IntroductionVaccines against SARS-CoV-2 and influenza require reformulation due to viral evolution. It remains unclear how vaccination against evolving antigens influences T-cell responses and the impact of reformulation on T-cell responses to new variants in immunocompromised hosts. Solid organ transplant recipients (SOTRs) had significantly lower antibody levels following vaccination and required repeated boosting during the COVID-19 pandemic.MethodsWith the introduction of the Omicron spike (S) to the bivalent mRNA vaccines in 2022, the relative contribution of T-cell responses cross-reactive for Omicron mutated S sequences was assessed via intracellular cytokine staining using peptide pools containing conserved or mutated S sequences.ResultsS-specific CD4 T cells recognize both conserved and Omicron mutated S sequences pre- and post-bivalent vaccination, even in the absence of evidence of prior infection as detected by T-cell responses to a novel peptide pool. CD4 T-cell responses to both conserved and Omicron mutated sequences correlated with antibody pseudo-neutralization of BA.5 S. Importantly, pre-bivalent conserved S CD4 T-cell responses significantly correlated with antibody pseudo-neutralization of BA.5 S post-bivalent.DiscussionThese results emphasize the importance of conserved and cross-reactive responses in vaccine immunogenicity, providing a mechanism through which repeated boosting enhances vaccine immunogenicity in SOTRs and other immunocompromised populations.

BACKGROUND:Anti-AnWj autoantibody production with concomitant antigen suppression rarely has been reported secondary to lymphoid malignancy. Anti-AnWj autoantibodies are often considered clinically insignificant; however, cases of posttransfusion hemolysis have been documented which require transfusion of AnWj-negative red blood cells (RBC). AnWj-negative RBC units are rare, thus options for long-term transfusion are limited. We report the novel use of sutimlimab, a classical complement pathway inhibitor, for severe anemia in a patient with a complement fixing anti-AnWj autoantibody. CASE PRESENTATION:A 57-year-old male with high-grade B-cell lymphoma presented with severe anemia and was found to have an anti-AnWj autoantibody of IgM and IgG isotypes and a complement-positive direct antiglobulin test. AnWj-positive RBC were provided for transfusion. His hemoglobin did not augment, and he developed evidence of hemolysis following crossmatch-incompatible RBC units. Transfusion of In(Lu) RBC showed initial response; however, his anemia persisted. Sutimlimab was subsequently initiated based on the complement fixing ability of the autoantibody. An improvement in hemoglobin, decrease in lactate dehydrogenase, and decrease in RBC-bound complement fragments were observed following sutimlimab administration. CONCLUSION:Management strategies for clinically significant anti-AnWJ are not well defined. To our knowledge, this is the first case using sutimlimab to manage complement-mediated hemolysis due to an auto-anti-AnWj antibody. While initial response to sutimlimab was favorable, the patient's comorbid lymphoma, multiple therapies, and short treatment period limit definitive conclusions regarding efficacy. Anti-complement therapy warrants further study for refractory antibody-mediated hemolysis with evidence of complement activation in the absence of compatible transfusions.

Although Kaposi sarcoma-associated herpesvirus (KSHV)-associated disease (KAD) has long been recognized as a complication of transplantation, in the past 5 years, the incidence of KAD among solid organ transplant recipients in the United States has increased greater than 5-fold, exposing gaps in screening and monitoring protocols. The United States lacks a coordinated framework for KSHV risk assessment and posttransplant monitoring, primarily because serologic and molecular testing is not yet widely available. Current laboratory-developed tests are not standardized across laboratories and analytes, testing capacity is insufficiently available nationwide, and most tests are not approved for clinical use. This diagnostic gap limits the ability to define the KSHV status of donors and recipients before transplantation, distinguish graft-mediated transmission from reactivation of preexisting infection, and interpret KAD risk across organ type and numerous host factors. International experiences and the Human Immunodeficiency Virus Organ Policy Equity Act in action cohort in the US provide context, but do not readily translate into US policy. We outlined here priorities for a US response, including generation of representative epidemiologic data, diagnostic standardization, consensus testing and monitoring strategies, and clinician education to support safe, efficient, evidence-based organ utilization.

The penile epithelium, encompassing multiple anatomical sites, is the primary location of human immunodeficiency virus (HIV) acquisition in heterosexual men. Although the per-contact risk of penile HIV acquisition is generally low, substantial global discrepancies in HIV prevalence still exist, particularly in low-income regions. In uncircumcised men, the immune milieu of the subpreputial space is a key determinant of HIV risk, with inflammation-mediated epithelial disruption and target cell recruitment facilitating viral infection. Specific bacterial components of the penile microbiome cause local inflammation and enhance susceptibility, while penile circumcision reduces HIV risk by both removing susceptible foreskin tissues and reducing the abundance of these bacteria. The penile urethra is also an important site of HIV acquisition, particularly among circumcised men, but determinants of urethral susceptibility remain poorly understood. Penile-vaginal sex induces transient inflammation and epithelial damage at both the subpreputial space and urethra, likely mediated by mechanical effects and/or the sexual exchange of pro-inflammatory bacteria. This review summarizes knowledge regarding the immunological and microbial determinants of penile HIV acquisition risk, highlights biological factors and sexual practices that shape the penile immune milieu, and discusses current advances in microbiome-targeting interventions as potential HIV prevention strategies.

BACKGROUND:National trends in cryoprecipitate transfusion and patient- and hospital-level factors associated with cryoprecipitate transfusion use among US hospitalizations are not well characterized. STUDY DESIGN AND METHODS:This descriptive study used the National Inpatient Sample (NIS) to estimate overall and sex-specific trends in cryoprecipitate transfusion from 2016 to 2022. Adult hospitalizations (≥18 years) receiving cryoprecipitate were included. The unit of analysis was the hospitalization record, and sampling weights were applied to produce nationally representative estimates. Factors associated with cryoprecipitate transfusion in 2022 were evaluated using multivariable Poisson regression. RESULTS:Between 2016 and 2022, there were 205,075,194 weighted hospitalizations, of which 181,950 (0.089%) involved cryoprecipitate transfusion. The prevalence of cryoprecipitate transfusion increased significantly from 0.063% in 2016 to 0.110% in 2022. In multivariable analysis, cryoprecipitate transfusion was more likely among patients aged 60-70 years (vs. 18-30 years; adjusted prevalence ratio [adjPR] = 2.34 [95% confidence intervals (CI) = 2.03-2.70]). Transfusion was also associated with non-White patients, those from higher-income areas, elective admissions (vs. nonelective admissions; adjPR = 1.48 [95% CI = 1.32-1.66]), larger hospital bed size (vs. small; adjPR = 2.71 [95% CI = 2.14-3.43]), and in metropolitan teaching hospitals (vs. nonteaching; adjPR = 3.04 [95% CI = 2.50-3.69]). The prevalence of cryoprecipitate transfusion was lower among females (adjPR = 0.59 [95% CI = 0.55-0.62]), Medicare-covered hospitalizations (vs. Private; adjPR = 0.85 [95% CI = 0.78-0.93]), and admission to private investor-own hospitals (vs. government nonfederal hospitals; adjPR = 0.56 [95% CI = 0.36-0.87]). DISCUSSION:Cryoprecipitate transfusion among US hospitalizations increased from 2016 to 2022, reflecting evolving transfusion practices and the need for continued evaluation of fibrinogen replacement strategies and appropriate cryoprecipitate utilization.

BACKGROUND:Data on the population-scale impact of dolutegravir (DTG)-based HIV regimens in sub-Saharan Africa are extremely limited. We used data from a surveillance cohort in southern Uganda to assess viral suppression and antiretroviral (ART) resistance over 10-years alongside DTG scale-up. METHODS:Consenting participants in the population-based Rakai Community Cohort Study between August 2011 and March 2023 aged 15-49 completed questionnaires and provided samples for HIV testing, viral load quantification, and viral deep-sequencing. We collected data on DTG utilization at HIV care clinics. We estimated the prevalence of HIV suppression and ART resistance using robust Poisson regression. Bayesian logistic regression quantified associations between resistance and individual-level suppression across surveys. RESULTS:Among 8781 people with HIV (PWH), suppression increased from 57.1% (2014, 95% confidence interval [CI], 55.4%-58.8%) to 90.3% (2022, 95% CI, 89.2%-91.4%). By 2020 84.4% (95% CI, 83.7%-85.2%) and 64.6% (95% CI, 63.9%-65.3%) of men and women on ART were on DTG. Among treatment-experienced viremic PWH, any intermediate/high resistance decreased from 51.1% (95% CI, 40.7%-64.2%, 2014) to 27.9% (95% CI, 21.3%-36.5%, 2022). Two of 258 (0.8%) 2022 participants harbored intermediate/high-level DTG resistance (inQ148R, inE138K, and inG140A). inS153Y (2-fold INSTI resistance) was observed in 23/306 (7.5%) of viremic individuals, with evidence of transmission. By 2022, NNRTI/NRTI resistance was not associated with a reduction in individual-level suppression (risk ratios: 1.15, 95% HPD: 0.93-1.39; 1.14, 0.86-1.42). CONCLUSIONS:Viral suppression increased during the DTG transition with minimal emerging intermediate/high-level resistance. Falling resistance among treatment-experienced PWH underscores the role of ART adherence in reducing viremia. The emergence of inS153Y justifies continued surveillance.

To validate the accuracy of previously published US seroprevalence estimates for hepatitis D virus (HDV) antibody, we retested National Health and Nutrition Examination Survey samples from 2007‒2018 using a different assay. We found the HDV seroprevalence among hepatitis B surface antigen positive participants aged ≥6 years to be 1.26%.

INTRODUCTION:Prior studies showed that some female bar workers (FBWs) may engage in sex work in Africa. However, population-level data on HIV burden among FBWs in African settings are rare. METHODS:We used five survey rounds of data (2011-2020) from the Rakai Community Cohort Study, a population-based HIV surveillance cohort in 36 inland agrarian/trading communities (HIV prevalence∼12%) and four Lake Victoria fishing communities(∼40%) in southern Uganda. Women reporting bar work as a primary or secondary occupation were identified and compared to non-FBWs. Primary outcomes included HIV seropositivity, incident infection, viral suppression (<200copies/ml) among women with HIV, and population prevalence of viremia. Prevalence ratios (PRs) and incidence rate ratios (IRRs) were estimated using Poisson regression with 95% confidence intervals (CIs). RESULTS:Among 23,556 female participants contributing 52,708 person-visits, 1,205(5.1%) self-identified as FBWs, who had significantly higher baseline HIV seroprevalence than non-FBWs (51.9%vs.18.5%;PR=2.81,95%CI=2.64-2.95). There were 356 incident infections over 39,228 person-years. HIV incidence among FBWs was 2.49/100 person-years compared to 0.87 among non-FBWs (age-adjusted IRR=3.64,95%CI=2.33-5.42). While HIV viral suppression was similar among participants living with HIV regardless of FBW status, the population prevalence of HIV viremia was 1.69 times higher among FBWs (95%CI=1.38-2.08). Among 179 HIV-seronegative FBWs surveyed in 2018-2020, 79.9%(143/179) were aware of PrEP, while only 13.4%(24/179) had ever used it, with just 2.8%(5/179) current users. CONCLUSIONS:FBWs in Uganda experience substantially higher HIV burden and acquisition risk compared to the general population. Prevention strategies tailored to the occupational context of bar work, including prioritization of HIV service delivery and access to oral and long-acting injectable PrEP, may substantially reduce HIV incidence among FBWs and their sexual partners.

Importance:Public concern and speculation have emerged around a possible link between neonatal male circumcision (NMC) and autism spectrum disorder (ASD). Evidence is limited and inconsistent. Objective:To examine associations between NMC and child ASD and autism-related traits and behaviors. Design, Setting, and Participants:This prospective cohort study was conducted among cohort sites participating in the Environmental Influences on Child Health Outcomes (ECHO) Cohort between February 2003 and September 2025. Statistical analyses were conducted from November 2025 to February 2026. The analysis included male, singleton children with data on NMC status and child ASD. Exposure:NMC status within 28 days of birth at a medical facility. Main outcomes and Measures:ASD diagnosis was based on parent report of diagnosis by a medical professional or documentation of criterion standard clinical assessments. Social Responsiveness Scale (SRS-2) T-scores assessed the presence and distribution of autism traits, and Diagnostic and Statistical Manual of Mental Disorders (Fifth Edition) Autism Spectrum Problems subscale T-scores from the Child Behavior Checklist (CBCL) 1.5/5 assessed the occurrence of child autism-related behaviors. Results:The sample included 2771 male children from 14 ECHO sites, of whom 1840 (66%) were circumcised before hospital discharge, and 192 (7%) had an autism diagnosis. Among 1840 circumcised males, 108 (6%) had autism, compared with 84 of 931 uncircumcised males (9%). Mean (SD) age at autism diagnosis was 3.8 (2.2) years. Among circumcised males, 31 (4%) were administered acetaminophen during the procedure, and 128 (7%) within the 30 days after birth. After adjusting for confounders, there was no association between NMC and ASD diagnosis (odds ratio [OR], 0.83; 95% CI, 0.59-1.17). After stratification by region, preterm birth, and neonatal intensive care unit admission, an inverse or no association was observed between NMC and ASD diagnosis. Adjusted analyses showed no associations between NMC and SRS-2 continuous (β = -0.62; 95% CI, -1.46 to 0.22) or binary (OR, 0.75; 95% CI, 0.48-1.15) T-scores. Similarly, no associations were observed between NMC and CBCL 1.5/5 continuous (β = 0.01; 95% CI, -0.54 to 0.56) or binary (OR, 1.30; 95% CI, 0.75-2.26) T-scores. Overall, inverse or no associations were observed across all strata for SRS-2 and CBCL 1.5/5 outcomes. Conclusions and Relevance:This cohort study yielded no evidence that NMC was associated with ASD risk, whether assessed by parent report of medical professional diagnosis or validated instruments measuring autism-related traits and behavior. These findings may provide reassurance for families who are considering or have elected NMC for their child.

Human Immunodeficiency Virus type 1 (HIV-1) is responsible for the global HIV/AIDS epidemic and the establishment of an integrated HIV-1 reservoir remains the primary obstacle to cure. Upon therapy interruption, reactivation of the persistent HIV-1 reservoir propagates viral rebound and mediates continued immunological decline. While furthering understanding of the HIV-1 reservoir is essential for HIV-1 cure, commonly used sequencing strategies are often limited by the reliance on short-read sequencing across separate assays to determine integration sites and proviral integrity - something that does not always adequately resolve complex human genomic repeats or low complexity regions. Simultaneous identification of proviral integration sites and proviral integrity at the single molecule level would enable HIV-1 reservoir characterization with minimal imputation or bioinformatic reconstruction. Here we present HIV Single Molecule Real Time Capture (HIV SMRTcap), a novel molecular and computational pipeline that directly and simultaneously identifies HIV-1 integration sites, defines proviral integrity, and characterizes clonal expansion of HIV-1 provirus-containing cells with single molecule resolution. In combination with long-read, single-molecule, real-time (SMRT) sequencing and custom analytic pipelines, HIV SMRTcap enables a highly comprehensive characterization of HIV-1 reservoirs. Moreover, we demonstrate here that HIV SMRTcap performs robustly across the major global subtypes (HIV-1 subtype A, B, C, D and A/D recombinant viruses), and can use both cell- and tissue-derived inputs, including samples from antiretroviral therapy (ART) treated individuals with undetectable viral loads. Our results demonstrate that HIV SMRTcap serves as a comprehensive, robust method for unbiased HIV-1 reservoir characterization. Used alone, or in combination with single-cell based methods, HIV SMRTcap will enable novel exploration of viral reservoirs across subtypes and in tissue-specific compartments, providing critical information needed to inform HIV-1 cure.

People with HIV-1 have higher risk for rejection after kidney transplantation but the mechanism is poorly understood. As HIV latency promotes immune dysregulation and chronic inflammation, we evaluated whether the size of the HIV latent viral reservoir (LVR) at baseline and through 52-weeks is associated with rejection in kidney transplant recipients with HIV from donors with and without HIV. Using the intact proviral DNA assay, we found no differences in the LVR between those who experienced rejection (n = 14) versus those who did not (N = 55) regardless of donor HIV status. These data support the feasibility of HIV+ to HIV+ organ transplantation. Clinical Trials Registration. NCT03500315.

Progressive Familial Intrahepatic Cholestasis type 2 (PFIC-2) is a rare autosomal recessive liver disorder caused by ABCB11 mutations impairing the bile salt export pump (BSEP). Liver transplantation is typically considered curative; however, a subset of patients develop antibody-induced BSEP deficiency (AIBD), a rare post-transplant complication driven by recipient IgG antibodies against graft BSEP. Patients often present with recurrent cholestasis and graft dysfunction. Therapeutic plasma exchange (TPE) is increasingly used to remove circulating antibodies, often alongside immunomodulatory therapies. We describe a patient with PFIC-2 who developed four distinct AIBD relapses over a 24-year period, beginning 12 years after transplantation. Each relapse was treated with a coordinated regimen including TPE, intravenous immunoglobulin (IVIg), rituximab, and optimized maintenance immunosuppression. TPE procedures were performed using the Spectra Optia system with one plasma volume exchange using citrate anticoagulation. Across all relapses, TPE was associated with rapid reductions in cholestatic markers, with the greatest improvements noted after apheresis initiation. TPE procedure intensity evolved over time, with earlier initiation and a gradual increase in the total number of exchanges per relapse. Biopsies demonstrated progressive cholestatic injury, yet graft function remained preserved and re-transplantation was avoided. Adverse events were infrequent and managed conservatively. This case highlights the potential role of early and sustained use of TPE as part of a multimodal strategy for managing recurrent AIBD. Consistent clinical and biochemical improvement across relapses supports incorporating TPE with immunosuppression and B-cell targeted therapy in similar presentations. Further studies are needed to clarify optimal timing, frequency, and treatment combinations.

Respiratory syncytial virus (RSV) antibody durability in immunosuppressed persons following RSV vaccination is unknown. In this observational cohort of immunosuppressed persons, peak responses occurred 1 month after vaccination, without significant waning by 6 months; adjuvanted vaccine recipients had higher responses. This suggests RSV antibody durability of at least 6 months and potential augmentation by adjuvanted vaccine.

Background:Novel HIV prevention interventions such as long-acting pre-exposure prophylaxis (PrEP) could substantially reduce HIV transmission in Africa. However, efficient implementation in high-prevalence settings where incidence has declined requires an understanding of the contemporary dynamics driving new infections. Methods:We identified incident HIV cases from a longitudinal, population-based cohort in Uganda. We individually matched cases to HIV-negative controls; traced and enrolled reported sexual partners; and enrolled female sex workers (FSWs) from reported venues. Conditional logistic regression, transmission modeling, and phylogenetics were used to characterize transmission networks. Findings:From 2021-2024, 38,899 HIV tests among 22,255 people identified 187 people with incident infections (47.6% male); 164 (88%) were enrolled and matched to 164 HIV-negative controls. Overall, 593 non-sex-worker partners (371 enrolled,62.6%), 146 FSW partners (21 enrolled,14.4%), and 28 venues (208 FSWs enrolled) were reported. Incident infection was most strongly predicted by partnership with a FSW (odds ratio:15.5; 95%CI:3.7-64.8), identified in 43.0% of male cases versus 6.3% of controls. Men with FSW partners had larger sexual networks than men without (median:6 vs 2 partners), and 91.2% of men with FSW partners also had non-sex-worker partners. Transmission modeling attributed 34.4% (95%CI:31.5-36.8%) of all male infections and 80.0% (95%CI:73.2-84.4%) of infections among male clients to sex with FSWs. Oral PrEP use among HIV-negative partners of incident cases was low (8.9% in women; 2.1% in men). Interpretation:Men with FSW partners accounted for a substantial share of incident HIV infections and had markedly higher odds of infection than men without such partnerships. Together with the high potential for onward transmission within male client networks, these findings suggest that inclusion of male clients in long-acting HIV prevention strategies could be highly efficient and impactful. Funding:National Institutes of Health, United States; Gates Foundation; National Health and Medical Research Council, Australia.

Background: Venous thromboembolism (VTE) is a frequent and often preventable cancer-related comorbidity. Objectives: This study evaluated national health care burden of patients hospitalized with cancer and VTE diagnoses. Methods: The 2021 Nationwide Inpatient Sample was used to generate nationally representative estimates of cancer-associated thrombotic events identified via International Classification of Diseases-10 coding. Adjusted odds ratios (aOR) for co-diagnosis rate and all-cause mortality, median hospital charges, and length of stay (LOS) for cancer admissions with and without VTE were calculated. Results: Of 28,443,009 adult US hospitalizations in 2021, 2,907,118 (10.2%) listed cancer as a diagnosis. Of these, 234,090 (8.1%) had co-diagnosis of VTE: pulmonary embolism (PE), 96,335 (41%); deep vein thrombosis (DVT), 172,315 (74%); and PE+DVT, 34,560 (15%). Median age for admissions with cancer and VTE was 67 years (IQR, 58-76 years), with 87.6% admissions classified as major/severe underlying illness. VTE and cancer occurred at significantly higher rates than noncancer admissions (adjusted odds ratio [aOR], 1.81; 95% CI, 1.79-1.83; P < .001; PE: aOR, 1.54; 95% CI, 1.51-1.56; P < .001); DVT: aOR, 1.94; 95% CI, 1.91-1.96; P < .001)]. Odds of all-cause mortality for cancer admissions with VTE was higher as than without (aOR, 1.61; 95% CI, 1.56-1.67; P < .001; DVT: aOR, 1.41; 95% CI, 1.36-1.47; P < .001; PE: aOR, 1.88; 95% CI, 1.79-1.97; P < .001). Analysis by race found Blacks had elevated VTE odds (aOR, 1.29; 95% CI, 1.26-1.33; P < .001), and Blacks with VTE had elevated mortality odds (aOR, 1.15; 95% CI, 1.11-1.19; P < .001), compared with non-Blacks. Cancer hospitalizations with VTE were associated with significantly longer median LOS (6 days [IQR, 3-11 days] vs 4 days [IQR, 2-8 days]; P < .001) and higher median hospital charges ($70,416 [IQR, $36,257-$146,218] vs $55,887 [IQR, $30,276-$105,637]; P < .001)]. Conclusions: This report on contemporary national data shows co-diagnosis of VTE and cancer is associated with significantly higher all-cause mortality, LOS, and total hospital expenditures than cancer admissions without VTE. These findings underscore importance of accurate VTE risk assessment for inpatients with cancer.

BACKGROUND Transplanting kidneys from donors with HIV to recipients with HIV has become standard clinical practice. However, donors with HIV may have higher prevalence of viral and bacterial infections and autoimmunity that could increase allograft rejection in recipients. METHODS We included deceased kidney donors (60 with HIV and 41 without HIV) who participated in a multicenter prospective study of HIV kidney transplantation between April 2018 and September 2021. Using phage immunoprecipitation sequencing, we compared the human antibody repertoire (allergens, autoantibodies, viruses, and bacterial toxins) between donors with and without HIV and evaluated their association with recipient allograft rejection. Moderated t tests were used to assess reactivity and a multivariate logistic regression model adjusted for donor sex and kidney donor profile index assessed the association between donor adenovirus reactivity and recipient allograft rejection. RESULTS Compared with donors without HIV, donors with HIV had lower BMI and were more likely to be African American. The median number of positive autoantibodies was marginally higher among donors with HIV (499 [IQR, 357, 579]) compared with that of donors without HIV (395 [IQR, 256, 538], P = 0.058). Donors with HIV additionally had significantly higher antibody reactivity to Epstein-Barr virus and cytomegalovirus ( q < 0.05). Among all donors with and without HIV, antibodies against adenovirus were significantly associated with increased rejection among recipients, including after adjusting for false discovery ( q < 0.05) and also adjusting for demographic factors using multivariable logistic regression (odds ratio = 4.97; 95% CI = 1.89–13.61). CONCLUSION The presence of antibodies against adenovirus infection in kidney donors with HIV may be associated with allograft rejection. TRIAL REGISTRATION ClinicalTrials.gov NCT03500315. FUNDING US NIH.

INTRODUCTION:COVID-19 convalescent plasma with high anti-SARS-CoV-2 antibody levels transfused within 6 months from donor collection was formally approved by the Food and Drug Administration in December 2024 for COVID-19 treatment in immunocompromised patients. Here we summarize the safety and efficacy data submitted for the Biologics License Application. AREAS COVERED:Safety evaluation in over 100,000 individuals in the expanded access program and 24,000 in randomized controlled trials, showed no serious adverse event increases. Robust randomized controlled trials established efficacy in four distinct disease stages: outpatient, inpatient, newly mechanically ventilated, and in those immunocompromised to prevent acute disease progression or eliminate persistent viral carriage. Pharmacokinetics revealed a three-liter distribution volume with viral specific antibody effective dose near 2-50 mg. Major SARS-CoV-2 antibody-mediated antiviral actions included direct neutralization by viral-binding interference to cell receptors and fragment-crystallizable mediated antiviral effects that reduce virions. Virus neutralization correlated with high anti-Spike antibody levels and antibody levels in the top donor plasma deciles retains therapeutic neutralization against future variants. EXPERT OPINION:With pandemic progression, the COVID-19 convalescent plasma safety and efficacy evidence quality increased. Ultimate regulatory approval required robust randomized control efficacy data. Future infectious disease outbreaks require randomized controlled trials in the convalescent plasma roadmap.

Specific anaerobic species within the penile microbiome - Bacteria Associated with Seroconversion, Inflammation and Immune Cells (BASIC) - have been linked to increased HIV-1 susceptibility. These bacteria can directly disrupt epithelial integrity and are believed to increase local inflammation, resulting in an increased density of HIV-susceptible T cells in the inner foreskin. It is currently unknown whether other immune cells bearing the HIV entry receptors, CD4 and CCR5, are also elevated in individuals with a high abundance of BASIC species. Using inner foreskin tissues and penile swabs from males undergoing voluntary medical male circumcision, we performed a retrospective cross-sectional study to assess the relationship between BASIC species and the tissue density of such immune cells, including CD68+ macrophages, CD11c+ dendritic cells, and CD207+ Langerhans cells. The most abundant cells in the inner foreskin expressing the HIV co-receptors were CD11c+ dendritic cells (48.6% of CD4+/CCR5+ cells), followed by CD68+ macrophages (28.6%), CD3+ T cells (18.8%), and CD207+ Langerhans-like (8.8%) cells. The absolute abundance of BASIC species was associated with elevated tissue densities of both CD4+/CCR5+ T cells (as previously reported) and a heterogeneous population of CD3-/CD4+/CCR5+ cells of myeloid origin. In the dermis, BASIC species abundance was linked to elevated densities of cells expressing CD11c, CD68, and CD207, as well as those co-expressing CD11c and CD207; furthermore, CD11c+ and CD207+ cells were farther from the basement membrane in participants with a high abundance of BASIC species. Myeloid cells were not elevated in participants with a high abundance of control taxa. In an integrated analysis including previously published data from this same cohort, myeloid-cell densities clustered tightly together, positively correlated with BASIC species and pro-inflammatory cytokines, and had trends to negative correlations with control taxa (significant for CD207+ cell density). Overall, our findings suggest that BASIC species are associated with a broader foreskin immune phenotype marked by increased densities of HIV-susceptible myeloid and T cells, alongside epithelial disruption.

This study examines trends in injecting methamphetamine and opioids among people who inject drugs entering drug treatment in the US.

INTRODUCTION:Literature on hospitalization incidence and risks among people with HIV (PWH) in the current antiretroviral therapy era is limited. METHODS:Using data (2017-2021) on PWH ≥ 40 years of age from the Advancing Clinical Therapeutics Globally HAILO Study, cumulative probabilities of first hospitalization were estimated using Kaplan-Meier plots. Cox proportional hazards regression was used to identify factors associated with first hospitalization. RESULTS:Among 891 participants (median age 50 years; 80% male), 38 with prevalent hospitalization at baseline were excluded. The remaining 853 participants had a follow-up of 2721 person-years, during which 170 (20%) had at least 1 hospitalization event (incidence rate, 6.2 per 100 person-years [95% confidence interval [CI] = 5.4-7.3]). The leading causes of hospitalization included infections (14%), elective surgery (13%), cardiovascular conditions (12%), and lung problems (12%). Former and current smokers had higher hospitalization risk (adjusted hazard ratio [aHR] 1.51 [95% CI = 1.03-2.20], aHR 1.85 [95% CI = 1.24-2.76], respectively) than never smokers. Hospitalization risk was higher for participants who were frail (aHR 2.31 [95% CI = 1.38-3.86]) compared with those who were robust (not frail), and lower in the Western region compared with the Northeast region (hazard ratio = 0.55, 95% CI: 0.32-0.93). Hospitalization risk was also higher for participants with diabetes (aHR 1.69 [95% CI = 1.13-2.52]). CONCLUSION:We observed a lower hospitalization risk than in previous studies among PWH. Interventions to reduce smoking, prevent frailty, and improve diabetes management may further lower hospitalization risk.