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BackgroundPeople with HIV (PWH) with access to antiretroviral therapy (ART) experience excess morbidity and mortality compared with uninfected patients, particularly those with persistent viremia and without CD4+ cell recovery. We compared outcomes for medical intensive care unit (MICU) survivors with unsuppressed (>500 copies/ml) and suppressed (≤500 copies/ml) HIV-1 RNA and HIV-uninfected survivors, adjusting for CD4+ cell count.SettingWe studied 4537 PWH [unsuppressed = 38%; suppressed = 62%; 72% Veterans Affairs-based (VA) and 10 531 (64% VA) uninfected Veterans who survived MICU admission after entering the Veterans Aging Cohort Study (VACS) between fiscal years 2001 and 2015.MethodsPrimary outcomes were all-cause 30-day and 6-month readmission and mortality, adjusted for demographics, CD4+ cell category (≥350 (reference); 200-349; 50-199

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.

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.

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.

Treating HCV infection reduces overall mortality and reduces the risk of multiple extrahepatic complications. Whether the reduction in mortality is primarily due to a reduction in liver-related causes or extrahepatic complications is unknown.We identified HCV-positive individuals treated for HCV, and propensity score-matched them to HCV-positive/untreated and HCV-uninfected individuals in ERCHIVES between 2002-2016. We extracted cause of death data from the National Center for Health Statistics' National Death Index. Viral hepatitis-associated liver-related mortality rates among treated and untreated HCV-infected persons were calculated by treatment and attainment of sustained virologic response (SVR).Among 50,674 HCV-positive/treated (Group A), 31,749 HCV-positive/untreated (Group B) and 73,526 HCV-uninfected persons (Group C), 8.6% in Group A, 35.0% in Group B, and 14.3% in Group C died. Among those who died, viral hepatitis-associated liver-related mortality rates per 100 patient-years (95% CI) were: 0.28 (0.27-0.30) for Group A; 1.44 (1.38-1.49) for Group B; and 0.06 (0.05-0.06) for Group C; (p0.0001 for both comparisons). Among HCV-positive/treated persons, rates were 0.06 (0.05-0.06) for those with SVR vs. 0.78 (0.74-0.83) for those without SVR. In competing risks Cox proportional hazards analysis, treatment with all-oral DAA regimens (adjusted hazard ratio 0.11; 95% CI 0.09-0.14) and SVR (adjusted hazard ratio 0.10; 95% CI 0.08-0.11) were associated with reduced hazards of liver-related mortality.Treatment for HCV is associated with a significant reduction in viral hepatitis-associated liver-related mortality, which is particularly pronounced in those treated with DAA regimens and those who attain SVR. This may account for a significant proportion of the reduction in all-cause mortality reported in previous studies.Treating hepatitis C virus (HCV) infection is known to reduce overall mortality. However, whether the reduction in mortality is primarily due to a reduction in liver-related causes or extrahepatic complications was previously unknown. Herein, we show that while treating HCV with direct-acting antiviral regimens has numerous extrahepatic benefits, a significant benefit can be attributed specifically to the reduction in liver-related mortality.

BACKGROUND: Liver fibrosis, is independently associated with incident heart failure (HF). Investigating the association between liver fibrosis and type of HF, specifically HF with reduced ejection fraction (EF; HFrEF) or HF with preserved ejection fraction (HFpEF), may provide mechanistic insight into this association. We sought to determine the association between liver fibrosis score (FIB-4) and type of HF, and to assess whether HIV or hepatitis C status modified this association. METHODS: We included patients alive on or after 4/1/2003 from the Veterans Aging Cohort Study. We followed patients without prevalent cardiovascular disease until their first HF event, death, last clinic visit, or 9/30/2015. We defined liver fibrosis as: likely advanced fibrosis (FIB-4 > 3.25), indeterminate (FIB-4 range 1.45–3.25), unlikely advanced fibrosis (FIB-4 < 1.45). Primary outcomes were HFrEF and HFpEF (defined using ICD-9 diagnoses for HF, and EF extracted from electronic medical records using natural language processing). Cox proportional hazards models were adjusted for potential confounders and used to estimate hazard ratios (HR). RESULTS: Among 108,708 predominantly male (96%) participants mean age was 49 years. Likely advanced fibrosis was present in 4% at baseline and was associated with an increased risk of HFpEF [HR (95% confidence interval)] [1.70 (1.3–2.3)]; and non-significantly with HFrEF [1.20 (0.9–1.7)]. These associations were not modified by HIV or hepatitis C status. CONCLUSION: Likely advanced fibrosis was independently associated with incident HFpEF but not HFrEF. This suggests that risk factors and/or mechanisms for liver fibrosis may have greater overlap with those for HFpEF than HFrEF.

BACKGROUND: SARS-CoV-2 infection in pregnancy is associated with a higher risk of pregnancy-related complications and neonatal respiratory distress and hospitalization. Effectiveness of SARS-CoV-2 vaccines in pregnant women is not known. METHODS: All women with confirmed pregnancy who presented to the national referral hospital in Qatar between December 20, 2020, and May 30, 2021, with at least 1 SARS-CoV-2 test and not testing prior to pregnancy were included. We determined the vaccine effectiveness of mRNA vaccines in preventing confirmed SARS-CoV-2 infection during pregnancy using both cohort and test-negative case-control designs. Analyses were adjusted for age group, nationality, and gestational age. RESULTS: Among 4534 pregnant women, there were 407 vaccinated and 407 unvaccinated women in the matched cohort analysis. Vaccine effectiveness was 87.6% (95%CI 44.1%–97.2%) at least 14 days after the second dose. There were 386 test-positive and 834 matched women in the test-negative case control analysis. Vaccine effectiveness was 86.8% (95%CI 47.5%–98.5%) at least 14 days after the second dose. Adjustment for age, nationality, and gestational age yielded similar results for both designs. In the test-negative analysis, vaccine effectiveness at least 14 days after the first dose but before the second dose was 40.8% (95% CI 0.0%–80.4%). Of the 386 test-positive pregnant women, 74 cases were Alpha variant, 163 cases were Beta variant, and 156 cases were variants of unknown status. There were 9 severe or critical disease cases and no deaths in the test-positive pregnant women, all of whom were unvaccinated. CONCLUSION: The mRNA vaccines provide a high level of protection against documented SARS-CoV-2 infection, which supports the inclusion of pregnant women in vaccination campaigns. FUNDING: Hamad Medical Corporation, Weill Cornell Medicine Qatar, and the Ministry of Public Health Qatar.

Aims Nipple discharge is a presentation commonly seen at breast clinics. It is conventionally evaluated with physical examination and sonography( or mammography). The aim of this study is to investigate the diagnostic value of magnetic resonance imaging (MRI) as an additional imaging tool in the evaluation of potential malignancy in patients presented with nipple discharge. Methods A retrospective evaluation of 85 patients with nipple discharge who underwent breast ultrasound (USS) and MRI between 04/06/2008 and 25/10/2019 was conducted. Clinical notes, radiographic reports and biopsy results were reviewed. Sensitivity, specificity, positive predictive value and negative predictive value of USS and MRI were calculated. Results Out of the 85 patients (all female; mean age 45.33 +/- 12.93 years old) with nipple discharge, 11 were found to have biopsy-proven malignancy (invasive ductal carcinoma/ ductal carcinoma in situ; 12.94% risk). USS failed to identify seven malignancies (27.27% sensitivity) while MRI missed three malignancies (72.72% sensitivity). USS falsely identified four malignancies from 74 patients with no malignancy (94.59% specificity) while MRI only falsely identified one case (98.65% specificity). For patients with negative USS results (U1/U2/U3) or negative MRI results (BI-RADS category 1,2 or 3), the negative predictive values of USS is 89.74% while that of MRI is 96.05%. The positive predictive values of USS and MRI are 42.86% and 88.88% respectively. Conclusion Compared to USS, MRI has a higher sensitivity, specificity, positive predictive value and predictive value. It will be a valuable addition to the standard nipple discharge evaluation workup to help rule out malignancy.

BackgroundDelays in transfer of patients from emergency department (ED) to stroke ward increases medical complications. We evaluate if a new risk-score ‘DHOW2’ (dysphagia, hemiplegia, observation-required, wet (incontinence) and weight) will identify high-risk patients and whether expedited admission of ‘high-DHOW2’ score patients to SW will result in fewer complications.MethodsThe DHOW2 score was designed to determine risk of complications following acute stroke. Phase I (279 patients) tested rates of complications with increasing DHOW2. Phase II (1091 patients), evaluated if early admission to the SW of high-DHOW2 patients will lead to fewer complications. Phase III (1257 patients) monitored implementation of the DHOW2 following completion of the study.FindingsMedical complications increased with higher-DHOW2 scores during all three phases; 0%–0.8% with DHOW2 of ≤3, 3.1%–6.5% with DHOW2 of 4–5 and 10.9%–14.1% with DHOW2 of ≥6 (p=InterpretationsThe DHOW2 score detects patients at risk of AS related medical complications. It is easy to implement in busy EDs where nurses can use the score to identify such patients. The risk stratification by DHOW2 and early transfer of high-scoring patients to SW is associated with significantly fewer complications.

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 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.

The development of oral vaccine formulation is crucial to facilitate an effective mass immunization program for various vaccine-preventable diseases. In this work, the efficacy of hepatitis B antigen delivered by bacterial nanocellulose/poly(acrylic acid) composite hydrogel microparticles (MPs) as oral vaccine carriers was assessed to induce both local and systemic immunity. Optimal pH-responsive swelling, mucoadhesiveness, protein drug loading, and drug permeability were characterized by MPs formulated with minimal irradiation doses and acrylic acid concentration. The composite hydrogel materials of bacterial nanocellulose and poly(acrylic acid) showed significantly greater antigen release in simulated intestinal fluid while ensuring the integrity of antigen. In in vivo study, mice orally vaccinated with antigen-loaded hydrogel MPs showed enhanced vaccine immunogenicity with significantly higher secretion of mucosal immunoglobulin A, compared to intramuscular vaccinated control. The splenocytes from the same group demonstrated lymphoproliferation and significant increased secretion of interleukin-2 cytokines upon stimulation with hepatitis B antigen. Expression of CD69 in CD4

ObjectivesThe contribution of depression to mortality in adults with and without HIV infection is unclear. We hypothesized that depression increases mortality risk and that this association is stronger among those with HIV infection.MethodsVeterans Aging Cohort Study (VACS) data were analysed from the first clinic visit on or after 1 April 2003 (baseline) to 30 September 2015. Depression definitions were: (1) major depressive disorder defined using International Classification of Diseases, Ninth Revision (ICD-9) codes; (2) depressive symptoms defined as Patient Health Questionnaire (PHQ)-9 scores ≥10. The outcome was all-cause mortality. Covariates were demographics, comorbid conditions and health behaviours.ResultsAmong 129140 eligible participants, 30% had HIV infection, 16% had a major depressive disorder diagnosis, and 24% died over a median follow-up time of 11years. The death rate was 25.3 [95% confidence interval (CI) 25.0-25.6] deaths per 1000 person-years. Major depressive disorder was associated with mortality [hazard ratio (HR) 1.04; 95% CI1.01, 1.07]. This association was modified by HIV status (interaction P-value=0.02). In HIV-stratified analyses, depression was significantly associated with mortality among HIV-uninfected veterans but not among those with HIV infection. Among those with PHQ-9 data (n=7372), 50% had HIV infection, 22% had PHQ-9 scores ≥10, and 28% died over a median follow-up time of 12years. The death rate was 27.3 (95% CI 26.1-28.5) per 1000 person-years. Depressive symptoms were associated with mortality (HR 1.16; 95% CI 1.04, 1.28). This association was modified by HIV status (interaction P-value=0.05). In HIV-stratified analyses, depressive symptoms were significantly associated with mortality among veterans with HIV infection but not among those without HIV infection.ConclusionsDepression was associated with all-cause mortality. This association was modified by HIV status and method of depression ascertainment.

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

Background HIV infection and depression are each associated with increased ischemic stroke risk. Whether depression is a risk factor for stroke within the HIV population is unknown. Methods and Results We analyzed data on 106 333 (33 528 HIV‐positive; 72 805 HIV‐negative) people who were free of baseline cardiovascular disease from an observational cohort of HIV‐positive people and matched uninfected veterans in care from April 1, 2003 through December 31, 2014. International Classification of Diseases, Ninth Revision ( ICD‐9 ) codes from medical records were used to determine baseline depression and incident stroke. Depression occurred in 19.5% of HIV‐positive people. After a median of 9.2 years of follow‐up, stroke rates were highest among people with both HIV and depression and lowest among those with neither condition. In Cox proportional hazard models, depression was associated with an increased risk of stroke for HIV‐positive people after adjusting for sociodemographic characteristics and cerebrovascular risk factors (hazard ratio [HR], 1.18; 95% CI: 1.03–1.34; 0.014). The depression‐stroke relationship was attenuated by alcohol use disorders, cocaine use, and baseline antidepressant use, and unaffected by combined antiretroviral therapy use or individual antiretroviral agents. A numerically higher HR of depression on stroke was found among those younger than 60 years. Conclusions Depression is associated with an increased risk of stroke among HIV‐positive people after adjusting for sociodemographic characteristics, traditional cerebrovascular risk factors, and HIV‐specific factors. Alcohol use disorders, cocaine use, and baseline antidepressant use accounted for some of the observed stroke risk. Depression may be a novel, independent risk factor for ischemic stroke in HIV, particularly among younger people.

Background: Metabolic syndrome (MetS) is widely prevalent in the South Asian (SA) population. The syndrome leads to a high risk of premature atherosclerosis and diabetes. Obesity, specifically abdo...

Pregnancy may increase the risk of adverse maternal and neonatal outcomes in SARS-CoV-2 infection. Effectiveness of SARS-CoV-2 vaccines in pregnant women is not known. Using a test-negative case-control study, we determined the vaccine effectiveness of mRNA vaccines in preventing confirmed SARS-CoV-2 infection in pregnant women at a national referral hospital, which handles > 75% of the deliveries in Qatar. Among 2,020 pregnant women who met the study criteria, 397 had a positive SARS-CoV-2 RT-PCR and 1,623 had a negative test. Vaccine effectiveness ≥ 14 days after the second dose was 67.7% (95%CI 30.5–86.9), while vaccine effectiveness ≥ 14 days after the first dose but before the second dose was 40.3% (95%CI 0.0-80.4). There were nine severe/critical disease cases, and no deaths in the PCR-positive pregnant women, all among unvaccinated. The mRNA vaccines provide high level of protection against documented SARS-CoV-2 infection, which supports including pregnant women in vaccination campaigns.

Prescription opioid use (POU) is often a precursor to opioid use disorder (OUD) and subsequent consequences. Persons with chronic hepatitis C virus infection (CHC) may be at a higher risk of POU due to a higher comorbidity burden and social vulnerability factors. We sought to determine the burden of POU and associated risk factors among persons with CHC in the context of social vulnerability. We identified CHC persons and propensity-score matched HCV− controls in the electronically retrieved Cohort of HCV-Infected Veterans and determined the frequency of acute, episodic long-term and chronic long-term POU and the prevalence of social vulnerability factors among persons with POU. We used logistic regression analysis to determine factors associated with POU. Among 160,856 CHC and 160,856 propensity-score matched HCV-controls, acute POU was recorded in 38.4% and 38.0% (P = 0.01) respectively. Episodic long-term POU was recorded in 3.9% in each group (P = 0.5), while chronic long-term POU was recorded in 28.4% and 19.2% (P

Background Impact of SARS‐CoV‐2 infection upon hospitalization, intensive care unit (ICU) admissions and mortality in persons with hepatitis C virus (HCV) infection is unknown. Methods We used the Electronically Retrieved Cohort of HCV infected Veterans (ERCHIVES) database to determine the impact of HCV infection upon the rates of acute care hospitalization, ICU admission and all‐cause mortality. We identified Veterans with chronic HCV infection and propensity score matched controls without HCV in ERCHIVES. We excluded those with HIV or hepatitis B virus coinfection. Results We identified 975 HCV+ and 975 propensity score matched HCV− persons with SARS‐CoV‐2 infection. Mean FIB‐4 score (±SD) was higher in those with HCV (1.9 ± 2.1 vs 1.2 ± 0.9; P 3.25, the rate‐ was 9.4 and 0.6 (P

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

Highlights • Among 16,912 HCW tested, 10.6% tested positive for COVID-19 • 5% acquired infection at a COVID-19 facility and 95% at a non-COVID-19 facility • Exposure to a colleague (45%) or a patient (29%) were reported at non-COVID sites • Full PPE adherence was 82% at COVID-19 but only 68% at non-COVID-19 facilities, Background Our aim was to determine the prevalence of COVID-19 infection in healthcare workers (HCW) in a national healthcare system and to understand the risk factors for infection. Methods The study was conducted at Hamad Medical Corporation in Qatar, a national healthcare system with 14 hospitals and >28,000 employees, between March 10-June 24, 2020. Data on COVID-19+ HCW were retrieved from the electronic health records and employment records, followed by an email survey and a focused telephone interview. Results Among 16,912 HCW tested, 10.6% tested positive. Hospitalization rate was 11.6%, 1.3% required supplemental oxygen, 0.6% needed intensive care unit admission and 0.3% required mechanical ventilation. There were no deaths. In a follow-up survey of 393 HCW, 5% reported acquiring infection at a COVID-19-designated facility and 95% at a non-COVID-19 facility having acquired the infection through accidental exposure to a colleague (45%) or a patient (29%). Full PPE adherence was 82% at COVID-19-designated but only 68% at non-COVID-19 facilities. Conclusions COVID-19 infection among HCW often occurs among those not directly working with COVID-19 patients. PPE use is less stringent in such settings. Risk of exposure and need for strict PPE must be stressed upon all HCW in all settings.

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 ($$\widehat{\beta }$$ β ^ =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 ($$\widehat{\beta }$$ β ^ =1.47, 95% CI 0.26, 2.67) and CD4 + cell count ($$\widehat{\beta }$$ β ^ = − 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.

Background Rate of SARS‐CoV‐2 infection and impact of liver fibrosis stage upon infection rates in persons with hepatitis C virus (HCV) infection are unknown. Methods We retrospectively analyzed the Electronically Retrieved Cohort of HCV Infected Veterans (ERCHIVES), a well‐established database of HCV infected Veterans in care. We excluded those with missing FIB‐4 score and those with HIV or hepatitis B virus coinfection. We determined the number of persons tested, proportion who tested positive for SARS‐CoV‐2, and the infection rate by age and liver fibrosis stage. Results Among 172,235 persons with HCV, 14,305 (8.3%) were tested for SARS‐CoV‐2 infection and 892 (6.2%) tested positive. Those with SARS‐CoV‐2 infection were older, more likely to be Black (55.2% vs. 37.8%), obese (body mass index >30kg/m2 36.2% vs. 29.7%) and have diabetes or stroke (p 3.25) were similar in both groups. Incidence rate/1,000 tested persons was much higher among Blacks (88.4; 95% CI 81.1,96.2) vs. Whites (37.5; 95% CI 33.1,42.4) but similar among those with cirrhosis (FIB‐4>3.25). The rates were also similar among those who were untreated for HCV vs. those treated with or without attaining a sustained virologic response. Conclusions Testing rates among persons with HCV are very low. Persons with infection are more likely to be Black, have a higher body mass index and diabetes or stroke. The degree of liver fibrosis does not appear to have an impact on infection rate.

Background Impact of COVID-19 upon acute care admission rates and patterns are unknown. We sought to determine the change in rates and types of admissions to tertiary and specialty care hospitals in the COVID-19 era compared with pre-COVID-19 era. Methods Acute care admissions to the largest tertiary care referral hospital, designated national referral centers for cardiac, cancer and maternity hospital in the State of Qatar during March 2020 (COVID-19 era) and January 2020 and March 2019 (pre-COVID-19 era) were compared. We calculated total admissions, and admissions for eight specific acute care conditions, in-hospital mortality rate and length of stay at each hospital. Results A total of 18,889 hospital admissions were recorded. A sharp decline ranging from 9%-75% was observed in overall admissions. A decline in both elective and non-elective surgeries was observed. A decline of 9%-58% was observed in admissions for acute appendicitis, acute coronary syndrome, stroke, bone fractures, cancer and live births, while an increase in admissions due to respiratory tract infections was observed. Overall length of stay was shorter in the COVID-19 period possibly suggesting lesser overall disease severity, with no significant change in in-hospital mortality. Unadjusted mortality rate for Qatar showed marginal increase in the COVID-19 period. Conclusions We observed a sharp decline in acute care hospital admissions, with a significant decline in admissions due to seven out of eight acute care conditions. This decline was associated with a shorter length of stay, but not associated with a change in in-hospital mortality rate., Highlights • The change in rate and types of admissions to acute care hospitals during the COVID-19 era compared with pre-COVID-19 era is unknown. • We observed a sharp decline in overall admission volumes and in seven of eight common diagnostic categories, while observing an increase in respiratory infections when comparing COVID-19 vs. pre-COVID-19 timeframe. • A statistically non-significant decrease in in-hospital mortality was observed, while the national statistics demonstrated a slight increase in mortality rate in the country. • It is critical to determine whether there is an association between declining acute care admissions and overall mortality rate in the community, and whether a surge of patients with more advanced disease may be anticipated after COVID-19 related restrictions are removed.

Objective To define the epidemiologic curve of COVID-19 in Qatar, determine factors associated with severe or critical illness, and study the temporal relation between public health measures and case finding Design Epidemiologic investigation Setting and Participants All confirmed COVID-19 cases in the State of Qatar between February 28 and April 18, 2020 Main Outcome Measures Number of total and daily new COVID-19 infections; demographic characteristics and comorbidity burden and severity of infection; factors associated with severe or critical illness Results Between February 28 and April 18, 2020 (11:00AM local time), 5,685 cases of COVID-19 were identified. Mean age (SD) was 35.8(12.0) years, 88.9% were male and 8.7% were Qatari nationals. Overall, 83.6% had no concomitant comorbidity, and 3.0% had 3 or more comorbidities. The overwhelming majority (90.9%) were asymptomatic or with minimal symptoms, with 2.0% having severe or critical illness. Presence of hypertension or diabetes were associated with a higher risk of severe or critical illness. Seven deaths were observed during the time interval studied. The epidemiologic curve indicated two distinct patterns of infection, a larger cluster among expatriate craft and manual workers, and a smaller one among Qatari nationals returning from abroad during the epidemic. Conclusion COVID-19 infections in Qatar started in two distinct clusters, but then became more widespread in the population through community transmission. Infections were mostly asymptomatic or with minimal symptoms and associated with very low mortality. Severe/critical illness was associated with presence of hypertension or diabetes. Article Summary Strengths and limitations of this study: National study with unified contact tracing and testing All testing done at a single lab, and all tests performed in the State of Qatar during the study period were included, providing a robust national estimate of the number of infected persons among those tested Comorbidities were retrieved from the electronic medical records using ICD-10 AM codes Exact geographic location and contact tracing data were not included in the current report It is possible that some persons still under care on the study end date may have progressed to more severe disease after that date What is already known on this topic As of May 3, 2020, over 3.4 million persons have been infected with SARS-CoV-2 and over 244,000 deaths have been reported in persons with COVID-19 infection. Those at higher risk of complications include persons over age 60 years and those with chronic comorbid conditions. Mortality rate varies widely among different countries, and this can be associated both to the capacity of the health system to provide effective intensive care including ventilators as well as other factors, including demographic differences. Public health measures seem effective, but there is debate on the extent to which the measures need to be aggressive or the duration for which they should be implemented. What this study adds This study reports on the epidemic curve in a population with a unique demographic structure, comprising an overwhelming majority of expatriates and young male craft and manual workers. This is also the first study that reports on the epidemic curve of an Arab country in the Eastern Mediterranean Region (EMR). The study also overlays major public health measures on the epidemic curve, to provide an understanding of the context in which the epidemic is progressing. Patients with confirmed COVID-19 in Qatar were young with few comorbidities. Case fatality rate was very low (only 7 deaths among 5,685 infected persons). Severe and critical illness were associated with presence of hypertension or diabetes.

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.

BACKGROUND AND AIMS: The patatin-like phospholipase domain containing 3 (PNPLA3) gene has been associated with development of alcoholic and non-alcoholic steatohepatitis. Using a newly developed and validated assay for PNPLA3, we explored the prevalence of gene polymorphisms in a cohort of HCV/HIV coinfected individuals to determine if there was an association with insulin resistance or hepatic fibrosis. METHODS: A high-resolution melting point (HRM) assay was developed and validated. The assay was used to evaluate samples obtained in the context of a clinical trial performed at ACTG sites across the U.S. in HIV-infected patients. Clinical features and treatment outcomes were assessed in relation to the PNPLA3 genotype. RESULTS: The HRM methodology demonstrated 100% concordance with results obtained by Sanger sequencing. Among 241 participants tested, 66.0% had the wildtype allele (CC) and the remainder had the aberrant PNPLA3 gene polymorphism in the homozygotic (GG) or heterozygotic (CG) form. Race and ethnicity were associated with PNPLA3 genotype but fibrosis stage, HOMA (Homeostatic Model Assessment of Insulin Resistance), and HCV treatment outcome was not. CONCLUSION: The HRM method is an effective, rapid technique for characterizing PNPLA3 genotype. In those with HCV/HIV infection, nearly 40% carry gene polymorphisms associated with development of NASH or ASH. Prospective studies should focus on this group to determine if they represent a subset of HIV-infected persons at increased risk of fibrotic progression.

Background Central nervous system (CNS) viral infections are an important cause of morbidity and mortality. No data are available regarding their epidemiology in Qatar. Design We retrospectively evaluated all cerebrospinal fluid findings from January 2011–March 2015 at Hamad Medical Corporation. Those with abnormal CSF finding were included in our study. We excluded those with missing medical records, no clinical evidence of viral CNS infection, or proven bacterial, fungal or tuberculosis CNS infection. CNS clinical findings were classified as meningitis, encephalitis or myelitis. Results Among 7690 patients with available CSF results, 550 cases met the inclusion criteria (meningitis 74.7%; encephalitis 25%; myelitis 0.4%). Two-thirds (65%) were male and 50% were between 16–60 years old. Viral etiology was confirmed in 38% (enterovirus, 44.3%; Epstein-Barr virus, 31%; varicella zoster virus, 12.4%). The estimated incidence was 6.4 per 100,000 population. Two persons died and the rest were discharged to home. Among those with confirmed viral etiology, 83.8% received ceftriaxone (mean duration 7.3 ± 5.2 days), 38% received vancomycin (mean duration 2.7 ± 5.4 days) and 38% received at least one other antibiotic. Intravenous acyclovir was continued for more than 48 h in patients with confirmed negative viral etiology (mean duration 5 ± 5.6 days). Conclusion Viral etiology is not uncommon among those evaluated for CNS infection in Qatar. Clinical outcomes are excellent in this group of patients. Antibiotics and acyclovir are overly used even when a viral etiology is confirmed. There is a need for clinician education regarding etiology and treatment of viral CNS infections.

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.

OBJECTIVE The objective of this study was to determine the magnitude of drug interactions between the hepatitis C virus (HCV) protease inhibitor boceprevir (BOC) and antiretroviral (ARV) agents in persons with HIV/HCV co-infection. METHODS Participants taking two nucleos(t)ide analogs with either efavirenz, raltegravir, or ritonavir-boosted atazanavir, darunavir, or lopinavir underwent intensive pharmacokinetic (PK) sampling for ARV 2 weeks before (week 2) and 2 weeks after initiating BOC (week 6) and for BOC at week 6. Geometric mean ratios (GMRs) and 90% confidence intervals (CIs) were used to compare ARV PK at weeks 2 and 6 and BOC PK at week 6 to historical data (HD) in healthy volunteers and HCV mono-infected patients. RESULTS ARV PK was available for 55 participants. BOC reduced atazanavir and darunavir exposures by 30 and 42%, respectively. BOC increased raltegravir maximum concentration (C max) by 71%. BOC did not alter efavirenz PK. BOC PK was available for 53 participants. BOC exposures were similar in these HIV/HCV co-infected participants compared with HD in healthy volunteers, but BOC minimum concentrations (C min) were lower with all ARV agents (by 34-73%) compared with HD in HCV mono-infected patients. CONCLUSIONS Effects of BOC on ARV PK in these HIV/HCV co-infected individuals were similar to prior studies in healthy volunteers. However, some differences in the effects of ARV on BOC PK were observed, indicating the magnitude of interactions may differ in HCV-infected individuals versus healthy volunteers. Findings highlight the need to conduct interaction studies with HCV therapies in the population likely to receive the combination.

Background Identifying hepatitis C virus (HCV)-positive persons at high risk of early complications can help prioritize treatment decisions. We conducted this study to compare Child-Turcotte-Pugh (CP), MELD, and FIB-4 scores for predicting clinical outcomes and to identify those at low risk of complications. Methods Within electronically retrieved cohort of HCV-infected veterans, we identified HCV-positive persons and excluded those with human immunodeficiency virus (HIV), hepatitis B surface antigen (HBsAg), prevalent hepatic decompensation (HD), hepatocellular carcinoma (HCC), and those treated for HCV. We calculated incidence rates for HD, HCC, and all-cause mortality at 1, 3, and 5 years after HCV diagnosis. Using receiver operating characteristic (ROC) curves, we determined the optimal cut-off values for each score for these outcomes. Results Among 21 116 persons evaluated, 89.7% were CP Class-A, 79.9% had MELD

Background Cohort studies identifying the incidence, complications and co-morbidities associated with community acquired pneumonia (CAP) are largely based on administrative datasets and rely on International Classification of Diseases (ICD) codes; however, the reliability of ICD codes for hospital admissions for CAP in people with HIV (PWH) has not been systematically assessed. Methods We used data from the Veterans Aging Cohort Study survey sample (N = 6824; 3410 PWH and 3414 uninfected) to validate the use of electronic health records (EHR) data to identify CAP hospitalizations when compared to chart review and to compare the performance in PWH vs. uninfected patients. We used different EHR algorithms that included a broad set of CAP ICD-9 codes, a set restricted to bacterial and viral CAP codes, and algorithms that included pharmacy data and/or other ICD-9 diagnoses frequently associated with CAP. We also compared microbiologic workup and etiologic diagnosis by HIV status among those with CAP. Results Five hundred forty-nine patients were identified as having an ICD-9 code compatible with a CAP diagnosis (13% of PWH and 4% of the uninfected, p P = 0.1) groups. Adding aspiration pneumonia (ICD-9 code 507) to any of the ICD-9 code/pharmacy combinations increased the number of cases but decreased the overall PPV. Allowing COPD exacerbation in the primary position improved the PPV among the uninfected group only (to 76%). More PWH than uninfected patients underwent microbiologic evaluation or had respiratory samples submitted. Conclusions ICD-9 code-based algorithms perform similarly to identify CAP in PLWH and uninfected individuals. Adding antimicrobial use data and allowing as primary diagnoses ICD-9 codes frequently used in patients with CAP improved the performance of the algorithms in both groups of patients. The algorithms consistently performed better among PWH.

For persons with baseline Fibrosis-4 1.46–3.25, cirrhosis incidence/1000 patient-years was 49.3 among hepatitis B virus (HBV)/hepatitis C virus (HCV) coinfected and 18.2 among HCV monoinfected (P = .03). Cirrhosis risk was numerically higher but statistically nonsignificant among HBV/HCV coinfected (hazards ratio [HR] 1.51; 95% confidence intervals [CI], .37–6.05) but lower among those who attained sustained virologic response (HR, .52; 95% CI, .42–.63).

Background Hepatic steatosis is prevalent in Western countries, but few studies have evaluated whether the frequency and severity of steatosis are greater in the setting of HIV infection. We compared the prevalence and severity of hepatic steatosis between HIV-infected (HIV+) and uninfected persons and identified factors associated with greater steatosis severity within both groups. Methods We performed a cross-sectional study among participants without cardiovascular disease who participated in a substudy of the Veterans Aging Cohort Study. Hepatic steatosis was defined by noncontrast computed tomography (CT) liver-to-spleen (L/S) attenuation ratio

Background The effects of interferon-based therapies for hepatitis C virus (HCV) upon the risk of diabetes are controversial. The effects of newer, directly acting antiviral agents (DAA) upon this risk are unknown. We sought to determine the effects of HCV treatment upon the risk and incidence of diabetes. Methods Using the Electronically Retrieved Cohort of HCV Infected Veterans (ERCHIVES) database for persons with chronic HCV infection (n = 242 680), we identified those treated with a pegylated interferon and ribavirin regimen (PEG/RBV, n = 4764) or a DAA-containing regimen (n = 21 279), after excluding those with diabetes at baseline, those with a human immunodeficiency virus or hepatitis B virus coinfection, and those treated with both PEG/RBV and DAA regimens. Age-, race-, sex-, and propensity score–matched controls (1:1) were also identified. Results Diabetes incidence rates per 1000 person-years were 20.6 (95% confidence interval [CI] 19.6–21.6) among untreated persons, 19.8 (95% CI 18.3–21.4) among those treated with PEG/RBV, and 9.89 (95% CI 8.7–11.1) among DAA-treated persons (P < .001). Among the treated, rates were 13.3 (95% CI 12.2–14.5) for those with a sustained virologic response (SVR) and 19.2 (95% CI 17.4–21.1) for those without an SVR (P < .0001). A larger reduction was observed in persons with more advanced fibrosis/cirrhosis (absolute difference 2.9 for fibrosis severity score [FIB-4] < 1.25; 5.7 for FIB-4 1.26–3.25; 9.8 for FIB-4 >3.25). DAA treatment (hazard ratio [HR] 0.53, 95% CI .46–.63) and SVR (HR 0.81, 95% CI .70–.93) were associated with a significantly reduced risk of diabetes. DAA-treated persons had longer diabetes-free survival rates, compared to untreated and PEG/RBV-treated persons. There was no significant difference in diabetes-free survival rates between untreated and PEG/RBV-treated persons. The results were similar in inverse probability of treatment and censoring weight models. Conclusions DAA therapy significantly reduces the incidence and risk of subsequent diabetes. Treatment benefits are more pronounced in persons with more advanced liver fibrosis.

Insomnia is associated with increased cardiovascular disease (CVD) risk in the general population and is highly prevalent in people with HIV. The CVD risk conferred by insomnia in the HIV population is unknown.Using the Veterans Aging Cohort Study Survey Cohort, insomnia symptoms were measured and dummy coded with the item, "Difficulty falling or staying asleep?" (5-point scale from no difficulty to bothers a lot). Incident CVD event ICD-9 codes (acute myocardial infarction, stroke, or coronary artery revascularization) were identified with the Department of Veterans Affairs (VA) and Medicare administrative data and VA fee-for-service data. Those with baseline CVD were excluded.HIV-infected (N = 3108) veterans had a median follow-up time of 10.8 years, during which 267 CVD events occurred. Compared to HIV-infected veterans with no difficulty falling or staying asleep, HIV-infected veterans bothered a lot by insomnia symptoms had an increased risk of incident CVD after adjusting for demographics [hazard ratio (HR) = 1.64, 95% confidence interval (CI): 1.16 to 2.31, P = 0.005], CVD risk factors (HR = 1.62, 95% CI: 1.14 to 2.30, P = 0.007), additional potential confounders (hepatitis C infection, renal disease, anemia, alcohol use, and cocaine use; HR = 1.70, 95% CI: 1.19 to 2.43, P = 0.003), and HIV-specific factors (HIV-1 RNA, CD4 T-cell count, and antiretroviral therapy; HR = 1.66, 95% CI: 1.16 to 2.37, P = 0.005). Additional adjustment for nonbenzodiazepine sleep medication (HR = 1.62, 95% CI: 1.13 to 2.32, P = 0.009) did not attenuate the association; however, it fell short of significance at P0.01 after adjustment for depressive symptoms (HR = 1.51, 95% CI: 0.98 to 2.32, P = 0.060) or antidepressant medication (HR = 1.51, 95% CI: 1.04 to 2.19, P = 0.031).Highly bothersome insomnia symptoms were significantly associated with incident CVD in HIV-infected veterans, suggesting that insomnia may be a novel, modifiable risk factor for CVD in HIV.

BACKGROUND: HIV, hepatitis C virus (HCV), and alcohol-related diagnoses (ARD) independently contribute increased risk of all-cause hospitalization. We sought to determine annual medical intensive care unit (MICU) admission rates and relative risk of MICU admission between 1997 and 2014 among people with and without HIV, HCV, and ARD, using data from the largest HIV and HCV care provider in the United States. SETTING: Veterans Health Administration. METHODS: Annual MICU admission rates were calculated among 155,550 patients in the Veterans Aging Cohort Study by HIV, HCV, and ARD status. Adjusted rate ratios and 95% confidence intervals (CIs) were estimated with Poisson regression. Significance of trends in age-adjusted admission rates were tested with generalized linear regression. Models were stratified by calendar period to identify shifts in MICU admission risk over time. RESULTS: Compared to HIV-/HCV-/ARD- patients, relative risk of MICU admission decreased among HIV-mono-infected patients from 61% (95% CI: 1.56 to 1.65) in 1997-2009% to 21% (95% CI: 1.16 to 1.27) in 2010-2014, increased among HCV-mono-infected patients from 22% (95% CI: 1.16 to 1.29) in 1997-2009% to 54% (95% CI: 1.43 to 1.67) in 2010-2014, and remained consistent among patients with ARD only at 46% (95% CI: 1.42 to 1.50). MICU admission rates decreased by 48% among HCV-uninfected patients (P-trend

SummaryBackground Directly acting antiviral agents (DAA) have been associated with hepatic decompensation, especially in patients with pre-treatment cirrhosis, but this risk is not well defined. Aims To determine the incidence of hepatic decompensation, liver transplantation, death and worsening renal function in patients treated with a Paritaprevir/ritonavir, Ombitasvir, Dasabuvir (PrOD), sofosbuvir/simeprevir or sofosbuvir/ledipasvir regimen. Methods We followed ERCHIVES participants treated with the above regimens for up to 12 weeks post-treatment. We excluded those with HIV, HBsAg+ and pre-existing diagnosis of hepatic decompensation and hepatocellular carcinoma. Results Of 3728 persons on PrOD, 1578 on sofosbuvir/simeprevir and 10 440 on sofosbuvir/ledipasvir, incidence rates (95% CI) of hepatic decompensation/1000 patient-years were 10.6 (5.89–17.36) for the PrOD, 32.4 (20.74–48.16) for the sofosbuvir/simeprevir and 13.0 (9.74–17.10) for the sofosbuvir/ledipasvir. Among those with baseline cirrhosis, these rates were 36.9 (19.1–64.5), 61.8 (38.2–94.5) and 41.1 (29.9–55.2) respectively, while among those without cirrhosis at baseline, these rates were 2.7 (0.6–8.0), 7.5 (1.5–21.8) and 2.7 (1.2–5.4). Advanced fibrosis was associated with increased risk of hepatic decompensation in all groups [HR (95% CI) per 0.5 unit increase in FIB-4 score: PrOD 1.11 (1.07–1.16); sofosbuvir/simeprevir 1.03 (1.01–1.05); sofosbuvir/ledipasvir 1.02 (1.01–1.03)]. There were no deaths. Proportion of persons with eGFR decrease >30 ml/min/1.73 m2 was higher among the PrOD group, but presence of cirrhosis did not appear to affect this. Conclusions The incidence of hepatic decompensation in persons treated with PrOD, up to 12 weeks after completion of treatment, was comparable to those treated with sofosbuvir/ledipasvir regimen, and was lower than among those treated with a sofosbuvir/simeprevir regimen. Such risk was predominantly observed in those with pre-treatment cirrhosis.

During HIV+ hepatitis C virus (HCV)+ coinfection CD14CD16 monocytes produce soluble immune-activation markers that predict disease progression and poor response to interferon (IFN)-α treatment. We evaluated relationships among immune activation, monocyte phenotype, CD4-memory T cells, and HCV-, cytomegalovirus-, and cytomegalovirus/Epstein-Barr virus/influenza-specific IFN-γ-response before and during IFN-α treatment. Effector-memory and central-memory CD4 T-cell frequencies were lower in HCV+ HIV+ donors than in uninfected donors and correlated negatively with HCV level, CD14CD16 monocytes, and plasma sCD14. sCD14 and CD14CD16 monocytes negatively correlated with IFN-α-dependent HCV decline. CD4 effector-memory T cells positively associated with cytomegalovirus/Epstein-Barr virus/influenza(CEF)-specific IFN-γ response, while sCD14 negatively associated with both CD4 effector-memory T cells and CEF-specific IFN-γ response. These data support a role for memory-CD4 T cells in HCV containment and link immune activation and CD14CD16-monocyte frequency to the failure of IFN-dependent HCV clearance.

Supplemental Digital Content is Available in the Text., Background: HIV infection and biomarkers of inflammation [measured by interleukin-6 (IL-6)], monocyte activation [soluble CD14 (sCD14)], and coagulation (D-dimer) are associated with morbidity and mortality. We hypothesized that these immunologic processes mediate (explain) some of the excess risk of mortality among HIV infected (HIV+) versus uninfected people independently of comorbid diseases. Methods: Among 2350 (1521 HIV+) participants from the Veterans Aging Cohort Study Biomarker Cohort (VACS BC), we investigated whether the association between HIV and mortality was altered by adjustment for IL-6, sCD14, and D-dimer, accounting for confounders. Participants were followed from date of blood draw for biomarker assays (baseline) until death or July 25, 2013. Analyses included ordered logistic regression and Cox Proportional Hazards regression. Results: During 6.9 years (median), 414 deaths occurred. The proportional odds of being in a higher quartile of IL-6, sCD14, or D-dimer were 2–3 fold higher for viremic HIV+ versus uninfected people. Mortality rates were higher among HIV+ compared with uninfected people [incidence rate ratio (95% CI): 1.31 (1.06 to 1.62)]. Mortality risk increased with increasing quartiles of IL-6, sCD14, and D-dimer regardless of HIV status. Adjustment for IL-6, sCD14, and D-dimer partially attenuated mortality risk among HIV+ people with unsuppressed viremia (HIV-1 RNA ≥10,000 copies per milliliter) compared with uninfected people—hazard ratio (95% CI) decreased from 2.18 (1.60 to 2.99) to 2.00 (1.45 to 2.76). Conclusions: HIV infection is associated with elevated IL-6, sCD14, and D-dimer, which are in turn associated with mortality. Baseline measures of these biomarkers partially mediate excess mortality risk among HIV+ versus uninfected people.

ObjectiveTo define the epidemiological curve of COVID-19 in Qatar and determine factors associated with severe or critical illness.DesignCase series of first 5685 COVID-19 cases in Qatar.Setting and participantsAll confirmed COVID-19 cases in the State of Qatar between 28 February and 18 April 2020.Main outcome measuresNumber of total and daily new COVID-19 infections; demographic characteristics and comorbidity burden and severity of infection; factors associated with severe or critical illness.ResultsBetween 28 February and 18 April 2020, 5685 cases of COVID-19 were identified. Median age was 34 (IQR 28–43) years, 88.9% were male and 8.7% were Qatari nationals. Overall, 83.6% had no concomitant comorbidity, and 3.0% had three or more comorbidities. The overwhelming majority (90.9%) were asymptomatic or with minimal symptoms, with 2.0% having severe or critical illness. Seven deaths were observed during the time interval studied. Presence of hypertension or diabetes was associated with a higher risk of severe or critical illness, but age was not. The epidemiological curve indicated two distinct patterns of infection, a larger cluster among expatriate craft and manual workers and a smaller one among Qatari nationals returning from abroad during the epidemic.ConclusionCOVID-19 infections in Qatar started in two distinct clusters, but then became more widespread in the population through community transmission. Infections were mostly asymptomatic or with minimal symptoms and associated with very low mortality. Severe/critical illness was associated with presence of hypertension or diabetes but not with increasing age.

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 3, 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 3 (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.

Background Bilirubin may protect against cardiovascular disease ( CVD ) by reducing oxidative stress. Whether elevated bilirubin reduces the risk of CVD events among HIV + individuals and if this differs from uninfected individuals remain unclear. We assessed whether bilirubin independently predicted the risk of CVD events among HIV + and uninfected participants in VACS (Veterans Aging Cohort Study). Methods and Results We conducted a prospective cohort study using VACS participants free of baseline CVD . Total bilirubin was categorized by quartiles. CVD as well as acute myocardial infarction, heart failure, and ischemic stroke events were assessed. Cox regression was used to evaluate hazard ratios of outcomes associated with quartiles of total bilirubin in HIV + and uninfected people after adjusting for multiple risk factors. There were 96 381 participants (30 427 HIV + ); mean age was 48 years, 48% were black, and 97% were men. There were 6603 total incident CVD events over a mean of 5.7 years. In adjusted models, increasing quartiles of baseline total bilirubin were associated with decreased hazards of all outcomes (hazard ratio, 0.86; 95% confidence interval, 0.80–0.91). Among HIV + participants, results persisted for heart failure, ischemic stroke, and total CVD , but nonsignificant associations were observed for acute myocardial infarction. Conclusions VACS participants (regardless of HIV status) with elevated bilirubin levels had a lower risk of incident total CVD , acute myocardial infarction, heart failure, and ischemic stroke events after adjusting for known risk factors. Future studies should investigate how this apparently protective effect of elevated bilirubin could be harnessed to reduce CVD risk or improve risk estimation among HIV + individuals.

Background Human tissues are invaluable resources for researchers worldwide. Biobanks are repositories of such human tissues and can have a strategic importance for genetic research, clinical care, and future discoveries and treatments. One of the aims of Qatar Biobank is to improve the understanding and treatment of common diseases afflicting Qatari population such as obesity and diabetes. Methods In this study we apply a panorama of state-of-the-art statistical methods and machine learning algorithms to investigate associations and risk factors for diabetes and obesity on a sample of 1000 Qatari population. Results Regarding diabetes, we identified pronounced associations and risk factors in Qatari population including magnesium, chloride, c-peptide of insulin, insulin, and uric acid. Similarly, for obesity, significant associations and risk factors include insulin, c-peptide of insulin, albumin, and uric acid. Moreover, our study has revealed interactions of hypomagnesemia with HDL-C, triglycerides, and free thyroxine. Conclusions Our study strongly confirms known associations and risk factors associated with diabetes and obesity in Qatari population as previously found in other population studies in different parts of the world. Moreover, interactions of hypomagnesemia with other associations and risk factors merit further investigations. Electronic supplementary material The online version of this article (10.1186/s12967-018-1472-0) contains supplementary material, which is available to authorized users.

Background Chronic kidney disease (CKD) was a relative contraindication to hepatitis C virus (HCV) treatment in the interferon/ribavirin era. Aim To determine the efficacy, tolerability and safety of sofosbuvir/ledipasvir (SOF/LDV) and paritaprevir/ritonavir/ombitasvir/dasabuvir (PrOD) regimens in persons with CKD. Methods We identified persons initiated on a SOF/LDV or PrOD regimen from October 30, 2014 to April 30, 2016. We excluded those with missing HCV genotype or eGFR values. We determined treatment completion and sustained virologic response (SVR) rates, and proportion developing worsening renal function or grade 3/4 haematologic toxicity. Results Among 13 663 persons on SOF/LDV±ribavirin, 14% and 1% persons had CKD Stage 3 and 4-5 respectively, 67.8% completed treatment, 98.2% achieved SVR. Treatment completion or SVR rates did not decline with advanced CKD or ribavirin administration. Among 3961 persons on PrOD±ribavirin, 9% and 3% persons had CKD Stage 3 and 4-5, respectively, 74.0% completed treatment and 98.2% achieved SVR. A decrease in treatment completion rates was seen in CKD stage 4-5 and those on ribavirin, but this did not impact SVR rates. A >10 mL/min/1.73 m2 drop in eGFR from baseline was observed in 30%-38% of persons with baseline eGFR ≥60 mL/min/1.73 m2 , but in only 0%-6% with CKD4-5. Grade 3/4 anaemia was more frequent in persons with CKD4-5, but ribavirin co-administration did not appear to affect this. Conclusions SOF/LDV and PrOD achieved high SVR rates in CKD population. Treatment completion rates were lower than expected. A decline in eGFR and development of anaemia were observed in a substantial proportion of persons, but the clinical implications remain unclear.

Background Progression of liver disease and clinical outcomes in HCV/HBV coinfected persons and how they differ from HCV monoinfected persons and HCV infected persons with resolved HBV infection are not well characterized. We compared incidence of cirrhosis, hepatic decompensation and overall mortality in these three groups. Methods Using the Electronically Retrieved Cohort of HCV-infected Veterans (ERCHIVES), we identified those with HCV infection only, HCV/HBV coinfection (HbsAg or HBV DNA or both positive) or HCV with resolved HBV (HbcAb+ in absence of HbsAg or HBV DNA positivity). We excluded those with HIV coinfection or hepatocellular carcinoma at or before baseline, and those who received any HCV or HBV treatment. Incident rates (95% CI) were determined for cirrhosis, first hepatic decompensation event and overall mortality in the three groups. Results We identified 60,368 HCV monoinfected (Gp A), 151 HCV/HBV coinfected (Gp B) and 19,802 HCV infected with resolved HBV infection (Gp C). Mean age was 61.0, 60.9, and 63.0 years in the three groups and 96.5%, 96.0%, and 97.9% were males. Median baseline FIB-4 index was 2.0, 2.2, and 2.1, respectively. Incident cirrhosis (among those without cirrhosis at baseline) was increased 2- to 2.5-fold in HCV/HBV coinfected persons with baseline FIB-4 of 1.46–3.25. Hepatic decompensation and mortality were also increased several-fold in the HCV/HBV coinfected who had minimal or mild/moderate fibrosis at baseline. However, among those with cirrhosis at baseline, the difference was small among HCV/HBV coinfected and the other groups. Conclusion HCV/HBV coinfected persons with minimal or mild/moderate fibrosis at baseline have a much higher risk of developing cirrhosis, hepatic decompensation and mortality. However, once cirrhosis has is established, the difference is diminished. This underscores the need to intervene early when HCV/HBV coinfected persons still have minimal or mild/moderate fibrosis. Disclosures All authors: No reported disclosures.

Background There are scant data regarding hepatitis C (HCV) virologic response to directly acting antiviral agents (DAAs) in chronic hepatitis B (HBV) and HCV coinfected persons. HCV treatment response in those with spontaneously cleared HBV infection is unknown. Methods All HCV-infected persons treated with a DAA regimen in ERCHIVES were identified and categorized into HBV/HCV-coinfected (HBsAg, HBV DNA or both positive), HCV-monoinfected, and resolved HBV (isolated HBcAb+). SVR rates were determined and compared for all groups. A logistic regression model was used to determine factors associated with SVR. Results Among 115 HCV/HBV-coinfected, 38,570 HCV-monoinfected persons, and 13,096 persons with resolved HBV, 31.6% of HCV/HBV-coinfected, 24.6% of HCV-monoinfected and 26.4% with resolved HBV had cirrhosis at baseline. SVR was achieved in 90.4% of HCV/HBV-coinfected, 83.4% of HCV-monoinfected and 84.5% of those with resolved HBV infection (P = 0.04 HCV/HBV vs. HCV monoinfected). In a logistic regression model, those with HCV/HBV were more likely to achieve SVR compared with HCV monoinfected (OR 2.25, 95% CI 1.17, 4.31). For HCV/HBV coinfected, the SVR rates dropped numerically with increasing severity of liver fibrosis (P-value non-significant). Factors associated with a lower likelihood of attaining SVR included cirrhosis at baseline (OR 0.85, 95% CI 0.80, 0.92), diabetes (OR 0.93, 95% CI 0.87, 0.99) and higher pretreatment HCV RNA (OR 0.86, 95% CI 0.84, 0.87). Conclusion HBV/HCV-coinfected persons have higher overall SVR rates with newer DAA regimens. The virologic response is graded, with decreasing SVR rates with increasing degree of liver fibrosis as determined by the FIB-4 scores. Disclosures All authors: No reported disclosures.

We aimed to assess the incidence and progression of chronic kidney disease (CKD) following hepatitis C virus (HCV) seroconversion. This retrospective cohort study included Veterans with a confirmed HCV seroconversion between 2001 and 2014 and Veterans with negative HCV testing over the same time period. The outcomes included development of advanced CKD (eGFR

Author(s): Attia, Engi F; McGinnis, Kathleen A; Feemster, Laura C; Akgun, Kathleen M; Butt, Adeel A; Graber, Christopher J; Fine, Michael J; Goetz, Matthew B; Rodriguez-Barradas, Maria C; Pisani, Margaret A; Tindle, Hilary A; Brown, Sheldon T; Soo Hoo, Guy W; Rimland, David; Gibert, Cynthia L; Huang, Laurence; Freiberg, Matthew S; Hough, Catherine L; Crothers, Kristina | Abstract: BackgroundPulmonary infections remain more common in HIV-infected (HIV+) compared with uninfected individuals. The increase in chronic lung diseases among aging HIV+ individuals may contribute to this persistent risk. We sought to determine whether chronic obstructive pulmonary disease (COPD) is an independent risk factor for different pulmonary infections requiring hospitalization among HIV+ patients.MethodsWe analyzed data from 41,993 HIV+ Veterans in the nationwide Veterans Aging Cohort Study Virtual Cohort from 1996 to 2009. Using International Classification of Diseases, Ninth Revision codes, we identified baseline comorbid conditions, including COPD, and incident community-acquired pneumonia (CAP), pulmonary tuberculosis (TB), and Pneumocystis jirovecii pneumonia (PCP) requiring hospitalization within 2 years after baseline. We used multivariable Poisson regression to determine incidence rate ratios (IRRs) associated with COPD for each type of pulmonary infection, adjusting for comorbidities, CD4 cell count, HIV viral load, smoking status, substance use, vaccinations, and calendar year at baseline.ResultsUnadjusted incidence rates of CAP, TB, and PCP requiring hospitalization were significantly higher among persons with COPD compared to those without COPD (CAP: 53.9 vs. 19.4 per 1000 person-years; TB: 8.7 vs. 2.8; PCP: 15.5 vs. 9.2; P ≤ 0.001). In multivariable Poisson regression models, COPD was independently associated with increased risk of CAP, TB, and PCP (IRR: 1.94, 95% confidence interval [CI]: 1.64 to 2.30; IRR: 2.60, 95% CI: 1.70 to 3.97; and IRR: 1.48, 95% CI: 1.10 to 2.01, respectively).ConclusionsCOPD is an independent risk factor for CAP, TB, and PCP requiring hospitalization among HIV+ individuals. As the HIV+ population ages, the growing burden of COPD may confer substantial risk for pulmonary infections.

We compared the Framingham risk score (FRS) for 10-year coronary heart disease (CHD) risk in age- and race-matched hepatitis C virus (HCV)-infected and HCV-uninfected persons: 114,073 HCV-infected (111,436 HCV-monoinfected and 2,637 HIV/HCV-coinfected) and 122,996 HCV-uninfected (121,380 HIV and HCV-uninfected and 1,616 HIV-monoinfected) males without cardiovascular disease, diabetes, or hepatitis B. In unadjusted analyses, FRS was similar between the HCV-infected and HCV-uninfected groups [median (interquartile range, IQR) risk points 13 (10–14) vs. 13 (10–14), p=0.192]. Cholesterol levels were lower and current smoking more prevalent in the HCV groups (both HCV and HIV/HCV) compared with the uninfected groups (p

Objectives Outcomes of community–acquired pneumonia (CAP) among HIV-infected older adults are unclear. Methods Associations between HIV infection and three CAP outcomes (30-day mortality, readmission within 30 days post-discharge, and hospital length of stay [LOS]) were examined in the Veterans Aging Cohort Study (VACS) of male Veterans, age ≥ 50 years, hospitalized for CAP from 10/1/2002 through 08/31/2010. Associations between the VACS Index and CAP outcomes were assessed in multivariable models. Results Among 117 557 Veterans (36 922 HIV-infected and 80 635 uninfected), 1203 met our eligibility criteria. The 30-day mortality rate was 5.3%, the mean LOS was 7.3 days, and 13.2% were readmitted within 30 days of discharge. In unadjusted analyses, there were no significant differences between HIV-infected and uninfected participants regarding the three CAP outcomes (P > 0.2). A higher VACS Index was associated with increased 30-day mortality, readmission, and LOS in both HIV-infected and uninfected groups. Generic organ system components of the VACS Index were associated with adverse CAP outcomes; HIV-specific components were not. Among HIV-infected participants, those not on antiretroviral therapy (ART) had a higher 30-day mortality (HR 2.94 [95% CI 1.51, 5.72]; P = 0.002) and a longer LOS (slope 2.69 days [95% CI 0.65, 4.73]; P = 0.008), after accounting for VACS Index. Readmission was not associated with ART use (OR 1.12 [95% CI 0.62, 2.00] P = 0.714). Conclusion Among HIV-infected and uninfected older adults hospitalized for CAP, organ system components of the VACS Index were associated with adverse CAP outcomes. Among HIV-infected individuals, ART was associated with decreased 30-day mortality and LOS.