Cardiometabolic health in people with HIV: expert consensus review.

OBJECTIVES: To develop consensus data statements and clinical recommendations to provide guidance for improving cardiometabolic health outcomes in people with HIV based on the knowledge and experience of an international panel of experts. METHODS: A targeted literature review including 281 conference presentations, peer-reviewed articles, and background references on cardiometabolic health in adults with HIV published between January 2016 and April 2022 was conducted and used to develop draft consensus data statements. Using a modified Delphi method, an international panel of 16 experts convened in workshops and completed surveys to refine consensus data statements and generate clinical recommendations. RESULTS: Overall, 10 data statements, five data gaps and 14 clinical recommendations achieved consensus. In the data statements, the panel describes increased risk of cardiometabolic health concerns in people with HIV compared with the general population, known risk factors, and the potential impact of antiretroviral therapy. The panel also identified data gaps to inform future research in people with HIV. Finally, in the clinical recommendations, the panel emphasizes the need for a holistic approach to comprehensive care that includes regular assessment of cardiometabolic health, access to cardiometabolic health services, counselling on potential changes in weight after initiating or switching antiretroviral therapy and encouraging a healthy lifestyle to lower cardiometabolic health risk. CONCLUSIONS: On the basis of available data and expert consensus, an international panel developed clinical recommendations to address the increased risk of cardiometabolic disorders in people with HIV to ensure appropriate cardiometabolic health management for this population.

Association of Syndemic Unhealthy Alcohol Use, Smoking, and Depressive Symptoms on Incident Cardiovascular Disease among Veterans With and Without HIV-Infection.

Unhealthy alcohol use, smoking, and depressive symptoms are risk factors for cardiovascular disease (CVD). Little is known about their co-occurrence - termed a syndemic, defined as the synergistic effect of two or more conditions-on CVD risk in people with HIV (PWH). We used data from 5621 CVD-free participants (51% PWH) in the Veteran's Aging Cohort Study-8, a prospective, observational study of veterans followed from 2002 to 2014 to assess the association between this syndemic and incident CVD by HIV status. Diagnostic codes identified cases of CVD (acute myocardial infarction, stroke, heart failure, peripheral artery disease, and coronary revascularization). Validated measures of alcohol use, smoking, and depressive symptoms were used. Baseline number of syndemic conditions was categorized (0, 1, ≥ 2 conditions). Multivariable Cox Proportional Hazards regressions estimated risk of the syndemic (≥ 2 conditions) on incident CVD by HIV-status. There were 1149 cases of incident CVD (52% PWH) during the follow-up (median 10.1 years). Of the total sample, 64% met our syndemic definition. The syndemic was associated with greater risk for incident CVD among PWH (Hazard Ratio [HR] 1.87 [1.47-2.38], p < 0.001) and HIV-negative veterans (HR 1.70 [1.35-2.13], p < 0.001), compared to HIV-negative with zero conditions. Among those with the syndemic, CVD risk was not statistically significantly higher among PWH vs. HIV-negative (HR 1.10 [0.89, 1.37], p = .38). Given the high prevalence of this syndemic combined with excess risk of CVD, these findings support linked-screening and treatment efforts.

Microvascular Disease, Peripheral Artery Disease, and Amputation.

BACKGROUND: The mechanism of adverse limb events associated with peripheral artery disease remains incompletely understood. We investigated whether microvascular disease is associated with amputation in a large cohort of veterans to determine whether microvascular disease diagnosed in any location increases the risk of amputation alone and in concert with peripheral artery disease. METHODS: Participants in the Veterans Aging Cohort Study were recruited from April 1, 2003 through December 31, 2014. We excluded participants with known prior lower limb amputation. Using time-updated Cox proportional hazards regression, we analyzed the effect of prevalent microvascular disease (retinopathy, neuropathy, and nephropathy) and peripheral artery disease status on the risk of incident amputation events after adjusting for demographics and cardiovascular risk factors. RESULTS: Among 125 674 veterans without evidence of prior amputation at baseline, the rate of incident amputation over a median of 9.3 years of follow-up was 1.16 per 1000 person-years, yielding a total of 1185 amputations. In time-updated multivariable-adjusted analyses, compared with those without peripheral artery disease or microvascular disease, microvascular disease alone was associated with a 3.7-fold (95% CI, 3.0-4.6) increased risk of amputation; peripheral artery disease alone conferred a 13.9-fold (95% CI, 11.3-17.1) elevated risk of amputation; and the combination of peripheral artery disease and microvascular disease was associated with a 22.7-fold (95% CI, 18.3-28.1) increased risk of amputation. CONCLUSIONS: Independent of traditional risk factors, the presence of microvascular disease increases the risk of amputation alone and synergistically increases risk in patients with peripheral artery disease. Further research is needed to understand the mechanisms by which this occurs.

Increased Fragility Fracture Rates in Older Men With Osteomyelitis.

In this study, we evaluated fracture incidence over a 10-year period among men with and without osteomyelitis from the Veterans Aging Cohort Study. Fracture incidence was significantly higher among those with osteomyelitis at all osteoporotic fracture sites after adjusting for key related risk factors. Future prospective studies are warranted.

Association of Viral Suppression With Lower AIDS-Defining and Non-AIDS-Defining Cancer Incidence in HIV-Infected Veterans: A Prospective Cohort Study.

Background: Viral suppression is a primary marker of HIV treatment success. Persons with HIV are at increased risk for AIDS-defining cancer (ADC) and several types of non-AIDS-defining cancer (NADC), some of which are caused by oncogenic viruses. Objective: To determine whether viral suppression is associated with decreased cancer risk. Design: Prospective cohort. Setting: Department of Veterans Affairs. Participants: HIV-positive veterans (n = 42 441) and demographically matched uninfected veterans (n = 104 712) from 1999 to 2015. Measurements: Standardized cancer incidence rates and Poisson regression rate ratios (RRs; HIV-positive vs. uninfected persons) by viral suppression status (unsuppressed: person-time with HIV RNA levels ≥500 copies/mL; early suppression: initial 2 years with HIV RNA levels <500 copies/mL; long-term suppression: person-time after early suppression with HIV RNA levels <500 copies/mL). Results: Cancer incidence for HIV-positive versus uninfected persons was highest for unsuppressed persons (RR, 2.35 [95% CI, 2.19 to 2.51]), lower among persons with early suppression (RR, 1.99 [CI, 1.87 to 2.12]), and lowest among persons with long-term suppression (RR, 1.52 [CI, 1.44 to 1.61]). This trend was strongest for ADC (unsuppressed: RR, 22.73 [CI, 19.01 to 27.19]; early suppression: RR, 9.48 [CI, 7.78 to 11.55]; long-term suppression: RR, 2.22 [CI, 1.69 to 2.93]), much weaker for NADC caused by viruses (unsuppressed: RR, 3.82 [CI, 3.24 to 4.49]; early suppression: RR, 3.42 [CI, 2.95 to 3.97]; long-term suppression: RR, 3.17 [CI, 2.78 to 3.62]), and absent for NADC not caused by viruses. Limitation: Lower viral suppression thresholds, duration of long-term suppression, and effects of CD4+ and CD8+ T-cell counts were not thoroughly evaluated. Conclusion: Antiretroviral therapy resulting in long-term viral suppression may contribute to cancer prevention, to a greater degree for ADC than for NADC. Patients with long-term viral suppression still had excess cancer risk. Primary Funding Source: National Cancer Institute and National Institute on Alcohol Abuse and Alcoholism of the National Institutes of Health.

The Differential Effects of Human Immunodeficiency Virus and Hepatitis C Virus on Bone Microarchitecture and Fracture Risk.

Background: Human immunodeficiency virus (HIV)/hepatitis C virus (HCV)-coinfected individuals have a significantly greater osteoporotic fracture risk than HIV-monoinfected persons, despite the fact that HIV/HCV coinfection has not been associated with lower bone mineral density (BMD) than HIV or HCV alone. To evaluate if changes in bone microarchitecture, measured by trabecular bone score (TBS), could explain these differences, we performed a prospective, cross-sectional cohort study of virologically suppressed HIV-infected subjects, untreated HCV-infected subjects, HIV/HCV-coinfected subjects, and uninfected controls. Methods: We enrolled 532 male subjects: 57 HIV/HCV coinfected, 174 HIV infected, 123 HCV infected, and 178 controls. We conducted analysis of covariance comparing BMD and TBS between groups, controlling for age, race, body mass index, and smoking. We used linear regression to evaluate predictors of BMD and TBS and evaluated the effects of severity of HCV infection and tenofovir disoproxil fumarate use. Results: Despite both infections being associated with decreased BMD, only HCV, but not HIV, was associated with lower TBS score. Also, HIV/HCV-coinfected subjects had lower TBS scores than HIV-monoinfected, HCV-monoinfected, and uninfected subjects. Neither the use of TDF or HCV viremia nor the severity of HCV liver disease was associated with lower TBS. Conclusions: HCV infection is associated with microarchitectural changes at the lumbar spine as assessed by the low TBS score, suggesting that microstructural abnormalities underlie some of the higher fracture risk in HCV infection. TBS might improve fracture risk prediction in HCV infection.

Depression and human immunodeficiency virus infection are risk factors for incident heart failure among veterans: Veterans Aging Cohort Study.

BACKGROUND: Both HIV and depression are associated with increased heart failure (HF) risk. Depression, a common comorbidity, may further increase the risk of HF among adults with HIV infection (HIV+). We assessed the association between HIV, depression, and incident HF. METHODS AND RESULTS: Veterans Aging Cohort Study (VACS) participants free from cardiovascular disease at baseline (n=81 427: 26 908 HIV+, 54 519 without HIV [HIV-]) were categorized into 4 groups: HIV- without major depressive disorder (MDD) [reference], HIV- with MDD, HIV+ without MDD, and HIV+ with MDD. International Classification of Diseases, Ninth Revision codes from medical records were used to determine MDD and the primary outcome, HF. After 5.8 years of follow-up, HF rates per 1000 person-years were highest among HIV+ participants with MDD (9.32; 95% confidence interval [CI], 8.20-10.6). In Cox proportional hazards models, HIV+ participants with MDD had a significantly higher risk of HF (adjusted hazard ratio, 1.68; 95% CI, 1.45-1.95) compared with HIV- participants without MDD. MDD was associated with HF in separate fully adjusted models for HIV- and HIV+ participants (adjusted hazard ratio, 1.21; 95% CI, 1.06-1.37; and adjusted hazard ratio, 1.29; 95% CI, 1.11-1.51, respectively). Among those with MDD, baseline antidepressant use was associated with lower risk of incident HF events (adjusted hazard ratio, 0.76; 95% CI, 0.58-0.99). CONCLUSIONS: Our study is the first to suggest that MDD is an independent risk factor for HF in HIV+ adults. These results reinforce the importance of identifying and managing MDD among HIV+ patients. Future studies must clarify mechanisms linking HIV, MDD, antidepressants, and HF and identify interventions to reduce HF morbidity and mortality in those with both HIV and MDD.

Core Warming of Coronavirus Disease 2019 Patients Undergoing Mechanical Ventilation: A Pilot Study.

Fever is a recognized protective factor in patients with sepsis, and growing data suggest beneficial effects on outcomes in sepsis with elevated temperature, with a recent pilot randomized controlled trial (RCT) showing lower mortality by warming afebrile sepsis patients in the intensive care unit (ICU). The objective of this prospective single-site RCT was to determine if core warming improves respiratory physiology of mechanically ventilated patients with coronavirus disease 2019 (COVID-19), allowing earlier weaning from ventilation, and greater overall survival. A total of 19 patients with mean age of 60.5 (±12.5) years, 37% female, mean weight 95.1 (±18.6) kg, and mean body mass index 34.5 (±5.9) kg/m2 with COVID-19 requiring mechanical ventilation were enrolled from September 2020 to February 2022. Patients were randomized 1:1 to standard of care or to receive core warming for 72 hours through an esophageal heat exchanger commonly utilized in critical care and surgical patients. The maximum target temperature was 39.8°C. A total of 10 patients received usual care and 9 patients received esophageal core warming. After 72 hours of warming, the ratio of arterial oxygen partial pressure to fractional inspired oxygen (PaO2/FiO2) ratios were 197 (±32) and 134 (±13.4), cycle thresholds were 30.8 (±6.4) and 31.4 (±3.2), ICU mortalities were 40% and 44%, 30-day mortalities were 30% and 22%, and mean 30-day ventilator-free days were 11.9 (±12.6) and 6.8 (±10.2) for standard of care and warmed patients, respectively (p = NS). This pilot study suggests that core warming of patients with COVID-19 undergoing mechanical ventilation is feasible and appears safe. Optimizing time to achieve febrile-range temperature may require a multimodal temperature management strategy to further evaluate effects on outcome. ClinicalTrials.gov Identifier: NCT04494867.

Left Atrial Mechanics and Diastolic Function Among People Living With Human Immunodeficiency Virus (from the Veterans Aging Cohort Study).

Human immunodeficiency virus (HIV) infection is associated with subclinical cardiomyopathy, diastolic dysfunction, and increased risk of cardiovascular death. However, the relationship between left atrial (LA) mechanics and left ventricular (LV) diastolic function has not been evaluated in people living with HIV (PLWH) relative to HIV-uninfected (HIV-) controls. This is a multicenter, cross-sectional cohort analysis using the HIV Cardiovascular Disease substudy of the Veterans Aging Cohort Study database, which aimed to examine a cohort of PLWH and HIV- veterans without known cardiovascular disease. A total of 277 subjects (180 PLWH, 97 HIV-) with echocardiograms were identified. LV and LA phasic strain were derived and diastolic function was evaluated. Relationship between LA strain, LV strain, and the degree of diastolic dysfunction were assessed using analysis of variance and ordinal logistic regression with propensity weighting. In the PLWH cohort, 91.7% were on antiretroviral therapy and 86.1% had HIV viral loads <500 copies/ml. The mean (± SD) duration of infection was 9.7 ± 4.9 years. Relative to HIV- veterans, PLWH did not differ in LA mechanics and proportion of diastolic dysfunction (p = 0.31). Using logistic regression with propensity weighting, we found no association between HIV status and degree of diastolic dysfunction. In both cohorts, LA reservoir strain and LA conduit strain were inversely and independently associated with the degree of diastolic dysfunction. Compared with HIV- veterans, PLWH who are primarily virally suppressed and antiretroviral-treated did not differ in LA strain or LV diastolic dysfunction. If confirmed in other cohorts, HIV viral suppression may curtail adverse alterations in cardiac structure and function.

Risk Factors for SARS-CoV-2 Infection and Severe Outcomes Among People With Human Immunodeficiency Virus: Cohort Study.

Background: Studies on COVID-19 in people with HIV (PWH) have had limitations. Further investigations on risk factors and outcomes of SARS-CoV-2 infection among PWH are needed. Methods: This retrospective cohort study leveraged the national OPTUM COVID-19 data set to investigate factors associated with SARS-CoV-2 positivity among PWH and risk factors for severe outcomes, including hospitalization, intensive care unit stays, and death. A subset analysis was conducted to examine HIV-specific variables. Multiple variable logistic regression was used to adjust for covariates. Results: Of 43 173 PWH included in this study, 6472 had a positive SARS-CoV-2 result based on a polymerase chain reaction test or antigen test. For PWH with SARS-CoV-2 positivity, higher odds were found for those who were younger (18-49 years), Hispanic White, African American, from the US South, uninsured, and a noncurrent smoker and had a higher body mass index and higher Charlson Comorbidity Index. For PWH with severe outcomes, higher odds were identified for those who were SARS-CoV-2 positive, older, from the US South, receiving Medicaid/Medicare or uninsured, a current smoker, and underweight and had a higher Charlson Comorbidity Index. In a subset analysis including PWH with HIV care variables (n = 5098), those with unsuppressed HIV viral load, a low CD4 count, and no antiretroviral therapy had higher odds of severe outcomes. Conclusions: This large US study found significant ethnic, racial, and geographic differences in SARS-CoV-2 infection among PWH. Chronic comorbidities, older age, lower body mass index, and smoking were associated with severe outcomes among PWH during the COVID-19 pandemic. SARS-CoV-2 infection was associated with severe outcomes, but once we adjusted for HIV care variables, SARS-CoV-2 was no longer significant; however, low CD4 count, high viral load, and lack of antiretroviral therapy had higher odds of severe outcomes.

Empiric guideline-recommended weight-based vancomycin dosing and mortality in methicillin-resistant Staphylococcus aureus bacteremia: a retrospective cohort study.

BACKGROUND: No studies have evaluated the effect of guideline-recommended weight-based dosing on in-hospital mortality of patients with methicillin-resistant Staphylococcus aureus bacteremia. METHODS: This was a multicenter, retrospective, cohort study of patients with methicillin-resistant Staphylococcus aureus bacteremia receiving at least 48 hours of empiric vancomycin therapy between 01/07/2002 and 30/06/2008. We compared in-hospital mortality for patients treated empirically with weight-based, guideline-recommended vancomycin doses (at least 15 mg/kg/dose) to those treated with less than 15 mg/kg/dose. We used a general linear mixed multivariable model analysis with variables identified a priori through a conceptual framework based on the literature. RESULTS: A total of 337 patients who were admitted to the three hospitals were included in the cohort. One-third of patients received vancomycin empirically at the guideline-recommended dose. Guideline-recommended dosing was not associated with in-hospital mortality in the univariable (16% vs. 13%, OR 1.26 [95%CI 0.67-2.39]) or multivariable (OR 0.71, 95%CI 0.33-1.55) analysis. Independent predictors of in-hospital mortality were ICU admission, Pitt bacteremia score of 4 or greater, age 53 years or greater, and nephrotoxicity. CONCLUSIONS: Empiric use of weight-based, guideline-recommended empiric vancomycin dosing was not associated with reduced mortality in this multicenter study.

Healthcare utilization and outcomes of spinal cord injured veterans with stage 3-4 pressure injuries.

BACKGROUND: Pressure injuries (PI) are a significant source of morbidity for individuals with spinal cord injury/disease (SCI/D). They are also associated with significant healthcare resource utilization including prolonged hospitalizations. However, the long-term outcomes in terms of wound recurrence-free survival, hospital readmission rates, and all-cause mortality in this population remain largely unknown. OBJECTIVE: To examine the clinical characteristics, healthcare utilization and outcomes of SCI Veterans hospitalized at the VA North Texas Health Care System (VANTHCS) SCI inpatient unit with stage 3 and 4 PI, and compare these between those who received a myocutaneous flap surgery (flap patients (FP)) and those treated medically (non-flap patients (NFP)). METHODS: A retrospective chart review was conducted of all adult patients admitted to the VANTHCS SCI/D unit with stage 3 or 4 pelvic PI between 1/1/2013 and 12/31/2018. Healthcare utilization and outcome information was extracted for pre-specified time points. RESULTS: 78 patients met criteria (113 hospitalizations; 27 FP; 51 NFP). Average length of stay (LOS) was 122 days; FP had a significantly higher LOS than NFP (P = 0.01). Average number of consults was 24. Estimated cost per hospitalization was $175,198. Readmission rate within 30 days was 12.39%. The mortality rate within 1 year of discharge was 21.57% for NFP, as opposed to 3.70% in the FP group. Only 5.00% of NFP wounds were healed at discharged with sustained healing at 1 year, significantly less than FP wounds (55.26%, P < 0.01). CONCLUSIONS: Despite the high investment in terms of healthcare utilization, outcomes in terms of wound healing are poor. Additionally, nearly 22% of NFP died within one year of discharge. This calls into question the utility of prolonged hospitalizations for PI in the SCI/D population in terms of wound treatment efficacy, healthcare costs, and patient morbidity/mortality.

Effect of Androgen Suppression on Clinical Outcomes in Hospitalized Men With COVID-19: The HITCH Randomized Clinical Trial.

Importance: SARS-CoV-2 entry requires the TMPRSS2 cell surface protease. Antiandrogen therapies reduce expression of TMPRSS2. Objective: To determine if temporary androgen suppression induced by degarelix improves clinical outcomes of inpatients hospitalized with COVID-19. Design, Setting, and Participants: The Hormonal Intervention for the Treatment in Veterans With COVID-19 Requiring Hospitalization (HITCH) phase 2, placebo-controlled, double-blind, randomized clinical trial compared efficacy of degarelix plus standard care vs placebo plus standard care on clinical outcomes in men hospitalized with COVID-19 but not requiring invasive mechanical ventilation. Inpatients were enrolled at 14 Department of Veterans Affairs hospitals from July 22, 2020, to April 8, 2021. Data were analyzed from August 9 to October 15, 2021. Interventions: Patients stratified by age, history of hypertension, and disease severity were centrally randomized 2:1 to degarelix, (1-time subcutaneous dose of 240 mg) or a saline placebo. Standard care included but was not limited to supplemental oxygen, antibiotics, vasopressor support, peritoneal dialysis or hemodialysis, intravenous fluids, remdesivir, convalescent plasma, and dexamethasone. Main Outcomes and Measures: The composite primary end point was mortality, ongoing need for hospitalization, or requirement for mechanical ventilation at day 15 after randomization. Secondary end points were time to clinical improvement, inpatient mortality, length of hospitalization, duration of mechanical ventilation, time to achieve a temperature within reference range, maximum severity of COVID-19, and the composite end point at 30 days. Results: The trial was stopped for futility after the planned interim analysis, at which time there were 96 evaluable patients, including 62 patients randomized to the degarelix group and 34 patients in the placebo group, out of 198 initially planned. The median (range) age was 70.5 (48-85) years. Common comorbidities included chronic obstructive pulmonary disorder (15 patients [15.6%]), hypertension (75 patients [78.1%]), cardiovascular disease (27 patients [28.1%]), asthma (12 patients [12.5%]), diabetes (49 patients [51.0%]), and chronic respiratory failure requiring supplemental oxygen at baseline prior to COVID-19 (9 patients [9.4%]). For the primary end point, there was no significant difference between the degarelix and placebo groups (19 patients [30.6%] vs 9 patients [26.5%]; P = .67). Similarly, no differences were observed between degarelix and placebo groups in any secondary end points, including inpatient mortality (11 patients [17.7%] vs 6 patients [17.6%]) or all-cause mortality (11 patients [17.7%] vs 7 patents [20.6%]). There were no differences between degarelix and placebo groups in the overall rates of adverse events (13 patients [21.0%] vs 8 patients [23.5%) and serious adverse events (19 patients [30.6%] vs 13 patients [32.4%]), nor unexpected safety concerns. Conclusions and Relevance: In this randomized clinical trial of androgen suppression vs placebo and usual care for men hospitalized with COVID-19, degarelix did not result in amelioration of COVID-19 severity. Trial Registration: ClinicalTrials.gov Identifier: NCT04397718.

Abacavir use and risk of acute myocardial infarction and cerebrovascular events in the highly active antiretroviral therapy era.

BACKGROUND: Some studies have suggested that exposure to antiretroviral therapy (ART) with abacavir is associated with an increased risk of acute myocardial infarction (AMI). METHODS: Using the Veterans Health Administration's Clinical Case Registry we calculated the risk of AMI and cerebrovascular events (CVA) associated with the cumulative use of abacavir and other nucleoside combinations. We also evaluated the impact of pre-existing chronic kidney disease on the selection of abacavir versus tenofovir in the last recorded ART regimen, and on highly active antiretroviral therapy-associated AMI and CVA risks. RESULTS: A total of 19,424 human immunodeficiency virus-infected patients contributed 76,376 patient-years of follow. After adjusting for age, hypercholesterolemia, hypertension, type 2 diabetes, and smoking, the hazard ratio (HR) for each year of abacavir use was 1.18 (95% confidence interval [CI], .92-1.50; P=.191) for AMI and 1.16 (95% CI, .98-1.37; P=.096) for CVA. Abacavir use was more common among patients with prior chronic kidney disease than was tenofovir use (12.46% versus 7.15%; P=.0001), and chronic kidney disease was associated with a significantly higher risk of AMI (HR, 2.41; 95% CI, 1.73-3.36), and CVA (HR, 1.80; 95% CI, 1.44-2.24). Compared with patients who received neither tenofovir nor abacavir, patients who received tenofovir had lower risk of AMI (HR, 0.16; 95% CI, .08-.33; P=.0001) and CVA (HR, 0.22; 95% CI, .15-.32; P=.001). Use of abacavir was associated with lower risk of CVA (HR, 0.60; 95% CI, .45-.79). CONCLUSIONS: We observed no association between cumulative or current abacavir use and AMI or CVA. Abacavir use was more common than was tenofovir use among patients with prior chronic kidney disease, and chronic kidney disease independently predicted higher rates of AMI and CVA.

Characteristics and Outcomes of Infectious Diseases Electronic COVID-19 Consultations at a Multisite Academic Health System.

Objective The need for clinicians to access Infectious Diseases (ID) consultants for clinical decision-making support increased during the Coronavirus Disease 2019 (COVID-19) pandemic. Traditional ID consultations with face-to-face (FTF) patient assessments are not always possible or practical during a pandemic and involve added exposure risk and personal protective equipment (PPE) use. Electronic consultations (e-consults) may provide an alternative and improve access to ID specialists during the pandemic. Methods We implemented ID e-consult platforms designed to answer clinical questions related to COVID-19 at three academic clinical institutions in Dallas, Texas. We conducted a retrospective review of all COVID-19 ID e-consults between March 16, 2020 and May 15, 2020 evaluating characteristics and outcomes of e-consults among the clinical sites. Results We completed 198 COVID-19 ID e-consults at participating institutions. The most common e-consult indications were for 63 (32%) repeat testing, 61 (31%) initial testing, 65 (33%) treatment options, and 61 (31%) Infection Prevention (IP). Based on the e-consult recommendation, 53 (27%) of patients were initially tested for COVID-19, 45 (23%) were re-tested, 44 (22%) of patients had PPE precautions initiated, and 37 (19%) had PPE precautions removed. The median time to consult completion was four hours and 8 (4%) consults were converted to standard FTF consults. Conclusion E-consult services can provide safe and timely access to ID specialists during the COVID-19 pandemic, minimizing the risk of infection to the patient and health care workers, while preserving PPE and testing supplies.

Statin exposure and risk of cancer in people with and without HIV infection.

OBJECTIVE: To determine whether statin exposure is associated with decreased cancer and mortality risk among persons with HIV (PWH) and uninfected persons. Statins appear to have immunomodulatory and anti-inflammatory effects and may reduce cancer risk, particularly among PWH as they experience chronic inflammation and immune activation. DESIGN: Propensity score-matched cohort of statin-exposed and unexposed patients from 2002 to 2017 in the Veterans Aging Cohort Study (VACS), a large cohort with cancer registry linkage and detailed pharmacy data. METHODS: We calculated Cox regression hazard ratios (HRs) and 95% confidence intervals (CI) associated with statin use for all cancers, microbial cancers (associated with bacterial or oncovirus coinfection), nonmicrobial cancers, and mortality. RESULTS: :The propensity score-matched sample (N = 47 940) included 23 970 statin initiators (31% PWH). Incident cancers were diagnosed in 1160 PWH and 2116 uninfected patients. Death was reported in 1667 (7.0%) statin-exposed, and 2215 (9.2%) unexposed patients. Statin use was associated with 24% decreased risk of microbial-associated cancers (hazard ratio 0.76; 95% CI 0.69-0.85), but was not associated with nonmicrobial cancer risk (hazard ratio 1.00; 95% CI 0.92-1.09). Statin use was associated with 33% lower risk of death overall (hazard ratio 0.67; 95% CI 0.63-0.72). Results were similar in analyses stratified by HIV status, except for non-Hodgkin lymphoma where statin use was associated with reduced risk (hazard ratio 0.56; 95% CI 0.38-0.83) for PWH, but not for uninfected (P interaction = 0.012). CONCLUSION: In both PWH and uninfected, statin exposure was associated with lower risk of microbial, but not nonmicrobial cancer incidence, and with decreased mortality.

Insomnia symptoms and biomarkers of monocyte activation, systemic inflammation, and coagulation in HIV: Veterans Aging Cohort Study.

BACKGROUND: Insomnia may be a risk factor for cardiovascular disease in HIV (HIV-CVD); however, mechanisms have yet to be elucidated. METHODS: We examined cross-sectional associations of insomnia symptoms with biological mechanisms of HIV-CVD (immune activation, systemic inflammation, and coagulation) among 1,542 people with HIV from the Veterans Aging Cohort Study (VACS) Biomarker Cohort. Past-month insomnia symptoms were assessed by the item, "Difficulty falling or staying asleep?," with the following response options: "I do not have this symptom" or "I have this symptom and…" "it doesn't bother me," "it bothers me a little," "it bothers me," "it bothers me a lot." Circulating levels of the monocyte activation marker soluble CD14 (sCD14), inflammatory marker interleukin-6 (IL-6), and coagulation marker D-dimer were determined from blood specimens. Demographic- and fully-adjusted (CVD risk factors, potential confounders, HIV-related factors) regression models were constructed, with log-transformed biomarker variables as the outcomes. We present the exponentiated regression coefficient (exp[b]) and its 95% confidence interval (CI). RESULTS: We observed no significant associations between insomnia symptoms and sCD14 or IL-6. For D-dimer, veterans in the "Bothers a Lot" group had, on average, 17% higher D-dimer than veterans in the "No Difficulty Falling or Staying Asleep" group in the demographic-adjusted model (exp[b] = 1.17, 95%CI = 1.01-1.37, p = .04). This association was nonsignificant in the fully-adjusted model (exp[b] = 1.09, 95%CI = 0.94-1.26, p = .27). CONCLUSION: We observed little evidence of relationships between insomnia symptoms and markers of biological mechanisms of HIV-CVD. Other mechanisms may be responsible for the insomnia-CVD relationship in HIV; however, future studies with comprehensive assessments of insomnia symptoms are warranted.

Community-Acquired Pneumonia and Risk of Cardiovascular Events in People Living With HIV.

Background Hospitalization with community-acquired pneumonia (CAP) is associated with an increased risk of cardiovascular disease (CVD) events in patients uninfected with HIV. We evaluated whether people living with HIV (PLWH) have a higher risk of CVD or mortality than individuals uninfected with HIV following hospitalization with CAP. Methods and Results We analyzed data from the Veterans Aging Cohort Study on US veterans admitted with their first episode of CAP from April 2003 through December 2014. We used Cox regression analyses to determine whether HIV status was associated with incident CVD events and mortality from date of admission through 30 days after discharge (30-day mortality), adjusting for known CVD risk factors. We included 4384 patients (67% [n=2951] PLWH). PLWH admitted with CAP were younger, had less severe CAP, and had fewer CVD risk factors than patients with CAP who were uninfected with HIV. In multivariable-adjusted analyses, CVD risk was similar in PLWH compared with HIV-uninfected (hazard ratio [HR], 0.89; 95% CI, 0.70-1.12), but HIV infection was associated with higher mortality risk (HR, 1.49; 95% CI, 1.16-1.90). In models stratified by HIV status, CAP severity was significantly associated with incident CVD and 30-day mortality in PLWH and patients uninfected with HIV. Conclusions In this study, the risk of CVD events during or after hospitalization for CAP was similar in PLWH and patients uninfected with HIV, after adjusting for known CVD risk factors and CAP severity. HIV infection, however, was associated with increased 30-day mortality after CAP hospitalization in multivariable-adjusted models. PLWH should be included in future studies evaluating mechanisms and prevention of CVD events after CAP.

A Multicenter, double-blind trial of a high-dose caspofungin treatment regimen versus a standard caspofungin treatment regimen for adult patients with invasive candidiasis.

BACKGROUND: The standard caspofungin treatment regimen (50 mg/day after a 70-mg dose on day 1) is effective and well tolerated for the treatment of invasive candidiasis, but experience with higher doses of caspofungin is limited. We evaluated the safety and efficacy of caspofungin at 3 times the standard dosing regimen. METHODS: Patients with proven invasive candidiasis were randomized to receive a standard or high-dose (150 mg/day) caspofungin treatment regimen. Safety was assessed in all patients as treated. Efficacy was assessed as a secondary objective in a full-analysis-set population. A favorable overall response was defined as symptom resolution and microbiological clearance at the end of caspofungin therapy. RESULTS: A total of 204 patients were included in the safety analysis (104 received the standard regimen, and 100 received the high-dose regimen), and 197 were included in the efficacy analysis (102 and 95 in the standard and high-dose treatment groups, respectively). Patient demographic characteristics, neutropenia status (6.7% and 8.0% had neutropenia, respectively), and Acute Physiology and Chronic Health Evaluation II scores (mean, 16.5 and 17, respectively) were similar between treatment groups. Significant drug-related adverse events occurred in 1.9% of patients receiving the standard regimen and 3.0% of patients receiving the high-dose regimen (difference, 1.1%; 95% confidence interval, -4.1% to 6.8%). The most-common drug-related adverse events in the standard and high-dose treatment groups were phlebitis (3.8% and 2.0%, respectively), increased alkaline phosphatase level (6.9% and 2.0%, respectively), and increased aspartate transaminase level (4.0% and 2.0%, respectively). Overall, 71.6% of patients who received the standard regimen and 77.9% of patients who received the high-dose regimen had favorable overall responses (difference, 6.3%; 95% confidence interval, -5.9% to 18.4%; not statistically significant). Mortality at 8 weeks after therapy was similar between groups. CONCLUSIONS: Both caspofungin dosing regimens were effective and well tolerated in patients with invasive candidiasis. No safety concerns were found for caspofungin at a dosage of 150 mg/day.