Association of Coronary Wall Thickening and Diminished Diastolic Function in Asymptomatic, Low Cardiovascular Disease-Risk Persons Living with HIV.

Purpose To assess early subclinical coronary artery disease (CAD) burden and its relation to myocardial function in asymptomatic persons living with HIV (PLWH) who are at low risk for cardiovascular disease (CVD). Materials and Methods In this prospective, HIPAA-compliant study (ClinicalTrials.gov NCT01656564 and NCT01399385) conducted from April 2010 to May 2013, 74 adult PLWH without known CVD and 25 matched healthy controls underwent coronary MRI to measure coronary vessel wall thickness (VWT) and echocardiography to assess left ventricular function. Univariable and multivariable linear regression analyses were used to evaluate statistical associations. Results For PLWH, the mean age was 49 years ± 11 (SD), and the median Framingham risk score was 3.2 (IQR, 0.5-6.6); for matched healthy controls, the mean age was 46 years ± 8 and Framingham risk score was 2.3 (IQR, 0.6-6.1). PLWH demonstrated significantly greater coronary artery VWT than did controls (1.47 mm ± 0.22 vs 1.34 mm ± 0.18; P = .006) and a higher left ventricular mass index (LVMI) (77 ± 16 vs 70 ± 13; P = .04). Compared with controls, PLWH showed altered association between coronary artery VWT and both E/A (ratio of left ventricular-filling peak blood flow velocity in early diastole [E wave] to that in late diastole [A wave]) (P = .03) and LVMI (P = .04). In the PLWH subgroup analysis, coronary artery VWT increase was associated with lower E/A (P < .001) and higher LVMI (P = .03), indicating restricted diastolic function. In addition, didanosine exposure was associated with increased coronary artery VWT and decreased E/A ratio. Conclusion Asymptomatic low-CVD-risk PLWH demonstrated increased coronary artery VWT in association with impaired diastolic function, which may be amenable to follow-up studies of coronary pathogenesis to identify potential effects on the myocardium and risk modification strategies. Keywords: Coronary Vessel Wall Thickness, Diastolic Function, HIV, MRI, Echocardiography, Atherosclerosis Clinical trial registration nos. NCT01656564 and NCT01399385 Supplemental material is available for this article. © RSNA, 2024.

The role of HIV as a risk modifier for coronary endothelial function in young adults.

BACKGROUND: People living with HIV have an increased risk of cardiovascular disease (CVD). Although coronary endothelial function (CEF) is an early direct indicator of CVD, only a few studies have been able to interrogate CEF directly. Most studies have examined vascular endothelial function through indirect assessment of brachial flow-mediated dilatation (FMD). However, peripheral arteries are significantly larger and manifest atherogenesis differently from the coronary arteries, and so produce conflicting results. Additionally, none of these studies focused on young adults who acquired HIV perinatally or in early childhood. OBJECTIVE: The present study investigates CEF in a unique population of young adults with lifelong HIV using direct magnetic resonance imaging (MRI) of coronary FMD (corFMD) with an in-house developed MRI-integrated isometric handgrip exercise system with continuous feedback and monitoring mechanisms (fmIHE). METHODS: Young adults who acquired HIV perinatally or in early childhood (n = 23) and group-matched healthy participants (n = 12) completed corFMD-MRI with fmIHE. CorFMD was measured as the coronary cross-sectional area response to the fmIHE. RESULTS: In univariable and multivariable regression analysis, HIV status was a significant risk modifier. CD8+ T-cell count and smoking pack-years and their interaction with HIV status were independently associated with impaired coronary artery response to fmIHE. In people living with HIV, corFMD was significantly inversely correlated with CD8+ T-cells and smoking pack-years. In a multivariable regression analysis adjusted for age and body mass index, CD8+ T-cells and smoking and their interaction with HIV status remained significant independent predictors of coronary endothelial dysfunction. DISCUSSION: In this unique population of young adults, HIV status was a significant risk modifier, and immune activation and smoking were associated with decreased CEF, directly measured from the coronary vascular response to fmIHE. CONCLUSIONS: Management of CVD risk factors such as smoking and developing strategies that target immune activation in people living with HIV are warranted.

Constitutively active Lyn kinase causes a cutaneous small vessel vasculitis and liver fibrosis syndrome.

Neutrophilic inflammation is a hallmark of many monogenic autoinflammatory diseases; pathomechanisms that regulate extravasation of damaging immune cells into surrounding tissues are poorly understood. Here we identified three unrelated boys with perinatal-onset of neutrophilic cutaneous small vessel vasculitis and systemic inflammation. Two patients developed liver fibrosis in their first year of life. Next-generation sequencing identified two de novo truncating variants in the Src-family tyrosine kinase, LYN, p.Y508*, p.Q507* and a de novo missense variant, p.Y508F, that result in constitutive activation of Lyn kinase. Functional studies revealed increased expression of ICAM-1 on induced patient-derived endothelial cells (iECs) and of ß2-integrins on patient neutrophils that increase neutrophil adhesion and vascular transendothelial migration (TEM). Treatment with TNF inhibition improved systemic inflammation; and liver fibrosis resolved on treatment with the Src kinase inhibitor dasatinib. Our findings reveal a critical role for Lyn kinase in modulating inflammatory signals, regulating microvascular permeability and neutrophil recruitment, and in promoting hepatic fibrosis.

Proteomic Analysis of Hepatic Fibrosis in Human Immunodeficiency Virus-Associated Nonalcoholic Fatty Liver Disease Demonstrates Up-regulation of Immune Response and Tissue Repair Pathways.

BACKGROUND: Human immunodeficiency virus (HIV)-associated nonalcoholic fatty liver disease (NAFLD) is characterized by a high prevalence of hepatic fibrosis as a strong clinical predictor of all-cause and liver-specific mortality risk. METHODS: We leveraged data from an earlier clinical trial to define the circulating proteomic signature of hepatic fibrosis in HIV-associated NAFLD. A total of 183 plasma proteins within 2 high-multiplex panels were quantified at baseline and at 12 months (Olink Cardiovascular III; Immuno-Oncology). RESULTS: Twenty proteins were up-regulated at baseline among participants with fibrosis stages 2-3 versus 0-1. Proteins most differentially expressed included matrix metalloproteinase 2 (P < .001), insulin-like growth factor-binding protein 7 (P = .001), and collagen α1(I) chain (P = .001). Proteins were enriched within pathways including response to tumor necrosis factor and aminopeptidase activity. Key proteins correlated directly with visceral adiposity and glucose intolerance and inversely with CD4+ T-cell count. Within the placebo-treated arm, 11 proteins differentially increased among individuals with hepatic fibrosis progression over a 12-month period (P < .05). CONCLUSIONS: Among individuals with HIV-associated NAFLD, hepatic fibrosis was associated with a distinct proteomic signature involving up-regulation of tissue repair and immune response pathways. These findings enhance our understanding of potential mechanisms and biomarkers of hepatic fibrosis in HIV.

IL-27 Modulates the Cytokine Secretion in the T Cell-Osteoclast Crosstalk During HIV Infection.

In People with HIV (PWH), chronic immune activation and systemic inflammation are associated with increased risk to develop comorbidities including bone loss. Numerous cells of the immune system, namely, T cells are involved in the regulation of the bone homeostasis and osteoclasts (OCs) activity. IL-27, a cytokine that belongs to the IL-12 family can regulate the secretion of pro- and anti-inflammatory cytokines by T cells, however its role in the setting of HIV is largely unknown. In the present study, we determined the impact of OCs in T cell secretion of cytokines and whether IL-27 can regulate this function. We found that the presence of OCs in the T cell cultures significantly enhanced secretion of IFNγ, TNFα, IL-17, RANKL, and IL-10 in both PWH and healthy controls. In PWH, IL-27 inhibited IL-17 secretion and downregulated surface expression of RANKL in CD4 T cells. All together these results suggest that in the context of HIV infection IL-27 may favor IFNγ and TNFα secretion at the sites of bone remodeling.

Associations Between Central Obesity and Lifelong Antiviral Therapy in Adults Living With HIV Acquired From Early Childhood.

BACKGROUND: Little is known regarding the long-term effects of antiretroviral (ARV) exposure on body composition for people living with HIV (PLWH) since early childhood. This study explores changes in body fat distribution in relation to ARV exposure. METHODS: We conducted a prospective study of adults with perinatal HIV (n = 70) using dual-energy X-ray absorptiometry and standard anthropometrics. Trunk to limb fat ratio and waist to hip ratio were compared cross-sectionally to 47 matched controls. Furthermore, changes in body composition and ARV exposure were evaluated longitudinally in a subset of 40 PLWH with a median follow-up of 7 years. RESULTS: Cross-sectional comparisons of PLWH with controls revealed significantly higher waist to hip ratio, trunk to limb fat ratio, HOMA-IR, and triglycerides, whereas BMI did not differ. Among PLWH with longitudinal follow-up, the prevalence of overweight increased from 27.5% to 52.5% and obesity from 12.5% to 25%; waist to hip and trunk to limb fat ratios also increased (P < 0.0001). Changes in waist to hip ratio were positively correlated with longer exposure during follow-up to darunavir (r = 0.36; P = 0.02), whereas increases in trunk to limb fat ratio were positively correlated with longer exposure to stavudine (r = 0.39; P = 0.01) and didanosine (r = 0.39; P = 0.01) but inversely associated with emtricitabine (r = -0.33; P = 0.04). Increases in waist to hip ratio were correlated with increases in triglyceride levels (r = 0.35; P = 0.03). CONCLUSION: This study presents strong evidence for persistent and worsening central adiposity in young adults with lifelong HIV and extensive ARV exposure. As this cohort ages, continued evaluation of the body composition and metabolic impact of lifelong ARV therapy is warranted to optimize long-term health.

The Role of Inflammation and Immune Activation on Circulating Endothelial Progenitor Cells in Chronic HIV Infection.

Endothelial inflammation and damage are the main drivers of cardiovascular risk/disease. Endothelial repair is mediated in part by recruitment of bone marrow endothelial progenitor/endothelial colony forming cells (EPC/ECFC). People with HIV (PWH) have increased cardiovascular risk and the impact of infection in endothelial repair is not well defined. The low frequencies and challenges to in vitro isolation and differentiation of EPC/ECFC from PBMCs had made it difficult to study their role in this context. We hypothesized that HIV driven inflammation induces phenotypic changes that reflects the impact of infection. To test this hypothesis, we evaluated expression of markers of trafficking, endothelial differentiation, and angiogenesis, and study their association with biomarkers of inflammation in a cohort of PWH. In addition, we investigated the relationship of circulating endothelial progenitors and angiogenic T cells, a T cell subset with angiogenic function. Using a flow cytometry approach, we identified two subsets of circulating progenitors LIN4-CD45-CD34+ and LIN4-CD45dimCD34+ in PWH. We found that the phenotype but not frequencies were associated with biomarkers of inflammation. In addition, the percentage of LIN4-CD45dimCD34+ was associated with serum levels of lipids. This data may provide a new tool to better address the impact of HIV infection in endothelial inflammation and repair.

Delineating tesamorelin response pathways in HIV-associated NAFLD using a targeted proteomic and transcriptomic approach.

NAFLD is a leading comorbidity in HIV with an exaggerated course compared to the general population. Tesamorelin has been demonstrated to reduce liver fat and prevent fibrosis progression in HIV-associated NAFLD. We further showed that tesamorelin downregulated hepatic gene sets involved in inflammation, tissue repair, and cell division. Nonetheless, effects of tesamorelin on individual plasma proteins pertaining to these pathways are not known. Leveraging our prior randomized-controlled trial and transcriptomic approach, we performed a focused assessment of 9 plasma proteins corresponding to top leading edge genes within differentially modulated gene sets. Tesamorelin led to significant reductions in vascular endothelial growth factor A (VEGFA, log2-fold change - 0.20 ± 0.35 vs. 0.05 ± 0.34, P = 0.02), transforming growth factor beta 1 (TGFB1, - 0.35 ± 0.56 vs. - 0.05 ± 0.43, P = 0.05), and macrophage colony stimulating factor 1 (CSF1, - 0.17 ± 0.21 vs. 0.02 ± 0.20, P = 0.004) versus placebo. Among tesamorelin-treated participants, reductions in plasma VEGFA (r = 0.62, P = 0.006) and CSF1 (r = 0.50, P = 0.04) correlated with a decline in NAFLD activity score. Decreases in TGFB1 (r = 0.61, P = 0.009) and CSF1 (r = 0.64, P = 0.006) were associated with reduced gene-level fibrosis score. Tesamorelin suppressed key angiogenic, fibrogenic, and pro-inflammatory mediators. CSF1, a regulator of monocyte recruitment and activation, may serve as an innovative therapeutic target for NAFLD in HIV. Clinical Trials Registry Number: NCT02196831.

Growth Hormone Releasing Hormone Reduces Circulating Markers of Immune Activation in Parallel with Effects on Hepatic Immune Pathways in Individuals with HIV-infection and Nonalcoholic Fatty Liver Disease.

BACKGROUND: The growth hormone (GH)/insulin-like growth factor-1 (IGF-1) axis modulates critical metabolic pathways; however, little is known regarding effects of augmenting pulsatile GH secretion on immune function in humans. This study used proteomics and gene set enrichment analysis to assess effects of a GH releasing hormone (GHRH) analog, tesamorelin, on circulating immune markers and liver tissue in people with human immunodeficiency virus (HIV) (PWH) and nonalcoholic fatty liver disease (NAFLD). METHODS: 92 biomarkers associated with immunity, chemotaxis, and metabolism were measured in plasma samples from 61 PWH with NAFLD who participated in a double-blind, randomized trial of tesamorelin versus placebo for 12 months. Gene set enrichment analysis was performed on serial liver biopsies targeted to immune pathways. RESULTS: Tesamorelin, compared to placebo, decreased interconnected proteins related to cytotoxic T-cell and monocyte activation. Circulating concentrations of 13 proteins were significantly decreased, and no proteins increased, by tesamorelin. These included 4 chemokines (CCL3, CCL4, CCL13 [MCP4], IL8 [CXCL8]), 2 cytokines (IL-10 and CSF-1), and 4 T-cell associated molecules (CD8A, CRTAM, GZMA, ADGRG1), as well as ARG1, Gal-9, and HGF. Network analysis indicated close interaction among the gene pathways responsible for these proteins, with imputational analyses suggesting down-regulation of a closely related cluster of immune pathways. Targeted transcriptomics using liver tissue confirmed a significant end-organ signal of down-regulated immune activation pathways. CONCLUSIONS: Long-term treatment with a GHRH analog reduced markers of T-cell and monocyte/macrophage activity, suggesting that augmentation of the GH axis may ameliorate immune activation in an HIV population with metabolic dysregulation, systemic and end organ inflammation. Clinical Trials Registration. NCT02196831.

Case Report: Fatal Complications of BK Virus-Hemorrhagic Cystitis and Severe Cytokine Release Syndrome Following BK Virus-Specific T-Cells.

BK virus (BKV)-hemorrhagic cystitis (HC) is a well-known and rarely fatal complication of hematopoietic stem cell transplantation (HSCT). Treatment for BKV-HC is limited, but virus-specific T-cells (VST) represent a promising therapeutic option feasible for use posttransplant. We report on the case of a 16-year-old male with dedicator of cytokinesis 8 (DOCK8) deficiency who underwent haploidentical HSCT complicated by severe BKV-HC, catastrophic renal hemorrhage, and VST-associated cytokine release syndrome (CRS). Gross hematuria refractory to multiple interventions began with initiation of posttransplant cyclophosphamide (PT/Cy). Complete left renal arterial embolization (day +43) was ultimately indicated to control intractable renal hemorrhage. Subsequent infusion of anti-BK VSTs was complicated by CRS and progressive multiorgan failure, with postmortem analysis confirming diagnosis of hepatic sinusoidal obstruction syndrome (SOS). This case illustrates opportunities for improvement in the management of severe BKV-HC posttransplant while highlighting rare and potentially life-threatening complications of BKV-HC and VST therapy.

Quantitative Benefit-Risk Assessment of P-gp-Mediated Drug-Drug Interactions of Dabigatran Coadministered With Pharmacokinetic Enhancers in Patients With Renal Impairment.

Drug-drug interactions (DDIs) between dabigatran and ritonavir/cobicistat are of major concern in people living with HIV, particularly in those with impaired renal function, because they can result in increased dabigatran exposure and thus an increased risk of major bleeding events. However, the extent of this interaction and subsequent need for dose adjustment in subjects with varying degrees of renal function is currently not yet fully understood. To close this knowledge gap, we conducted an integrated population physiologically-based pharmacokinetic/pharmacodynamic analysis linking changes in dabigatran exposure due to DDIs and varying degrees of renal function to the probability of experiencing an ischemic stroke or major bleeding event within 1 year. The results of our analysis suggest that coadministration of dabigatran etexilate (dabigatran prodrug) and ritonavir/cobicistat should be avoided in subjects with severe renal impairment. A 2-hour dose separation or dabigatran etexilate dose reduction to 110 mg b.i.d. (twice daily) should be considered in subjects with moderate renal impairment when coadministered with ritonavir, while the dabigatran etexilate dose should be further reduced to 75 mg b.i.d. when coadministered with cobicistat. No dabigatran etexilate dose adjustment is needed in subjects with normal renal function receiving ritonavir, but dabigatran etexilate dose reduction to 110 mg b.i.d. should be considered when coadministered with cobicistat.

Clinical Predictors of Liver Fibrosis Presence and Progression in Human Immunodeficiency Virus-Associated Nonalcoholic Fatty Liver Disease.

BACKGROUND: Nonalcoholic fatty liver disease (NAFLD) affects more than one-third of people living with human immunodeficiency virus (HIV). Nonetheless, its natural history is poorly understood, including which patients are most likely to have a progressive disease course. METHODS: We leveraged a randomized trial of the growth hormone-releasing hormone analogue tesamorelin to treat NAFLD in HIV. Sixty-one participants with HIV-associated NAFLD were randomized to tesamorelin or placebo for 12 months with serial biopsies. RESULTS: In all participants with baseline biopsies (n = 58), 43% had hepatic fibrosis. Individuals with fibrosis had higher NAFLD Activity Score (NAS) (mean ± standard deviation [SD], 3.6 ± 2.0 vs 2.0 ± 0.8; P < .0001) and visceral fat content (mean ± SD, 284 ± 91 cm2 vs 212 ± 95 cm2; P = .005), but no difference in hepatic fat or body mass index. Among placebo-treated participants with paired biopsies (n = 24), 38% had hepatic fibrosis progression over 12 months. For each 25 cm2 higher visceral fat at baseline, odds of fibrosis progression increased by 37% (odds ratio, 1.37 [95% confidence interval, 1.03-2.07]). There was no difference in baseline NAS between fibrosis progressors and nonprogressors, though NAS rose over time in the progressor group (mean ± SD, 1.1 ± 0.8 vs -0.5 ± 0.6; P < .0001). CONCLUSIONS: In this longitudinal study of HIV-associated NAFLD, high rates of hepatic fibrosis and progression were observed. Visceral adiposity was identified as a novel predictor of worsening fibrosis. In contrast, baseline histologic characteristics did not relate to fibrosis progression.

Relationship of IGF-1 and IGF-Binding Proteins to Disease Severity and Glycemia in Nonalcoholic Fatty Liver Disease.

CONTEXT: Growth hormone (GH) and IGF-1 help regulate hepatic glucose and lipid metabolism, and reductions in these hormones may contribute to development of nonalcoholic fatty liver disease (NAFLD). OBJECTIVE: To assess relationships between hepatic expression of IGF1 and IGF-binding proteins (IGFBPs) and measures of glycemia and liver disease in adults with NAFLD. Secondarily to assess effects of GH-releasing hormone (GHRH) on circulating IGFBPs. DESIGN: Analysis of data from a randomized clinical trial of GHRH. SETTING: Two US academic medical centers. PARTICIPANTS: Participants were 61 men and women 18 to 70 years of age with HIV-infection, ≥5% hepatic fat fraction, including 39 with RNA-Seq data from liver biopsy. MAIN OUTCOME MEASURES: Hepatic steatosis, inflammation, and fibrosis by histopathology and measures of glucose homeostasis. RESULTS: Hepatic IGF1 mRNA was significantly lower in individuals with higher steatosis and NAFLD Activity Score (NAS) and was inversely related to glucose parameters, independent of circulating IGF-1. Among the IGFBPs, IGFBP2 and IGFBP4 were lower and IGFBP6 and IGFBP7 (also known as IGFBP-related protein 1) were higher with increasing steatosis. Hepatic IGFBP6 and IGFBP7 mRNA levels were positively associated with NAS. IGFBP7 mRNA increased with increasing fibrosis. Hepatic IGFBP1 mRNA was inversely associated with glycemia and insulin resistance, with opposite relationships present for IGFBP3 and IGFBP7. GHRH increased circulating IGFBP-1 and IGFBP-3, but decreased IGFBP-2 and IGFBP-6. CONCLUSIONS: These data demonstrate novel relationships of IGF-1 and IGFBPs with NAFLD severity and glucose control, with divergent roles seen for different IGFBPs. Moreover, the data provide new information on the complex effects of GHRH on IGFBPs.

Effects of tesamorelin on hepatic transcriptomic signatures in HIV-associated NAFLD.

Nonalcoholic fatty liver disease (NAFLD) is a common comorbidity among people living with HIV that has a more aggressive course than NAFLD among the general population. In a recent randomized placebo-controlled trial, we demonstrated that the growth hormone-releasing hormone analog tesamorelin reduced liver fat and prevented fibrosis progression in HIV-associated NAFLD over 1 year. As such, tesamorelin is the first strategy that has shown to be effective against NAFLD among the population with HIV. The current study leveraged paired liver biopsy specimens from this trial to identify hepatic gene pathways that are differentially modulated by tesamorelin versus placebo. Using gene set enrichment analysis, we found that tesamorelin increased hepatic expression of hallmark gene sets involved in oxidative phosphorylation and decreased hepatic expression of gene sets contributing to inflammation, tissue repair, and cell division. Tesamorelin also reciprocally up- and downregulated curated gene sets associated with favorable and poor hepatocellular carcinoma prognosis, respectively. Notably, among tesamorelin-treated participants, these changes in hepatic expression correlated with improved fibrosis-related gene score. Our findings inform our knowledge of the biology of pulsatile growth hormone action and provide a mechanistic basis for the observed clinical effects of tesamorelin on the liver.

Brief Report: Adiponectin Levels Linked to Subclinical Myocardial Fibrosis in HIV.

BACKGROUND: Persons living with HIV (PLWH) are at an increased risk of myocardial dysfunction and metabolic disturbances represent one of several potential contributing factors. Adiponectin is an adipokine that enhances insulin sensitivity with potential cardioprotective effects. We therefore investigated the relationship between myocardial fibrosis, adiponectin, and related metabolic parameters to better understand the pathophysiologic mechanisms of myocardial injury in PLWH. METHODS: This is a prospective, cross-sectional study of PLWH without known cardiovascular disease (n = 87) and 28 healthy matched controls. Diffuse myocardial fibrosis and epicardial adipose tissue (EAT) were evaluated using cardiac magnetic resonance imaging and cardiac computed tomography. RESULTS: Myocardial fibrosis was increased in PLWH and was correlated with adiponectin (r = 0.26, P = 0.004) and EAT (r = -0.42, P < 0.0001). Myocardial fibrosis was not associated with smoking pack years or CD4/CD8 ratio. In multivariate analysis that included body mass index, HIV status (P = 0.04), female sex (P < 0.0001), higher adiponectin (P = 0.046) and lower EAT (P = 0.01) were independently associated with myocardial fibrosis. CONCLUSION: We describe a novel association between serum adiponectin and subclinical intramyocardial fibrosis, as well as a significant inverse relationship between intramyocardial fibrosis and EAT. Adiponectin may represent a target for preventing myocardial injury in the future; however, our findings reflect the complexity of the metabolic interactions of adiponectin and epicardial adipose as factors associated with the myocardial architecture.

Utilization of Direct Oral Anticoagulants in People Living with Human Immunodeficiency Virus: Observational Data from the District of Columbia Cohort.

BACKGROUND: Direct oral anticoagulants (DOACs) have become first-line treatment for venous thrombotic events. DOAC prescribing trends among people living with human immunodeficiency virus (PWH) are not well described. The coadministration of DOACs with the antiretroviral (ARV) pharmacokinetic boosters ritonavir (RTV) or cobicistat (COBI) may be complicated by pharmacokinetic interactions. METHODS: A longitudinal cohort study was conducted using the D.C. Cohort Database in Washington, D.C., from January 2011 to March 2017, to describe oral anticoagulant prescribing among PWH ≥ 18 years old and the prevalence of DOAC use with RTV or COBI. Data collection included demographic and clinical characteristics, ARV and anticoagulant prescriptions, and International Classification of Diseases Ninth and Tenth Edition diagnosis codes. RESULTS: Among 8315 PWH, there were 236 anticoagulant prescriptions (96 DOAC, 140 warfarin) for 206 persons. PWH prescribed anticoagulants were predominantly Black (82%) and male (82%), with a mean age at anticoagulant initiation of 56 years. DOAC use increased from 3% of total anticoagulant prescribing in 2011 to 43% in 2016, accounting for 64% of all newly recorded anticoagulant prescriptions by 2016. There were 19 bleeding events recorded among 16 individuals. Despite the Food and Drug Administration label recommendation to avoid rivaroxaban with boosted ARVs, 41% remained on boosted ARVs after rivaroxaban initiation. CONCLUSIONS: DOAC use increased substantially in PWH by 2016. Although rivaroxaban is not recommended with RTV or COBI, concomitant use was recorded in 41% of rivaroxaban recipients in this cohort. As DOAC usage increases, clinicians need to be aware of potential DOAC/ARV interactions in order to select the most appropriate oral anticoagulant and monitoring plan for PWH.

Metabolic Changes in Chronic Hepatitis C Patients Who Carry IFNL4-ΔG and Achieve Sustained Virologic Response With Direct-Acting Antiviral Therapy.

BACKGROUND: Clearance of hepatitis C virus (HCV) results in rapid changes in metabolic parameters early in direct-acting antiviral (DAA) therapy. Long-term changes after sustained virologic response (SVR) remain unknown. METHODS: We investigated longitudinal changes in metabolic and inflammatory outcomes in chronic hepatitis C (CHC) patients: low-density lipoprotein (LDL), high-density lipoprotein, triglycerides, alanine aminotransferase (ALT), and aspartate aminotransferase (AST) using a general linear model for repeated measurements at 5 clinical time points and by human immunodeficiency virus (HIV) coinfection and IFNL4 genotype. RESULTS: The mean LDL increased markedly during DAA therapy (pre-DAA, 86.6 to DAA, 107.4 mg/dL; P < .0001), but then it decreased to 97.7 mg/dL by post-SVR year 1 (P < .001 compared with DAA; P = .0013 compared with SVR). In patients who carry the IFNL4-ΔG allele, mean LDL increased during treatment, then decreased at post-SVR year 1; however, in patients with TT/TT, genotype did not change during and after DAA treatment. The mean ALT and AST normalized rapidly between pre-DAA and DAA, whereas only mean ALT continued to decrease until post-SVR. Metabolic and inflammatory outcomes were similar by HIV-coinfection status. CONCLUSIONS: Changes in LDL among CHC patients who achieved SVR differed by IFNL4 genotype, which implicates the interferon-λ4 protein in metabolic changes observed in HCV-infected patients.

Reproductive and sexual health knowledge, experiences, and milestones in young adults with life-long HIV.

Reproductive and sexual health outcomes of adults with perinatal human immunodeficiency virus (PHIV) have not been well-characterized. This prospective cross-sectional study of 35 adult persons living with HIV (PLWH) from early life and 20 matched HIV-negative controls assessed quality of life, depressive symptoms, HIV transmission knowledge, and sexual/reproductive behaviors through self-report questionnaires. PLWH scored significantly worse than controls on depressive symptoms (p = 0.04) and two of six quality of life domains (p = 0.03, p = 0.0002). In contrast, PLWH scored significantly higher on transmission knowledge in the context of family planning (p = 0.002). PLWH were more likely to learn about sex from healthcare providers (p = 0.002) and were more confident in their sexual/reproductive health knowledge (p < 0.05). Both groups reported inconsistent condom use, but PLWH were more likely to have planned pregnancies (p = 0.005) and to share pregnancy planning with their partners (p < 0.05). Despite the challenges of living with a chronic stigmatized condition, adults with PHIV were knowledgeable about HIV transmission and family planning and demonstrated sexual practices and reproductive outcomes similar to age-matched controls. However, sub-optimal rates of viral suppression, inconsistent condom use, and the psychosocial impact of living with HIV continue to require the attention of healthcare provides for young adults with PHIV.