each group to neutralize infection. In addition, there was a statistically significant difference in ADCC, with elite controllers exhibiting significantly lower levels of ADCC than the other five groups. We detected IgA anti-gp120 antibodies, but did not correlate their presence with either DP or ADCC levels. The results are consistent with the interpretation that the humoral antibody response to the antigens assessed here represents a signature of the level of viremia but does not correlate with clinical status of HIV infection., Competing Interests: Author Disclosure Statement No competing financial interests exist.