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Eugenia L Siegler,1 Jerad H Moxley,1 Marshall J Glesby2 1Division of Geriatrics and Palliative Care, Weill Cornell Medicine, New York, NY, 10065, USA; 2Division of Infectious Diseases, Weill Cornell Medicine, New York, NY, 10065, USACorrespondence: Eugenia L SieglerDivision of Geriatrics and Palliative Medicine, Weill Cornell Medicine, 525 E. 68th Street, Box 39, New York, NY, 10065, USATel +1 212 746 1729Fax +1 212 746 4888Email els2006@med.cornell.eduPurpose: People with HIV (PWH) are living longer lives and likely experiencing accentuated aging. Comprehensive geriatric assessment (CGA) has been proposed as a way to identify and help meet each individual patient’s needs.Patients and Methods: We performed a retrospective review of the results of CGA in an HIV clinic in New York City. CGA included assessment of basic and instrumental activities of daily living, screens for depression, anxiety, frailty, cognition, and quality of life, along with general discussion of concerns and goals. We compared the group of PWH referred for CGA to those of comparable age who were not referred to determine the factors that were associated with referral. We carried out a descriptive analysis of those undergoing CGA, along with regression to determine factors associated with poorer PHQ-2 depression scores and higher VACS score.Results: A total of 105 patients underwent full CGA during the study period. Mean age of referred patients was 66.5 years, ranging from 50 to 84 years (SD 7.99). More than 92% were virally suppressed. Compared with their non-referred counterparts over 50, referred patients were older and had more functional comorbidities like cerebrovascular disease, neuropathy, and urinary incontinence. More than half complained of fatigue, and 2/3 noted poor memory. Almost 60% were frail or prefrail. Ninety patients were asked about their goals, and the most commonly cited were related to health or finances; fifteen patients were unable to articulate any goals. Having fewer goals and noting weight loss or fatigue were predictive of higher scores on the PHQ-2 depression screen.Conclusion: Although most older PWH undergoing CGA can manage their ADL, many have concerns and deficits beyond their comorbidities. CGA offers an important window into the psychosocial concerns and needs of older PWH.Keywords: comprehensive geriatric assessment, comorbidity, frailty, IADL

Background: Herpes zoster (HZ) is common among HIV-infected individuals, but the impacts of highly active antiretroviral therapy (HAART) and HAART adherence on HZ risk have not been well studied.Methods: The effects of HAART and HAART adherence on HZ incid

BACKGROUND: The role of structured treatment interruption (STI) before optimized antiretroviral therapy (ART) in patients with drug-resistant human immunodeficiency virus type 1 (HIV-1) is uncertain. METHODS: AIDS Clinical Trial Group protocol A5086 was a prospective trial of 41 patients with multiple drug class-resistant HIV who were randomized to undergo a 16-week STI followed by optimized ART (STI) or immediate optimized ART (no STI). The primary end point was the proportion of subjects with HIV-1 RNA loads <400 copies/mL 48 weeks after randomization. RESULTS: Of 39 evaluable patients, 4 (19%) in the STI arm and 6 (33%) in the no STI arm had HIV-1 RNA loads <400 copies/mL at 48 weeks (P=.44). Median changes from baseline in CD4+ cell counts and HIV-1 RNA loads were similar for both arms. Standard genotypes at the end of STI showed nearly complete reversion to wild-type virus in a minority of patients (n=5; 28%). Virus with 3-drug class resistance reemerged even when ART included only 1 or 2 drug classes. Single-genome sequencing showed that each genome encoded resistance mutations for 3 drug classes. CONCLUSIONS: A 16-week STI before optimized ART did not improve virologic response. Genetic analyses strongly suggest that virologic failure resulted from the reemergence of virus present before STI that encoded 3-drug class resistance on the same genome. Copyright © 2006 Infectious Diseases Society of America [ABSTRACT FROM AUTHOR]

BACKGROUND: An increased incidence of osteonecrosis of the femoral head has been reported in patients infected with human immunodeficiency virus (HIV). The purpose of this study was to review the pathologic specimens of HIV-positive patients who had undergone total hip arthroplasty (THA) and compare them with those of THA patients who were HIV-negative. The surgical outcomes of these HIV-positive patients were also reviewed. METHODS: 40 HIV-positive patients who underwent 54 THAs at our institution were identified. The primary pathologic diagnosis for the femoral heads of these patients was osteonecrosis in 35 cases, degenerative joint disease in 11 cases, and other diagnoses in 8 cases. RESULTS: There was a higher incidence of osteonecrosis in HIV-positive patients. At the most recent follow-up, 4 patients had died and 1 patient had a significant Staphylococcus aureus infection of the hip. INTERPRETATION: There was a significant difference in the pathologic diagnoses of the HIV-positive group and the HIV-negative group, implicating HIV infection as a risk factor for osteonecrosis. Also, the risk of infectious complications is lower in our study than previously reported in other studies of HIV-positive patients who have undergone THA. [ABSTRACT FROM AUTHOR]

OBJECTIVE: To determine the prevalence of abnormal neurologic findings and cerebrospinal fluid abnormalities in hospitalized patients with serologic evidence of latent syphilis. DESIGN: Cross-sectional survey. METHODS: Consecutively admitted hospital inpatients from an inner-city population were screened for serologic evidence of syphilis with reactive plasma reagin and confirmatory fluorescent treponemal antibody absorption assays. In those with reactive tests, such clinical findings as a history of treatment for syphilis, neurologic abnormalities, presence of human immunodeficiency virus infection, and rapid plasma reagin titer were correlated with cerebrospinal fluid white blood cell count, protein level, and VDRL result. RESULTS: Of 490 consecutive patients, 52 (11%) had serologic evidence of syphilis. Forty-three (83%) of these underwent lumbar puncture. Of the 43, 31 (72%) were seronegative for human immunodeficiency virus and 12 (28%) were seropositive. No patient had a reactive cerebrospinal fluid VDRL test. Cerebrospinal fluid abnormalities were seen in 32% of human immunodeficiency virus-seronegative patients and in 67% of human immunodeficiency virus-seropositive patients. Cerebrospinal fluid abnormalities were not predicted by history of treatment for syphilis, abnormal neurologic findings, or an elevated rapid plasma reagin titer. Cerebrospinal fluid IgG indexes in patients with elevated cerebrospinal fluid protein levels suggested that the protein abnormalities were not caused by local antibody production. Nonreactive cerebrospinal fluid fluorescent treponemal antibody absorption tests suggest that the cerebrospinal fluid abnormalities were not the result of neurosyphilis. CONCLUSIONS: There was a high prevalence of cerebrospinal fluid abnormalities in hospitalized patients with latent syphilis detected by routine screening. Because of the nonspecificity of the cerebrospinal fluid findings, routine lumbar puncture for such patients appears to contribute little to the treatment of latent syphilis. [ABSTRACT FROM AUTHOR]

Long COVID (LongC) is associated with a myriad of symptoms including cognitive impairment. We reported at the beginning of the COVID-19 pandemic that neuronal-enriched or L1CAM+ extracellular vesicles (nEVs) from people with LongC contained proteins associated with Alzheimer's disease (AD). Since that time, a subset of people with prior COVID infection continue to report neurological problems more than three months after infection. Blood markers to better characterize LongC are elusive. To further identify neuronal proteins associated with LongC, we maximized the number of nEVs isolated from plasma by developing a hybrid EV Microfluidic Affinity Purification (EV-MAP) technique. We isolated nEVs from people with LongC and neurological complaints, AD, and HIV infection with mild cognitive impairment. Using the OLINK platform that assesses 384 neurological proteins, we identified 11 significant proteins increased in LongC and 2 decreased (BST1, GGT1). Fourteen proteins were increased in AD and forty proteins associated with HIV cognitive impairment were elevated with one decreased (IVD). One common protein (BST1) was decreased in LongC and increased in HIV. Six proteins (MIF, ENO1, MESD, NUDT5, TNFSF14 and FYB1) were expressed in both LongC and AD and no proteins were common to HIV and AD. This study begins to identify differences and similarities in the neuronal response to LongC versus AD and HIV infection.

Clinical severity scores facilitate comparisons to understand risk factors for severe illness. For the 2022 multinational monkeypox clade IIb virus outbreak, we developed a 7-item Mpox Severity Scoring System (MPOX-SSS) with initial variables refined by data availability and parameter correlation. Application of MPOX-SSS to the first 200 patients diagnosed with mpox revealed higher scores in those treated with tecovirimat, presenting >3 days after symptom onset, and with CD4 counts <200 cells/mm3. For individuals evaluated repeatedly, serial scores were concordant with clinical observations. The pilot MPOX-SSS demonstrated good discrimination, distinguished change over time, and identified higher scores in expected groups., Competing Interests: Potential conflicts of interest. J. Z., W. F., T. J. W. are part of the NIH funded study of tecovirimat for mpox (STOMP) leadership team. All authors have submitted the ICMJE Form for Disclosure of Potential Conflicts of Interest., (© The Author(s) 2023. Published by Oxford University Press on behalf of Infectious Diseases Society of America. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.)

Cardiometabolic diseases and abnormalities have recently emerged as independent risk factors of coronavirus disease 2019 (COVID-19) severity, including hospitalizations, invasive mechanical ventilation, and mortality. Determining whether and how this observation translates to more effective long-term pandemic mitigation strategies remains a challenge due to key research gaps. Specific pathways by which cardiometabolic pathophysiology affects humoral immunity against severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), and vice versa, remain unclear. This review summarizes current evidence of the bidirectional influences between cardiometabolic diseases (diabetes, adiposity, hypertension, CVDs) and SARS-CoV-2 antibodies induced from infection and vaccination based on human studies. Ninety-two studies among >408,000 participants in 37 countries on 5 continents (Europe, Asia, Africa, and North and South America) were included in this review. Obesity was associated with higher neutralizing antibody titers following SARS-CoV-2 infection. Most studies conducted prior to vaccinations found positive or null associations between binding antibodies (levels, seropositivity) and diabetes; after vaccinations, antibody responses did not differ by diabetes. Hypertension and CVDs were not associated with SARS-CoV-2 antibodies. Findings underscore the importance of elucidating the extent that tailored recommendations for COVID-19 prevention, vaccination effectiveness, screening, and diagnoses among people with obesity could reduce disease burden caused by SARS-CoV-2., (Copyright © 2023 The Author(s). Published by Elsevier Inc. All rights reserved.)

Introduction: Since early in the HIV epidemic, emphysema has been identified among people with HIV (PWH) and has been associated with increased mortality. Smoking cessation is key to risk reduction. Health maintenance for PWH and emphysema should ensure appropriate vaccination and lung cancer screening. Treatment should adhere to inhaler guidelines for the general population, but inhaled corticosteroid (ICS) should be used with caution. Frontiers in treatment include targeted therapeutics. Major knowledge gaps exist in the epidemiology of and optimal care for PWH and emphysema, particularly in low and middle-income countries (LMIC)., Areas Covered: Topics addressed include risk factors, pathogenesis, current treatment and prevention strategies, and frontiers in research., Expert Opinion: There are limited data on the epidemiology of emphysema in LMIC, where more than 90% of deaths from COPD occur and where the morbidity of HIV is most heavily concentrated. The population of PWH is aging, and age-related co-morbidities such as emphysema will only increase in salience. Over the next 5 years, the authors anticipate novel trials of targeted therapy for emphysema specific to PWH, and we anticipate a growing body of evidence to inform optimal clinical care for lung health among PWH in LMIC.

Background: The recent mpox outbreak has disproportionately affected people with HIV (PWH) and resulted in the first widespread use of the novel antiviral tecovirimat. Whether treatment outcomes differ between PWH and those without HIV is unknown., Objective: To compare the clinical presentation and treatment outcomes of PWH and HIV-negative persons with mpox virus (MPXV) infection treated with tecovirimat., Design: Retrospective cohort study of patients treated with tecovirimat for confirmed MPXV infection from June to August 2022., Setting: Two academic medical centers in New York City., Participants: The study included 196 persons treated with tecovirimat from 20 June to 29 August 2022. Of 154 testing positive for MPXV, 72 were PWH and 4 had a CD4 count lower than 0.20 × 10 9 cells/L., Measurements: Patient demographic characteristics, clinical presentation, treatment outcomes, and safety data for tecovirimat., Results: Indications for tecovirimat treatment were similar between the PWH and HIV-negative groups. Four participants had serious adverse events; none were attributed to tecovirimat. Three of these 4 participants had HIV infection, and 2 had CD4 counts less than 0.20 × 10 9 cells/L. Twenty-two percent of participants had nonsevere adverse effects. Groups had similar rates of hospitalization, indications for treatment, and co-occurring infections, but PWH had fewer days from symptom onset to treatment (7.5 vs. 10). There was no difference in treatment outcomes, including days to improvement or rate of persistent symptoms., Limitation: Patients with mpox who were not treated with tecovirimat were not followed routinely and therefore lacked comparable outcome data, limiting evaluation of efficacy., Conclusion: In our cohort of patients treated with tecovirimat for severe mpox, HIV status did not seem to affect treatment outcomes., Primary Funding Source: National Institutes of Health., Competing Interests: Disclosures: Disclosures can be viewed at www.acponline.org/authors/icmje/ConflictOfInterestForms.do?msNum=M22-3132.

Extracellular vesicles (EVs) are nanoparticles with a role in intercellular communication. Cell-free mitochondrial DNA (cf-mtDNA) has been associated with cognitive dysfunction in people with HIV (PWH). We conducted a nested case-control study to test the hypothesis that plasma EVs are associated with cf-mtDNA and cognitive dysfunction in older PWH. A machine learning-based model identified total EVs, including select EV subpopulations, as well as urine cf-mtDNA and 4-meter walk time carry power to predict the neurocognitive impairment. These features resulted in an AUC-ROC of 0.845 + / - 0.109 (0.615, 1.00)., (© 2023. The Author(s) under exclusive licence to The Journal of NeuroVirology, Inc.)

Previously, two men were cured of HIV-1 through CCR5Δ32 homozygous (CCR5Δ32/Δ32) allogeneic adult stem cell transplant. We report the first remission and possible HIV-1 cure in a mixed-race woman who received a CCR5Δ32/Δ32 haplo-cord transplant (cord blood cells combined with haploidentical stem cells from an adult) to treat acute myeloid leukemia (AML). Peripheral blood chimerism was 100% CCR5Δ32/Δ32 cord blood by week 14 post-transplant and persisted through 4.8 years of follow-up. Immune reconstitution was associated with (1) loss of detectable replication-competent HIV-1 reservoirs, (2) loss of HIV-1-specific immune responses, (3) in vitro resistance to X4 and R5 laboratory variants, including pre-transplant autologous latent reservoir isolates, and (4) 18 months of HIV-1 control with aviremia, off antiretroviral therapy, starting at 37 months post-transplant. CCR5Δ32/Δ32 haplo-cord transplant achieved remission and a possible HIV-1 cure for a person of diverse ancestry, living with HIV-1, who required a stem cell transplant for acute leukemia., Competing Interests: Declaration of interests The authors declare no competing interests., (Copyright © 2023 The Authors. Published by Elsevier Inc. All rights reserved.)

Background: The diagnosis of urinary tract infection (UTI) is challenging among hospitalized older adults, particularly among those with altered mental status., Objective: To determine the diagnostic accuracy of procalcitonin (PCT) for UTI in hospitalized older adults., Design: We performed a prospective cohort study of older adults (≥65 years old) admitted to a single hospital with evidence of pyuria on urinalysis. PCT was tested on initial blood samples. The reference standard was a clinical definition that included the presence of a positive urine culture and any symptom or sign of infection referable to the genitourinary tract. We also surveyed the treating physicians for their clinical judgment and performed expert adjudication of cases for the determination of UTI., Participants: Two hundred twenty-nine study participants at a major academic medical center., Main Measures: We calculated the area under the receiver operating characteristic curve (AUC) of PCT for the diagnosis of UTI., Key Results: In this study cohort, 61 (27%) participants met clinical criteria for UTI. The median age of the overall cohort was 82.6 (IQR 74.9-89.7) years. The AUC of PCT for the diagnosis of UTI was 0.56 (95% CI, 0.46-0.65). A series of sensitivity analyses on UTI definition, which included using a decreased threshold for bacteriuria, the treating physicians' clinical judgment, and independent infectious disease specialist adjudication, confirmed the negative result., Conclusions: Our findings demonstrate that PCT has limited value in the diagnosis of UTI among hospitalized older adults. Clinicians should be cautious using PCT for the diagnosis of UTI in hospitalized older adults., (© 2021. Society of General Internal Medicine.)

The 2022 outbreak of monkeypox virus infection has expanded far beyond regions in which the disease was previously endemic. Monkeypox has a wide range of manifestations, some of which are unique to this outbreak. Novel clinical presentations, testing limitations, and a lack of available treatments have contributed to delays in recognition, diagnosis, and treatment of monkeypox. As health care workers and governments fight this rare viral infection, which may become a routine diagnosis, early recognition of potential signs and symptoms along with appropriate testing is essential to prevent continuing spread and potential endemicity.

Objective: People living with HIV (PLWH) frequently experience pain, which often co-occurs with psychological symptoms and may impact functional outcomes. We investigated cross-sectional associations between pain, depressive symptoms, and inflammation, and then explored whether pain was related to poorer physical function among older PLWH., Methods: We examined data from PLWH aged 54 to 78 years ( n = 162) recruited from a single outpatient program for a larger study on HIV and aging. Participants reported depressive symptoms (10-item Center for Epidemiological Studies Depression Scale) and then attended a biomedical visit in which they reported past-month pain (Medical Outcomes Study-HIV pain subscale), completed physical function assessments, and provided blood samples (assayed for interleukin 6, interferon-γ, tumor necrosis factor α, and C-reactive protein). Links between pain, depressive symptoms, inflammation, and physical function were tested using linear regression models., Results: PLWH with greater depressive symptoms experienced more pain than did those with fewer depressive symptoms ( B = 1.31, SE = 0.28, p < .001), adjusting for age, sex, race, body mass index, smoking, disease burden, time since HIV diagnosis, and medication use. Higher composite cytokine levels were associated with worse pain ( B = 5.70, SE = 2.54, p = .027 in adjusted model). Poorer physical function indicators, including slower gait speed, weaker grip strength, recent falls, and prefrail or frail status, were observed among those with worse pain. Exploratory mediation analyses suggested that pain may partially explain links between depressive symptoms and several physical function outcomes., Conclusions: Pain is a potential pathway linking depressive symptoms and inflammation to age-related health vulnerabilities among older PLWH; longitudinal investigation of this pattern is warranted. PLWH presenting with pain may benefit from multidisciplinary resources, including behavioral health and geriatric medicine approaches., (Copyright © 2022 The Author(s). Published by Wolters Kluwer Health, Inc. on behalf of the American Psychosomatic Society.)

Background: Older people with HIV experience more comorbidities and geriatric syndromes than their HIV-negative peers, perhaps due to residual inflammation despite suppressive antiretroviral therapy. Cell-free mitochondrial DNA (cfmtDNA) released during necrosis-mediated cell death potentially acts as both mediator and marker of inflammatory dysregulation. Thus, we evaluated plasma cfmtDNA as a potential biomarker of geriatric syndromes., Methods: Participants underwent the Montreal Cognitive Assessment (MoCA), frailty testing, and measurement of plasma cfmtDNA by qPCR and inflammatory markers including C-reactive protein, interleukin-6 (IL-6), interferon gamma, and tumor necrosis factor alpha in this cross-sectional study., Results: Across 155 participants, the median age was 60 years (Q1, Q3: 56, 64), one-third were female, and 92% had HIV-1 viral load <200 copies/mL. The median MoCA score was 24 (21, 27). The plasma cfmtDNA level was higher in those with cognitive impairment (MoCA <23) ( P = 0.02 by the t test) and remained significantly associated with cognitive impairment in a multivariable logistic regression model controlling for age, sex, race, CD4 T-cell nadir, HIV-1 viremia, and depression. Two-thirds of participants met the criteria for a prefrail or frail state; higher plasma cfmtDNA was associated with slow walk and exhaustion but not overall frailty state. Cognitive dysfunction was not associated with C-reactive protein, IL-6, interferon gamma, or tumor necrosis factor alpha, and frailty state was only associated with IL-6., Conclusions: Plasma cfmtDNA may have a role as a novel biomarker of cognitive dysfunction and key components of frailty. Longitudinal investigation of cfmtDNA is warranted to assess its utility as a biomarker of geriatric syndromes in older people with HIV., Competing Interests: E.L.S., M.C.R., and Y.-S.Z. have no conflicts of interest. C.D.J is a consultant for TheraTechnologies. K.C.H. receives consulting fees from Faeth Therapeutics, Inc.; is on the review board for PESI, Inc.; and receives personal fees for reviewing professional nutrition education programing for PESI, Inc. The spouse of H.M.D.-V. holds employment at Elanco. The spouse of M.E.C. is a cofounder and shareholder and serves on the Scientific Advisory Board of Proterris, Inc. M.J.G. reports research support to the institution (Weill Cornell) from Gilead Sciences and Regeneron; is a consultant for Enzychem, Regeneron, ReAlta Life Sciences, and Sobi and receives royalties from Springer and UpToDate., (Copyright © 2022 Wolters Kluwer Health, Inc. All rights reserved.)

Introduction: Lifestyle improvements are key modifiable risk factors for Type 2 diabetes mellitus (DM) however specific influences of biologically active dietary metabolites remain unclear. Our objective was to compare non-targeted plasma metabolomic profiles of women with versus without confirmed incident DM. We focused on three lipid classes (fatty acyls, prenol lipids, polyketides)., Materials and Methods: Fifty DM cases and 100 individually matched control participants (80% with human immunodeficiency virus [HIV]) were enrolled in a case-control study nested within the Women's Interagency HIV Study. Stored blood samples (1-2 years prior to DM diagnosis among cases; at the corresponding timepoint among matched controls) were assayed in triplicate for metabolomics. Time-of-flight liquid chromatography mass spectrometry with dual electrospray ionization modes was utilized. We considered 743 metabolomic features in a two-stage feature selection approach with conditional logistic regression models that accounted for matching strata., Results: Seven features differed by DM case status (all false discovery rate-adjusted q<0.05). Three flavonoids (two flavanones, one isoflavone) were respectively associated with lower odds of DM (all q<0.05), and sorbic acid was associated with greater odds of DM (all q<0.05)., Conclusion: Flavonoids were associated with lower odds of incident DM while sorbic acid was associated with greater odds of incident DM., Competing Interests: The authors have declared that no competing interests exist.

Objectives: People living with human immunodeficiency virus (PLWH) treated with antiretrovirals have life spans similar to their HIV-negative peers. Yet, they experience elevated inflammation-related multimorbidity. Drawing on biopsychosocial determinants of health may inform interventions, but these links are understudied in older PLWH. We investigated cross-sectional relationships between psychosocial factors (mood, loneliness, and stigma), inflammatory markers, and age-related health outcomes among 143 PLWH aged 54-78 years., Method: Participants provided blood samples for serum cytokine and C-reactive protein (CRP) analyses, completed surveys assessing psychosocial factors and health, and completed frailty assessments. Regression models tested relationships between key psychosocial-, inflammation, and age-related health variables, adjusting for relevant sociodemographic and clinical factors., Results: Participants with more depressive symptoms had higher composite cytokine levels than those with fewer depressive symptoms (β = 0.22, t(126) = 2.71, p = .008). Those with higher cytokine levels were more likely to be prefrail or frail (adjusted odds ratio = 1.72, 95% confidence interval = 1.01-2.93) and reported worse physical function (β = -0.23, t(129) = -2.64, p = .009) and more cognitive complaints (β = -0.20, t(129) = -2.16, p = .03) than those with lower cytokine levels. CRP was not significantly related to these outcomes; 6-month fall history was not significantly related to inflammatory markers., Discussion: Novel approaches are needed to manage comorbidities and maximize quality of life among older PLWH. Illustrating key expected biopsychosocial links, our findings highlight several factors (e.g., depressive symptoms, poorer physical function) that may share bidirectional relationships with chronic inflammation, a key factor driving morbidity. These links may be leveraged to modify factors that drive excessive health risk among older PLWH., (© The Author(s) 2021. Published by Oxford University Press on behalf of The Gerontological Society of America. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.)

Background: Older adults with HIV (OAH) experience more comorbidities and geriatric syndromes than their HIV-negative peers, perhaps because of chronic inflammation. Cell-free mitochondrial DNA (cfmtDNA) released from cells undergoing necrosis-mediated cell death potentially acts as both a mediator and marker of inflammatory dysregulation. We hypothesized that urinary cfmtDNA would be associated with frailty, body composition, and fall history in OAH., Methods: OAH completed frailty testing, a psychosocial survey, body composition assessment, and measurement of urine cfmtDNA and urine albumin:creatinine in this cross-sectional study. Urine cfmtDNA was measured by quantative polymerase chain reaction and normalized to urinary creatinine., Results: Across 150 participants, the mean age was 61 years (SD 6 years), half identified as Black, one-third were women, and 93% had HIV-1 viral load <200 copies/mL. Two-thirds met criteria for a prefrail or frail state. Those with unintentional weight loss had higher urine cfmtDNA concentrations (P = 0.03). Higher urine cfmtDNA was inversely associated with the skeletal muscle index (β = -0.19, P < 0.01) and fat mass index (β = -0.08, P = 0.02) in separate multiple linear regression models adjusted for age, sex, and presence of moderate-severe albuminuria., Conclusions: In this cross-sectional study of OAH, higher levels of urine cfmtDNA were more common in subjects with less robust physical condition, including unintentional weight loss and less height-scaled body mass of fat and muscle. These findings suggest urine cfmtDNA may reflect pathophysiologic aging processes in OAH, predisposing them to geriatric syndromes. Longitudinal investigation of urine cfmtDNA as a biomarker of geriatric syndromes is warranted., Competing Interests: K.C.H. reports personal fees from Faeth Therapeutics, Inc., other from PESI, Inc, outside the submitted work; M.E.C. is supported by the NIH. The spouse of M.E.C. is a cofounder and shareholder and serves on the Scientific Advisory Board of Proterris, and S.K.G. is supported by unrestricted research grants from the NIH, Indiana University, and GlaxoSmithKline/ViiV. He has also received advisory fees from GlaxoSmithKline/ViiV and Gilead Sciences. E.L.S reports a grant from Gilead Sciences during the conduct of the study, and M.J.G. reports grants from Gilead Sciences, during the conduct of the study, grants and personal fees from Regeneron, personal fees from Sobi, personal fees from UpToDate, and personal fees from Springer, outside the submitted work. The remaining authors report no conflicts of interest., (Copyright © 2021 Wolters Kluwer Health, Inc. All rights reserved.)

The efficacy of convalescent plasma for coronavirus disease 2019 (COVID-19) is unclear. Although most randomized controlled trials have shown negative results, uncontrolled studies have suggested that the antibody content could influence patient outcomes. We conducted an open-label, randomized controlled trial of convalescent plasma for adults with COVID-19 receiving oxygen within 12 d of respiratory symptom onset ( NCT04348656 ). Patients were allocated 2:1 to 500 ml of convalescent plasma or standard of care. The composite primary outcome was intubation or death by 30 d. Exploratory analyses of the effect of convalescent plasma antibodies on the primary outcome was assessed by logistic regression. The trial was terminated at 78% of planned enrollment after meeting stopping criteria for futility. In total, 940 patients were randomized, and 921 patients were included in the intention-to-treat analysis. Intubation or death occurred in 199/614 (32.4%) patients in the convalescent plasma arm and 86/307 (28.0%) patients in the standard of care arm-relative risk (RR) = 1.16 (95% confidence interval (CI) 0.94-1.43, P = 0.18). Patients in the convalescent plasma arm had more serious adverse events (33.4% versus 26.4%; RR = 1.27, 95% CI 1.02-1.57, P = 0.034). The antibody content significantly modulated the therapeutic effect of convalescent plasma. In multivariate analysis, each standardized log increase in neutralization or antibody-dependent cellular cytotoxicity independently reduced the potential harmful effect of plasma (odds ratio (OR) = 0.74, 95% CI 0.57-0.95 and OR = 0.66, 95% CI 0.50-0.87, respectively), whereas IgG against the full transmembrane spike protein increased it (OR = 1.53, 95% CI 1.14-2.05). Convalescent plasma did not reduce the risk of intubation or death at 30 d in hospitalized patients with COVID-19. Transfusion of convalescent plasma with unfavorable antibody profiles could be associated with worse clinical outcomes compared to standard care., (© 2021. The Author(s).)

Acute lung injury (ALI) often causes severe trauma that may progress to significant morbidity and mortality. ALI results from a combination of the underlying clinical condition of the patient (e.g., inflammation) with a secondary insult such as viral pneumonia or a blood transfusion. While the secondary insult may be variable, the rapidly progressive disease process leading to pulmonary failure is typically mediated by an overwhelming innate immunological or inflammatory reaction driven by excessive complement and neutrophil-mediated inflammatory responses. We recently developed a 'two-hit' ALI rat model mediated by lipopolysaccharide followed by transfusion of incompatible human erythrocytes resulting in complement activation, neutrophil-mediated ALI and free DNA in the blood indicative of neutrophil extracellular trap formation. The objective of this study was to evaluate the role of peptide inhibitor of complement C1 (RLS-0071), a classical complement pathway inhibitor and neutrophil modulator in this animal model. Adolescent male Wistar rats were infused with lipopolysaccharide followed by transfusion of incompatible erythrocytes in the presence or absence of RLS-0071. Blood was collected at various time points to assess complement C5a levels, free DNA and cytokines in isolated plasma. Four hours following erythrocyte transfusion, lung tissue was recovered and assayed for ALI by histology. Compared to animals not receiving RLS-0071, lungs of animals treated with a single dose of RLS-0071 showed significant reduction in ALI as well as reduced levels of C5a, free DNA and inflammatory cytokines in the blood. These results demonstrate that RLS-0071 can modulate neutrophil-mediated ALI in this novel rat model., Competing Interests: The authors have read the journal’s policy and the authors of this manuscript have the following competing interests: Alana Sampson, Brittany Lassiter, Pamela Hair, Adrianne Enos, Kenji Cunnion and Neel Krishna are employees of ReAlta Life Sciences. Neel Krishna and Kenji Cunnion have ownership of ReAlta shares and Kenji Cunnion serves as on the Board of Directors of ReAlta Life Sciences. Neel K Krishna and Kenji M Cunnion are listed as inventors on patents that describe PIC1 molecules. The authors would like to declare the following patents/patent applications associated with this research: 8,241,843 methods for regulating complement cascade proteins using astrovirus coat protein and derivatives thereof, 15/738,786 synthetic peptide compounds and methods of use, 16/400,486 synthetic peptide compounds and methods of use, 8,906,845 peptide compounds to regulate the complement system, 9,422,337 peptide compounds to regulate the complement system, 10,005,818 derivative peptide compounds and methods of use, 9,914,753 peptide compounds to regulate the complement system, 10,414,799 peptide compounds to regulate the complement system, 16/534,200 peptide compounds to regulate the complement system, 16/242,550 PIC1 inhibition of myeloperoxidase oxidative activity in an animal model. The commercial affiliation with ReAlta Life Sciences does not alter our adherence to PLOS ONE policies on sharing data and materials.

India has the highest rates of tuberculosis (TB) globally and a high prevalence of malnutrition; however, the interplay between host nutritional status, inflammation, and the gut microbiome in active tuberculosis disease (ATBD) is less well-studied. We examined differences in gut microbial composition and diversity based on undernutrition and inflammation status among outpatients with ATBD at the time of treatment initiation. During this exploratory cross-sectional study, outpatients (N = 32) with ATBD (confirmed by Xpert MTB/RIF) were enrolled in anti-TB treatment initiated at a hospital in rural southern India. The 16S rRNA sequencing was used to assess the composition of the gut microbiome. We assessed multiple markers of nutritional status, including micronutrient status concentrations (vitamin D [25(OH)D], vitamin B12, ferritin), anthropometry (body mass index, mid-upper arm circumference, and height), and C-reactive protein (CRP), as indicators of inflammation. We found that 25(OH)D was positively associated with the relative abundance of Oscillospira spp., a butyrate-producing genus linked with anti-inflammation effects, and that ferritin was positively associated with Proteobacteria taxa, which have been associated with worse inflammation in other studies. Finally, we found a greater abundance of inflammation-associated taxa from the Proteobacteria phylum and lower alpha-diversity indices among those who were underweight or who had low mid-upper arm circumference or short stature. In summary, we found differences in the gut microbiota composition and diversity among those with undernutrition compared with those with adequate nutrition status at the time of initiation of treatment among patients with ATBD in India. Clinical implications of these findings will need to be examined by larger longitudinal studies.

Background: Multiplex polymerase chain reaction (PCR) panels allow for rapid detection or exclusion of pathogens causing meningitis and encephalitis (ME). The clinical impact of rapid multiplex PCR ME panel results on the duration of empiric antibiotic therapy is not well characterized., Methods: We performed a retrospective prepost study at our institution that evaluated the clinical impact of a multiplex PCR ME panel among adults with suspected bacterial meningitis who received empiric antibiotic therapy and underwent lumbar puncture in the emergency department. The primary outcome was the duration of empiric antibiotic therapy., Results: The positive pathogen detection rates were similar between pre- and post-multiplex PCR ME panel periods (17.5%, 24 of 137 vs 20.3%, 14 of 69, respectively). The median duration of empiric antibiotic therapy was significantly reduced in the post-multiplex PCR ME panel period compared with the pre-multiplex PCR ME panel period (34.7 vs 12.3 hours, P =  .01). At any point in time, 46% more patients in the post-multiplex PCR ME panel period had empiric antibiotic therapy discontinued or de-escalated compared with the pre-multiplex PCR ME panel period (sex- and immunosuppressant use-adjusted hazard ratio 1.46, P =  .01). The median hospital length of stay was shorter in the post-multiplex PCR ME panel period (3 vs 4 days, P =  .03)., Conclusions: The implementation of the multiplex PCR ME panel for bacterial meningitis reduced the duration of empiric antibiotic therapy and possibly hospital length of stay compared with traditional microbiological testing methods., (© The Author(s) 2021. Published by Oxford University Press on behalf of Infectious Diseases Society of America.)

As they age, people living with HIV (PLWH) experience greater rates of inflammation-related health conditions compared to their HIV-negative peers. Because early life adversity can exaggerate proinflammatory effects of later physiological challenges, inflammation may be higher among PLWH with these combined risks, which could inform intervention approaches to mitigate multimorbidity. In this cross-sectional analysis, we investigated individual and combined effects of childhood sexual abuse (CSA) history and physiological burden (Veterans Aging Cohort Study Index scores) on serum cytokine and C-reactive protein (CRP) levels among PLWH. Participants (n ​= ​131; age 54 and older) were patients at an outpatient HIV clinic who completed a psychosocial survey and biomedical research visit as part of a larger study. 93% were virally suppressed, and 40% reported experiencing sexual abuse in childhood. Composite cytokine levels (summarizing IL-6, TNF-α, IFN-γ), CRP, and disease burden did not differ significantly between those who had a history of CSA and those who did not. Participants with greater disease burden had higher composite cytokine levels ( r  ​= ​0.29, p  ​= ​0.001). The disease burden by CSA interaction effect was a significant predictor of composite cytokine levels (but not CRP), and remained significant after controlling for age, sex, race, BMI, anti-inflammatory medication use, selective serotonin reuptake inhibitor use, depressive symptoms, and smoking status (F(1, 114) ​= ​5.68, p  ​= ​0.02). In follow-up simple slopes analysis, greater disease burden was associated with higher cytokine levels among those with CSA history (b ​= ​0.03, SE ​= ​0.008, p <0.001), but not among those without CSA history. Further, in the context of greater disease burden, individuals with a CSA history tended to have higher cytokine levels than those without a CSA history (b ​= ​0.38, SE ​= ​0.21, p ​= ​0.07). These data suggest that the physiological sequelae of childhood trauma may persist into older age among those with HIV. Specifically, links between physiological burden and inflammation were stronger among survivors of CSA in this study. The combined presence of CSA history and higher disease burden may signal a greater need for and potential benefit from interventions to reduce inflammation, an area for future work., Competing Interests: Dr. Derry has an unrelated financial relationship (spouse employment) with Elanco. Dr. Glesby is a consultant to Sobi, ReAlta Life Sciences, Enzychem, and Regeneron and receives royalties from Springer and UpToDate. Dr. Glesby’ institution has received research support from Gilead Sciences and Regeneron to support his work., (© 2021 The Authors.)

Background: Convalescent plasma has been used for numerous viral diseases including influenza, severe acute respiratory syndrome, Middle East respiratory syndrome and Ebola virus; however, evidence to support its use is weak. SARS-CoV-2 is a novel coronavirus responsible for the 2019 global pandemic of COVID-19 community acquired pneumonia. We have undertaken a randomized controlled trial to assess the efficacy and safety of COVID-19 convalescent plasma (CCP) in patients with SARS-CoV-2 infection., Methods: CONCOR-1 is an open-label, multicentre, randomized trial. Inclusion criteria include the following: patients > 16 years, admitted to hospital with COVID-19 infection, receiving supplemental oxygen for respiratory complications of COVID-19, and availability of blood group compatible CCP. Exclusion criteria are : onset of respiratory symptoms more than 12 days prior to randomization, intubated or imminent plan for intubation, and previous severe reactions to plasma. Consenting patients are randomized 2:1 to receive either approximately 500 mL of CCP or standard of care. CCP is collected from donors who have recovered from COVID-19 and who have detectable anti-SARS-CoV-2 antibodies quantified serologically. The primary outcome is intubation or death at day 30. Secondary outcomes include ventilator-free days, length of stay in intensive care or hospital, transfusion reactions, serious adverse events, and reduction in SARS-CoV-2 viral load. Exploratory analyses include patients who received CCP containing high titre antibodies. A sample size of 1200 patients gives 80% power to detect a 25% relative risk reduction assuming a 30% baseline risk of intubation or death at 30 days (two-sided test; α = 0.05). An interim analysis and sample size re-estimation will be done by an unblinded independent biostatistician after primary outcome data are available for 50% of the target recruitment (n = 600)., Discussion: This trial will determine whether CCP will reduce intubation or death non-intubated adults with COVID-19. The trial will also provide information on the role of and thresholds for SARS-CoV-2 antibody titres and neutralization assays for donor qualification., Trial Registration: Clinicaltrials.gov NCT04348656 . Registered on 16 April 2020.

Objectives: To determine links between objectively and subjectively measured physical function and cognitive function among HIV-positive older adults, a growing yet understudied group with elevated risk for multimorbidity. Methods: At a biomedical research visit, 162 participants completed objective tests of gait speed (4-m walk), grip strength (dynamometer), and cognitive function (Montreal Cognitive Assessment, MoCA) and reported their well-being (Medical Outcomes Study-HIV survey). Results: Those with faster gait speed had better overall cognitive function than those with slower gait speed ( b = 3.98, SE = 1.30, p = .003) in an adjusted regression model controlling for age, sex, race, height, preferred language, and assistive device use. Grip strength was not significantly associated with overall cognitive function. Self-rated cognitive function was weakly related to MoCA scores ( r = .26) and gait speed ( r = .14) but was strongly associated with emotional well-being ( r = .53). Discussion: These observed, expected connections between physical and cognitive function could inform intervention strategies to mitigate age-related declines for older adults with HIV.

Antimicrobial resistance (AMR) is a fundamental global concern analogous to climate change threatening both public health and global development progress. Infections caused by antimicrobial-resistant pathogens pose serious threats to healthcare and human capital. If the increasing rate of AMR is left uncontrolled, it is estimated that it will lead to 10 million deaths annually by 2050. This global epidemic of AMR necessitates radical interdisciplinary solutions to better detect antimicrobial susceptibility and manage infections. Rapid diagnostics that can identify antimicrobial-resistant pathogens to assist clinicians and health workers in initiating appropriate treatment are critical for antimicrobial stewardship. In this review, we summarize different technologies applied for the development of rapid diagnostics for AMR and antimicrobial susceptibility testing (AST). We briefly describe the single-cell technologies that were developed to hasten the AST of infectious pathogens. Then, the different types of genotypic and phenotypic techniques and the commercially available rapid diagnostics for AMR are discussed in detail. We conclude by addressing the potential of current rapid diagnostic systems being developed as point-of-care (POC) diagnostic tools and the challenges to adapt them at the POC level. Overall, this review provides an insight into the current status of rapid and POC diagnostic systems for AMR.

Background: The spread of SARS-CoV-2 and the COVID-19 pandemic have caused significant morbidity and mortality worldwide. The clinical characteristics and outcomes of hospitalized patients with SARS-CoV-2 and HIV co-infection remain uncertain., Methods: We conducted a matched retrospective cohort study of adults hospitalized with a COVID-19 illness in New York City between March 3, 2020, and May 15, 2020. We matched 30 people with HIV (PWH) with 90 control group patients without HIV based on age, sex, and race/ethnicity. Using electronic health record data, we compared demographic characteristics, clinical characteristics, and clinical outcomes between PWH and control patients., Results: In our study, the median age (interquartile range) was 60.5 (56.6-70.0) years, 20% were female, 30% were black, 27% were white, and 24% were of Hispanic/Latino/ethnicity. There were no significant differences between PWH and control patients in presenting symptoms, duration of symptoms before hospitalization, laboratory markers, or radiographic findings on chest x-ray. More patients without HIV required a higher level of supplemental oxygen on presentation than PWH. There were no differences in the need for invasive mechanical ventilation during hospitalization, length of stay, or in-hospital mortality., Conclusions: The clinical manifestations and outcomes of COVID-19 among patients with SARS-CoV-2 and HIV co-infection were not significantly different than patients without HIV co-infection. However, PWH were hospitalized with less severe hypoxemia, a finding that warrants further investigation., (© The Author(s) 2020. Published by Oxford University Press on behalf of Infectious Diseases Society of America.)

Objectives: Our study goal was to evaluate a set of nutritional indicators among adults with confirmed or suspected active tuberculosis disease in southern India, given the limited literature on this topic. Study objectives were to assess the: I) double burden of malnutrition at individual and population levels; II) relative performance of anthropometric indicators (body mass index, waist circumference) in diabetes screening; and III) associations between vitamin D and metabolic abnormalities., Design: Cross-sectional study., Setting: Hospital in rural southern India., Participants: Among adult patients (n = 834), we measured anthropometry, body composition, and biomarkers (vitamin D, glycated hemoglobin, hemoglobin) of nutritional status. Subsets of participants provided blood and sputum samples., Results: Among participants, 91.7% had ≥ 1 malnutrition indicator; 34.6% had both undernutrition and overnutrition indicators. Despite the fact that >80% of participants would be considered low-risk in diabetes screening based on low body mass index and waist circumference, approximately one-third had elevated glycated hemoglobin (≥ 5.7%). The lowest quintile of serum 25-hydroxyvitamin D was associated with an increased risk of glycated hemoglobin ≥ 5.7% (adjusted risk ratio 1.61 [95% CI 1.02, 2.56]) compared to the other quintiles, adjusting for age and trunk fat., Conclusions: Malnutrition and diabetes were prevalent in this patient population; since both can predict poor prognosis of active tuberculosis disease, including treatment outcomes and drug resistance, this emphasizes the importance of dual screening and management of under- and overnutrition-related indicators among patients with suspected or active tuberculosis disease. Further studies are needed to determine clinical implications of vitamin D as a potential modifiable risk factor in metabolic abnormalities, and whether population-specific body mass index and waist circumference cut-offs improve diabetes screening., Competing Interests: E.A.Y., J.L.F., P.M.B., W.B., and D.G.R. have no conflicts of interest. S.M. is an unpaid board member of and holds equity stake in a diagnostic start-up focused on developing assays for low-cost and point-of-care measurement of certain nutrients from a drop of blood using results from his research as a faculty member at Cornell University. M.J.G. receives funding to his institution from Gilead Sciences for an investigatorinitiated study unrelated to the current work. There are no further patents, products in development or marketed products to declare. This does not alter our adherence to PLOS ONE policies on sharing data and materials.

: Globally, the proportion of older people living with HIV (PLWH) is growing and the burden of noncommunicable diseases, including cardiac and renal disease, is increasing. There are few studies of renal disease and cardiac risk in older PLWH. This study investigates the relationship between albuminuria and cardiac risk as estimated by the Atherosclerotic Cardiovascular Disease 10-year risk calculator. We report that albuminuria is associated with a higher Atherosclerotic Cardiovascular Disease risk score in both diabetic and nondiabetic older PLWH.

Antimicrobial resistance is recognized as one of the greatest emerging threats to public health. Antimicrobial resistant (AMR) microorganisms affect nearly 2 million people a year in the United States alone and place an estimated $20 billion burden on the healthcare system. The rise of AMR microorganisms can be attributed to a combination of overprescription of antimicrobials and a lack of accessible diagnostic methods. Delayed diagnosis is one of the primary reasons for empiric therapy, and diagnostic methods that enable rapid and accurate results are highly desirable to facilitate evidence-based treatment. This is particularly true for clinical situations at the point-of-care where access to state-of-the-art diagnostic equipment is scarce. Here, we present a capillary-based antimicrobial susceptibility testing platform (cAST), a unique approach that offers accelerated assessment of antimicrobial susceptibility in a low-cost and simple testing format. cAST delivers an expedited time-to-readout by means of optical assessment of bacteria incubated in a small capillary form factor along with a resazurin dye. cAST was designed using a combination of off-the-shelf and custom 3D-printed parts, making it extremely suitable for use in resource-limited settings. We demonstrate that growth of bacteria in cAST is approximately 25% faster than in a conventional microplate, further validate the diagnostic performance with clinical isolates, and show that cAST can deliver accurate antimicrobial susceptibility test results within 4-8 h.

Diabetes mellitus (DM) is associated with expansion of proinflammatory lymphocyte subsets. We investigated the relationship of total white blood cell (WBC) count and lymphocyte subsets with incident DM in the Women's Interagency HIV Study (WIHS). Higher CD4 and CD8 T cell counts, lymphocyte count, and total WBC count were associated with incident DM among both women with and without HIV, although the association of CD8 was not statistically significant among women without HIV.

Background: The intestinal microbiota contributes to the pathogenesis of obesity and metabolic disorders. People living with HIV (PLWH) have a higher risk for the development of visceral adiposity with accompanying worsened cardiovascular risk., Setting: Convenience sample from an HIV clinic and research unit., Methods: To understand the relationship between adiposity and intestinal dysbiosis, we compared the gut microbiota and inflammatory markers in a cross-sectional study of viscerally obese, generally obese, and lean PLWH. Fecal intestinal microbiota was characterized by 16S ribosomal DNA sequencing. Abdominal CTs quantified subcutaneous adipose tissue and visceral adipose tissue (SAT; VAT). Serum high sensitivity C-reactive protein, adiponectin, leptin, IL-6, MCP-1, and sCD14 were assayed., Results: We studied 15, 9, and 11 participants with visceral obesity, general obesity, and lean body type, respectively. The generally obese group were all women and 2/3 African American, whereas the visceral obesity and lean groups were predominantly white and men who have sex with men. Markers of systemic inflammation and sCD14 were higher in general obesity compared with lean. sCD14 was positively correlated with VAT, but not SAT. Bacterial diversity was significantly reduced in participants with visceral and general obesity and composition of intestinal microbiota was significantly different from lean body types. Bacterial alpha diversity was negatively correlated with VAT area, waist/hip ratio, and sCD14, but not with SAT area., Conclusions: In this exploratory study, obesity in general was associated with dysbiotic intestinal microbiota. The relationships of VAT to bacterial diversity and sCD14 suggest that dysbiosis in viscerally obese PLWH could be associated with heightened inflammatory state.

C1q/tumor necrosis factor (TNF)-related proteins (CTRPs) have been linked to energy homeostasis and vascular health. People with HIV are susceptible to cardiometabolic disease, but the contributions of different CTRPs are unknown. We investigated the associations of HIV and related factors with serum CTRPs, and CTRPs' relationships with cardiometabolic phenotypes. This involved a cross-sectional analysis of participants in the Women's Interagency HIV Study aged ≥35 with ( n  = 209) and without ( n  = 92) HIV who underwent carotid ultrasound in 2004-2005 and had stored serum available for measurement of total adiponectin and CTRPs 1, 3, 5, and 9. The Benjamini/Hochberg procedure was used to control the study-wide false-positive rate. HIV-positive women had significantly higher adiponectin than HIV-negative women after adjustment for sociodemographic, behavioral, and clinical variables [beta = 0.29 (95% confidence interval 0.11-0.47)]. Among HIV-positive women, lower CD4 count was associated with higher adiponectin and history of AIDS with higher CTRP9, but these were only nominally significant. There was no relationship between HIV status and CTRP 1, 3, or 5, nor was antiretroviral therapy or viral load associated with any CTRP. In the entire cohort, higher adiponectin was associated with significantly lower fasting glucose and insulin resistance, while higher CTRP5 [beta = -0.02 (-0.033 to -0.007)]-and, at a nominal level, CTRPs 1 and 3-was associated with significantly lower carotid intima-media thickness. In conclusion, in this sample of middle-aged women, HIV serostatus was positively associated with adiponectin, but not CTRPs. In turn, serum adiponectin was inversely associated with glucose dysregulation, whereas CTRP5 was inversely associated with carotid intima-media thickness. Further research is needed to determine CTRPs' role in atherosclerosis.

Background: Inflammation is a key component of immune response to infections and pathogenesis of metabolic and cardiovascular diseases. Inflammatory biomarkers, including alpha-1-acid glycoprotein (AGP), are considered prognostic tools for predicting risk, monitoring response to therapy, and adjusting nutritional biomarkers for accurate interpretation. Serum is considered a primary source of biomarkers; urine and saliva are increasingly being explored and utilized as rapidly accessible, noninvasive biofluids requiring minimal sample processing and posing fewer biohazard risks., Methods: A lateral flow immunoassay was developed for an established mobile-based platform to quantify AGP in human serum, urine, and saliva. Assay performance was assessed with purified AGP in buffer, diluted human serum samples ( n = 16) banked from a trial in people living with HIV, and saliva and urine ( n = 15 each) from healthy participants. Reference methods were conventional clinical chemistry analyzer or commercial ELISA. Bootstrap analysis was used to train and validate sample calibration., Findings: The correlation between the assay and reference method for serum was 0.97 ( P < 0.001). Mean (95% CI) best fit line slope was 1.0 (0.88, 1.15) and intercept was -0.003 (-0.08, 0.09). The correlation for urine was 0.93, and for saliva was 0.97 (both P < 0.001). The median CV for the LFIA for AGP in buffer was 13.2% and for all samples was 28.7%., Interpretation: The performance of the assay indicated potential use as a rapid, low sample volume input, and easy method to quantify AGP that can be licensed and adopted by commercial manufacturers for regulatory approvals and production. This has future applications for determining inflammatory status either alone or in conjunction with other inflammatory proteins such as C-reactive protein for prognostic, monitoring, or nutritional status applications, including large-scale country level surveys conducted by the DHS and those recommended by the WHO., Competing Interests: Competing interests statement: DE and SM have an equity interest in VitaMe Technologies (DBA VitaScan), which is commercializing similar diagnostic technology that is described herein. MG receives funding to his institution from Gilead Sciences for an investigator-initiated study unrelated to the current work. There are no further patents, products in development or marketed products to declare. BMG, JLF, TR: no conflicts of interest.