Receipt of Smoking Cessation Medications Among People With and Without Human Immunodeficiency Virus in the Veterans Aging Cohort Study (2003-2018).

Background: Nicotine replacement therapy, bupropion, and varenicline are smoking cessation medications (SCMs) shown to be similarly effective in people with and without human immunodeficiency virus (PWH and PWoH, respectively), although rates of receipt of these medications are unknown. Methods: We identified patients in the Veterans Aging Cohort Study with electronic health record-documented current smoking using clinical reminder data for tobacco use (2003-2018). We measured receipt of SCMs using Veterans Affairs pharmacy data for outpatient prescriptions filled 0-365 days after current smoking documentation. We used log-linear, Poisson-modified regression models to evaluate the relative risk (RR) for receiving SCM by human immunodeficiency virus (HIV) status, the annual rate of receipt, and rate difference among PWH relative to PWoH. Results: The sample included 92 632 patients (29 086 PWH), reflecting 381 637 documentations of current smoking. From 2003 to 2018, the proportion receiving SCMs increased from 15% to 34% for PWH and from 17% to 32% among PWoH. There was no statistical difference in likelihood of receiving SCM by HIV status (RR, 1.010; 95% confidence interval [CI], .994-1.026). Annual rates of receiving SCM increased for PWH by 4.3% per year (RR, 1.043; 95% CI, 1.040-1.047) and for PWoH by 3.7% per year (RR, 1.037; 95% CI, 1.036-1.038; rate difference +0.6% [RR, 1.006; 95% CI, 1.004-1.009]). Conclusions: In a national sample of current smokers, receipt of SCM doubled over the 16-year period, and differences by HIV status were modest. However, fewer than 35% of current smokers receive SCM annually. Efforts to improve SCM receipt should continue for both groups given the known dangers of smoking.

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.

Polypharmacy and medical intensive care unit (MICU) admission and 10-year all-cause mortality risk among hospitalized patients with and without HIV.

OBJECTIVE: Medical intensive care unit (MICU) admissions have been declining in people with HIV infection (PWH), but frequency of outpatient polypharmacy (prescription of ≥5 chronic medications) has increased. Among those hospitalized, we examined whether outpatient polypharmacy is associated with subsequent 1-year MICU admission or 10-year all-cause mortality, and if the association varies by HIV status. DESIGN: Retrospective cohort study. METHODS: Using a national electronic health record cohort of Veterans in care, we ascertained outpatient polypharmacy during fiscal year (FY) 2009 and followed patients for 1-year MICU admission and 10-year mortality. We assessed associations of any polypharmacy (yes/no and categorized ≤4, 5-7, 8-9, and ≥10 medications) with 1-year MICU admission and 10-year mortality using logistic and Cox regressions, respectively, adjusted for demographics, HIV status, substance use, and severity of illness. RESULTS: Among 9898 patients (1811 PWH) hospitalized in FY2010, prior outpatient polypharmacy was common (51%). Within 1 year, 1532 (15%) had a MICU admission and within 10 years, 4585 (46%) died. Polypharmacy was associated with increased odds of 1-year MICU admission, in both unadjusted (odds ratio (OR) 1.36 95% CI: (1.22, 1.52)) and adjusted models, aOR (95% CI) = 1.28 (1.14, 1.43) and with 10-year mortality in unadjusted, hazard ratio (HR) (95% CI) = 1.40 (1.32, 1.48), and adjusted models, HR (95% CI) = 1.26 (1.19, 1.34). Increasing levels of polypharmacy demonstrated a dose-response with both outcomes and by HIV status, with a stronger association among PWH. CONCLUSIONS: Among hospitalized patients, prior outpatient polypharmacy was associated with 1-year MICU admission and 10-year all-cause mortality after adjusting for severity of illness in PWH and PWoH.

Predictors of mortality and morbidity in critically ill COVID-19 patients: An experience from a low mortality country.

Background and Aims: Clinical characteristics and factors associated with mortality in patients admitted to the intensive care unit (ICU) in countries with low case fatality rates (CFR) are unknown. We sought to determine these in a large cohort of critically ill COVID-19 patients in Qatar and explore the early mortality predictors. Methods: We retrospectively studied the clinical characteristics and outcomes in patients admitted to the ICU at the national referral hospital for COVID-19 patients in Qatar. Logistic regression analysis was used to determine factors associated with mortality. Results: Between March 7 and July 16, 2020, a total of 1079 patients with COVID-19 were admitted to the ICU. The median (IQR) age of patients was 50 (41-59) years. Diabetes (47.3%) and hypertension (42.6%) were the most common comorbidities. In-hospital mortality was 12.6% overall and 25.9% among those requiring mechanical ventilation. Factors independently associated with mortality included older age ([OR]; 2.3 [95% CI; 1.92-2.75] for each 10-year increase in age, p < 0.001), chronic kidney disease (OR; 1.9 [95% CI; 1.02-3.54], p = 0.04), active malignancy (OR; 6.15 [95% CI; 1.79-21.12], p = 0.004), lower platelet count at ICU admission (OR; 1.41 [95% CI; 1.13-1.75] for each 100 × 103/µl decrease, p = 0.002), higher neutrophil-to-lymphocyte ratio at admission (OR; 1.01 [95% CI; 1-1.02] for each 1- point increase, p = 0.016), higher serum ferritin level at admission (OR; 1.05 [(95% CI; 1.02-1.08] for each 500 µg/L increase, p = 0.002), and higher serum bilirubin level at admission (OR; 1.19 [95% CI; 1.04-1.36] for each 10 µmol/L increase, p = 0.01). Conclusions: The mortality rate among critically ill COVID-19 patients is low in Qatar compared to other countries. Older age, chronic kidney disease, active malignancy, higher neutrophil-to-lymphocyte ratios, lower platelet counts, higher serum ferritin levels, and higher serum bilirubin levels are independent predictors of in-hospital mortality.

Association between HIV and incident pulmonary hypertension in US Veterans: a retrospective cohort study.

BACKGROUND: Pulmonary hypertension incidence based on echocardiographic estimates of pulmonary artery systolic pressure in people living with HIV remains unstudied. We aimed to determine whether people living with HIV have higher incidence and risk of pulmonary hypertension than uninfected individuals. METHODS: In this retrospective cohort study, we evaluated data from participants in the Veterans Aging Cohort Study (VACS) referred for echocardiography with baseline pulmonary artery systolic pressure measures of 35 mm Hg or less. Incident pulmonary hypertension was defined as pulmonary artery systolic pressure higher than 35 mm Hg on subsequent echocardiogram. We used Poisson regression to estimate incidence rates (IRs) of pulmonary hypertension by HIV status. We then estimated hazard ratios (HRs) by HIV status using Cox proportional hazards regression. We further categorised veterans with HIV by CD4 count or HIV viral load to assess the association between pulmonary hypertension risk and HIV severity. Models included age, sex, race or ethnicity, prevalent heart failure, chronic obstructive pulmonary disease, hypertension, smoking status, diabetes, body-mass index, estimated glomerular filtration rate, hepatitis C virus infection, liver cirrhosis, and drug use as covariates. FINDINGS: Of 21 314 VACS participants with at least one measured PASP on or after April 1, 2003, 13 028 VACS participants were included in the analytic sample (4174 [32%] with HIV and 8854 [68%] without HIV). Median age was 58 years and 12 657 (97%) were male. Median follow-up time was 3·1 years (IQR 0·9-6·8) spanning from April 1, 2003, to Sept 30, 2017. Unadjusted IRs per 1000 person-years were higher in veterans with HIV (IR 28·6 [95% CI 26·1-31·3]) than in veterans without HIV (IR 23·4 [21·9-24·9]; p=0·0004). The risk of incident pulmonary hypertension was higher among veterans with HIV than among veterans without HIV (unadjusted HR 1·25 [95% CI 1·12-1·40], p<0·0001). After multivariable adjustment, this association was slightly attenuated but remained significant (HR 1·18 [1·05-1·34], p=0·0062). Veterans with HIV who had a CD4 count lower than 200 cells per µL or of 200-499 cells per µL had a higher risk of pulmonary hypertension than did veterans without HIV (HR 1·94 [1·49-2·54], p<0·0001, for those with <200 cell µL and HR 1·29 [1·08-1·53], p=0·0048, for those with 200-499 cells per µL). Similarly, veterans with HIV who had HIV viral loads of 500 copies per mL or more had a higher risk of pulmonary hypertension than did veterans without HIV (HR 1·88 [1·46-2·42], p<0·0001). INTERPRETATION: HIV is associated with pulmonary hypertension incidence, adjusting for risk factors. Low CD4 cell count and high HIV viral load contribute to increased pulmonary hypertension risk among veterans with HIV. Thus, as with other cardiopulmonary diseases, suppression of HIV should be prioritised to lessen the burden of pulmonary hypertension in people living with HIV. FUNDING: National Heart, Lung, and Blood Institute (National Institutes of Health, USA); National Institute on Alcohol Abuse and Alcoholism (National Institutes of Health, USA).

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.

Natural history of hepatitis C virus infection in a large national seroconversion cohort in the direct-acting antiviral agent era: Results from ERCHIVES.

Hepatitis C virus (HCV) natural history studies are limited by not knowing the time of infection, small numbers and non-representative populations. No studies are available from the direct-acting antiviral agents (DAA) era. We created the largest known cohort of persons with HCV with a known window of seroconversion in the DAA era. We compared the annual cumulative incident events and incidence rate/1000 person-years of follow-up for liver cirrhosis, hepatic decompensation, hepatocellular carcinoma (HCC) and mortality from the time of seroconversion among untreated and those treated and attaining a sustained virologic response (SVR). Among 12,881 persons in the final analyses, 10,417 had never been treated for HCV, 2464 (23.6%) were treated with a DAA regimen and 1836 (74.5%) attained SVR. After 9 years of follow-up, cirrhosis was diagnosed in 17.4% of untreated and 13.6% of the SVR group. Overall, 29.5% in the untreated versus 3.5% in the SVR group died. Incidence rates/1000 person-years of follow-up (95% CI) for untreated versus SVR group were 22.7 (21.6, 23.9) versus 19.5 (17.0, 21.9) for cirrhosis (p = 0.03), 0.1 (0.03, 0.2) versus 0.07 (-0.07, 0.2) for HCC (p = 0.74) and 35.4 (34.0, 36.8) versus 4.53 (3.4, 5.7) for mortality (p < 0.0001). After excluding those with alcohol-related diagnoses at baseline, the difference in cirrhosis was not statistically significant. Cirrhosis and mortality occur early and steadily increase over the first decade after acquiring HCV infection, while HCC is rarely observed. Those treated with a DAA regimen have sharply lower cirrhosis and mortality rates, particularly among those without alcohol abuse or dependence.

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.

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.

HIV- and HCV-specific markers and echocardiographic pulmonary artery systolic pressure among United States veterans.

Hepatitis C virus (HCV) may increase pulmonary hypertension (PH) risk among people living with HIV (PLWH). Prior studies on this topic have been relatively small and examined selected populations. We determine whether HIV/HCV coinfection is associated with higher pulmonary artery systolic pressure (PASP) and prevalent echocardiographic PH. We performed a cross-sectional analysis of 6032 (16% HIV/HCV coinfected) Veterans Aging Cohort Study participants enrolled 4/1/2003-9/30/2012 with echocardiographic PASP measures. We performed multiple linear and logistic regression analyses to determine whether HIV/HCV mono- or co-infection were associated with PASP and PH compared to uninfected individuals. Individuals with HIV/HCV coinfection displayed a higher PASP than uninfected individuals ([Formula: see text]=1.10, 95% CI 0.01, 2.20) but there was no association between HIV/HCV coinfection and prevalent PH. Subset analyses examined HIV and HCV disease severity markers separately and jointly. Among PLWH, HCV coinfection ([Formula: see text]=1.47, 95% CI 0.26, 2.67) and CD4 + cell count ([Formula: see text]= - 0.68, 95% CI - 1.10, - 0.27), but not HIV viral load nor ART regimen, were associated with PASP. Among people with HCV, neither HIV coinfection nor HCV biomarkers were associated with PASP. Among US veterans referred for echocardiography, HIV/HCV coinfection was not associated with a clinically significant elevation in pulmonary pressure. Lower absolute CD4 + T-cell count was inversely associated with PASP which warrants further investigation in prospective studies.

Volume and Acuity of Emergency Department Visits Prior To and After COVID-19.

BACKGROUND: There are scant data regarding the change in volume and acuity of patients presenting to emergency departments (EDs) after Coronavirus Disease 2019 (COVID-19), compared with the pre-COVID-19 era. OBJECTIVE: To determine ED volumes and triage acuity prior to and after COVID-19. METHODS: We determined the volume of patients presenting to four large EDs affiliated with general, cardiac, cancer, and obstetrics hospitals, and the acuity of presenting illness (using the Canadian Triage Acuity Scale [CTAS]) for March and April 2020 and compared them with the same months in 2019 and January 2020. Together, these facilities see over 80% of the ED visits in Qatar. The first COVID-19 patient in Qatar was diagnosed on February 29, 2020. RESULTS: A total of 192,157 ED visits were recorded during the study period. There was a 20-43% overall drop in number of ED visits, with significant variability across hospitals. The Heart Hospital experienced the sharpest decline (33-89%), and the National Center for Cancer Care and Research experienced the least decline in volumes. The decline was observed across all CTAS levels, with the largest decline observed in individuals presenting with CTAS 1 and 2 (26-69% decline month by month). No increase in overall number of deaths or crude mortality rate was observed in the COVID-19 era, according to national statistics. CONCLUSIONS: Sharp declines in ED visits and the triage acuity seen in both general and specialty hospitals raise the concern that severely ill patients may not be seeking timely care, and a surge may be expected once current restrictions on movement are lifted.

Hepatocellular carcinoma occurs frequently and early after treatment in HCV genotype 3 infected persons treated with DAA regimens.

BACKGROUND: There are conflicting data regarding the risk of hepatocellular carcinoma (HCC) after direct-acting antiviral agent (DAA) treatment. Risk of HCC in HCV genotype-3 infected persons after DAA therapy is not well known. METHODS: We prospectively studied HCV infected persons initiated on a DAA regimen between October 2014 and March 2017 at two centers in Pakistan. All persons were free of HCC at study initiation. HCC was confirmed based on characteristic CT scan findings. Patients were followed for 12 months after the completion of therapy. RESULTS: A total of 662 persons initiated treatment. Median age (IQR) was 50 (41, 57) years and 48.8% were male. At baseline, 49.4% were cirrhotic, 91% were genotype 3 and 91.9% attained SVR. Treatment regimens used were: Sofosbuvir (SOF)/ribavirin (RBV)/pegylated interferon (PEG-IFN), 25.2%; SOF/RBV, 62.4%; SOF/RBV/daclatasavir (DCV), 10.6%; SOF/DCV, 2.0%. Incident HCC was detected in 42 patients (12.8%) in the 12-month period after treatment completion and was exclusively observed in those with cirrhosis. In multivariable Cox regression analysis, SVR was associated with a reduction in HCC risk (HR, 95% CI: 0.35, 0.14,0.85). In Kaplan-Meier plots by treatment regimen, those treated with SOF/RBV, SOF/RBV/DCV, or SOF/DCV regimens had a shorter HCC-free survival compared with those treated with a SOF/RBV/PEG-IFN regimen. CONCLUSION: In a predominantly genotype 3 cohort, incident HCC occurred frequently and early after treatment completion, and exclusively in those with pre-treatment cirrhosis. SVR reduced the risk of HCC. Treating HCV infected persons before development of cirrhosis may reduce risk of HCC.

Receipt and predictors of smoking cessation pharmacotherapy among veterans with and without HIV.

Smoking is highly prevalent among people living with HIV (PLWH) and increases cardiovascular risk. Pharmacotherapies such as nicotine replacement therapy (NRT), bupropion, and varenicline help to reduce smoking, though rates of receipt among PLWH compared with HIV-uninfected persons are unknown. Among 814 PLWH and 908 uninfected patients enrolled in the Veterans Aging Cohort Study (2012-2017) who reported current smoking, we used marginal multivariable log-linear regression models to estimate adjusted relative risks (ARR) of receiving pharmacotherapy by HIV status. We also assessed patient-level factors associated with pharmacotherapy receipt within each group. In multivariable analyses, receipt of NRT was less likely among PLWH relative to uninfected participants (ARR 0.77, 95% CI 0.67, 0.89). In both populations, documented mental health disorders and contemplation to quit were associated with greater likelihood of receiving pharmacotherapy. Further research is needed to explore potential treatment disparities.

Impact of Direct Acting Antiviral Agent Therapy upon Extrahepatic Manifestations of Hepatitis C Virus Infection.

PURPOSE OF REVIEW: Direct acting antiviral agents (DAAs) have emerged as simple, short, safe, and effective treatments for chronic hepatitis C (CHC) infection. CHC is a systemic disease with frequent and multiple extrahepatic manifestations. The beneficial effects of DAA treatment regimens extend beyond improvement in liver-related outcomes to amelioration of extra hepatic manifestations and are likely to have economic implications. The purpose of this review is to evaluate the effect of DAAs on extra hepatic manifestations of CHC virus infection. RECENT FINDINGS: Recent studies indicate that DAAs are associated with reduction in all-cause mortality, even in patients without significant hepatic fibrosis. They are also associated with reduction in incident cardiovascular disease and diabetes. DAAs are the mainstay of treatment in HCV-associated cryoglobulinemia and lymphoma. Successful HCV therapy with DAAs also improves patient-related outcomes such as health-related quality of life. DAAs improve extrahepatic manifestations of CHC virus infection. Future studies are needed to evaluate the long-term durability of treatment response and for accounting amelioration of extrahepatic manifestations into the cost effectiveness of DAA regimens.

Association of Syndemic Unhealthy Alcohol Use, Cigarette Use, and Depression With All-Cause Mortality Among Adults Living With and Without HIV Infection: Veterans Aging Cohort Study.

BACKGROUND: The prevalence and risk of concurrent unhealthy drinking, cigarette use, and depression on mortality among persons living with HIV (PLWH) is unclear. This study applied a syndemic framework to assess whether these co-occurring conditions increase mortality and whether such risk is differential by HIV status. METHODS: We evaluated 6721 participants (49.8% PLWH) without baseline cancer from the Veterans Aging Cohort Study, a prospective, observational cohort of PLWH and matched uninfected veterans enrolled in 2002 and followed through 2015. Multivariable Cox proportional hazards regressions estimated risk of a syndemic score (number of conditions: that is, unhealthy drinking, cigarette use, and depressive symptoms) on all-cause mortality by HIV status, adjusting for demographic, health status, and HIV-related factors. RESULTS: Fewer than 10% of participants had no conditions; 25.6% had 1, 51.0% had 2, and 15.0% had all 3. There were 1747 deaths (61.9% PLWH) during the median follow-up (11.4 years). Overall, age-adjusted mortality rates/1000 person-years increased with a greater number of conditions: (0: 12.0; 1: 21.2; 2: 30.4; 3: 36.3). For 3 conditions, the adjusted hazard ratio of mortality was 36% higher among PLWH compared with uninfected participants with 3 conditions (95% confidence interval, 1.07-1.72; P = .013), after adjusting for health status and HIV disease progression. Among PLWH and uninfected participants, mortality risk persisted after adjustment for time-updated health status. CONCLUSIONS: Syndemic unhealthy drinking, cigarette use, and depression are common and are associated with higher mortality risk among PLWH, underscoring the need to screen for and treat these conditions.

Direct-Acting Antiviral Therapy for HCV Infection Is Associated With a Reduced Risk of Cardiovascular Disease Events.

BACKGROUND & AIMS: Infection with hepatitis virus C (HCV) is associated with an increased risk of cardiovascular disease (CVD) events. It is not clear whether treatment with direct-acting antiviral (DAA) agents affects risk of CVD. METHODS: We searched the Electronically Retrieved Cohort of HCV-Infected Veterans database for patients with chronic HCV infection (n = 242,680) and identified patients who had been treated with a pegylated interferon and ribavirin regimen (n = 4436) or a DAA-containing regimen (n = 12,667). Treated patients were matched for age, race, sex, and baseline values with patients who had never received treatment for HCV infection (controls). All subjects were free of any CVD event diagnosis of HCV infection at baseline. The primary outcome was incident CVD events, identified by International Classification of Diseases, Ninth Edition, Clinical Modification or International Classification of Diseases, Tenth Edition code, in the different groups and in patients with vs without a sustained virologic response to therapy. RESULTS: There were 1239 (7.2%) incident CVD events in the treated groups and 2361 (13.8%) events in the control group. Incidence rates were 30.9 per 1000 patient-years (95% CI 29.6-32.1) in the control group and 20.3 per 1000 patient-years (95% CI 19.2-21.5) in the treated groups (P < .0001). Treatment with pegylated interferon and ribavirin (hazard ratio 0.78; 95% CI 0.71-0.85) or a DAA regimen (hazard ratio 0.57; 95% CI 0.51-0.65) was associated with a significantly lower risk of a CVD event compared with no treatment (controls). Incidence rates for CVD events were 23.5 per 1000 patient-years (95% CI 21.8-25.3) in the group treated with the pegylated interferon and ribavirin regimen, 16.3 per 1000 patient-years (95% CI 14.7-18.0) in the group treated with a DAA regimen, and 30.4 (95% CI 29.2-31.7) in the control group. A sustained virologic response was associated with a lower risk of incident CVD events (hazard ratio 0.87; 95% CI 0.77-0.98). CONCLUSIONS: In an analysis of a cohort of HCV-infected veterans, treatment of HCV infection was associated with a significant decrease in risk of CVD events. Patients treated with a DAA regimen and patients who achieved sustained virologic responses had the lowest risk for CVD events.

The Association Between HIV Infection and the Use of Palliative Care in Patients Hospitalized With Heart Failure.

BACKGROUND: The number of adults with heart failure (HF) and HIV infection is increasing. These patients may benefit from palliative care (PC). OBJECTIVES: Determine the association between HIV infection, other HIV characteristics, and PC among hospitalized patients with HF in the Veterans Health Administration (VHA). DESIGN: Nested case-control study of patients with HF hospitalized from 2003 to 2015 and enrolled in the Veterans Aging Cohort Study. SETTING/PATIENTS: Two hundred and ten hospitalized patients with HF who received PC matched to 1042 patients with HF who did not receive PC, by age, discharge date, and left ventricular ejection fraction. MEASUREMENTS: Palliative care use was the primary outcome. Independent variables included HIV infection identified by International Classification of Diseases Ninth Revision code and further characterized as the primary diagnosis for hospitalization, unsuppressed HIV-1 RNA, CD4 counts <200 cells/mm3, and other covariates. We examined associations between independent variables and PC using conditional logistic regression. RESULTS: The sample was 99% male, mean age was 64 years (standard deviation ±10), 54% of cases and 59% of controls were black, and 30% of cases and 31% of controls were HIV-infected. In adjusted models, HIV as the primary diagnosis for hospitalization (odds ratio [OR]: 3.69, 95% confidence interval [CI]: 1.30-10.52), unsuppressed HIV-1 RNA (OR: 2.62, 95% CI: 1.31-5.24), and CD4 counts <200 cells/mm3 (OR: 3.47; 1.78-6.77), but not HIV infection (OR: 0.79, 95% CI: 0.55-1.13), were associated with PC. CONCLUSIONS: HIV characteristics indicative of severe disease are associated with PC for hospitalized VHA patients with HF. Increasing access to PC for patients with HF and HIV is warranted.

HCV treatment initiation in persons with chronic kidney disease in the directly acting antiviral agents era: Results from ERCHIVES.

BACKGROUND: Newer direct acting antiviral agents against HCV (DAAs) are safe and efficacious in persons with chronic kidney disease (CKD). Whether approval of newer DAAs has resulted in more persons with CKD initiating HCV treatment remains unknown. METHODS: We identified HCV+ persons in ERCHIVES between October 1999 and July 2016. We excluded HIV+ and HBsAg+ and those with missing baseline HCV RNA and baseline eGFR data. We identified persons initiated on any approved DAA-regimen through July 2016, by CKD stage. Logistic regression analyses were used to determine factors associated with treatment initiation. RESULTS: Among 83 706 evaluable persons, 21.1% initiated treatment. Rates differed significantly by CKD stage: 22.1% for eGFR>90 mL/min/1.73 m2 and CKD stage-2; 14.9% for CKD stage 3; and 8.0% for CKD stage-4/5. Those with CKD stage-3 were 33% less likely and those with CKD stage-4/5 were 60% less likely to initiate treatment with a DAA compared with those with baseline eGFR>90 mL/min/1.73 m2 . Treatment initiation was less likely in HCV genotype 2 (OR 0.59; 95%CI 0.53,0.66) or 3 (OR 0.53; 95%CI 0.47,0.61) and those with diabetes (OR 0.87, 95% CI 0.81,0.94), cardiovascular disease (OR 0.77, 95% CI 0.70,0.84), alcohol abuse or dependence (OR 0.74, 95% CI 0.70,0.79) or cirrhosis (OR 0.86, 95% CI 0.80,0.92) at baseline. CONCLUSIONS: Persons with more advanced CKD are less likely to receive treatment for HCV despite recent data on safety and efficacy. Strategies are needed to improve treatment rates in the HCV/CKD population.

The short-term incidence of hepatocellular carcinoma is not increased after hepatitis C treatment with direct-acting antivirals: An ERCHIVES study.

Recent studies have reported higher rates of hepatocellular carcinoma (HCC) in individuals treated with direct-acting antivirals (DAAs). However, making definitive conclusions has been challenging because of the heterogeneous populations and methodologies of these reports. We investigated whether DAA use is associated with higher rates of incident HCC compared to treatment with interferon (IFN)-based regimens. We performed a retrospective, population-based cohort study using the Electronically Retrieved Cohort of HCV Infected Veterans (ERCHIVES) database. In a cohort of 17,836 persons, sustained virological response (SVR) was achieved by 66.6% and 96.2% of the IFN and DAA groups, respectively. Among all treated persons, risk of HCC was not higher in the DAA group compared to the IFN group (hazard ratio, 1.07; 95% confidence interval, 0.55, 2.08). Among persons with cirrhosis who achieved SVR, neither the HCC incidence rate nor HCC-free survival were significantly different in the DAA group compared to the IFN group (21.2 vs. 22.8 per 1,000 person-years; P = 0.78 and log-rank P = 0.17, respectively). Untreated persons with cirrhosis had a significantly higher HCC incidence rate (45.3 per 1,000 person-years) compared to those treated with either IFN or DAAs (P = 0.03). Both groups of treated persons had significantly lower probability of HCC development compared to untreated persons (log-rank, P = 0.0004). CONCLUSION: DAA treatment is not associated with a higher risk of HCC in persons with cirrhosis with chronic HCV infection in the short term. Previously reported higher rates of HCC associated with DAA treatment may be explained by both the presence of relatively fewer baseline HCC risk factors in persons treated with IFN as well as selection bias, given that DAA regimens were used to treat persons at higher risk for developing HCC. (Hepatology 2018;67:2244-2253).

Validation of the ICD-9 Diagnostic Code for Palliative Care in Patients Hospitalized With Heart Failure Within the Veterans Health Administration.

BACKGROUND: Patients with heart failure (HF) are at increased risk of unmet palliative care needs. The International Classification of Diseases, Ninth Revision ( ICD-9) code, V66.7, can identify palliative care services. However, code validity for specialist palliative care in the Veterans Health Administration (VHA) has not been determined. OBJECTIVE: To validate the ICD-9 code for specialist palliative care and determine common reasons for specialist palliative care consultation among VHA patients hospitalized with HF. DESIGN: Electronic health record review of data from the Veterans Aging Cohort Study. SETTING/PARTICIPANTS: The sample included 100 patients hospitalized with HF from 2003 to 2012. MEASUREMENTS: Data from 50 patients with V66.7 were matched by age, race, site of care, hospital length of stay, intensive care unit admission, and fiscal year of study discharge to 50 patients with HF without V66.7 who had died within a year of hospitalization. We calculated positive and negative predictive values (PPV, NPV), sensitivity, and specificity. RESULTS: All patients included in the sample were male, 66% black ethnicity, and mean age = 65 years (standard deviations [SD] ± 10.5 for cases; SD ± 9.8 for matches). Specialist palliative care was documented for 49 of 50 patients with V66.7 (PPV = 98%, 95% confidence interval [CI]: 88-99) and 9 of 50 patients without the code (NPV = 82%, 95% CI: 68-91). Sensitivity was 84% (95% CI: 72-92), and specificity was 98% (95% CI: 86-99). Establishing goals of care was the most frequent reason for palliative care consultation (43% of the sample). CONCLUSION: The ICD-9 code V66.7 identifies specialist palliative care for hospitalized patients with HF in the VHA. Replication of findings in other data sources and populations is needed.