Aaron A. R. Tobian

Despite antiretroviral therapy, the latent viral reservoir (LVR) remains the primary barrier to human immunodeficiency virus (HIV) cure. Both hematopoietic and solid organ transplantation (SOT) have provided optimism for cure and significant insights into LVR composition and maintenance. There have been 13 reported cases of acquired cure, all in individuals receiving allogeneic hematopoietic stem cell transplants (allo-HSCT). While infeasible for most, these cases have provided important lessons about the LVR. Impacts of SOT on the LVR have also been investigated. In kidney transplantation where recipients were T-cell depleted, the LVR initially decreased before rebounding and eventually surpassed the LVR of recipients without T-cell depletion. Despite transplanting a large lymphoid organ, studies have found no impact of HIV+ liver transplants on LVR size in recipients. Given that SOTs are more accessible globally than allo-HSCTs, lessons learned about the LVR from these studies can inform potential cure avenues that may be more feasible and attainable.

Background: Artificial intelligence (AI)/machine learning (ML) are poised to transform transfusion medicine across the vein‐to‐vein continuum, from donor recruitment to recipient outcomes. Large datasets generated from millions of donations and transfusions create opportunities for predictive modeling, precision medicine, improved safety, and operational efficiency. This review outlines key applications of AI in blood banking and transfusion medicine using a comprehensive vein‐to‐vein framework. Methods: The review synthesizes perspectives from blood services and hospital‐based transfusion practices. Applications are discussed across donor recruitment, collections, testing, inventory management, hospital transfusion services, and education. Finally, AI safety, including ethical, regulatory, privacy, and implementation challenges, is addressed. This is a narrative, non‐exhaustive review; given the rapidly evolving pace of AI/ML capabilities, this synthesis should be interpreted as a framework for ongoing surveillance rather than a fixed inventory of applications. Results: Donor‐focused applications include personalized recruitment, individualized iron management, and fairness auditing to reduce inequities. In supply chain operations, ML can improve demand forecasting, minimize waste, and optimize inventory. Federated learning may support multi‐institutional collaboration without sharing raw data. Omics and genomic applications can enable high‐throughput analysis, phenotype prediction, and precision transfusion support for rare blood types and alloimmunized patients. In hospitals, AI can augment hemovigilance by identifying/predicting adverse transfusion reactions, while large language models and retrieval‐augmented generation may enhance decision support, patient blood management, and education through adaptive learning. Conclusion: AI holds substantial promise to improve transfusion safety, efficiency, equity, and sustainability. Realizing this potential will require robust governance, model validation across diverse populations, privacy safeguards, bias mitigation, reproducibility, regulatory oversight, and human‐in‐the‐loop implementation.

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.

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.

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.

Background: Acquired hypofibrinogenemia poses significant bleeding risks. Concentrated sources of fibrinogen, whether cryoprecipitate or fibrinogen concentrates, are widely used. This scoping review aimed to identify and map the available evidence on fibrinogen supplementation. Study Design and Methods: We used the JBI Manual and PRISMA‐ScR guidelines. We included patients of all ages treated with fibrinogen supplementation. The concept was treatment with cryoprecipitate or fibrinogen concentrate (prophylactically or therapeutically); and context was any clinical setting worldwide. Eligible studies included randomized trials and observational studies with comparator arms. Comprehensive searches of three databases were performed on February 21, 2025. Primary studies meeting inclusion criteria were selected. UpSet data visualizations displayed studies with intersecting sets of characteristics. Results: From 8181 references screened, 134 met inclusion criteria, of which 61 were randomized trials and 16 propensity‐matched observational cohort studies. The highest proportion of trials focused on cardiovascular surgery (28/61; 46%) then trauma (12/61; 20%) populations and mainly assessed use of fibrinogen therapeutically (34/61; 56%). More trials evaluated fibrinogen concentrate (53/61; 87%) compared to cryoprecipitate (8/61; 13%). Commonly reported outcomes included bleeding, transfusion needs, or mortality. Studies inconsistently reported dosing, timing, and definitions of hypofibrinogenemia. Studies evaluating certain key populations—including obstetrics and pediatrics—were limited. All but one propensity‐matched study was in either cardiovascular surgery or trauma. Discussion: There is a growing body of literature informing use of fibrinogen supplementation, particularly in cardiovascular surgery and trauma populations. Meta‐analyses appear feasible to inform evidence‐based guideline development; however, variability in dosing, timing, and definitions highlights the need for more harmonized research.

Introduction: Literature on hospitalization incidence and risks among people with HIV (PWH) in the current antiretroviral therapy era is limited. Methods: Using data (2017 to 2021) on PWH ≥40 years of age from the Advancing Clinical Therapeutics Globally (ACTG) 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% 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 to those that were robust (not frail), and lower in the Western region compared with the Northeast region (HR= 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.

SUMMARY: 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