Prevalence and Correlates of Physical Inactivity Among Individuals with HIV During the First COVID-19 Wave: A Cross-sectional Survey.

Physical activity is associated with improved health outcomes among people with HIV (PWH). In the recent pandemic context, policies designed to mitigate COVID-19 transmission may result in an increase in sedentary lifestyle and decreased physical activity. In this study, we aimed to characterize self-reported physical activity and factors associated with physical inactivity during the first wave of the COVID-19 pandemic among a sample of PWH engaged in care. We also described whether psychological coping strategies measured by the Brief COPE differed based on physical activity levels. Among 260 surveyed PWH in two HIV clinics in the US Northeast, 28.5% (n = 74) met the criteria for being physically active according to the Centers for Disease Control and Prevention (CDC)'s physical activity guidelines. Receiving care in New Haven, CT, presence of a detectable HIV viral load, every day tobacco use, and unhealthy alcohol use were associated with physical inactivity. Problem-focused coping, emotion-focused coping, and avoidance-focused coping strategies were found to be protective against physical inactivity. In adjusted analysis, only problem-focused coping continued to be significantly associated with lower odds of reporting physical inactivity. Efforts are urgently needed to promote physical activity among PWH, including among those without problem-focused coping strategies.

RESUMEN: La actividad física se asocia con mejores resultados de salud entre las personas con VIH (PCV). En el contexto de la reciente pandemia, las políticas diseñadas para mitigar la transmisión de COVID-19 pueden resultar en un aumento del estilo de vida sedentario y una disminución de la actividad física. En este estudio, nuestro objetivo fue caracterizar la actividad física autoinformada y los factores asociados con la inactividad física durante la primera ola de la pandemia de COVID-19 entre una muestra de PCV dedicados a la atención. También describimos si las estrategias psicológicas de afrontamiento medidas por el Brief COPE diferían según los niveles de actividad física. Entre las 260 PCV encuestadas en dos clínicas de VIH en el noreste de EE. UU., el 28,5% (n = 74) cumplía con los criterios para ser físicamente activo de acuerdo con las pautas de actividad física del Centros para el Control y la Prevención de Enfermedades (CDC). Recibir atención en New Haven, CT, la presencia de una carga viral de VIH detectable, el consumo diario de tabaco, y el consumo insano de alcohol se asociaron con la inactividad física. Se encontró que el afrontamiento centrado en el problema, el afrontamiento centrado en la emoción, y las estrategias de afrontamiento centradas en la evitación, protegen contra la inactividad física. En el análisis ajustado, solo el afrontamiento centrado en el problema siguió estando significativamente asociado con menores probabilidades de informar sobre la inactividad física. Se necesitan esfuerzos urgentes para promover la actividad física entre las PCV, incluso entre aquellas que no tienen estrategias de afrontamiento centradas en el problema.

Dectin-1 stimulation promotes a distinct inflammatory signature in the setting of HIV-infection and aging.

Dectin-1 is an innate immune receptor that recognizes and binds ß-1, 3/1, 6 glucans on fungi. We evaluated Dectin-1 function in myeloid cells in a cohort of HIV-positive and HIV-negative young and older adults. Stimulation of monocytes with ß-D-glucans induced a pro-inflammatory phenotype in monocytes of HIV-infected individuals that was characterized by increased levels of IL-12, TNF-α, and IL-6, with some age-associated cytokine increases also noted. Dendritic cells showed a striking HIV-associated increase in IFN-α production. These increases in cytokine production paralleled increases in Dectin-1 surface expression in both monocytes and dendritic cells that were noted with both HIV and aging. Differential gene expression analysis showed that HIV-positive older adults had a distinct gene signature compared to other cohorts characterized by a robust TNF-α and coagulation response (increased at baseline), a persistent IFN-α and IFN-γ response, and an activated dendritic cell signature/M1 macrophage signature upon Dectin-1 stimulation. Dectin-1 stimulation induced a strong upregulation of MTORC1 signaling in all cohorts, although increased in the HIV-Older cohort (stimulation and baseline). Overall, our study demonstrates that the HIV Aging population has a distinct immune signature in response to Dectin-1 stimulation. This signature may contribute to the pro-inflammatory environment that is associated with HIV and aging.

Expanded or Risk Factor-Based Annual Screening for Hepatitis C Virus (HCV) Among Persons With HIV: Which Is the Best Approach?

Introduction. Universal one-time screening for hepatitis C virus (HCV) is recommended for all adults. For persons with HIV (PWH), guidelines recommend HCV screening at entry into care and annually in men who have unprotected sex with other men (MSM) and persons who inject drugs (PWID). Public health experts recommend expanded annual screening in all PWH given concerns for undiagnosed new HCV diagnoses when risk factors are not assessed. Electronic medical record (EMR) with clinical decision support using a Best Practice Advisory (BPA) tool can aid HCV risk factor assessment. We conducted a prospective study among three HIV clinics to compare the two screening approaches. Methods. Two clinics implemented the EMR-triggered risk factor-based screening; one clinic used the expanded screening approach. We evaluated BPA uptake and compared HCV testing and positivity rates from August 12, 2019 to March 12, 2020. Results. In the risk factor-based screening clinics, of 1,343 PWH, 239 tests were performed with 139 attributed to the BPA (testing rate 10%). At the expanded screening site, among 434 patients, 237 HCV tests were performed (testing rate 55%). The risk factor-based screening sites were less likely to test for HCV (odds ratio [OR] = 0.0884, p < .01) and identify positive cases (OR = 0.55, p = .025). Conclusions. An EMR-based clinical-decision support tool was successfully implemented for HCV risk factor-based screening resulting in a lower HCV annual screening rate compared with an expanded approach. Although in this group of HIV clinics with limited longitudinal follow-up, no previously undiagnosed HCV cases were detected, additional work is needed to guide the design of the best approach.

Qualitative assessment of anti-SARS-CoV-2 spike protein immunogenicity (QUASI) after COVID-19 vaccination in older people living with HIV.

OBJECTIVES: Effective and safe COVID-19 vaccines have been developed and have resulted in decreased incidence and severity of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection and can decrease secondary transmission. However, there are concerns about dampened immune responses to COVID-19 vaccination among immunocompromised patients, including people living with HIV (PLWH), which may blunt the vaccine's efficacy and durability of protection. This study aimed to assess the qualitative SARS-CoV-2 vaccine immunogenicity among PLWH after vaccination. METHODS: We conducted targeted COVID-19 vaccination (all received BNT162b2 vaccine) of PLWH (aged ≥ 55 years per state guidelines) at Yale New Haven Health System and established a longitudinal survey to assess their qualitative antibody responses at 3 weeks after the first vaccination (and prior to receipt of the second dose of the COVID-19 vaccine) (visit 1) and at 2-3 weeks after the second vaccination (visit 2) but excluded patients with prior COVID-19 infection. Our goal was to assess vaccine-induced immunity in the population we studied. Qualitative immunogenicity testing was performed using Healgen COVID-19 anti-Spike IgG/IgM rapid testing. Poisson regression with robust standard errors was used to determine factors associated with a positive IgG response. RESULTS: At visit 1, 45 of 78 subjects (57.7%) tested positive for SARS-CoV-2 anti-Spike IgG after the first dose of COVID-19 vaccine. Thirty-nine subjects returned for visit 2. Of these, 38 had positive IgG (97.5%), including 20 of 21 subjects (95.2%) with an initial negative anti-Spike IgG. Our bivariate analysis suggested that participants on an antiretroviral regimen containing integrase strand transfer inhibitors [relative risk (RR) = 1.81, 95% confidence interval (CI): 0.92-3.56, p = 0.085] were more likely to seroconvert after the first dose of the COVID-19 vaccine, while those with a CD4 count < 500 cells/µL (RR = 0.59, 95% CI: 0.33-1.05, p = 0.071), and those diagnosed with cancer or another immunosuppressive condition (RR = 0.49, 95% CI: 0.18-1.28, p = 0.15) may have been less likely to seroconvert after the first dose of the COVID-19 vaccine. The direction of these associations was similar in the multivariate model, although none of these findings reached statistical significance (RRintegrase inhibitor  = 1.71, 95% CI: 0.90-3.25, p = 0.10; RRCD4 count  = 0.68, 95% CI: 0.39-1.19, p = 0.18; RRcancer or another immunosuppressive condition  = 0.50, 95% CI: 0.19-1.33, p = 0.16). With regard to immunogenicity, we were able to record very high rates of new seroconversion following the second dose of the COVID-19 vaccine. CONCLUSIONS: Our study suggests that completing a two-dose series of BNT162b2 vaccine is critical for PLWH given suboptimal seroconversion rates after the first dose and subsequent improved seroconversion rates after the second dose.

Race and ethnicity do not impact eligibility for remdesivir: A single-center experience.

As the Coronavirus-2019 (COVID-19) pandemic continues, multiple therapies are rapidly being evaluated for efficacy in clinical trials. Clinical trials should be racially and ethnically representative of the population that will eventually benefit from these medications. There are multiple potential barriers to racial and ethnic minority enrollment in clinical trials, one of which could be that inclusion and exclusion criteria select for certain racial or ethnic groups disproportionately. In this observational cohort study at a single health care system, we examined if there were differences in eligibility for treatment with remdesivir based on clinical trial criteria for racial and ethnic minorities compared to non-Hispanic Whites. 201 electronic medical record charts were reviewed manually. Self-identified Whites were older than other racial or ethnic groups. At the time of presentation, Black, Latinx, and White participants met inclusion criteria for remdesivir at similar rates (72%, 80%, and 73% respectively), and exclusion criteria at similar rates (43%, 38% and 49% for Black, Latinx and White participants respectively). In this study, there was no difference in eligibility for remdesivir based on race or ethnicity alone.

Decreased Overall Survival in HIV-associated Non-small-cell Lung Cancer.

INTRODUCTION: This study aimed to compare demographics, disease characteristics, and outcomes of patients with HIV-infection with non-small-cell lung cancer (NSCLC) with the general NSCLC population. PATIENTS AND METHODS: A retrospective cohort study was used to compare the HIV-infected and -uninfected groups. Medical records of all patients who were HIV-positive diagnosed with NSCLC between 2000 and 2016 at Yale New Haven Hospital (New Haven, CT) were reviewed and compared with the general Yale NSCLC population regarding demographics, NSCLC characteristics, treatment, and survival. Log-rank tests and Kaplan-Meier curves were used to analyze survival differences. Unadjusted and adjusted Cox proportional hazard models were used to assess predictors of survival. RESULTS: Thirty-five patients with HIV-NSCLC and 5187 general patients with NSCLC were identified. The median age at cancer diagnosis was 54 years (interquartile range [IQR], 49-59 years) for patients with HIV-NSCLC versus 68 years (IQR, 61-76 years) for patients with NSCLC (P < .001). Both groups had high rates of tobacco use. At the time of NSCLC diagnosis, 80% of patients with HIV-NSCLC were on antiretroviral therapy, 60% had an HIV-1 RNA < 400 copies/mL, and their median CD4 was 407 cells/µL (IQR, 218-592 cells/µL). Histology, cancer stage, and first-line cancer treatment regimens were not significantly different between groups. The overall median survival was 12.4 months (95% confidence interval [CI], 7.2-20.4 months) for patients with HIV-NSCLC versus 22.8 months (95% CI, 21.2-24.1 months) for general patients with NSCLC. Patients with HIV-NSCLC had decreased survival at 2 years (P = .028) and 3 years (P = .014) compared with general patients with NSCLC. HIV status was an independent risk factor for poorer outcomes when controlling for other factors (hazard ratio, 1.8; 95% CI, 1.24-2.62). CONCLUSION: Despite similar histology, stage, and treatment between groups, patients with HIV had worse outcomes for NSCLC.

Impact of Aging and HIV Infection on the Function of the C-Type Lectin Receptor MINCLE in Monocytes.

Both aging and HIV infection are associated with an enhanced pro-inflammatory environment that contributes to impaired immune responses and is mediated in part by innate immune pattern-recognition receptors. MINCLE is a C-type lectin receptor that recognizes trehalose-6,6'-dimycolate or "cord factor," the most abundant glycolipid in Mycobacterium tuberculosis. Here, we evaluated MINCLE function in monocytes in a cohort of HIV-infected and uninfected young (21-35 years) and older adults (≥60 years) via stimulation of peripheral blood mononuclear cells with trehalose-6,6-dibehenate, a synthetic analog of trehalose-6,6'-dimycolate and measurement of cytokine production (interleukin [IL]-10, IL-12, IL-6, tumor necrosis factor-α) by multicolor flow cytometry. Our studies show an age- and HIV-associated increase in cytokine multifunctionality of monocytes both at the population and single cell level that was dominated by IL-12, IL-10, and IL-6. These findings provide insight into the host response to M. tuberculosis and possible sources for the pro-inflammatory environment seen in aging and HIV infection.

Prevalence and Correlates of Unhealthy Alcohol and Drug Use Among Men Who Have Sex with Men Prescribed HIV Pre-exposure Prophylaxis in Real-World Clinical Settings.

Pre-exposure prophylaxis (PrEP) is effective in preventing HIV acquisition among men who have sex with men (MSM). However, little is known about unhealthy substance use among MSM initiating PrEP in real-world settings. Unhealthy substance use is a risk factor for HIV acquisition and non-adherence to treatment, and may also impact PrEP use. MSM who were prescribed PrEP from 2015 to 2017 at clinics in Providence, Rhode Island and New Haven, Connecticut were recruited to participate in a prospective observational study. Structured clinical assessments were used to assess demographics, HIV risk behaviors, and unhealthy alcohol (alcohol use disorders identification test [AUDIT]-C scores ≥ 4) and drug use (use of any drugs in the past 3 months). Bivariate and multivariate analyses were performed to determine demographics and behaviors associated with unhealthy alcohol and drug use. Among 172 MSM initiating PrEP, 64% were white and 40% were 25-34 years old. Participants reported a median of 3 (IQR 2-7) sexual partners in the last 3 months; 20% reported an HIV positive partner. Unhealthy alcohol and any drug use were reported by 54 and 57%, respectively, and 76% reported at least one of the two. The majority of drug use reported was marijuana and poppers (41 and 26% of participants, respectively). Relative to those without unhealthy alcohol use, unhealthy alcohol use was independently associated with any drug use (adjusted odds ratio [AOR] = 2.57, 95% CI 1.32-5.01). Frequent drug use was associated with younger age (< 25 years, AOR 4.27, 95% CI 1.51-12.09). Unhealthy alcohol use is common among MSM taking PrEP. Drug use other than marijuana and poppers was uncommon among our cohort. Further efforts may be needed to understand the influence of unhealthy alcohol and other substance use on PrEP outcomes and to engage MSM who use drugs for PrEP.

Unusual presentation of disseminated Nocardia abscessus infection in a patient with AIDS.

A 40-year-old man with AIDS presented with symptoms of a chronic cough, subacute headache, generalised weakness with falls, urinary and faecal incontinence, and acute onset subcutaneous nodules. A chest CT scan showed multiple cavitary and nodular pulmonary infiltrates. MRI of his brain and spinal cord revealed innumerable ring-enhancing lesions. Pathological examination of the purulent material obtained from his subcutaneous lesions, as well as transbronchial tissue specimens obtained by biopsy, revealed beaded and branching Gram-positive rods, subsequently identified by 16S RNA sequencing to be Nocardia abscessus species. We observed an excellent therapeutic response to a combination antimicrobial therapy with resolution of the subcutaneous, pulmonary and central nervous system (CNS) lesions. Infections caused by N. abscessus are rare and typically occur in immunocompromised patients. In this article, we will review the presentation, diagnosis and treatment of N. abscessus infection.

Steroid-exacerbated HIV-associated cutaneous Kaposi's sarcoma immune reconstitution inflammatory syndrome: 'Where a good intention turns bad'.

A 51-year-old man with head and neck skin lesions was diagnosed with Kaposi's sarcoma (KS) as his initial presentation of acquired immunodeficiency syndrome. Following initiation of antiretroviral therapy and subsequent full virologic suppression, his facial lesions worsened, consistent with immune reconstitution inflammatory syndrome (IRIS). He was started on glucocorticoids in an attempt to ameliorate the KS-IRIS but experienced paradoxical worsening of the KS lesions. Steroids were subsequently discontinued and he required chemotherapy for severe and cosmetically disfiguring skin lesions. This article describes the potential for worsening of KS lesions in individuals started on glucocorticoids for KS-IRIS as this has been reported rarely in published literature. The mechanisms underlying this phenomenon remain poorly understood but potential explanations are offered in the case discussion. This article aims to raise clinician awareness on the harms of steroid use in patients with KS-IRIS.

Trends in hospital deaths among human immunodeficiency virus-infected patients during the antiretroviral therapy era, 1995 to 2011.

OBJECTIVE: Mortality in hospitalized human immunodeficiency virus (HIV)-infected patients is not well described. We sought to characterize in-hospital deaths among HIV-infected patients in the antiretroviral (ART) era and identify factors associated with mortality. METHODS: We reviewed the medical records of hospitalized HIV-infected patients who died from January 1, 1995 to December 31, 2011 at an urban teaching hospital. We evaluated trends in early and late ART use and deaths due to acquired immunodeficiency syndrome (AIDS) and non-AIDS, and identified clinical and demographic correlates of non-AIDS deaths. RESULTS: In-hospital deaths declined significantly from 1995 to 2011 (P < 0.0001); those attributable to non-AIDS increased (43% to 70.5%, P < 0.0001). Non-AIDS deaths were most commonly caused by non-AIDS infection (20.3%), cardiovascular (11.3%) and liver disease (8.5%), and non-AIDS malignancy (7.8%). Patients with non-AIDS compared to AIDS-related deaths were older (median age 48 vs 40 years, P < 0.0001), more likely to be on ART (74.1% vs 55.8%, P = 0.0001), less likely to have a CD4 count of <200 cells/mm(3) (47.2% vs 97.1%, P < 0.0001), and more likely to have an HIV viral load of ≤400 copies/mL (38.1% vs 4.1%, P < 0.0001). Non-AIDS deaths were associated with 4.5 and 4.2 times greater likelihood of comorbid underlying liver and cardiovascular disease, respectively. CONCLUSIONS: Non-AIDS deaths increased significantly during the ART era and are now the most common cause of in-hospital deaths; non-AIDS infection, cardiovascular and liver disease, and malignancies were major contributors to mortality. Higher CD4 cell count, liver, and cardiovascular comorbidities were most strongly associated with non-AIDS deaths. Interventions targeting non-AIDS-associated conditions are needed to reduce inpatient mortality among HIV-infected patients.

Infectious mimicry complicates diagnosis in hemophagocytic syndrome caused by anaplastic large-cell lymphoma.

Hemophagocytic syndrome (HPS) arises secondary to genetic, rheumatologic, neoplastic, and infectious causes. We discuss a patient whose presentation was consistent with systemic infection but was discovered to have HPS of unknown etiology. The presenting symptoms, as well as unremarkable malignancy and rheumatologic workups, led to the pursuit of an infectious cause, but the patient was ultimately discovered to have an occult anaplastic large-cell lymphoma (ALCL). This case demonstrates the diagnostic challenges that result from infectious mimicry in the context of HPS-first, in distinguishing noninfectious HPS from the systemic inflammation that can result from a widespread infectious process, second, in the identification of the precipitating cause of HPS. While evidence of these challenges has been suggested by the limited literature on HPS and ALCL, our case illustrates the diagnostic dilemma that arises when tissue biopsy does not quickly reveal an etiology. It is important that all physicians be aware that HPS can mimic infection and be prepared to redirect the workup when an infectious etiology for HPS cannot be identified.

Complicated left-sided native valve endocarditis in adults: risk classification for mortality.

CONTEXT: Complicated left-sided native valve endocarditis causes significant morbidity and mortality in adults. Lack of valid data regarding estimation of prognosis makes management of this condition difficult. OBJECTIVE: To derive and externally validate a prognostic classification system for adults with complicated left-sided native valve endocarditis. DESIGN, SETTING, AND PATIENTS: Retrospective observational cohort study conducted from January 1990 to January 2000 at 7 Connecticut hospitals among 513 patients older than 16 years who experienced complicated left-sided native valve endocarditis and who were divided into derivation (n = 259) and validation (n = 254) cohorts. MAIN OUTCOME MEASURE: All-cause mortality at 6 months after baseline. RESULTS: In the derivation and validation cohorts, the 6-month mortality rates were 25% and 26%, respectively. Five baseline features were independently associated with 6-month mortality (comorbidity [P =.03], abnormal mental status [P =.02], moderate to severe congestive heart failure [P =.01], bacterial etiology other than viridans streptococci [P<.001 except Staphylococcus aureus, P =.004], and medical therapy without valve surgery [P =.002]) and were used to create a prognostic classification system. In the derivation cohort, patients were classified into 4 groups with increasing risk for 6-month mortality: 5%, 15%, 31%, and 59% (P<.001). In the validation cohort, a similar risk among the 4 groups was observed: 7%, 19%, 32%, and 69% (P<.001). CONCLUSIONS: Adults with complicated left-sided native valve endocarditis can be accurately risk stratified using baseline features into 4 groups of prognostic severity. This prognostic classification system might be useful for facilitating management decisions.