In a single-center retrospective follow-up study, no difference in retention in care or virologic suppression was noted between rapid and delayed initiation of antiretroviral therapy at 6-year follow up in participants who were antiretroviral naive. Further study is needed to assess the long-term impact of rapidly starting antiretroviral therapy.

In a single-center retrospective follow-up study, no difference in retention in care or virologic suppression was noted between rapid and delayed initiation of antiretroviral therapy at 6-year follow up in participants who were antiretroviral naive. Further study is needed to assess the long-term impact of rapidly starting antiretroviral therapy.

Abstract Background Current DHHS guidelines recommend starting ART in PWH immediately or as soon as possible after HIV diagnosis to improve ART uptake, linkages to care and virologic suppression (VS). But there is little data measuring the longitudinal impact of rapidly starting ART. We previously showed that rapidly starting ART significantly decreased time to VS. This study compares the longitudinal effects of rapid ART start versus delayed ART initiation on retention in care and VS in a previously defined cohort of PWH. Methods IRB-approved follow up study of a single-center, retrospective cohort. The original cohort included all newly diagnosed, antiretroviral-naïve adult patients seen in the Ryan White Clinic (RWC) at a single site for their initial visit between 1/1/15-12/31/15 (delayed ART) and 1/1/17-12/31/17 (rapid ART): Table 1 and Table 2. In the original cohort, primary outcome of time from HIV diagnosis to VS [VL < 200 copies/ml (cp/ml)] was compared between groups. For the current study, the primary outcomes of VS (VL < 50 cp/ml) and retention in care (documented visit at study site or documented transition of care) were measured in the original cohort participants from 1/1/23-12/31/23. Reasons for lack of retention in care were death and loss to follow up. Results In the original cohort, 72 patients were screened and 60 met inclusion criteria; (24 delayed ART, 36 rapid ART). The long-term outcomes for VS and retention in care are shown in Table 3. 11/24 (delayed) and 23/36 (rapid) remained engaged in care at the study institution (p=.193). 9/11 (82%) and 22/23 (96%) maintained VS (p=.239), in the delayed ART and rapid ART, respectively. Participants were more likely to be retained in care (at study site or with documented transition in care) in the rapid ART group (11/22 delayed ART vs. 31/35 rapid ART, p=.002) If not retained in care at the study site, delayed ART participants were more likely to be lost to follow up versus having a documented transition in care or death [11/13 delayed ART vs 4/13 rapid ART, (p=.015)]. Conclusion A previous study showed a shortened time to VS with rapid start of ART. Long-term retention in care may be significantly improved with rapid start of ART and requires further study. Rapid start may also demonstrate a trend towards increased VS. Disclosures All Authors: No reported disclosures

Background Coronary plaque is common among people with HIV (PWH) with low-to-moderate traditional atherosclerotic cardiovascular disease (ASCVD) risk. Objectives The purpose of this study was to determine the association of high-sensitivity cardiac troponin T (hs-cTnT) levels with coronary plaque characteristics and evaluate if hs-cTnT improves identification of these features beyond traditional ASCVD risk factors among PWH. Methods Among PWH receiving stable antiretroviral therapy with low-to-moderate ASCVD risk and no known history of ASCVD, hs-cTnT levels and measures of plaque by coronary computed tomography angiography were assessed. Primary outcomes included the association of hs-cTnT level with the presence of any plaque, vulnerable plaque, coronary artery calcium (CAC) score, and Leaman score. Assessment of model discrimination of hs-cTnT for plaque characteristics was also performed. Results The cohort included 708 U.S. participants with a mean age of 51 ± 6 years, 119 (17%) females, a median ASCVD risk score of 4.4% (Q1-Q3: 2.5%-6.6%), and a median hs-cTnT level of 6.7 ng/L (detectable level ≥6 ng/L in 61%). Any plaque was present in 341 (48%), vulnerable plaque in 155 (22%), CAC>100 in 68 (10%), and a Leaman score >5 in 105 (15%). After adjustment for ASCVD risk score, participants with hs-cTnT >9.6 ng/L (highest category) versus an undetectable level (<6 ng/L) had a greater relative risk for any plaque (1.37, 95% CI: 1.12-1.67), vulnerable plaque (1.47, 95% CI: 1.16-1.87), CAC>100 (2.58, 95% CI: 1.37-4.83), and Leaman score >5 (2.13, 95% CI: 1.32-3.46). The addition of hs-cTnT level modestly improved the discrimination of ASCVD risk score to identify critical plaque features. Conclusions In PWH without known ASCVD, hs-cTnT levels were strongly associated with and improved prediction of subclinical coronary plaque. (Evaluating the Use of Pitavastatin to Reduce the Risk of Cardiovascular Disease in HIV-Infected Adults [REPRIEVE]; NCT02344290)

Timely initiation of antiretroviral therapy (ART) for non-occupational post-exposure prophylaxis (nPEP) is crucial in preventing HIV infection and advancing efforts to end the HIV epidemic (EHE). nPEP must be administered within 72 h of high-risk exposure, ideally within 24 h. Pharmacies may play a role in increasing access to nPEP and facilitating referrals for additional care, such as PrEP. Recent legislation permits pharmacist-prescribed nPEP (PDP), though provider attitudes toward this change have not been studied. A survey querying physicians and medical trainees (students and residents) was conducted in 2024 during an annual state medical association conference. The survey included 24 questions on nPEP knowledge and attitudes towards pharmacist-prescribed nPEP (PDP). The survey was administered in person using electronic tablets, with voluntary participation incentivized by a monetary reward. Statistical analysis was conducted using SAS (9.4 version) software, with differences in responses between physicians and trainees evaluated. P values < 0.05 were considered statistically significant. Of 89 respondents (56

Abstract Background The most effective treatment for fungal prosthetic joint infections remains unclear. Most cases are treated with two-stage revisions combined with systemic antifungal medications. To date, the largest studies of total hip arthroplasty and total knee arthroplasty fungal infections have included 37 and 45 patients, respectively. Methods A retrospective record review of patients admitted in two health systems between January 1, 2007 and December 31, 2018 with prosthetic joints and a deep culture of the joint positive for fungal organisms was performed as well as a review of the literature. A Pubmed and Embase search of the English-language literature from Jan 1, 1980 to Jan 1, 2023 was performed with review of the pertinent references for cases meeting the following case definition: individual with prosthetic joint and positive deep tissue culture for fungus. Results 159 patients fit criteria. 73 patients had knee replacements, 62 patients had hip replacements, and 5 had other joint involvement. 52% were female. 137 patients had yeast involvement, with Candida species being predominant, while 11 had mold and 11 with dimorphic infections. 55 patients were treated with two-stage revisions, 44 received one-stage revisions, 32 received debridement only or Girdlestone procedure, and 1 required amputation. 141 reported details on antifungal therapy. After performing multivariate analysis, polyene treatment was found to be associated with higher rate of recovery, p=0.042. However, there was a trend towards recurrence requiring surgical intervention in patients treated with polyenes, p=0.067. 22.6% had a poor outcome, including recurrence, amputation, or death. Conclusion Surprisingly, polyenes did not underperform when compared to other antifungal therapy. Prospective research assessing optimal surgical treatment modality and antifungal therapy is needed as this infection is associated with high morbidity and mortality. Disclosures All Authors: No reported disclosures

Background: Sepsis is a threat to global health, and domestically is the major cause of in-hospital mortality. Due to increases in inpatient morbidity and mortality resulting from sepsis, healthcare providers (HCPs) would accrue significant benefits from identifying the syndrome early and treating it promptly and effectively. Prompt and effective detection, diagnosis, and treatment of sepsis requires frequent monitoring and assessment of patient vital signs and other relevant data present in the electronic health record. Methods: This study explored the development of machine learning-based models to generate a novel sepsis risk index (SRI) which is an intuitive 0-100 marker that reflects the risk of a patient acquiring sepsis or septic shock and assists in timely diagnosis. Machine learning models were developed and validated using openly accessible critical care databases. The model was developed using a single database (from one institution) and validated on a separate database consisting of patient data collected across multiple ICUs. Results: The developed model achieved an area under the receiver operating characteristic curve of 0.82 and 0.84 for the diagnosis of sepsis and septic shock, respectively, with a sensitivity and specificity of 79.1% [75.1, 82.7] and 73.3% [72.8, 73.8] for a sepsis diagnosis and 83.8% [80.8, 86.5] and 73.3% [72.8, 73.8] for a septic shock diagnosis. Conclusion: The SRI provides critical care HCPs with an intuitive quantitative measure related to the risk of a patient having or acquiring a life-threatening infection. Evaluation of the SRI over time may provide HCPs the ability to initiate protective interventions (e.g., targeted antibiotic therapy).

Using multiple pharmacies has been linked to negative outcomes including increased inappropriate drug use, toxicity, and mortality, yet up to half of all patients in the US use multiple pharmacies. A pilot survey was administered to measure pharmacy use in people living with HIV (PWH) and examine the associated attitudes and outcomes. In a midwestern HIV clinic, a convenience sample was surveyed based on using single (SPU) versus multiple pharmacies (MPU). One hundred forty-two subjects participated (69 SPU; 73 MPU): 75% male, 59% white, and > 70% being ≥ 40 years old. There was a trend towards increased recall of self-reported CD4 and viral load status for SPUs vs MPUs [OR 2.26 (95%, 0.91–5.64)]. SPU participants indicated acquiring all meds in one place [Likert Scale weighted average (LS WA) = 4.45], proximity (LS WA = 3.64), the identification of adverse effects (LS WA = 4.17), and concerns about missing potential drug-drug interactions (LS WA = 4.06) as reasons for preferring a single pharmacy. The desire to keep HIV status private (LS WA = 3.65) was noted as a significant reason for using a separate pharmacy specifically for acquiring antiretrovirals in MPU participants. Results indicate patients often have justifiable reasons for using single versus multiple pharmacies.

Objective: The objective of this review is to compare ibalizumab, fostemsavir, and lenacapavir, present the clinical trials evaluating each agent, and provide guidance on their use in highly-treatment experienced (HTE) population living with HIV (PWH). Data sources: A search of PubMed and clinicaltrials.gov was conducted using the search terms: ibalizumab, fostemsavir, and lenacapavir. Study selection and data extraction: English-language, clinical publications were included. Data synthesis: Ibalizumab, fostemsavir, and lenacapavir, are each first-in-class agents, that have major differences in mechanism of action, route and frequency of administration, pharmacokinetic parameters, including elimination half-life, potential for drug-drug interactions, safety profiles, and cost. Each has been shown, when combined with an optimized background regimen (OBR) with at least one other active agent, to achieve virologic suppression in HTE-PWH. Conclusion: In HTE-patients, adding ibalizumab, fostemsavir, and/or lenacapavir to at least one other active agent can lead to virologic suppression in this difficult to treat population. Monotherapy with any of these agents is not recommended and will lead to a high likelihood of drug resistance. Selection of which agent(s) to include with an OBR will depend on other patient factors including concomitant medications, acceptance of formulations (oral vs. subcutaneous vs. intravenous infusion), and potential access (both insurance-based and transportation). Adherence to all agents in the regimen is paramount to successful outcomes.

Abstract Background Multiple pharmacy use has been linked to decreased patient adherence, inappropriate drug use, adverse drug reactions, and increased mortality. Despite negative outcomes, multi-pharmacy use has increased and nearly half of all patients in the US now use multiple pharmacies. In this study, the attitudes towards multiple pharmacy use (MPU) versus single pharmacy use (SPU) for PLWH (people living with HIV) were assessed. Methods A convenience sample of patients in a single midwestern Ryan White clinic was surveyed. There were 24 questions with two additional questions for users of multiple pharmacies. Questions were related to patient demographics, current CD4 count (CD4), viral load (VL) status, amount of time to receive medications, missed doses, comorbidities, and patient preferences. A 5-point Likert Scale (LS; 1 = strongly disagree, 5 = strongly agree) was used to assess reasons for SPU versus MPU, including for MPU if antiretroviral medications were filled separately. Results 142 patients participated (69 SPUs; 73 MPUs). Few differences between SPUs and MPUs for demographic indicators were identified (Table 1). SPUs were more likely to use private/commercial insurance versus government-sponsored insurance and use fewer non-HIV medications. There was no difference between groups in self-reported undetectable VL. There was a trend towards increased recall of self-reported CD4 and VL status for SPUs vs MPUs. SPUs indicated that proximity (LS weighted average (WA) = 3.64), getting all meds in one place (LS WA = 4.45), and the identification of adverse effects (LS WA = 4.17) and drug-drug interactions (LS WA = 4.06) as reasons for preferring to use a single pharmacy. For MPUs who indicated they used a separate pharmacy specifically for antiretroviral medications, the need to keep HIV status private (LS weighted average = 3.65) was noted as a significant reason.Table 1.Respondents DemographicsTable 1(cont). Respondent Demographics Conclusion SPUs chose a single pharmacy for reasons of convenience and safety. MPUs who chose to fill their antiretroviral therapy at a separate pharmacy stated concerns for stigma/privacy as a major contributing factor. Patient preferences should be strongly considered regarding SPU or MPU. Interestingly, MPUs were less likely to be aware of their clinical status. Disclosures All Authors: No reported disclosures

HIV affects an estimated 1.2 million individuals in the United States and is disproportionately concentrated among African Americans, Latinos, and people of multiple races. Post-exposure prophylaxis (PEP) substantially decreases HIV transmission when started within 72 h after exposure, but problems of accessibility have hindered its widespread usage in communities at risk for HIV infection. Pharmacy-initiated PEP access was first permitted in New York City in 2017, allowing pharmacists to provide a 7-day supply of PEP without a prescription for consumers at high risk for HIV infection. It was expected that the broad reach and accessibility of community pharmacies would increase timely access to PEP for all individuals, especially those who already face significant barriers to accessing the healthcare system. Since then, eleven other states have followed suit and expanded the scope of outpatient pharmacy practice in order to increase the availability of HIV PEP but prescribing laws in over 75% of the US have not been changed. Much of the existing literature on HIV prevention focuses on PrEP access barriers with limited information on PEP access in the US. In this paper, we review the current status of pharmacist-initiated PEP in the US as part of the End the HIV Epidemic (EHE) initiative.

Translation: The University of Toledo Journal of Medical Sciences is the online journal launched by the University of Toledo. Manuscripts will be considered on the understanding that they report original work and are not under consideration for publication by any other journal. The journal publishes original articles reporting experimental results of basic or clinical research, case reports, and reviews. The journal uses a single blind peer review system and each manuscript, based on the results presented in its original submission, will be evaluated by two student reviewers and one faculty reviewer. This process will provide an opportunity for medical students, graduate students, residents, fellows and faculty to publish research observation in a timely manner.

Translation: The University of Toledo Journal of Medical Sciences is the online journal launched by the University of Toledo. Manuscripts will be considered on the understanding that they report original work and are not under consideration for publication by any other journal. The journal publishes original articles reporting experimental results of basic or clinical research, case reports, and reviews. The journal uses a single blind peer review system and each manuscript, based on the results presented in its original submission, will be evaluated by two student reviewers and one faculty reviewer. This process will provide an opportunity for medical students, graduate students, residents, fellows and faculty to publish research observation in a timely manner.

Long-acting cabotegravir (CAB-LA) provides an exciting new option for pre-exposure prophylaxis (PrEP) in multiple populations. In this Perspective, we consider the unique pharmacokinetics of CAB-LA and the potential impact on the prescribing of CAB-LA, specifically in cis-women of reproductive potential.

Mycobacterium kansasii is a nontuberculous mycobacterium that causes pulmonary symptoms, commonly associated with underlying conditions, including malignancy, prior transplant, and HIV. However, rarely does Mycobacterium kansasii present with pleural effusion. We present a case of a 56-year-old female who presented with dyspnea and chest pain, and sputum culture was positive for acid-fast bacilli. A CT scan revealed a left-sided pleural effusion. Based on a thorough review of the literature using Embase and PubMed, we found that only 22 cases of a Mycobacterium kansasii pleural effusion have been reported. We provide a discussion on maintaining a broad differential in the treatment of immunocompromised individuals with Mycobacterium infection.

Serratia marcescens is a gram-negative bacillus that is an opportunistic agent in respiratory tract infections, urinary tract infections, and septicemia. It is rarely a cause of infective endocarditis, but in cases of endocarditis, it follows a rapid and devastating course. A previously healthy female in her mid-50s presented with fever, abdominal pain, right lower extremity pain, and diarrhea. Blood cultures were positive for S. marcescens, and additional evaluation revealed infarction in the spleen and kidneys, raising concern for endocarditis with associated embolic phenomena. The patient was subsequently found to have an embolus in the right popliteal artery and underwent a right popliteal thromboembolectomy. Antimicrobial therapy with cefepime and gentamicin was begun. A transesophageal echocardiogram revealed a large, mobile mitral valve vegetation. Care was complicated by intracranial hemorrhage, and the decision was made to withdraw care. A review of the databases Embase and PubMed revealed 63 additional cases of S. marcescens endocarditis. Analysis of these cases demonstrated a preponderance of aortic and mitral valve involvement, not tricuspid valve involvement, despite a risk factor of intravenous drug use in over 60% of cases. Mortality was 50%, and sequelae such as congestive heart failure and renal insufficiency occurred in the majority of survivors. In conclusion, S. marcescens is a rare but devastating cause of endocarditis with a primary risk factor of intravenous drug use but with a predilection for left-sided valvular lesions, not right-sided lesions.

Objective The study sought to investigate the disease state-dependent risk profiles of patient demographics and medical comorbidities associated with adverse outcomes of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infections. Materials and Methods A covariate-dependent, continuous-time hidden Markov model with 4 states (moderate, severe, discharged, and deceased) was used to model the dynamic progression of COVID-19 during the course of hospitalization. All model parameters were estimated using the electronic health records of 1362 patients from ProMedica Health System admitted between March 20, 2020 and December 29, 2020 with a positive nasopharyngeal PCR test for SARS-CoV-2. Demographic characteristics, comorbidities, vital signs, and laboratory test results were retrospectively evaluated to infer a patient's clinical progression. Results The association between patient-level covariates and risk of progression was found to be disease state dependent. Specifically, while being male, being Black or having a medical comorbidity were all associated with an increased risk of progressing from the moderate disease state to the severe disease state, these same factors were associated with a decreased risk of progressing from the severe disease state to the deceased state. Discussion Recent studies have not included analyses of the temporal progression of COVID-19, making the current study a unique modeling-based approach to understand the dynamics of COVID-19 in hospitalized patients. Conclusion Dynamic risk stratification models have the potential to improve clinical outcomes not only in COVID-19, but also in a myriad of other acute and chronic diseases that, to date, have largely been assessed only by static modeling techniques.

The effects of normal and altered intestinal microbiota on murine retroviral transmission via the gastrointestinal tract (GIT) are diverse. The role of orally administered antibiotic treatment (ABX) on viral transmission, GIT microbial dysbiosis and subsequent pathogenesis of Moloney Murine Leukemia virus–temperature sensitive 1 (ts1) on BALB/c mice were studied. BALB/c mice were divided into four groups: ABXts1 —Treatment/Infection; ABX —Treatment/No infection; ts1 —No treatment/Infection; Ctrl (control)—No treatment/No infection. ABXts1 and ABX groups showed a significant phylogenetic shift (ANOSIM p-value = 0.001) in alpha and beta diversity comparisons for microbial community composition compared to Ctrl group. Mice in the ABXts1 and ABX groups showed megacolon compared to ts1 and Ctrl groups; ABXts1 and ts1 groups showed hepatosplenomegaly, thymus enlargement, and mesenteric lymphadenopathy compared to ABX and Ctrl groups. Ctrl group had no abnormal manifestations. ABX treatment and ts1 infection uniquely affect microbial community when compared to control: ABXts1 and ABX groups significantly reduce microbiome diversity by over 80% and ts1 group by over 30%. ABXts1 and ts1 groups’ viral load and clinical manifestations of infection were comparable; antibiotic treatment did not notably affect ts1 infection. Transmission and pathophysiology of ts1 infection were not significantly altered by the microbial composition of the GI tract, but ts1 viral infection did result in microbial dysbiosis independent of antibiotic treatment.

The combination of machine learning (ML) and electronic health records (EHR) data may be able to improve outcomes of hospitalized COVID-19 patients through improved risk stratification and patient outcome prediction. However, in resource constrained environments the clinical utility of such data-driven predictive tools may be limited by the cost or unavailability of certain laboratory tests. We leveraged EHR data to develop an ML-based tool for predicting adverse outcomes that optimizes clinical utility under a given cost structure. We further gained insights into the decision-making process of the ML models through an explainable AI tool. This cohort study was performed using deidentified EHR data from COVID-19 patients from ProMedica Health System in northwest Ohio and southeastern Michigan. We tested the performance of various ML approaches for predicting either increasing ventilatory support or mortality. We performed post hoc analysis to obtain optimal feature sets under various budget constraints. We demonstrate that it is possible to achieve a significant reduction in cost at the expense of a small reduction in predictive performance. For example, when predicting ventilation, it is possible to achieve a 43% reduction in cost with only a 3% reduction in performance. Similarly, when predicting mortality, it is possible to achieve a 50% reduction in cost with only a 1% reduction in performance. This study presents a quick, accurate, and cost-effective method to evaluate risk of deterioration for patients with SARS-CoV-2 infection at the time of clinical evaluation.