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PurposeThe risk of prostate cancer among persons living with human immunodeficiency virus (PWH) is not well understood and may be obscured by different opportunities for detection.Materials and methodsWe identified 123,472 (37,819 PWH and 85,653 comparators) men enrolled in the Veterans Aging Cohort Study, a prospective national cohort of PWH and demographically matched, uninfected comparators in 2000-2015. We calculated rates of prostate specific antigen (PSA) testing by human immunodeficiency virus (HIV) status and fit multivariable Poisson models comparing the rates of PSA testing, prostate biopsy, and cancer incidence.ResultsThe mean age at enrollment was 52 years. Rates of PSA testing were lower in PWH versus uninfected comparators (0.58 versus 0.63 tests per person-year). Adjusted rates of PSA screening and prostate biopsy were lower among PWH (incidence rate ratio [IRR] 0.87, 95% CI 0.75-0.84 and IRR 0.79 95% CI 0.74-0.83, respectively). The crude IRR for prostate cancer was lower in PWH versus controls (IRR 0.90, 95% CI 0.83-0.97). However, in a multivariable model adjusting for PSA testing, cancer incidence was similar by HIV status (IRR=0.93, 95% CI 0.86-1.01, p=0.08). Among patients who received a prostate biopsy, incidence of prostate cancer did not differ significantly by HIV status (IRR 1.06, 95% CI 0.98-1.15, p=0.15). Among incident cancers, there were significant differences in the distributions of Gleason grade (p=0.05), but not cancer stage (p=0.14) by HIV status.ConclusionsWhen accounting for less PSA testing among PWH, the incidence of prostate cancer was similar by HIV status. These findings suggest that less screening contributed to lower observed incidence of prostate cancer in PWH.

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;

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.

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

OBJECTIVE: Lung 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. DESIGN: We 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. METHODS: We compared rates of 15 major short-term surgical complications by HIV status. RESULTS: Use 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. CONCLUSIONS: In 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.

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.

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 129 140 eligible participants, 30% had HIV infection, 16% had a major depressive disorder diagnosis, and 24% died over a median follow-up time of 11 years. 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% CI 1.01, 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 12 years. 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.

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.

BACKGROUND: Viral 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. OBJECTIVE: To determine whether viral suppression is associated with decreased cancer risk. DESIGN: Prospective cohort. SETTING: Department of Veterans Affairs. PARTICIPANTS: HIV-positive veterans (n = 42 441) and demographically matched uninfected veterans (n = 104 712) from 1999 to 2015. MEASUREMENTS: Standardized 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

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

RationaleThe epidemiology and prognostic impact of increased pulmonary pressure among HIV-infected individuals in the antiretroviral therapy era is not well described.ObjectivesTo examine the prevalence, clinical features, and outcomes of increased echocardiographic pulmonary pressure in HIV-infected and -uninfected individuals.MethodsThis study evaluated 8,296 veterans referred for echocardiography with reported pulmonary artery systolic pressure (PASP) estimates from the Veterans Aging Cohort study, an observational cohort of HIV-infected and -uninfected veterans matched by age, sex, race/ethnicity, and clinical site. The primary outcome was adjusted mortality by HIV status.Measurements and main resultsPASP was reported in 2,831 HIV-infected and 5,465 HIV-uninfected veterans (follow-up [mean ± SD], 3.8 ± 2.6 yr). As compared with uninfected veterans, HIV-infected veterans with HIV viral load greater than 500 copies/ml (odds ratio, 1.27; 95% confidence interval [CI], 1.05-1.54) and those with CD4 cell count less than 200 cells/μl (odds ratio, 1.28; 95% CI, 1.02-1.60) had a higher prevalence of PASP greater than or equal to 40 mm Hg. As compared with uninfected veterans with a PASP less than 40 mm Hg, HIV-infected veterans with a PASP greater than or equal to 40 mm Hg had an increased risk of death (adjusted hazard ratio, 1.78; 95% CI, 1.57-2.01). This risk persisted even among participants without prevalent comorbidities (adjusted hazard ratio, 3.61; 95% CI, 2.17-6.01). The adjusted risk of mortality in HIV-infected veterans was higher at all PASP values than in uninfected veterans, including at values currently considered to be normal.ConclusionsHIV-infected people with high HIV viral loads or low CD4 cell counts have a higher prevalence of increased PASP than uninfected people. Mortality risk in HIV-infected veterans increases at lower values of PASP than previously recognized and is present even among those without prevalent comorbidities. These findings may inform clinical decision-making regarding screening and surveillance of pulmonary hypertension in HIV-infected individuals.

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

ImportanceWith improved survival, heart failure (HF) has become a major complication for individuals with human immunodeficiency virus (HIV) infection. It is unclear if this risk extends to different types of HF in the antiretroviral therapy (ART) era. Determining whether HIV infection is associated with HF with reduced ejection fraction (HFrEF), HF with preserved ejection fraction (HFpEF), or both is critical because HF types differ with respect to underlying mechanism, treatment, and prognosis.ObjectivesTo investigate whether HIV infection increases the risk of future HFrEF and HFpEF and to assess if this risk varies by sociodemographic and HIV-specific factors.Design, setting, and participantsThis study evaluated 98 015 participants without baseline cardiovascular disease from the Veterans Aging Cohort Study, an observational cohort of HIV-infected veterans and uninfected veterans matched by age, sex, race/ethnicity, and clinical site, enrolled on or after April 1, 2003, and followed up through September 30, 2012. The dates of the analysis were October 2015 to November 2016.ExposureHuman immunodeficiency virus infection.Main outcomes and measuresOutcomes included HFpEF (EF≥50%), borderline HFpEF (EF 40%-49%), HFrEF (EF

BACKGROUND: HIV 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. METHODS: We 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. FINDINGS: We 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). INTERPRETATION: In 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. FUNDING: US 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.

ImportanceWith the advent of highly effective antiretroviral therapy and improved survival, human immunodeficiency virus (HIV)-infected people are living longer and are now at an increased risk for cardiovascular disease (CVD). There is an urgent need to identify novel risk factors and primary prevention approaches for CVD in HIV. Although depression is prevalent in HIV-infected adults and is associated with future CVD in the general population, its association with CVD events has not been examined in the HIV-infected population.ObjectiveTo examine whether depressive disorders are prospectively associated with incident acute myocardial infarction (AMI) in a large cohort of adults with HIV.Design, setting, and participantsIncluded in this cohort study were 26 144 HIV-infected veterans without CVD at baseline (1998-2003) participating in the US Department of Veterans Affairs Veterans Aging Cohort Study from April 1, 2003, through December 31, 2009. At baseline, 4853 veterans (19%) with major depressive disorder (MDD; International Classification of Diseases, Ninth Revision [ICD-9] codes 296.2 and 296.3) and 2296 (9%) with dysthymic disorder (ICD-9 code 300.4) were identified. The current analysis was conducted from January 2015 to November 2015.Main outcomes and measuresIncident AMI (defined by discharge summary documentation, enzyme/electrocardiography evidence of AMI, inpatient ICD-9 code for AMI (410), or AMI as underlying cause of death [International Statistical Classification of Diseases and Related Health Problems, Tenth Revision code 121]) between the enrollment date and December 31, 2009.ResultsThe mean (SD) age of those with MDD was 47.3 (7.9) years and for those without MDD was 48.2 (9.7) years. During 5.8 years of follow-up, 490 AMI events (1.9%) occurred. Baseline MDD was associated with incident AMI after adjusting for demographics (hazard ratio [HR], 1.31; 95% CI, 1.05-1.62), CVD risk factors (HR, 1.29; 95% CI, 1.04-1.60), and HIV-specific factors (HR, 1.30; 95% CI, 1.05-1.62). Further adjustment for hepatitis C, renal disease, substance abuse, and hemoglobin level (HR, 1.25; 95% CI, 1.00-1.56) and antidepressant use (HR, 1.12; 95% CI, 0.87-1.42) attenuated associations. Baseline dysthymic disorder was not associated with incident AMI.Conclusions and relevanceWe report novel evidence that HIV-infected adults with MDD have a 30% increased risk for AMI than HIV-infected adults without MDD after adjustment for many potential confounders. Our findings raise the possibility that MDD may be independently associated with incident atherosclerotic CVD in the HIV-infected population.

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.

BACKGROUND:The Patient Protection and Affordable Care Act encourages healthcare systems to track quality-of-care measures; little is known about their impact on mortality rates. The objective of this study was to assess associations between HIV quality of care and mortality rates. METHODS:A longitudinal survival analysis of the Veterans Aging Cohort Study included 3038 human immunodeficiency virus (HIV)-infected patients enrolled between June 2002 and July 2008. The independent variable was receipt of ≥80% of 9 HIV quality indicators (QIs) abstracted from medical records in the 12 months after enrollment. Overall mortality rates through 2014 were assessed from the Veterans Health Administration, Medicare, and Social Security National Death Index records. We assessed associations between receiving ≥80% of HIV QIs and mortality rates using Kaplan-Meier survival analysis and adjusted Cox proportional hazards models. Results were stratified by unhealthy alcohol and illicit drug use. RESULTS:The majority of participants were male (97.5%) and black (66.8%), with a mean (standard deviation) age of 49.0 (8.8) years. Overall, 25.9% reported past-year unhealthy alcohol use and 28.4% reported past-year illicit drug use. During 24 805 person-years of follow-up (mean [standard deviation], 8.2 [3.3] years), those who received ≥80% of QIs experienced lower age-adjusted mortality rates (adjusted hazard ratio, 0.75; 95% confidence interval, .65-.86). Adjustment for disease severity attenuated the association. CONCLUSIONS:Receipt of ≥80% of select HIV QIs is associated with improved survival in a sample of predominantly male, black, HIV-infected patients but was insufficient to overcome adjustment for disease severity. Interventions to ensure high-quality care and address underlying chronic illness may improve survival in HIV-infected patients.

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.

OBJECTIVES:Community viral load (CVL) estimates vary based on analytic methods. We extended the CVL concept and used data from the Veterans Health Administration (VA) to determine trends in the health care system viral load (HSVL) and its sensitivity to varying definitions of the clinical population and assumptions regarding missing data. METHODS:We included HIV-infected patients in the Veterans Aging Cohort Study, 2000-2010, with at least one documented CD4 count, HIV-1 RNA or antiretroviral prescription (n = 37 318). We created 6-month intervals including patients with at least one visit in the past 2 years. We assessed temporal trends in clinical population size, patient clinical status and mean HSVL and explored the impact of varying definitions of the clinical population and assumptions about missing viral load. RESULTS:The clinical population size varied by definition, increasing from 16 000-19 000 patients in 2000 to 23 000-26 000 in 2010. The proportion of patients with suppressed HIV-1 RNA increased over time. Over 20% of patients had no viral load measured in a given interval or the past 2 years. Among patients with a current HIV-1 RNA, mean HSVL decreased from 97 800 HIV-1 RNA copies/mL in 2000 to 2000 copies/mL in 2010. When current HIV-1 RNA data were unavailable and the HSVL was recalculated using the last available HIV-1 RNA, HSVL decreased from 322 300 to 9900 copies/mL. HSVL was underestimated when using only current data in each interval. CONCLUSIONS:The CVL concept can be applied to a health care system, providing a measure of health care quality. Like CVL, HSVL estimates depend on definitions of the clinical population and assumptions about missing data.

OBJECTIVES:Community viral load (CVL) estimates vary based on analytic methods. We extended the CVL concept and used data from the Veterans Health Administration (VA) to determine trends in the health care system viral load (HSVL) and its sensitivity to varying definitions of the clinical population and assumptions regarding missing data. METHODS:We included HIV-infected patients in the Veterans Aging Cohort Study, 2000-2010, with at least one documented CD4 count, HIV-1 RNA or antiretroviral prescription (n = 37 318). We created 6-month intervals including patients with at least one visit in the past 2 years. We assessed temporal trends in clinical population size, patient clinical status and mean HSVL and explored the impact of varying definitions of the clinical population and assumptions about missing viral load. RESULTS:The clinical population size varied by definition, increasing from 16 000-19 000 patients in 2000 to 23 000-26 000 in 2010. The proportion of patients with suppressed HIV-1 RNA increased over time. Over 20% of patients had no viral load measured in a given interval or the past 2 years. Among patients with a current HIV-1 RNA, mean HSVL decreased from 97 800 HIV-1 RNA copies/mL in 2000 to 2000 copies/mL in 2010. When current HIV-1 RNA data were unavailable and the HSVL was recalculated using the last available HIV-1 RNA, HSVL decreased from 322 300 to 9900 copies/mL. HSVL was underestimated when using only current data in each interval. CONCLUSIONS:The CVL concept can be applied to a health care system, providing a measure of health care quality. Like CVL, HSVL estimates depend on definitions of the clinical population and assumptions about missing data.

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

BACKGROUND: HIV infection is associated with increased risk of cardiovascular disease (CVD) in men. Whether HIV is an independent risk factor for CVD in women has not yet been established. METHODS AND RESULTS: We analyzed data from the Veterans Aging Cohort Study on 2187 women (32% HIV infected [HIV(+)]) who were free of CVD at baseline. Participants were followed from their first clinical encounter on or after April 01, 2003 until a CVD event, death, or the last follow-up date (December 31, 2009). The primary outcome was CVD (acute myocardial infarction [AMI], unstable angina, ischemic stroke, and heart failure). CVD events were defined using clinical data, International Classification of Diseases, Ninth Revision, Clinical Modification codes, and/or death certificate data. We used Cox proportional hazards models to assess the association between HIV and incident CVD, adjusting for age, race/ethnicity, lipids, smoking, blood pressure, diabetes, renal disease, obesity, hepatitis C, and substance use/abuse. Median follow-up time was 6.0 years. Mean age at baseline of HIV(+) and HIV uninfected (HIV(-)) women was 44.0 versus 43.2 years (P

BackgroundIt is unclear if the risk of liver disease associated with different levels of alcohol consumption is higher for patients infected with human immunodeficiency virus (HIV) or chronic hepatitis C virus (HCV). We evaluated associations between alcohol use categories and advanced hepatic fibrosis, by HIV and chronic HCV status.MethodsWe performed a cross-sectional study among participants in the Veterans Aging Cohort Study who reported alcohol consumption at enrollment (701 HIV/HCV-coinfected; 1410 HIV-monoinfected; 296 HCV-monoinfected; 1158 HIV/HCV-uninfected). Alcohol use category was determined by the Alcohol Use Disorders Identification Test-Consumption (AUDIT-C) questionnaire and alcohol-related diagnoses and was classified as nonhazardous drinking, hazardous/binge drinking, or alcohol-related diagnosis. Advanced hepatic fibrosis was defined by FIB-4 index >3.25.ResultsWithin each HIV/HCV group, the prevalence of advanced hepatic fibrosis increased as alcohol use category increased. For each alcohol use category, advanced hepatic fibrosis was more common among HIV-infected than uninfected (nonhazardous: 6.7% vs 1.4%; hazardous/binge: 9.5% vs 3.0%; alcohol-related diagnosis: 19.0% vs 8.6%; P < .01) and chronic HCV-infected than uninfected (nonhazardous: 13.6% vs 2.5%; hazardous/binge: 18.2% vs 3.1%; alcohol-related diagnosis: 22.1% vs 6.5%; P < .01) participants. Strong associations with advanced hepatic fibrosis (adjusted odds ratio [95% confidence interval]) were observed among HIV/HCV-coinfected patients with nonhazardous drinking (14.2 [5.91-34.0]), hazardous/binge drinking (18.9 [7.98-44.8]), and alcohol-related diagnoses (25.2 [10.6-59.7]) compared with uninfected nonhazardous drinkers.ConclusionsAdvanced hepatic fibrosis was present at low levels of alcohol consumption, increased with higher alcohol use categories, and was more prevalent among HIV-infected and chronic HCV-infected patients than uninfected individuals. All alcohol use categories were strongly associated with advanced hepatic fibrosis in HIV/HCV-coinfected patients.

BackgroundThe incidence and determinants of hepatic decompensation have been incompletely examined among patients co-infected with HIV and hepatitis C virus (HCV) in the antiretroviral therapy (ART) era, and few studies have compared outcome rates with those of patients with chronic HCV alone.ObjectiveTo compare the incidence of hepatic decompensation between antiretroviral-treated patients co-infected with HIV and HCV and HCV-monoinfected patients and to evaluate factors associated with decompensation among co-infected patients receiving ART.DesignRetrospective cohort study.SettingVeterans Health Administration.Patients4280 co-infected patients who initiated ART and 6079 HCV-monoinfected patients receiving care between 1997 and 2010. All patients had detectable HCV RNA and were HCV treatment-naive.MeasurementsIncident hepatic decompensation, determined by diagnoses of ascites, spontaneous bacterial peritonitis, or esophageal variceal hemorrhage.ResultsThe incidence of hepatic decompensation was greater among co-infected than monoinfected patients (7.4% vs. 4.8% at 10 years; P < 0.001). Compared with HCV-monoinfected patients, co-infected patients had a higher rate of hepatic decompensation (hazard ratio [HR] accounting for competing risks, 1.56 [95% CI, 1.31 to 1.86]). Co-infected patients who maintained HIV RNA levels less than 1000 copies/mL still had higher rates of decompensation than HCV-monoinfected patients (HR, 1.44 [CI, 1.05 to 1.99]). Baseline advanced hepatic fibrosis (FIB-4 score >3.25) (HR, 5.45 [CI, 3.79 to 7.84]), baseline hemoglobin level less than 100 g/L (HR, 2.24 [CI, 1.20 to 4.20]), diabetes mellitus (HR, 1.88 [CI, 1.38 to 2.56]), and nonblack race (HR, 2.12 [CI, 1.65 to 2.72]) were each associated with higher rates of decompensation among co-infected patients.LimitationObservational study of predominantly male patients.ConclusionDespite receiving ART, patients co-infected with HIV and HCV had higher rates of hepatic decompensation than HCV-monoinfected patients. Rates of decompensation were higher for co-infected patients with advanced liver fibrosis, severe anemia, diabetes, and nonblack race.Primary funding sourceNational Institutes of Health.

BACKGROUND: Compared to uninfected people, human immunodeficiency virus (HIV)-infected individuals may have an increased risk of acute myocardial infarction (AMI). Currently, HIV-infected people are treated to the same blood pressure (BP) goals (

BackgroundHIV is associated with end-organ diseases of aging via unclear mechanisms. Longitudinally assessing how HIV infection and ART initiation affect biomarkers of end organ function/disease could clarify these mechanisms. We investigated longitudinal changes in clinical biomarkers following 1) HIV infection and 2) ART initiation with evidence of viral suppression.MethodsCohortVeterans Aging COHORT Study Virtual COHORT (VACS VC). VACS VC is a longitudinal cohort of HIV infected (HIV+) and race-ethnicity, sex, age, and clinical site-matched uninfected Veterans enrolled in the same calendar year.Inclusion criteriaa negative and successively positive (>six months) HIV antibody test. We used Wilcoxon signedrank tests to analyze 1) the effect of HIV infection on lipids, renal, hepatic and hematologic/cardiovascular biomarkers and 2)whether ART initiation with HIV-1 RNA

PurposeLarge, observational HIV cohorts play an important role in answering questions which are difficult to study in randomized trials; however, they often lack detailed information regarding previous antiretroviral treatment (ART). Knowledge of ART treatment history is important when ascertaining the long-term impact of medications, co-morbidities, or adverse reactions on HIV outcomes.MethodsWe performed a retrospective study to validate a prediction algorithm for identifying ART-naïve patients using the Veterans Aging Cohort Study's Virtual Cohort-an observational cohort of 40 594 HIV-infected veterans nationwide. Medical records for 3070 HIV-infected patients were reviewed to determine history of combination ART treatment. An algorithm using Virtual Cohort laboratory data was used to predict ART treatment status and compared to medical record review.ResultsAmong 3070 patients' medical records reviewed, 1223 were eligible for analysis. Of these, 990 (81%) were ART naïve at cohort entry based on medical record review. The prediction algorithm's sensitivity was 86%, specificity 47%, positive predictive value (PPV) 87%, and negative predictive value 45%, using a viral load threshold of

ObjectivesHuman immunodeficiency virus (HIV)-infected (HIV+) patients on combination antiretroviral therapy are living longer but have increased risk for aging-associated disease which may lead to increasing critical care requirements. We compare medical ICU admission characteristics and outcomes among HIV infected and demographically similar uninfected patients (uninfected) and considered whether an index which combines routine clinical biomarkers (the Veterans Aging Cohort Study Index) predicts 30-day medical ICU mortality.DesignObservational data analyses (Veterans Aging Cohort Study).SettingEight Veterans Affairs medical centers nationwide.PatientsHIV infected and uninfected with a medical ICU admission between 2002 and 2010.InterventionNone.Measurements and main resultsMedical ICU admission was determined using bedsection (Veterans Affairs) and revenue center codes (Medicare). For Veterans Affairs admissions, we used clinical data to calculate Veterans Aging Cohort Study Index scores and multivariable logistic regression to determine factors associated with 30-day mortality. Overall, 539 of 3,620 (15%) HIV infected and 375 of 3,639 (10%) uninfected had a medical ICU admission; 72% and 78%, respectively, were Veterans Affairs based. HIV+ patients were younger at admission (p < 0.0001). Although most HIV+ patients were on antiretroviral therapy (71%) with undetectable HIV-1 RNA (54%), compared with uninfected they were more commonly admitted with respiratory diagnoses or infections (21% vs. 12%), were more likely to require mechanical ventilation (17% vs. 9%; p = 0.001), and had a higher mortality rate (18.6% vs. 11.2%, p = 0.003). Cardiovascular diagnoses were less common among HIV infected (18% vs. 29%; p < 0.0001). In logistic regression (c-statistic 0.87), a 5-point increment in Veterans Aging Cohort Study Index was associated with an odds ratio of death of 1.22 (95% confidence interval 1.14-1.30) among HIV infected and of 1.50 (95% confidence interval 1.29-1.76) among uninfected; infection/sepsis and respiratory diagnoses were also associated with mortality.ConclusionsMedical ICU admission was frequent, 30-day mortality higher, and mechanical ventilation more common in HIV infected compared with uninfected. The Veterans Aging Cohort Study Index calculated at medical ICU admission predicted 30-day mortality for HIV infected and uninfected. As more individuals age with HIV, their requirements for medical ICU care may be greater than demographically similar uninfected individuals.

ImportanceWhether people infected with human immunodeficiency virus (HIV) are at an increased risk of acute myocardial infarction (AMI) compared with uninfected people is not clear. Without demographically and behaviorally similar uninfected comparators and without uniformly measured clinical data on risk factors and fatal and nonfatal AMI events, any potential association between HIV status and AMI may be confounded.ObjectiveTo investigate whether HIV is associated with an increased risk of AMI after adjustment for all standard Framingham risk factors among a large cohort of HIV-positive and demographically and behaviorally similar (ie, similar prevalence of smoking, alcohol, and cocaine use) uninfected veterans in care.Design and settingParticipants in the Veterans Aging Cohort Study Virtual Cohort from April 1, 2003, through December 31, 2009.ParticipantsAfter eliminating those with baseline cardiovascular disease, we analyzed data on HIV status, age, sex, race/ethnicity, hypertension, diabetes mellitus, dyslipidemia, smoking, hepatitis C infection, body mass index, renal disease, anemia, substance use, CD4 cell count, HIV-1 RNA, antiretroviral therapy, and incidence of AMI.Main outcome measureAcute myocardial infarction.ResultsWe analyzed data on 82 459 participants. During a median follow-up of 5.9 years, there were 871 AMI events. Across 3 decades of age, the mean (95% CI) AMI events per 1000 person-years was consistently and significantly higher for HIV-positive compared with uninfected veterans: for those aged 40 to 49 years, 2.0 (1.6-2.4) vs 1.5 (1.3-1.7); for those aged 50 to 59 years, 3.9 (3.3-4.5) vs 2.2 (1.9-2.5); and for those aged 60 to 69 years, 5.0 (3.8-6.7) vs 3.3 (2.6-4.2) (P < .05 for all). After adjusting for Framingham risk factors, comorbidities, and substance use, HIV-positive veterans had an increased risk of incident AMI compared with uninfected veterans (hazard ratio, 1.48; 95% CI, 1.27-1.72). An excess risk remained among those achieving an HIV-1 RNA level less than 500 copies/mL compared with uninfected veterans in time-updated analyses (hazard ratio, 1.39; 95% CI, 1.17-1.66).Conclusions and relevanceInfection with HIV is associated with a 50% increased risk of AMI beyond that explained by recognized risk factors.

ObjectiveWith improved survival of HIV-infected persons on antiretroviral therapy and growing prevalence of non-AIDS diseases, we asked whether the VACS Index, a composite measure of HIV-associated and general organ dysfunction predictive of all-cause mortality, predicts hospitalization and medical intensive care unit (MICU) admission. We also asked whether AIDS and non-AIDS conditions increased risk after accounting for VACS Index score.MethodsWe analyzed data from the Veterans Aging Cohort Study (VACS), a prospective study of HIV-infected Veterans receiving care between 2002 and 2008. Data were obtained from the electronic medical record, VA administrative databases, and patient questionnaires and were used to identify comorbidities and calculate baseline VACS Index scores. The primary outcome was first hospitalization within 2 years of VACS enrollment. We used multivariable Cox regression to determine risk factors associated with hospitalization and logistic regression to determine risk factors for MICU admission, given hospitalization.ResultsOf 3410 patients, 1141 were hospitalized within 2 years; 203 (17.8%)/1141 patients included an MICU admission. Median VACS Index scores were 25 (no hospitalization), 34 (hospitalization only), and 51 (MICU). In adjusted analyses, a 5-point increment in VACS Index score was associated with 10% higher risk of hospitalization and MICU admission. In addition to VACS Index score, Hispanic ethnicity, current smoking, hazardous alcohol use, chronic obstructive pulmonary disease, hypertension, diabetes, and prior AIDS-defining event predicted hospitalization. Among those hospitalized, VACS Index score, cardiac disease, and prior cancer predicted MICU admission.ConclusionsThe VACS Index predicted hospitalization and MICU admission as did current smoking, hazardous alcohol use, and AIDS and certain non-AIDS diagnoses.