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BackgroundCOVID-19 has disproportionately affected older adults and certain racial and ethnic groups in the United States. Data quantifying the disease burden, as well as describing clinical outcomes during hospitalization among these groups, are needed. ObjectiveWe aimed to describe interim COVID-19 hospitalization rates and severe clinical outcomes by age group and race and ethnicity among US veterans by using a multisite surveillance network. MethodsWe implemented a multisite COVID-19 surveillance platform in 5 Veterans Affairs Medical Centers located in Atlanta, Bronx, Houston, Palo Alto, and Los Angeles, collectively serving more than 396,000 patients annually. From February 27 to July 17, 2020, we actively identified inpatient cases with COVID-19 by screening admitted patients and reviewing their laboratory test results. We then manually abstracted the patients' medical charts for demographics, underlying medical conditions, and clinical outcomes. Furthermore, we calculated hospitalization incidence and incidence rate ratios, as well as relative risk for invasive mechanical ventilation, intensive care unit admission, and case fatality rate after adjusting for age, race and ethnicity, and underlying medical conditions. ResultsWe identified 621 laboratory-confirmed, hospitalized COVID-19 cases. The median age of the patients was 70 years, with 65.7% (408/621) aged ≥65 years and 94% (584/621) male. Most COVID-19 diagnoses were among non-Hispanic Black (325/621, 52.3%) veterans, followed by non-Hispanic White (153/621, 24.6%) and Hispanic or Latino (112/621, 18%) veterans. Hospitalization rates were the highest among veterans who were ≥85 years old, Hispanic or Latino, and non-Hispanic Black (430, 317, and 298 per 100,000, respectively). Veterans aged ≥85 years had a 14-fold increased rate of hospitalization compared with those aged 18-29 years (95% CI: 5.7-34.6), whereas Hispanic or Latino and Black veterans had a 4.6- and 4.2-fold increased rate of hospitalization, respectively, compared with non-Hispanic White veterans (95% CI: 3.6-5.9). Overall, 11.6% (72/621) of the patients required invasive mechanical ventilation, 26.6% (165/621) were admitted to the intensive care unit, and 16.9% (105/621) died in the hospital. The adjusted relative risk for invasive mechanical ventilation and admission to the intensive care unit did not differ by age group or race and ethnicity, but veterans aged ≥65 years had a 4.5-fold increased risk of death while hospitalized with COVID-19 compared with those aged

BackgroundAlthough unhealthy alcohol use is associated with increased morbidity and mortality among people with HIV (PWH), many are ambivalent about engaging in treatment and experience variable responses to treatment. We describe the rationale, aims, and study design for the Financial Incentives, Randomization, with Stepped Treatment (FIRST) Trial, a multi-site randomized controlled efficacy trial.MethodsPWH in care recruited from clinics across the United States who reported unhealthy alcohol use, had a phosphatidylethanol (PEth) >20 ng/mL, and were not engaged in formal alcohol treatment were randomized to integrated contingency management with stepped care versus treatment as usual. The intervention involved two steps; Step 1: Contingency management (n = 5 sessions) with potential rewards based on 1) short-term abstinence; 2) longer-term abstinence; and 3) completion of healthy activities to promote progress in addressing alcohol consumption or conditions potentially impacted by alcohol; Step 2: Addiction physician management (n = 6 sessions) plus motivational enhancement therapy (n = 4 sessions). Participants' treatment was stepped up at week 12 if they lacked evidence of longer-term abstinence. Primary outcome was abstinence at week 24. Secondary outcomes included alcohol consumption (assessed by TLFB and PEth) and the Veterans Aging Cohort Study (VACS) Index 2.0 scores; exploratory outcomes included progress in addressing medical conditions potentially impacted by alcohol. Protocol adaptations due to the COVID-19 pandemic are described.ConclusionsThe FIRST Trial is anticipated to yield insights on the feasibility and preliminary efficacy of integrated contingency management with stepped care to address unhealthy alcohol use among PWH.Clinicaltrialsgov identifier: NCT03089320.

BackgroundDexamethasone decreases mortality in coronavirus disease 2019 (COVID-19) patients on intensive respiratory support (IRS) but is of uncertain benefit if less severely ill. We determined whether early (within 48 h) dexamethasone was associated with mortality in patients hospitalised with COVID-19 not on IRS.MethodsWe included patients admitted to US Veterans Affairs hospitals between 7 June 2020 and 31 May 2021 within 14 days after a positive test for severe acute respiratory syndrome coronavirus 2. Exclusions included recent prior corticosteroids and IRS within 48 h. We used inverse probability of treatment weighting (IPTW) to balance exposed and unexposed groups, and Cox proportional hazards models to determine 90-day all-cause mortality.ResultsOf 19 973 total patients (95% men, median age 71 years, 27% black), 15 404 (77%) were without IRS within 48 h. Of these, 3514 out of 9450 (34%) patients on no oxygen received dexamethasone and 1042 (11%) died; 4472 out of 5954 (75%) patients on low-flow nasal cannula (NC) only received dexamethasone and 857 (14%) died. In IPTW stratified models, patients on no oxygen who received dexamethasone experienced 76% increased risk for 90-day mortality (hazard ratio (HR) 1.76, 95% CI 1.47-2.12); there was no association with mortality among patients on NC only (HR 1.08, 95% CI 0.86-1.36).ConclusionsIn patients hospitalised with COVID-19, early initiation of dexamethasone was common and was associated with no mortality benefit among those on no oxygen or NC only in the first 48 h; instead, we found evidence of potential harm. These real-world findings do not support the use of early dexamethasone in hospitalised COVID-19 patients without IRS.

ObjectiveTobacco use/smoking for epidemiologic studies is often derived from electronic health record (EHR) data, which may be inaccurate. We previously compared smoking from the United States Veterans Health Administration (VHA) EHR clinical reminder data with survey data and found excellent agreement. However, the smoking clinical reminder items changed October 1, 2018. We sought to use the biomarker salivary cotinine (cotinine ≥30) to validate current smoking from multiple sources.Materials and methodsWe included 323 Veterans Aging Cohort Study participants with cotinine, clinical reminder, and self-administered survey smoking data from October 1, 2018 to September 30, 2019. We included International Classification of Disease (ICD)-10 codes F17.21 and Z72.0. Operating characteristics and kappa statistics were calculated.ResultsParticipants were mostly male (96%), African American (75%) and mean age was 63 years. Of those identified as currently smoking based on cotinine, 86%, 85%, and 51% were identified as currently smoking based on clinical reminder, survey, and ICD-10 codes, respectively. Of those identified as not currently smoking based on cotinine, 95%, 97%, and 97% were identified as not currently smoking based on clinical reminder, survey, and ICD-10 codes. Agreement with cotinine was substantial for clinical reminder (kappa = .81) and survey (kappa = .83), but only moderate for ICD-10 (kappa = .50).DiscussionTo determine current smoking, clinical reminder, and survey agreed well with cotinine, whereas ICD-10 codes did not. Clinical reminders could be used in other health systems to capture more accurate smoking information.ConclusionsClinical reminders are an excellent source for self-reported smoking status and are readily available in the VHA EHR.

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;

AbstractChronic obstructive pulmonary disease (COPD) is common in people living with HIV (PLWH). We sought to evaluate the appropriateness of COPD diagnosis and management in PLWH, comparing results to HIV-uninfected persons.We conducted a cross-sectional analysis of Veterans enrolled in the Examinations of HIV-Associated Lung Emphysema study, in which all participants underwent spirometry at enrollment and reported respiratory symptoms on self-completed surveys. Primary outcomes were misdiagnosis and under-diagnosis of COPD, and the frequency and appropriateness of inhaler prescriptions. Misdiagnosis was defined as having an International Classification of Diseases (ICD)-9 diagnosis of COPD without spirometric airflow limitation (post-bronchodilator forced expiratory volume in 1-second [FEV1]/Forced vital capacity [FVC]

BackgroundWe ascertained incidence of opportunistic infections (OIs) in people with human immunodeficiency virus (PWH) with cancer undergoing chemotherapy with non-human immunodeficiency virus (HIV) comparators.MethodsWe identified 2106 PWH and 2981 uninfected Veterans with cancer who received at least 1 dose of chemotherapy between 1996 and 2017 from the Veterans Aging Cohort Study. We ascertained incident OIs within 6 months of chemotherapy amongst zoster, cytomegalovirus, tuberculosis, Candida esophagitis, Pneumocystis jirovecii pneumonia (PCP), toxoplasmosis, Cryptococcosis, atypical Mycobacterium infection, Salmonella bacteremia, histoplasmosis, coccidioidomycosis, or progressive multifocal leukoencephalopathy. We used Poisson methods to calculate OI incidence rates by HIV status, stratifying for hematological and nonhematological tumors. We compared OI rates by HIV status, using inverse probability weights of HIV status, further adjusting for PCP prophylaxis.ResultsWe confirmed 106 OIs in 101 persons. Adjusted OI incidence rate ratios (IRRs) indicated higher risk in PWH for all cancers (IRR, 4.8; 95% confidence interval [CI], 2.8-8.2), hematological cancers (IRR, 8.2; 95% CI, 2.4-27.3), and nonhematological cancers (IRR, 3.9; 95% CI, 2.1-7.2). Incidence rate ratios were not significantly higher in those with CD4 >200 cells/mm3 and viral load 200/mm3.ConclusionsVeterans with HIV undergoing chemotherapy had higher rates of OIs than uninfected Veterans, particularly those with hematological cancers, but not in PWH with HIV controlled disease. Our study does not support systematic PCP prophylaxis in solid tumors in PWH with HIV controlled disease.

ObjectiveTo 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.DesignPropensity 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.MethodsWe 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).ConclusionIn both PWH and uninfected, statin exposure was associated with lower risk of microbial, but not nonmicrobial cancer incidence, and with decreased mortality.

Introduction: Early in the COVID-19 pandemic, the Centers for Disease Control and Prevention (CDC) rapidly initiated COVID-19 surveillance by leveraging existing hospital networks to assess disease burden among hospitalized inpatients and inform prevention efforts. Materials and Methods: The Surveillance Platform for Enteric and Respiratory Infectious Organisms at Veterans Affairs Medical Centers (SUPERNOVA) is a network of five United States Veterans Affairs Medical Centers which serves nearly 400,000 Veterans annually and conducts laboratory-based passive and active monitoring for pathogens associated with acute gastroenteritis and acute respiratory illness among hospitalized Veterans. This paper presents surveillance methods for adapting the SUPERNOVA surveillance platform to prospectively evaluate COVID-19 epidemiology during a public health emergency, including detecting, characterizing, and monitoring patients with and without COVID-19 beginning in March 2020. To allow for case-control analyses, patients with COVID-19 and patients with non-COVID-19 acute respiratory illness were included. Results: SUPERNOVA included 1,235 participants with COVID-19 and 707 participants with other acute respiratory illnesses hospitalized during February through December 2020. Most participants were male (93.1%), with a median age of 70 years, and 45.8% non-Hispanic Black and 32.6% non-Hispanic White. Among those with COVID-19, 28.2% were transferred to an intensive care unit, 9.4% received invasive mechanical ventilation, and 13.9% died. Compared with controls, after adjusting for age, sex, and race/ethnicity, COVID-19 case-patients had significantly higher risk of mortality, respiratory failure, and invasive mechanical ventilation, and longer hospital stays. Discussion: Strengths of the SUPERNOVA platform for COVID-19 surveillance include the ability to collect and integrate multiple types of data, including clinical and illness outcome information, and SARS-CoV-2 laboratory test results from respiratory and serum specimens. Analysis of data from this platform also enables formal comparisons of participants with and without COVID-19. Surveillance data collected during a public health emergency from this key U.S. population of Veterans will be useful for epidemiologic investigations of COVID-19 spectrum of disease, underlying medical conditions, virus variants, and vaccine effectiveness, according to public health priorities and needs.

BackgroundHepatocellular carcinoma (HCC) may develop in the absence of cirrhosis in HIV, and determining how often this occurs can provide insights into mechanisms of carcinogenesis. Studies evaluating the prevalence of cirrhosis in the setting of HCC among people living with HIV (PLWH) often rely on noninvasive markers, such as the Fibrosis-4 Index for Hepatic Fibrosis (FIB-4). However, the accuracy of FIB-4 for cirrhosis in the setting of HCC has not been determined among PLWH.MethodsWe conducted a cross-sectional study among PLWH in the Veterans Aging Cohort Study with VA cancer registry-confirmed HCC diagnosed between 1999 and 2015. FIB-4 was calculated using the age, alanine aminotransferase, aspartate aminotransferase, and platelet count obtained closest to, but within 1 year before, HCC diagnosis. Medical records were reviewed within 1 year before HCC diagnosis to determine the cirrhosis status. We evaluated the area under the receiver-operating characteristic curve and performance characteristics of FIB-4 for confirmed cirrhosis.ResultsIncident HCC was diagnosed in 302 PLWH. After medical record review, 203 (67.2%, 95% confidence interval: 61.6% to 72.5%) had evidence of cirrhosis. FIB-4 identified patients with cirrhosis with an area under the receiver-operating characteristic curve of 0.67 (95% confidence interval: 0.60 to 0.73). FIB-4 scores >5.0 had a positive predictive value >80% and specificity of >77%, negative predictive value of

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.

BackgroundCohort 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.MethodsWe 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.ResultsFive 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

BackgroundDespite increasing incidence of hepatocellular carcinoma (HCC) among HIV-infected patients, it remains unclear if HIV-related factors contribute to development of HCC. We examined if higher or prolonged HIV viremia and lower CD4+ cell percentage were associated with HCC.MethodsWe conducted a cohort study of HIV-infected individuals who had HIV RNA, CD4+, and CD8+ cell counts and percentages assessed in the Veterans Aging Cohort Study (1999-2015). HCC was ascertained using Veterans Health Administration cancer registries and electronic records. Cox regression was used to determine hazard ratios (HR, 95% confidence interval [CI]) of HCC associated with higher current HIV RNA, longer duration of detectable HIV viremia (≥500 copies/mL), and current CD4+ cell percentage less than 14%, adjusting for traditional HCC risk factors. Analyses were stratified by previously validated diagnoses of cirrhosis prior to start of follow-up.ResultsAmong 35 659 HIV-infected patients, 302 (0.8%) developed HCC over 281 441 person-years (incidence rate = 107.3 per 100 000 person-years). Among patients without baseline cirrhosis, higher HIV RNA (HR = 1.25, 95% CI = 1.12 to 1.40, per 1.0 log10 copies/mL) and 12 or more months of detectable HIV (HR = 1.47, 95% CI = 1.02 to 2.11) were independently associated with higher risk of HCC. CD4+ percentage less than 14% was not associated with HCC in any model. Hepatitis C coinfection was a statistically significant predictor of HCC regardless of baseline cirrhosis status.ConclusionAmong HIV-infected patients without baseline cirrhosis, higher HIV RNA and longer duration of HIV viremia increased risk of HCC, independent of traditional HCC risk factors. This is the strongest evidence to date that HIV viremia contributes to risk of HCC in this group.

BackgroundLiver 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.MethodsWe 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

BackgroundNorovirus is an important cause of epidemic acute gastroenteritis (AGE), yet the burden of endemic disease in adults has not been well documented. We estimated the prevalence and incidence of outpatient and community-acquired inpatient norovirus AGE at 4 Veterans Affairs Medical Centers (VAMC) (Atlanta, Georgia; Bronx, New York; Houston, Texas; and Los Angeles, California) and examined trends over 4 surveillance years.MethodsFrom November 2011 to September 2015, stool specimens collected within 7 days of AGE symptom onset for clinician-requested diagnostic testing were tested for norovirus, and positive samples were genotyped. Incidence was calculated by multiplying norovirus prevalence among tested specimens by AGE-coded outpatient encounters and inpatient discharges, and dividing by the number of unique patients served.ResultsOf 1603 stool specimens, 6% tested were positive for norovirus; GII.4 viruses (GII.4 New Orleans [17%] and GII.4 Sydney [47%]) were the most common genotypes. Overall prevalence and outpatient and inpatient community-acquired incidence followed a seasonal pattern, with higher median rates during November-April (9.2%, 376/100 000, and 45/100 000, respectively) compared to May-October (3.0%, 131/100 000, and 13/100 000, respectively). An alternate-year pattern was also detected, with highest peak prevalence and outpatient and inpatient community-acquired norovirus incidence rates in the first and third years of surveillance (14%-25%, 349-613/100 000, and 43-46/100 000, respectively).ConclusionsThis multiyear analysis of laboratory-confirmed AGE surveillance from 4 VAMCs demonstrates dynamic intra- and interannual variability in prevalence and incidence of outpatient and inpatient community-acquired norovirus in US Veterans, highlighting the burden of norovirus disease in this adult population.

BackgroundNorovirus is an important cause of epidemic acute gastroenteritis (AGE), yet the burden of endemic disease in adults has not been well documented. We estimated the prevalence and incidence of outpatient and community-acquired inpatient norovirus AGE at 4 Veterans Affairs Medical Centers (VAMC) (Atlanta, Georgia; Bronx, New York; Houston, Texas; and Los Angeles, California) and examined trends over 4 surveillance years.MethodsFrom November 2011 to September 2015, stool specimens collected within 7 days of AGE symptom onset for clinician-requested diagnostic testing were tested for norovirus, and positive samples were genotyped. Incidence was calculated by multiplying norovirus prevalence among tested specimens by AGE-coded outpatient encounters and inpatient discharges, and dividing by the number of unique patients served.ResultsOf 1603 stool specimens, 6% tested were positive for norovirus; GII.4 viruses (GII.4 New Orleans [17%] and GII.4 Sydney [47%]) were the most common genotypes. Overall prevalence and outpatient and inpatient community-acquired incidence followed a seasonal pattern, with higher median rates during November-April (9.2%, 376/100 000, and 45/100 000, respectively) compared to May-October (3.0%, 131/100 000, and 13/100 000, respectively). An alternate-year pattern was also detected, with highest peak prevalence and outpatient and inpatient community-acquired norovirus incidence rates in the first and third years of surveillance (14%-25%, 349-613/100 000, and 43-46/100 000, respectively).ConclusionsThis multiyear analysis of laboratory-confirmed AGE surveillance from 4 VAMCs demonstrates dynamic intra- and interannual variability in prevalence and incidence of outpatient and inpatient community-acquired norovirus in US Veterans, highlighting the burden of norovirus disease in this adult population.

BackgroundHepatic 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.MethodsWe 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:Inflammation in human immunodeficiency virus (HIV)-infected patients is associated with poorer health outcomes. Whether inflammation as measured by the neutrophil-to-lymphocyte ratio (NLR) and platelet-to-lymphocyte ratio (PLR) adds information to existing prognostic indices is not known. Methods:We analyzed data from 2000 to 2012 in the Veterans Aging Cohort Study (VACS), overall and stratified by HIV/hepatitis C virus status (n = 89 786). We randomly selected a visit date at which all laboratory values of interest were available within 180 days; participants with HIV received at least 1 year of antiretroviral therapy. We followed patients for (1) mortality and (2) hepatic decompensation (HD) and analyzed associations using Cox regression, adjusted for a validated mortality risk index (VACS Index 2.0). In VACS Biomarker Cohort, we considered correlation with biomarkers of inflammation: interleukin-6, D-dimer, and soluble CD-14. Results:Neutrophil-to-lymphocyte ratio and PLR demonstrated strong unadjusted associations with mortality (P < .0001) and HD (P < .0001) and were weakly correlated with other inflammatory biomarkers. Although NLR remained statistically independent for mortality, as did PLR for HD, the addition of NLR and PLR to the VACS Index 2.0 did not result in significant improvement in discrimination compared with VACS Index 2.0 alone for mortality (C-statistic 0.767 vs 0.758) or for HD (C-statistic 0.805 vs 0.801). Conclusions:Neutrophil-to-lymphocyte ratio and PLR were strongly associated with mortality and HD and weakly correlated with inflammatory biomarkers. However, most of their association was explained by VACS Index 2.0. Addition of NLR and PLR to VACS 2.0 did not substantially improve discrimination for either outcome.

ObjectiveLung cancer is the leading cause of cancer death in people living with HIV (PWH). Surgical resection is a key component of potentially curative treatment regimens for early-stage lung cancers, but its safety is unclear in the setting of HIV. From a national cohort, we assessed potential differences in the risk of major lung cancer surgery complications by HIV status.DesignWe linked clinical and cancer data from the Veterans Aging Cohort Study (VACS) and Veterans Affairs Corporate Data Warehouse to outcomes from the Veterans Affairs Surgical Quality Improvement Program (VASQIP) and identified 8371 patients (137 PWH, 8234 uninfected) who underwent lung cancer surgeries between 2000 and 2016.MethodsWe compared rates of 15 major short-term surgical complications by HIV status.ResultsUse of surgical resection for early-stage lung cancer did not differ by HIV status. Lung cancer surgery postoperative (30-day) mortality was 2.0% for PWH and did not differ by HIV status (P = 0.9). Pneumonia was the most common complication for both PWH and uninfected veterans, but did not differ significantly in prevalence between groups (11.0% for PWH versus 9.4%; P = 0.5). The frequency of complications did not differ by HIV status for any complication (all P > 0.3). There were no significant predictors of postoperative complications for PWH.ConclusionsIn a national antiretroviral-era cohort of lung cancer patients undergoing surgical lung resection, short-term outcomes after surgery did not differ significantly by HIV status. Concerns regarding short-term surgical complications should have limited influence on treatment decisions for PWH with lung cancer.

BackgroundHIV, 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.SettingVeterans Health Administration.MethodsAnnual 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.ResultsCompared 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

PurposePharmacoepidemiologic studies using electronic health record data could serve an important role in assessing safety and effectiveness of direct-acting antiviral therapy for chronic hepatitis C virus (HCV) infection, but the validity of these data needs to be determined. We evaluated the accuracy of pharmacy fill records in the national Veterans Health Administration (VA) Corporate Data Warehouse (CDW) as compared to facility-level electronic health record.MethodsPatients prescribed a direct-acting antiviral regimen at five VA sites between 2014 and 2016 were randomly selected and reviewed. A random sample of patients with chronic HCV infection without evidence of HCV treatment during the study period also underwent chart review. We calculated positive predictive value and negative predictive value overall and by site.ResultsOf the 501 patients who received a total of 2416 prescriptions, 494 were validated using data extracted from CDW 6 months after the study period, yielding a positive predictive value of 98.6% (95% confidence interval, 97.6%-99.6%). Of the 100 patients with chronic HCV infection without prescriptions for HCV treatment, 99 were confirmed not to have received antiviral treatment (negative predictive value, 99.0%; 95% confidence interval, 97.1%-100%).ConclusionsThese findings provide assurance to researchers who use national VA CDW data for retrospective cohort studies that the CDW contains accurate information on HCV therapies in the modern treatment era.

BackgroundViral suppression is a primary marker of HIV treatment success. Persons with HIV are at increased risk for AIDS-defining cancer (ADC) and several types of non-AIDS-defining cancer (NADC), some of which are caused by oncogenic viruses.ObjectiveTo determine whether viral suppression is associated with decreased cancer risk.DesignProspective cohort.SettingDepartment of Veterans Affairs.ParticipantsHIV-positive veterans (n = 42 441) and demographically matched uninfected veterans (n = 104 712) from 1999 to 2015.MeasurementsStandardized cancer incidence rates and Poisson regression rate ratios (RRs; HIV-positive vs. uninfected persons) by viral suppression status (unsuppressed: person-time with HIV RNA levels ≥500 copies/mL; early suppression: initial 2 years with HIV RNA levels

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). 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. 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.

OBJECTIVE:Aging people living with HIV (PLWH) face an increased burden of comorbidities, including chronic obstructive pulmonary disease (COPD). The impact of COPD on mortality in HIV remains unclear. We examined associations between markers of COPD and mortality among PLWH and uninfected study participants. DESIGN:Longitudinal analysis of the Examinations of HIV-Associated Lung Emphysema (EXHALE) cohort study. METHODS:EXHALE includes 196 PLWH and 165 uninfected smoking-matched study participants who underwent pulmonary function testing and computed tomography (CT) to define COPD and were followed. We determined associations between markers of COPD with mortality using multivariable Cox regression models, adjusted for smoking and the Veterans Aging Cohort Study (VACS) Index, a validated predictor of mortality in HIV. RESULTS:Median follow-up time was 6.9 years; the mortality rate was 2.7/100 person-years among PLWH and 1.7/100 person-years among uninfected study participants (P = 0.11). The VACS Index was associated with mortality in both PLWH and uninfected study participants. In multivariable models, pulmonary function and CT characteristics defining COPD were associated with mortality in PLWH: those with airflow obstruction (forced expiratory volume in 1 s/ forced vital capacity 10% burden) had 2.4 times the risk of death [hazard ratio 2.4 (95% confidence interval 1.1-5.5)] compared with those with ≤ 10% emphysema. In uninfected subjects, pulmonary variables were not significantly associated with mortality, which may reflect fewer deaths limiting power. CONCLUSION:Markers of COPD were associated with greater mortality in PWLH, independent of the VACS Index. COPD is likely an important contributor to mortality in contemporary PLWH.

BackgroundPatients with human immunodeficiency virus (HIV) and/or chronic hepatitis C virus (HCV) infection may be prescribed statins as treatment for metabolic/cardiovascular disease, but it remains unclear if the risk of acute liver injury (ALI) is increased for statin initiators compared to nonusers in groups classified by HIV/HCV status.MethodsWe conducted a cohort study to compare rates of ALI in statin initiators vs nonusers among 7686 HIV/HCV-coinfected, 8155 HCV-monoinfected, 17739 HIV-monoinfected, and 36604 uninfected persons in the Veterans Aging Cohort Study (2000-2012). We determined development of (1) liver aminotransferases >200 U/L, (2) severe ALI (coagulopathy with hyperbilirubinemia), and (3) death, all within 18 months. Cox regression was used to determine propensity score-adjusted hazard ratios (HRs) with 95% confidence intervals (CIs) of outcomes in statin initiators compared to nonusers across the groups.ResultsAmong HIV/HCV-coinfected patients, statin initiators had lower risks of aminotransferase levels >200 U/L (HR, 0.66 [95% CI, .53-.83]), severe ALI (HR, 0.23 [95% CI, .12-.46]), and death (HR, 0.36 [95% CI, .28-.46]) compared with statin nonusers. In the setting of chronic HCV alone, statin initiators had reduced risks of aminotransferase elevations (HR, 0.57 [95% CI, .45-.72]), severe ALI (HR, 0.15 [95% CI, .06-.37]), and death (HR, 0.42 [95% CI, .32-.54]) than nonusers. Among HIV-monoinfected patients, statin initiators had lower risks of aminotransferase increases (HR, 0.52 [95% CI, .40-.66]), severe ALI (HR, 0.26 [95% CI, .13-.55]), and death (HR, 0.19 [95% CI, .16-.23]) compared with nonusers. Results were similar among uninfected persons.ConclusionsRegardless of HIV and/or chronic HCV status, statin initiators had a lower risk of ALI and death within 18 months compared with statin nonusers.

Liver fibrosis is common, particularly in individuals who are infected with human immunodeficiency virus (HIV). HIV-infected individuals have excess congestive heart failure (CHF) risk compared with uninfected people. It remains unknown whether liver fibrosis stage influences the CHF risk or if HIV or hepatitis C virus (HCV) infection modifies this association. Our objectives were to assess whether 1) stage of liver fibrosis is independently associated with incident CHF and 2) the association between stage of liver fibrosis and incident CHF is modified by HIV/HCV status. Participants alive on or after April 1, 2003, in the Veterans Aging Cohort Study were included. Those without prevalent cardiovascular disease were followed until their first CHF event, death, last follow-up date, or December 31, 2011. Liver fibrosis was measured using the fibrosis 4 index (FIB-4), which is calculated using age, aminotransferases, and platelets. Cox proportional hazards regression models were adjusted for cardiovascular disease risk factors. Among 96,373 participants over 6.9 years, 3844 incident CHF events occurred. FIB-4 between 1.45 and 3.25 (moderate fibrosis) and FIB-4 > 3.25 (advanced fibrosis/cirrhosis) were associated with CHF (hazard ratio [95% confidence interval], 1.17 [1.07-1.27] and 1.65 [1.43-1.92], respectively). The association of advanced fibrosis/cirrhosis and incident CHF persisted regardless of HIV/HCV status.ConclusionModerate and advanced liver fibrosis/cirrhosis are associated with an increased risk of CHF. The association for advanced fibrosis/cirrhosis persists even among participants without hepatitis C and/or HIV infection. Assessing liver health may be important for reducing the risk of future CHF events, particularly among HIV and hepatitis C infected people among whom cardiovascular disease risk is elevated and liver disease is common. (Hepatology 2017;66:1286-1295).

ObjectivesObesity prevalence among people living with HIV (HIV+) is rising. HIV and obesity are proinflammatory states, but their combined effect on inflammation (measured by interleukin 6, IL-6), altered coagulation (D-dimer), and monocyte activation (soluble CD14, sCD14) is unknown. We hypothesized inflammation increases when obesity and HIV infection co-occur.MethodsThe Veterans Aging Cohort Study survey cohort is a prospective, observational study of predominantly male HIV+ veterans and veterans uninfected with HIV; a subset provided blood samples. Inclusion criteria for this analysis were body mass index ≥ 18.5 kg/m and biomarker measurement. Dependent variables were IL-6, sCD14, and D-dimer quartiles. Obesity/HIV status was the primary predictor. Unadjusted and adjusted logistic regression models were constructed.ResultsData were analyzed for 1477 HIV+ and 823 uninfected participants. Unadjusted median IL-6 levels were significantly higher and sCD14 levels significantly lower in obese/HIV+ compared with nonobese/uninfected (P

BackgroundHIV infection is independently associated with risk of lung cancer, but few data exist for the relation between longitudinal measurements of immune function and lung-cancer risk in people living with HIV.MethodsWe followed up participants with HIV from the Veterans Aging Cohort Study for a minimum of 3 years between Jan 1, 1998, and Dec 31, 2012, and used cancer registry data to identify incident cases of lung cancer. The index date for each patient was the later of the date HIV care began or Jan 1, 1998. We excluded patients with less than 3 years' follow-up, prevalent diagnoses of lung cancer, or incomplete laboratory data. We used Cox regression models to investigate the relation between different time-updated lagged and cumulative exposures (CD4 cell count, CD8 cell count, CD4/CD8 ratio, HIV RNA, and bacterial pneumonia) and risk of lung cancer. Models were adjusted for age, race or ethnicity, smoking, hepatitis C virus infection, alcohol use disorders, drug use disorders, and history of chronic obstructive pulmonary disease and occupational lung disease.FindingsWe identified 277 cases of incident lung cancer in 21 666 participants with HIV. In separate models for each time-updated 12 month lagged, 24 month simple moving average cumulative exposure, increased risk of lung cancer was associated with low CD4 cell count (p trend=0·001), low CD4/CD8 ratio (p trend=0·0001), high HIV RNA concentration (p=0·004), and more cumulative bacterial pneumonia episodes (12 month lag only; p trend=0·0004). In a mutually adjusted model including these factors, CD4/CD8 ratio and cumulative bacterial pneumonia episodes remained significant (p trends 0·003 and 0·004, respectively).InterpretationIn our large HIV cohort in the antiretroviral therapy era, we found evidence that dysfunctional immune activation and chronic inflammation contribute to the development of lung cancer in the setting of HIV infection. These findings could be used to target lung-cancer prevention measures to high-risk groups.FundingUS National Institutes of Health.

Background After adjustment for cardiovascular risk factors and despite higher mortality, those with human immunodeficiency virus (HIV+) have a greater risk of acute myocardial infarction (AMI) than uninfected individuals.Methods We included HIV+ individuals who started combination antiretroviral therapy (cART) in the Veterans Aging Cohort Study (VACS) from 1996 to 2012. We fit multivariable proportional hazards models for baseline, time-updated and cumulative measures of HIV-1 RNA, CD4 counts, and the VACS Index. We used the trapezoidal rule to build the following cumulative measures: viremia copy-years, CD4-years, and VACS Index score-years, captured 180 days after cART initiation until AMI, death, last clinic visit, or 30 September 2012. The primary outcomes were incident AMI (Medicaid, Medicare, and Veterans Affairs International Classification of Diseases-9 codes) and death.Results A total of 8168 HIV+ individuals (53 861 person-years) were analyzed with 196 incident AMIs and 1710 deaths. Controlling for known cardiovascular risk factors, 6 of the 9 metrics predicted AMI and all metrics predicted mortality. Time-updated VACS Index had the lowest Akaike information criterion among all models for both outcomes. A time-updated VACS Index score of 55+ was associated with a hazard ratio (HR) of 3.31 (95% confidence interval [CI], 2.11-5.20) for AMI and a HR of 31.77 (95% CI, 26.17-38.57) for mortality.Conclusions Time-updated VACS Index provided better AMI and mortality prediction than CD4 count and HIV-1 RNA, suggesting that current health determines risk more accurately than prior history and that risk assessment can be improved by biomarkers of organ injury.

ObjectiveUtilizing the Veterans Aging Cohort Study, the largest HIV cohort in North America, we conducted one of the few comprehensive comparisons of cancer incidence time trends in HIV-infected (HIV+) versus uninfected persons during the antiretroviral therapy (ART) era.DesignProspective cohort study.MethodsWe followed 44 787 HIV+ and 96 852 demographically matched uninfected persons during 1997-2012. We calculated age-, sex-, and race/ethnicity-standardized incidence rates and incidence rate ratios (IRR, HIV+ versus uninfected) over four calendar periods with incidence rate and IRR period trend P values for cancer groupings and specific cancer types.ResultsWe observed 3714 incident cancer diagnoses in HIV+ and 5760 in uninfected persons. The HIV+ all-cancer crude incidence rate increased between 1997-2000 and 2009-2012 (P trend = 0.0019). However, after standardization, we observed highly significant HIV+ incidence rate declines for all cancer (25% decline; P trend

BackgroundHIV 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.MethodsAmong 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.ResultsDuring 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).ConclusionsHIV 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.

HIV+/HCV+ persons with isolated HBcAb have a higher prevalence of advanced fibrosis than persons who are non-immune to HBV, who have resolved HBV, or who are HbsAb+ only.

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.

BackgroundBoth HIV and depression are associated with increased heart failure (HF) risk. Depression, a common comorbidity, may further increase the risk of HF among adults with HIV infection (HIV+). We assessed the association between HIV, depression, and incident HF.Methods and resultsVeterans Aging Cohort Study (VACS) participants free from cardiovascular disease at baseline (n=81 427: 26 908 HIV+, 54 519 without HIV [HIV-]) were categorized into 4 groups: HIV- without major depressive disorder (MDD) [reference], HIV- with MDD, HIV+ without MDD, and HIV+ with MDD. International Classification of Diseases, Ninth Revision codes from medical records were used to determine MDD and the primary outcome, HF. After 5.8 years of follow-up, HF rates per 1000 person-years were highest among HIV+ participants with MDD (9.32; 95% confidence interval [CI], 8.20-10.6). In Cox proportional hazards models, HIV+ participants with MDD had a significantly higher risk of HF (adjusted hazard ratio, 1.68; 95% CI, 1.45-1.95) compared with HIV- participants without MDD. MDD was associated with HF in separate fully adjusted models for HIV- and HIV+ participants (adjusted hazard ratio, 1.21; 95% CI, 1.06-1.37; and adjusted hazard ratio, 1.29; 95% CI, 1.11-1.51, respectively). Among those with MDD, baseline antidepressant use was associated with lower risk of incident HF events (adjusted hazard ratio, 0.76; 95% CI, 0.58-0.99).ConclusionsOur study is the first to suggest that MDD is an independent risk factor for HF in HIV+ adults. These results reinforce the importance of identifying and managing MDD among HIV+ patients. Future studies must clarify mechanisms linking HIV, MDD, antidepressants, and HF and identify interventions to reduce HF morbidity and mortality in those with both HIV and MDD.

Background.  End-stage liver disease (ESLD) is an important cause of morbidity among human immunodeficiency virus (HIV)/hepatitis C virus (HCV)-coinfected patients. Quantifying the risk of this outcome over time could help determine which coinfected patients should be targeted for risk factor modification and HCV treatment. We evaluated demographic, clinical, and laboratory variables to predict risk of ESLD in HIV/HCV-coinfected patients receiving antiretroviral therapy (ART). Methods.  We conducted a retrospective cohort study among 6016 HIV/HCV-coinfected patients who received ART within the Veterans Health Administration between 1997 and 2010. The main outcome was incident ESLD, defined by hepatic decompensation, hepatocellular carcinoma, or liver-related death. Cox regression was used to develop prognostic models based on baseline demographic, clinical, and laboratory variables, including FIB-4 and aspartate aminotransferase-to-platelet ratio index, previously validated markers of hepatic fibrosis. Model performance was assessed by discrimination and decision curve analysis. Results.  Among 6016 HIV/HCV patients, 532 (8.8%) developed ESLD over a median of 6.6 years. A model comprising FIB-4 and race had modest discrimination for ESLD (c-statistic, 0.73) and higher net benefit than alternative strategies of treating no or all coinfected patients at relevant risk thresholds. For FIB-4 >3.25, ESLD risk ranged from 7.9% at 1 year to 26.0% at 5 years among non-blacks and from 2.4% at 1 year to 14.0% at 5 years among blacks. Conclusions.  Race and FIB-4 provided important predictive information on ESLD risk among HIV/HCV patients. Estimating risk of ESLD using these variables could help direct HCV treatment decisions among HIV/HCV-coinfected patients.

Background.  End-stage liver disease (ESLD) is an important cause of morbidity among human immunodeficiency virus (HIV)/hepatitis C virus (HCV)-coinfected patients. Quantifying the risk of this outcome over time could help determine which coinfected patients should be targeted for risk factor modification and HCV treatment. We evaluated demographic, clinical, and laboratory variables to predict risk of ESLD in HIV/HCV-coinfected patients receiving antiretroviral therapy (ART). Methods.  We conducted a retrospective cohort study among 6016 HIV/HCV-coinfected patients who received ART within the Veterans Health Administration between 1997 and 2010. The main outcome was incident ESLD, defined by hepatic decompensation, hepatocellular carcinoma, or liver-related death. Cox regression was used to develop prognostic models based on baseline demographic, clinical, and laboratory variables, including FIB-4 and aspartate aminotransferase-to-platelet ratio index, previously validated markers of hepatic fibrosis. Model performance was assessed by discrimination and decision curve analysis. Results.  Among 6016 HIV/HCV patients, 532 (8.8%) developed ESLD over a median of 6.6 years. A model comprising FIB-4 and race had modest discrimination for ESLD (c-statistic, 0.73) and higher net benefit than alternative strategies of treating no or all coinfected patients at relevant risk thresholds. For FIB-4 >3.25, ESLD risk ranged from 7.9% at 1 year to 26.0% at 5 years among non-blacks and from 2.4% at 1 year to 14.0% at 5 years among blacks. Conclusions.  Race and FIB-4 provided important predictive information on ESLD risk among HIV/HCV patients. Estimating risk of ESLD using these variables could help direct HCV treatment decisions among HIV/HCV-coinfected patients.

ObjectiveTo determine predictors and variations in the rate of newly diagnosed HIV infection among persons who underwent routine (ie, non-risk based) rather than risk-based HIV testing in Veterans Health Administration (VHA) facilities.MethodsRetrospective observational study of the HIV infection new rates during the period when VHA policy called for routine (2009-2012) versus risk-based (2006-2009) HIV testing. Source data for testing results at 18 VHA facilities were obtained from the VHA National Corporate Data Warehouse.ResultsNew HIV diagnoses were established in 0.14% (95% confidence interval (CI): 0.12 to 0.46) of the 210,957 patients tested in the routine testing period versus 0.46% (95% CI: 0.42 to 1.29) of the 89,652 patients tested in the risk-based testing period. Among persons aged 65-74 years and 75 years or older, the new diagnosis rates were 0.07% (95% CI: 0.04 to 0.09) and 0.02% (95% CI: 0.00 to 0.03), respectively, and thus less than the generally accepted cost-effective threshold of 0.10%. Among African Americans, the upper bound of the 95% CI of the crude rate of new diagnoses during the routine-testing period was greater than 0.1% across all age strata. When assessed by year of testing, the adjusted rates of new diagnoses fell from 0.20% in 2010 to 0.10% in 2012.ConclusionsRoutine HIV testing is cost-effective among persons younger than 65 years. Among older patients, risk-based testing may be a more efficient and cost-effective approach. This will be increasingly relevant if rates of new HIV diagnoses in persons undergoing routine testing continue to decrease.

ObjectiveGiven conflicting data regarding the association of HIV infection and ischemic stroke risk, we sought to determine whether HIV infection conferred an increased ischemic stroke risk among male veterans.MethodsThe Veterans Aging Cohort Study-Virtual Cohort consists of HIV-infected and uninfected veterans in care matched (1:2) for age, sex, race/ethnicity, and clinical site. We analyzed data on 76,835 male participants in the Veterans Aging Cohort Study-Virtual Cohort who were free of baseline cardiovascular disease. We assessed demographics, ischemic stroke risk factors, comorbid diseases, substance use, HIV biomarkers, and incidence of ischemic stroke from October 1, 2003, to December 31, 2009.ResultsDuring a median follow-up period of 5.9 (interquartile range 3.5-6.6) years, there were 910 stroke events (37.4% HIV-infected). Ischemic stroke rates per 1,000 person-years were higher for HIV-infected (2.79, 95% confidence interval 2.51-3.10) than for uninfected veterans (2.24 [2.06-2.43]) (incidence rate ratio 1.25 [1.09-1.43]; p < 0.01). After adjusting for demographics, ischemic stroke risk factors, comorbid diseases, and substance use, the risk of ischemic stroke was higher among male veterans with HIV infection compared with uninfected veterans (hazard ratio 1.17 [1.01-1.36]; p = 0.04).ConclusionsHIV infection is associated with an increased ischemic stroke risk among HIV-infected compared with demographically and behaviorally similar uninfected male veterans.

BackgroundTraditional cardiovascular disease risk factors (CVDRFs) increase the risk of acute myocardial infarction (AMI) among HIV-infected (HIV+) participants. We assessed the association between HIV and incident AMI within CVDRF strata.MethodsCohort-81,322 participants (33% HIV+) without prevalent CVD from the Veterans Aging Cohort Study Virtual Cohort (prospective study of HIV+ and matched HIV- veterans) participated in this study. Veterans were followed from first clinical encounter on/after April 1, 2003, until AMI/death/last follow-up date (December 31, 2009). Predictors-HIV, CVDRFs (total cholesterol, cholesterol-lowering agents, blood pressure, blood pressure medication, smoking, diabetes) used to create 6 mutually exclusive profiles: all CVDRFs optimal, 1+ nonoptimal CVDRFs, 1+ elevated CVDRFs, and 1, 2, 3+ major CVDRFs. Outcome-Incident AMI [defined using enzyme, electrocardiogram (EKG) clinical data, 410 inpatient ICD-9 (Medicare), and/or death certificates]. Statistics-Cox models adjusted for demographics, comorbidity, and substance use.ResultsOf note, 858 AMIs (42% HIV+) occurred over 5.9 years (median). Prevalence of optimal cardiac health was

Human Immunodeficiency Virus- (HIV-) infected persons have a higher risk for acute myocardial infarction (AMI) than HIV-uninfected persons. Earlier studies suggest that HIV viral load, CD4+ T-cell count, and antiretroviral therapy are associated with cardiovascular disease (CVD) risk. Whether CD8+ T-cell count is associated with CVD risk is not clear. We investigated the association between CD8+ T-cell count and incident AMI in a cohort of 73,398 people (of which 97.3% were men) enrolled in the U.S. Veterans Aging Cohort Study-Virtual Cohort (VACS-VC). Compared to uninfected people, HIV-infected people with high baseline CD8+ T-cell counts (>1065 cells/mm3) had increased AMI risk (adjusted HR=1.82, P