Strongyloides stercoralis is a soil transmitted helminth endemic to tropical and subtropical areas that can persist for decades in immunocompetent human hosts as a chronic asymptomatic infection. The use of corticosteroids, a mainstay of treatment for patients hospitalized with severe coronavirus disease (COVID-19), can trigger a life-threatening Strongyloides hyperinfection syndrome and disseminated disease. We identified 22 previously published cases of strongyloidiasis occurring in individuals with COVID-19, with one death reported among the seven patients who had Strongyloides hyperinfection syndrome. A total of seventeen patients had previously received corticosteroids, and of the five with no prior corticosteroid use, one presented with hyperinfection syndrome. We identify the key challenges in the diagnosis and treatment of Strongyloides within the context of COVID-19, including our imprecise knowledge of the global distribution of Strongyloides, the overlapping symptoms and signs of COVID-19 and Strongyloides hyperinfection syndrome, the limited utility of eosinophilia as a clinical marker for strongyloidiasis in this setting, the lack of validated algorithms to screen for Strongyloides prior to corticosteroid use, and the paucity of treatment options for critically ill patients with COVID-19 who cannot take oral ivermectin. Future research should focus on improved diagnostic methods and population prevalence estimates, optimizing the approaches for Strongyloides screening in persons with COVID-19 (including clinical trial participants and strategies for resource-limited settings) and better defining the role of pre-emptive treatment.

People with HIV (PWH) are disproportionally affected by mpox and at risk of severe complications. We assessed mpox knowledge, adoption of preventive behaviors, and vaccination attitudes among PWH enrolled in a longitudinal HIV cohort in Washington, DC, the DC Cohort. We conducted uni- and multivariable analyses comparing participants by vaccination status and HIV risk group, and multinomial regression to identify factors associated with vaccine acceptance. Among 430 PWH, 378 (87.9%) were aware of mpox. Among 373 participants with vaccination status data, 101 (27.1%) were vaccinated, 129 (34.6%) planned to vaccinate, and 143 (38.3%) did not plan to vaccinate. The three vaccination groups differed significantly by age, race, education, HIV risk group, recent STI status, and level of mpox worry (all p < 0.05). A higher proportion of men who have sex with men (MSM) reported limiting their number of sexual partners compared to non-MSM (p < 0.0001). Multinomial regression models comparing vaccinated to unvaccinated PWH found age, education, mode of HIV transmission/gender, and survey period were significantly associated with vaccination status (all p < 0.05). High levels of mpox awareness were observed among this cohort of PWH with more MSM employing risk reduction behaviors and being vaccinated. Ensuring that PWH, regardless of gender, sexual orientation, or age, understand the risks of mpox may improve vaccination uptake.

Trained immunity (TRIM) enhances innate immune responses through epigenetic and metabolic reprogramming but may become maladaptive, contributing to chronic inflammation. In people living with HIV (PLWH), maladaptive TRIM has been proposed but remains insufficiently characterized. We examined inflammatory cytokine production in monocyte-derived macrophages (MDMs) obtained from PLWH and age-matched individuals without HIV infection. Baseline cytokine output and responses to stimulation of Toll-like receptors (TLR) were measured. We further examined whether TRIM influenced susceptibility to HIV infection in MDMs derived from monocytes exposed to extracellular vesicles carrying the HIV-1 Nef protein (Nef EVs). Baseline IL-6 production did not differ between unstimulated MDMs from PLWH and uninfected controls. Although sex-associated differences were initially observed, these effects were no longer significant after adjustment for infection duration. IL-6 responses following TLR2 and TLR7 stimulation, but not TLR4 stimulation, were significantly amplified in PLWH-derived MDMs, consistent with a trained phenotype. Similar trends were observed in sex-stratified analyses but did not reach statistical significance. The magnitude of unstimulated IL-6 production positively correlated with duration of HIV infection, suggesting cumulative TRIM imprinting over time. Despite heightened inflammatory responsiveness, TRIM did not reduce susceptibility to HIV infection in Nef EV-exposed MDMs, indicating functional maladaptation rather than protective priming. These findings provide evidence of maladaptive TRIM in PLWH, characterized by preserved basal cytokine output but exaggerated inflammatory responses to innate immune stimulation without antiviral benefit. The association with infection duration supports progressive innate immune reprogramming as a contributor to HIV-associated inflammation. No statistically significant differences in trained immune responses were observed between male and female PLWH after accounting for duration of infection. Further studies are needed to define the mechanisms underlying this maladaptation and its clinical consequences.

The high proportion of people with HIV (PWH) in the 2022–2023 mpox outbreak has raised questions surrounding the association between HIV and mpox. The objectives of this study were to evaluate the association between engagement in HIV-associated healthcare and mpox diagnosis, as well as to characterize cases of mpox among PWH. The DC Cohort is a longitudinal cohort of PWH in Washington, DC. We conducted a 5:1 (controls:cases) nested case-cohort study on male participants, matching age and care site. Cases were participants with an identified mpox diagnosis. Conditional logistic regression was used to assess the impact of indicators of engagement in HIV-associated healthcare on mpox diagnosis. We identified 70 cases of mpox in DC Cohort participants randomly matched to 323 controls, for a total of 393 participants included in the analysis. Study participants were primarily non-Hispanic Black (72.3%) with a median age of 41 (IQR: 36, 50). There was no association between engagement in care and mpox diagnosis; however, low CD4 was associated with increased odds of mpox diagnosis (aOR: 4.60 (95% CI: 1.23, 17.11)). Among a cohort of PWH, engagement in care was not associated with mpox diagnosis, suggesting that the overrepresentation of PWH among mpox cases is not due to surveillance bias.

Background: Trained immunity (TRIM) enhances innate immune responses through epigenetic and metabolic reprogramming but can become maladaptive, contributing to chronic inflammation. In people living with HIV (PLWH), maladaptive TRIM has been proposed but remains insufficiently defined. Methods: We examined inflammatory cytokine production in monocyte-derived macrophages (MDMs) obtained from PLWH and age-matched individuals without HIV infection. Baseline cytokine output and responses to Toll-like receptor (TLR) stimulation were measured. We also assessed whether TRIM influenced susceptibility of MDMs to HIV infection. Results: Unstimulated MDMs from male, but not female, PLWH produced significantly higher levels of IL-6 compared with uninfected controls. IL-6 production positively correlated with duration of HIV infection, suggesting cumulative TRIM imprinting. TLR engagement markedly amplified cytokine responses in PLWH-derived MDMs, consistent with a trained phenotype. Despite enhanced inflammatory responsiveness, TRIM did not confer protection from HIV infection of MDMs, indicating functional maladaptation rather than beneficial priming. Conclusions: These findings provide evidence of maladaptive TRIM in PLWH, characterized by persistent inflammation and heightened cytokine responsiveness. The observed sex-specific differences suggest distinct TRIM programming in male and female PLWH. Further studies are needed to elucidate mechanisms driving these disparities and to determine their impact on HIV-associated inflammation and clinical outcomes.