Severity and Number of Substances Used are Independently Associated with Antiretroviral Therapy Adherence Over Time among People with HIV in the Current Treatment Era.

Substance use is associated with decreased antiretroviral therapy (ART) adherence among people with HIV (PWH). Adherence plays a significant role in mediating the negative effects of substance use on HIV suppression and is a principal modifiable patient-level factor in improving HIV suppression and reducing ART drug resistance. Understanding substance use and ART adherence, particularly with rapidly changing substance use epidemiology and ART regimens, is vital to improving HIV care. Among 10,557 PWH (2010-2021) from 8 academic clinical sites nationally we examined longitudinal associations of substance use severity and number of substances used (measured using AUDIT-C and modified ASSIST) with patient-reported ART adherence (visual analog scale). Alcohol (68% any use, 18% unhealthy use [AUDIT-C > 4 men, > 3 women]), marijuana (33%), and methamphetamine (9%) use were most reported. Polysubstance use was common (32%). Both higher severity substance use and higher number of substances used were associated with lower ART adherence. Severity of methamphetamine use had the strongest dose-response association with ART adherence (low severity [ASSIST 1-3]: -3.05%, 95% CI: -4.23%, -1.87%; moderate [ASSIST 4-26]: -6.20%, 95% CI: -7.08%, -5.33%; high [ASSIST > 26]: -10.77%, 95% CI: -12.76%, -8.78%). Severe substance use, especially methamphetamine, and higher number of illicit drugs used were associated with declines in adherence at levels that were likely clinically meaningful in the modern era of ART. Findings support integrating substance use care with HIV care and potential benefits of harm reduction strategies for improving adherence such as encouraging lower levels of substance use and fewer number of substances used.

Smoking and Type 1 Versus Type 2 Myocardial Infarction Among People With HIV in the United States.

ABSTRACT: Smoking is a myocardial infarction (MI) risk factor among people with HIV (PWH). Questions persist regarding the role of smoking behaviors and measurements (e.g., intensity, duration) on MI risk. We used Cox proportional hazards regression to compare the association of smoking parameterization with incidents of type 1 and type 2 MI and whether smoking intensity or duration improves MI risk prediction among PWH. Among 11,637 PWH, 37% reported currently smoking, and there were 346 MIs. Current smoking was associated with type 1 (84% increased risk) but not type 2 MI in adjusted analyses. The type 1 MI model with pack years had the best goodness of fit compared with other smoking parameterizations. Ever or never parameterization and smoking diagnosis data had significantly poorer model fit. These results highlight the importance of differentiating MI types and performing patient-based smoking assessments to improve HIV care and research rather than relying on smoking status from diagnoses.

Differences in internalized HIV stigma across subpopulations of people with HIV in care across the United States.

BACKGROUND: Few studies have examined which subgroups of people with HIV (PWH) carry the greatest burden of internalized HIV stigma (IHS), which may be important to care provision and interventions. METHODS: PWH in the CFAR Network of Integrated Clinical Systems (CNICS) longitudinal, US-based, multisite, clinical care cohort completed tablet-based assessments during clinic visits including a four-item, Likert scale (low 1-5 high), IHS instrument. Associations between sociodemographic characteristics and IHS scores were assessed in adjusted linear regression models. RESULTS: Twelve thousand six hundred and fifty-six PWH completed the IHS assessment at least once from February 2016 to November 2022, providing 28 559 IHS assessments. At baseline IHS assessment, the mean age was 49 years, 41% reported White, 38% Black/African American, and 16% Latine race/ethnicity, and 80% were cisgender men. The mean IHS score was 2.04, with all subgroups represented among those endorsing IHS. In regression analyses, younger PWH and those in care fewer years had higher IHS scores. In addition, cisgender women vs. cisgender men, PWH residing in the West vs. the Southeast, and those with sexual identities other than gay/lesbian had higher IHS scores. Compared with White-identifying PWH, those who identified with Black/African American or Latine race/ethnicity had lower IHS scores. Age stratification revealed patterns related to age category, including specific age-related differences by gender, geographic region and race/ethnicity. DISCUSSION: IHS is prevalent among PWH, with differential burden by subgroups of PWH. These findings highlight the benefits of routine screening for IHS and suggest the need for targeting/tailoring interventions to reduce IHS among PWH.

Venous Thromboembolism Among People With HIV: Design, Implementation, and Findings of a Centralized Adjudication System in Clinical Care Sites Across the United States.

BACKGROUND: People with HIV (PWH) are at increased risk for venous thromboembolism (VTE). We conducted this study to characterize VTE including provoking factors among PWH in the current treatment era. METHODS: We included PWH with VTE between 2010 and 2020 at 6 sites in the CFAR Network of Integrated Clinical Systems cohort. We ascertained for possible VTE using diagnosis, VTE-related imaging, and VTE-related procedure codes, followed by centralized adjudication of primary data by expert physician reviewers. We evaluated sensitivity and positive predictive value of VTE ascertainment approaches. VTEs were classified by type and anatomic location. Reviewers identified provoking factors such as hospitalizations, infections, and other potential predisposing factors such as smoking. RESULTS: We identified 557 PWH with adjudicated VTE: 239 (43%) had pulmonary embolism with or without deep venous thrombosis, and 318 (57%) had deep venous thrombosis alone. Ascertainment with clinical diagnoses alone missed 6% of VTEs identified with multiple ascertainment approaches. DVTs not associated with intravenous lines were most often in the proximal lower extremities. Among PWH with VTE, common provoking factors included recent hospitalization (n = 134, 42%), infection (n = 133, 42%), and immobilization/bed rest (n = 78, 25%). Only 57 (10%) PWH had no provoking factor identified. Smoking (46%), HIV viremia (27%), and injection drug use (22%) were also common. CONCLUSIONS: We conducted a robust adjudication process that demonstrated the benefits of multiple ascertainment approaches followed by adjudication. Provoked VTEs were more common than unprovoked events. Nontraditional and modifiable potential predisposing factors such as viremia and smoking were common.

Evaluating the Sick Quitting Hypothesis for Frailty Status and Reducing Alcohol Use Among People With HIV in a Longitudinal Clinical Cohort Study.

ABSTRACT: "Sick quitting," a phenomenon describing reductions in alcohol consumption following poor health, may explain observations that alcohol appears protective for frailty risk. We examined associations between frailty and reductions in drinking frequency among people with HIV (PWH). At six Centers for AIDS Research Network of Integrated Clinical Systems (CNICS) sites between January 2012 and August 2021, we assessed whether frailty, measured through validated modified frailty phenotype, precedes reductions in drinking frequency. We associated time-updated frailty with quitting and reducing frequency of any drinking and heavy episodic drinking (HED), adjusted for demographic and clinical characteristics in Cox models. Among 5,654 PWH reporting drinking, 60% reported >monthly drinking and 18% reported ≥monthly HED. Over an average of 5.4 years, frail PWH had greater probabilities of quitting (HR: 1.56, 95% confidence interval [95% CI] [1.13-2.15]) and reducing (HR: 1.35, 95% CI [1.13-1.62]) drinking frequency, as well as reducing HED frequency (HR: 1.58, 95% CI [1.20-2.09]) versus robust PWH. Sick quitting likely confounds the association between alcohol use and frailty risk, requiring investigation for control.

Associations of hepatitis C virus (HCV) antibody positivity with opioid, stimulant, and polysubstance injection among people who inject drugs (PWID) in rural U.S. communities.

BACKGROUND: People who inject drugs (PWID) in the rural U.S. often inject stimulants, alone or with opioids. The impact of these substance use patterns may influence HCV risk behaviors. This analysis examines the associations of HCV antibody positivity with injecting only opioids, only stimulants (methamphetamine/cocaine), and opioids and stimulants together among rural PWID. METHODS: The Rural Opioid Initiative (ROI) consists of eight research sites that enrolled people who use drugs in rural communities in ten U.S. states from 2018 to 2020. This cross-sectional analysis included adult participants who resided in a study area and injected any drug in the past 30 days. The primary outcome was HCV antibody positivity. The exposure of interest was injection drug use classified as only opioids, only stimulants, separate injections of opioids and stimulants, and same-syringe injection of both in the past 30 days. We used multivariable log-binomial regression with generalized linear mixed models to generate prevalence ratios (P.R.) adjusted for demographics, injection history, health insurance, and substance use treatment. RESULTS: Among 3,084 participants enrolled in the ROI, 1,982 met inclusion criteria. Most participants injected opioids and stimulants in the same syringe (34%) or separately (21%), followed by injecting only stimulants (26%), and injecting only opioids (19%). Half (51%) were HCV antibody positive. Compared to people who injected only stimulants, HCV antibody positivity was more prevalent among people who injected opioids alone (aPR=1.62, 95% CI:(1.29-2.03)), injected both opioids and stimulants separately (aPR=1.61, 95% CI:(1.32-1.95)), and in the same syringe (aPR=1.54, 95% CI:(1.28-1.85)). CONCLUSION: HCV antibody positivity, indicating prior exposure, was highest among those who had recently injected opioids, alone or with stimulants. Additional nucleic acid testing is necessary to confirm active infection. More research is needed to determine the underlying causes of HCV antibody positivity by injection use.

Tobacco Smoking and Pack-Years Are Associated With Frailty Among People With HIV.

BACKGROUND: Tobacco smoking increases frailty risk among the general population and is common among people with HIV (PWH) who experience higher rates of frailty at younger ages than the general population. METHODS: We identified 8608 PWH across 6 Centers for AIDS Research Network of Integrated Clinical Systems sites who completed ≥2 patient-reported outcome assessments, including a frailty phenotype measuring unintentional weight loss, poor mobility, fatigue, and inactivity, and scored 0-4. Smoking was measured as baseline pack-years and time-updated never, former, or current use with cigarettes/day. We used Cox models to associate smoking with risk of incident frailty (score ≥3) and deterioration (frailty score increase by ≥2 points), adjusted for demographics, antiretroviral medication, and time-updated CD4 count. RESULTS: The mean follow-up of PWH was 5.3 years (median: 5.0), the mean age at baseline was 45 years, 15% were female, and 52% were non-White. At baseline, 60% reported current or former smoking. Current (HR: 1.79; 95% confidence interval: 1.54 to 2.08) and former (HR: 1.31; 95% confidence interval: 1.12 to 1.53) smoking were associated with higher incident frailty risk, as were higher pack-years. Current smoking (among younger PWH) and pack-years, but not former smoking, were associated with higher risk of deterioration. CONCLUSIONS: Among PWH, smoking status and duration are associated with incident and worsening frailty.

Associations between alcohol and cigarette use and type 1 and 2 myocardial infarction among people with HIV.

OBJECTIVES: People with HIV have a higher risk of myocardial infarction (MI) than the general population, with a greater proportion of type 2 MI (T2MI) due to oxygen demand-supply mismatch compared with type 1 (T1MI) resulting from atherothrombotic plaque disruption. People living with HIV report a greater prevalence of cigarette and alcohol use than do the general population. Alcohol use and smoking as risk factors for MI by type are not well studied among people living with HIV. We examined longitudinal associations between smoking and alcohol use patterns and MI by type among people living with HIV. DESIGN AND METHODS: Using longitudinal data from the Centers for AIDS Research Network of Integrated Clinical Systems cohort, we conducted time-updated Cox proportional hazards models to determine the impact of smoking and alcohol consumption on adjudicated T1MI and T2MI. RESULTS: Among 13 506 people living with HIV, with a median 4 years of follow-up, we observed 177 T1MI and 141 T2MI. Current smoking was associated with a 60% increase in risk of both T1MI and T2MI. In addition, every cigarette smoked per day was associated with a 4% increase in risk of T1MI, with a suggestive, but not significant, 2% increase for T2MI. Cigarette use had a greater impact on T1MI for men than for women and on T2MI for women than for men. Increasing alcohol use was associated with a lower risk of T1MI but not T2MI. Frequency of heavy episodic alcohol use was not associated with MI. CONCLUSIONS: Our findings reinforce the prioritization of smoking reduction, even without cessation, and cessation among people living with HIV for MI prevention and highlight the different impacts on MI type by gender.

Development of Frail RISC-HIV: a Risk Score for Predicting Frailty Risk in the Short-term for Care of People with HIV.

OBJECTIVE: Frailty is common among people with HIV (PWH), so we developed frail risk in the short-term for care (RISC)-HIV, a frailty prediction risk score for HIV clinical decision-making. DESIGN: We followed PWH for up to 2 years to identify short-term predictors of becoming frail. METHODS: We predicted frailty risk among PWH at seven HIV clinics across the United States. A modified self-reported Fried Phenotype captured frailty, including fatigue, weight loss, inactivity, and poor mobility. PWH without frailty were separated into training and validation sets and followed until becoming frail or 2 years. Bayesian Model Averaging (BMA) and five-fold-cross-validation Lasso regression selected predictors of frailty. Predictors were selected by BMA if they had a greater than 45% probability of being in the best model and by Lasso if they minimized mean squared error. We included age, sex, and variables selected by both BMA and Lasso in Frail RISC-HIV by associating incident frailty with each selected variable in Cox models. Frail RISC-HIV performance was assessed in the validation set by Harrell's C and lift plots. RESULTS: Among 3170 PWH (training set), 7% developed frailty, whereas among 1510 PWH (validation set), 12% developed frailty. BMA and Lasso selected baseline frailty score, prescribed antidepressants, prescribed antiretroviral therapy, depressive symptomology, and current marijuana and illicit opioid use. Discrimination was acceptable in the validation set, with Harrell's C of 0.76 (95% confidence interval: 0.73-0.79) and sensitivity of 80% and specificity of 61% at a 5% frailty risk cutoff. CONCLUSIONS: Frail RISC-HIV is a simple, easily implemented tool to assist in classifying PWH at risk for frailty in clinics.

Vaporized Nicotine (E-Cigarette) and Tobacco Smoking Among People With HIV: Use Patterns and Associations With Depression and Panic Symptoms.

BACKGROUND: Vaporized nicotine (VN) use is increasing among people with HIV (PWH). We examined demographics, patterns of use, depression, and panic symptoms associated with VN and combustible cigarette (CC) use among PWH. METHODS: We analyzed VN use among PWH in care at 7 US sites. PWH completed a set of patient-reported outcomes, including substance use and mental health. We categorized VN use as never vs. ever with the frequency of use (days/month) and CC use as never, former, or current. We used relative risk regression to associate VN and CC use, depression, and panic symptoms. Linear regression estimated each relationship with VN frequency. Models were adjusted for demographics. RESULTS: Among 7431 PWH, 812 (11%) reported ever-using VN, and 264 (4%) reported daily use. Half (51%) of VN users concurrently used CC. VN users were more likely than those without use to be younger, to be White, and to report ever-using CC. PWH reporting former CC use reported ≥8.5 more days per month of VN use compared with never CC use [95% confidence interval (95% CI): 5.5 to 11.5 days/month] or current CC use (95% CI: 6.6 to 10.5 days/month). Depression (relative risk: 1.20 [95% CI: 1.02 to 1.42]) and panic disorder (1.71 [95% CI: 1.43 to 2.05]) were more common among PWH ever-using VN. Depression was common among PWH using VN (27%) and CC (22%), as was panic disorder (21% for VN and 16% for CC). CONCLUSION: Our study elucidated demographic associations with VN use among PWH, revealed the overlap of VN and CC use, and associations with depression/panic symptoms, suggesting roles of VN in self-medication and CC substitution, warranting further longitudinal/qualitative research.

Associations between drug and alcohol use, smoking, and frailty among people with HIV across the United States in the current era of antiretroviral treatment.

OBJECTIVE: To examine associations between frailty and drug, alcohol, and tobacco use among a large diverse cohort of people with HIV (PWH) in clinical care in the current era. METHODS: PWH at 7 sites across the United States completed clinical assessments of patient-reported measures and outcomes between 2016 and 2019 as part of routine care including drug and alcohol use, smoking, and other domains. Frailty was assessed using 4 of the 5 components of the Fried frailty phenotype and PWH were categorized as not frail, pre-frail, or frail. Associations of substance use with frailty were assessed with multivariate Poisson regression. RESULTS: Among 9336 PWH, 43% were not frail, 44% were prefrail, and 13% were frail. Frailty was more prevalent among women, older PWH, and those reporting current use of drugs or cigarettes. Current methamphetamine use (1.26: 95% CI 1.07-1.48), current (1.65: 95% CI 1.39-1.97) and former (1.21:95% CI 1.06-1.36) illicit opioid use, and former cocaine/crack use (1.17: 95% CI 1.01-1.35) were associated with greater risk of being frail in adjusted analyses. Current smoking was associated with a 61% higher risk of being frail vs. not frail (1.61: 95% CI 1.41-1.85) in adjusted analyses. CONCLUSIONS: We found a high prevalence of prefrailty and frailty among a nationally distributed cohort of PWH in care. This study identified distinct risk factors that may be associated with frailty among PWH, many of which, such as cigarette smoking and drug use, are potentially modifiable.

Tobacco smoking and binge alcohol use are associated with incident venous thromboembolism in an HIV cohort.

BACKGROUND: People with HIV (PWH) are at increased risk of cardiovascular comorbidities and substance use is a potential predisposing factor. We evaluated associations of tobacco smoking and alcohol use with venous thromboembolism (VTE) in PWH. METHODS: We assessed incident, centrally adjudicated VTE among 12 957 PWH within the Centers for AIDS Research Network of Integrated Clinical Systems (CNICS) cohort between January 2009 and December 2018. Using separate Cox proportional hazards models, we evaluated associations of time-updated alcohol and cigarette use with VTE, adjusting for demographic and clinical characteristics. Smoking was evaluated as pack-years and never, former, or current use with current cigarettes per day. Alcohol use was parameterized using categorical and continuous alcohol use score, frequency of use, and binge frequency. RESULTS: During a median of 3.6 years of follow-up, 213 PWH developed a VTE. One-third of PWH reported binge drinking and 40% reported currently smoking. In adjusted analyses, risk of VTE was increased among both current (HR: 1.44, 95% CI: 1.02-2.03) and former (HR: 1.44, 95% CI: 0.99-2.07) smokers compared to PWH who never smoked. Additionally, total pack-years among ever-smokers (HR: 1.10 per 5 pack-years; 95% CI: 1.03-1.18) was associated with incident VTE in a dose-dependent manner. Frequency of binge drinking was associated with incident VTE (HR: 1.30 per 7 days/month, 95% CI: 1.11-1.52); however, alcohol use frequency was not. Severity of alcohol use was not significantly associated with VTE. CONCLUSIONS: Current smoking and pack-year smoking history were dose-dependently associated with incident VTE among PWH in CNICS. Binge drinking was also associated with VTE. Interventions for smoking and binge drinking may decrease VTE risk among PWH.

Current Antiretroviral Treatment Among People With Human Immunodeficiency Virus in the United States: Findings from the Centers for AIDS Research Network of Integrated Clinic Systems Cohort.

Among 14 049 people with human immunodeficiency virus in care in 2019-2020, 96% were treated with antiretroviral therapy (ART). Current antiretroviral treatment patterns highlight high uptake of guideline-recommended ART regimens including second-generation integrase strand transfer inhibitors (dolutegravir and bictegravir) and tenofovir alafenamide, especially in antiretroviral-naive individuals initiating ART.

CMV and HSV Pneumonia After Immunosuppressive Agents for Treatment of Cytokine Release Syndrome Due to Chimeric Antigen Receptor-modified T (CAR-T)-Cell Immunotherapy.

Pneumonia due to cytomegalovirus and herpes simplex virus-1 caused substantial morbidity after hematopoietic cell transplantation before the institution of preventative approaches. End-organ disease from herpesviruses is poorly described after chimeric antigen receptor-modified T-cell immunotherapy. We report 2 cases of cytomegalovirus pneumonia and 1 case of herpes simplex virus-1 gingivostomatitis, esophagitis, and pneumonia after chimeric antigen receptor-modified T-cell immunotherapy for the treatment of hematologic malignancies.

Fatal infection with enterocolitis from methicillin-resistant Staphylococcus aureus and the continued value of culture in the era of molecular diagnostics.

MRSA enterocolitis is under-recognized in the setting of PCR testing. In this case report, we describe risk factors, the importance of stool culture, and the third published case of MRSA enterocolitis in a patient with leukemia. In addition, we performed a retrospective analysis of all stool cultures at our institution that have grown Staphylococcus aureus, and we describe an additional five cases. We also report the diagnostic yield of organisms detected by culture, but not on the FilmArray panel. While rare, these cases demonstrate that MRSA in stool may indicate a severe and potentially life-threatening infection, particularly in immunocompromised persons.

Severe COVID-19 initially presenting as mesenteric adenopathy.

Coronavirus disease 2019 (COVID-19) can present with abdominal pain in children and adults. Most imaging findings have been limited to characteristic lung findings, as well as one report of bowel-ischemia-related findings in adults. We report a case of COVID-19 in a healthy teenager who initially presented with isolated mesenteric adenopathy, typically a self-limited illness, which progressed to severe illness requiring intensive care before complete recovery. The boy tested negative for COVID-19 twice by polymerase chain reaction (PCR) from upper respiratory swabs before sputum PCR resulted positive. A high index of suspicion should be maintained for COVID-19 given the continued emergence of new manifestations of the disease.

Current management of Clostridioides (Clostridium) difficile infection in adults: a summary of recommendations from the 2017 IDSA/SHEA clinical practice guideline.

Clostridioides (formerly Clostridium) difficile infection (CDI) is the most common cause of health care­associated infectious diarrhea in the developed world. The Infectious Diseases Society of America and the Society for Healthcare Epidemiology of America clinical guidelines on CDI were updated in 2017. The update reflects a decline in the incidence of CDI caused by ribotype 027 and an increased incidence of community­associated CDI, current challenges in CDI diagnosis, the importance of antibiotic stewardship and contact and isolation precautions in infection prevention and control, and many significant changes in CDI management. This review summarizes and examines these new guidelines, how they compare to other recommendations, and more recent data on CDI management.