People with HIV have higher rates of certain comorbidities, particularly cardiovascular disease and some malignancies, than people without HIV. As somatic mutations associated with agerelated clonal haematopoiesis (CH) are linked to similar comorbidities in the general population, we hypothesized that CH may be more prevalent in people with HIV. To address this issue, we established a prospective cohort study recruiting 220 HIV-positive and 226 HIVnegative participants aged 55 years or older in Australia. Demographic characteristics, clinical data and peripheral blood were collected to assess for the presence of CH mutations and identify potential risk factors for and clinical sequelae of CH. Investigators testing for CH were blinded to participants' HIV status. In total, 132 CH mutations were identified in 99 (22.2%) of 446 participants. CH was more prevalent in HIV-positive participants than HIV-negative participants (27.7% vs. 16.8%, p =0.006), overall and across all age groups. HIV infection was associated with an increased odds of having CH (adjusted odds ratio 2.10, 95% confidence interval 1.30-3.38, p=0.002). The most common genes mutated were DNMT3A (48.5%), TET2 (20.5%) and ASXL1 (11.4%). CH and HIV infection were independently associated with increases in blood parameters and biomarkers associated with inflammation. These data suggest a selective advantage for the emergence of CH in the context of chronic infection and inflammation related to HIV infection.

Summary T follicular helper (Tfh) cells provide critical help to B cells during the germinal center (GC) reaction to facilitate generation of protective humoral immunity. Accessing the human lymph node (LN) to study the commitment of CD4 T cells to GC Tfh cell differentiation during in vivo vaccine responses is difficult. We used ultrasound guided fine needle biopsy to monitor recall responses in axillary LNs to seasonal influenza vaccination in healthy volunteers. Specific expansion of GC cell subsets occurred exclusively within draining LNs five days postvaccination. Draining LN GC Tfh and precursor-Tfh cells express higher levels of CD38, ICOS, and Ki67, indicating they were significantly more activated, motile, and proliferating, compared to contralateral LN cells. These observations provide insight into the early expansion phase of the human Tfh lineage within LNs during a vaccine induced memory response and highlights early LN immune responses may not be reflected in the periphery.

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Animal mating systems are driven by the temporal and spatial distribution of sexually receptive females. In mammals, ground-dwelling squirrels represent an ideal clade for testing predictions regarding the effects of these parameters on male reproductive strategies. While the majority of ground squirrel species have a short, highly synchronous annual breeding season that occurs immediately after females emerge from hibernation, the Mexican or Rio Grande ground squirrel ( Ictidomys parvidens ) differs markedly in having an extended mating season (2 months) and a long delay between emergence from hibernation and female receptivity (1–2 months). Both traits are expected to favor polygyny by increasing the chances that a male can secure matings with multiple females (e.g., females that come into estrus on different days). To test this prediction, we used microsatellite markers to characterize the mating system of a population of Rio Grande ground squirrels from Carlsbad, New Mexico. Our analyses indicated a high frequency of multiple paternity of litters in this population. Paternity was not related to spatial overlap between known mothers and assigned fathers, suggesting that territory defense is unlikely to be an effective male reproductive strategy in the study population. Dominance interactions among males were frequent, with heavier males typically winning dyadic interactions. Surprisingly, however, males with lower dominance scores appeared to have higher reproductive success, as did males that were active over a greater extent of the study site. Collectively, these results suggest that the mating system of the Rio Grande ground squirrel is best described as scramble competition polygyny, with the primary male reproductive strategy consisting of searching for estrous females. Similar patterns of male–male competition have been reported for a few other ground squirrel species, providing potentially important opportunities for comparative studies of the factors favoring this form of male reproductive strategy.

ACTIV-3/TICO Study Group* Background: Ensovibep (MP0420) is a designed ankyrin repeat protein, a novel class of engineered proteins, under investigation as a treatment of SARS-CoV-2 infection.Objective: To investigate if ensovibep, in addition to remdesivir and other standard care, improves clinical outcomes among patients hospitalized with COVID-19 compared with standard care alone.