Characterizing Indicators of Engagement in HIV-Associated Healthcare and Clinical Outcomes among People with HIV and Mpox in Washington, DC: A Nested Case-Control Study of the DC Cohort.

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.

Strongyloides and COVID-19: Challenges and Opportunities for Future Research.

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.

HIV treatment with dolutegravir and doravirine: rationale for selection and clinical outcomes in a highly treatment experienced population.

Dolutegravir and doravirine are individually safe and effective antiretroviral therapy (ART) components, but their combined use has not been studied in clinical trials and is not recommended in HIV treatment guidelines. We noted persons with HIV (PWH) receiving dolutegravir with doravirine at our Washington, DC, infectious disease clinic and undertook a service evaluation to understand why providers selected this ART, whether HIV virologic suppression was achieved and identify adverse effects of concomitant use. Case registry and prescriptions data identified 21 PWH receiving concomitant dolutegravir and doravirine with mean follow-up 576.1 days (range 413-751); frequent reasons for switching were multiple ART resistance (57.1%), proton pump inhibitor usage (28.6%) and renal failure (28.6%), with 52.4% switched from protease inhibitor or cobicistat-boosted regimens. Dolutegravir with doravirine alone was prescribed for 60%, and additional ART in 40%. During 12 months follow-up mean CD4 was 585.9 (baseline 570.7) with undetectable viral load in 77.8% (baseline 66.7%). No discontinuations for drug-related adverse events or virologic failure occurred. Dolutegravir with doravirine was well tolerated in small numbers of highly treatment experienced PWH at our clinic, achieving virologic suppression in most. Establishing the efficacy and safety of dolutegravir with doravirine for HIV treatment in randomized trials remains important.

Identifying Geographic Areas of Washington, DC, With Increased Potential for Sexual HIV Transmission Among People With HIV With STIs and Concurrent Elevated HIV RNA: Data From the DC Cohort.

Background: The Undetectable = Untransmittable (U = U) campaign advances the goal of ending the HIV epidemic by promoting durable viral suppression and therefore reducing sexual transmission. We used geospatial analysis to assess the potential for sexual HIV transmission by ZIP code of residence in the District of Columbia (DC) using data from the DC Cohort Longitudinal HIV Study (DC Cohort), a city-wide cohort of persons with HIV (PWH). Methods: DC Cohort participants aged ≥13 years were included in the study period between April 1, 2016, and March 31, 2018. Potential for sexual HIV transmission was defined as the proportion of participants with incident sexually transmitted infection (STI; gonorrhea, chlamydia, syphilis) and with HIV RNA ≥200 copies/mL from 9 months before to 3 months after STI diagnosis. We performed geographic information system (GIS) analysis to determine the ZIP codes with the highest potential for sexual HIV transmission. Results: Of 3467 participants, 367 (10.6%) had at least 1 incident STI, with 89.4% residing in 11 of the 20 residential ZIP codes in DC. Of the 367 participants with an incident STI, at least 1 HIV RNA was available for 348 (94.8%). Ninety-seven (27.9%) individuals with an incident STI had HIV RNA ≥200 copies/mL in the defined time window. Of these 97, 66 (68.0%) resided in 5 of the 20 DC ZIP codes. Conclusions: In DC, 5 ZIP codes of residence accounted for the majority of the estimated potential for HIV transmission among participants in the DC Cohort. These results support focused neighborhood-level interventions to help end the HIV epidemic.

Polymicrobial native valve endocarditis due to Bacillus cereus and Cardiobacterium hominis.

We present a case of polymicrobial subacute bacterial endocarditis and bacteremia with Bacillus cereus and Cardiobacterium hominis in a 72-year-old man with pre-existing mitral valve disease and prior mitral valve repair who presented with renal failure and glomerulonephritis. Bacillus is often a contaminant in blood cultures but has been rarely implicated in patients with invasive infections such as endocarditis. Intravenous drug use, prosthetic heart valves, valvular heart disease and venous catheters are the most frequently described risk factors for Bacillus bacteremia and endocarditis in the medical literature. Management is challenging as Bacillus is resistant to penicillin and cephalosporin antibiotics due to production of beta-lactamase. Polymicrobial endocarditis is uncommon and when it occurs typically involves Staphylococcal species. To our knowledge, this is the first reported case of polymicrobial endocarditis in which both Bacillus and a HACEK organism are implicated.

Gene therapy for Parkinson's disease.

Current pharmacological and surgical treatments for Parkinson's disease offer symptomatic improvements to those suffering from this incurable degenerative neurological disorder, but none of these has convincingly shown effects on disease progression. Novel approaches based on gene therapy have several potential advantages over conventional treatment modalities. These could be used to provide more consistent dopamine supplementation, potentially providing superior symptomatic relief with fewer side effects. More radically, gene therapy could be used to correct the imbalances in basal ganglia circuitry associated with the symptoms of Parkinson's disease, or to preserve or restore dopaminergic neurons lost during the disease process itself. The latter neuroprotective approach is the most exciting, as it could theoretically be disease modifying rather than simply symptom alleviating. Gene therapy agents using these approaches are currently making the transition from the laboratory to the bedside. This paper summarises the theoretical approaches to gene therapy for Parkinson's disease and the findings of clinical trials in this rapidly changing field.