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1.  Hepatic safety and antiretroviral effectiveness in HIV-infected patients receiving naltrexone 
Background
We sought to determine the impact of naltrexone on hepatic enzymes and HIV biomarkers in HIV-infected patients.
Methods
We used data from the Veterans Aging Cohort Study-Virtual Cohort, an electronic database of administrative, pharmacy and laboratory data. We restricted our sample to HIV-infected patients who received an initial oral naltrexone prescription, of at least seven days duration. We examined aspartate aminotransferase (AST) and alanine aminotransferase (ALT) and HIV biomarker (CD4 and HIV RNA) values for the 365 days prior to, during, and for the 365 days post-naltrexone prescription. We also examined cases of liver enzyme elevation (LEE; defined as greater than 5 times baseline ALT or AST or greater than 3.5 times baseline if baseline ALT or AST was greater than or equal to 40 IU/L).
Results
Of 114 HIV-infected individuals, 97% were male, 65% white, 57% Hepatitis C co-infected, median age was 49 years; 89% of the sample had a history of alcohol dependence and 32% had opioid dependence. Median duration of naltrexone prescription was 49 (interquartile range 30–83) days, representing 9,525 person-days of naltrexone use. Mean ALT and AST levels remained below the upper limit of normal. Two cases of LEE occurred. Mean CD4 count remained stable and mean HIV RNA decreased after naltrexone prescription.
Conclusions
In HIV-infected patients, oral naltrexone is rarely associated with clinically significant ALT or AST changes and does not have a negative impact on biologic parameters. Therefore, HIV-infected patients with alcohol or opioid dependence can be treated with naltrexone.
doi:10.1111/j.1530-0277.2011.01601.x
PMCID: PMC3221963  PMID: 21797892
2.  Validating Smoking Data From the Veteran’s Affairs Health Factors Dataset, an Electronic Data Source 
Nicotine & Tobacco Research  2011;13(12):1233-1239.
Introduction:
We assessed smoking data from the Veterans Health Administration (VHA) electronic medical record (EMR) Health Factors dataset.
Methods:
To assess the validity of the EMR Health Factors smoking data, we first created an algorithm to convert text entries into a 3-category smoking variable (never, former, and current). We compared this EMR smoking variable to 2 different sources of patient self-reported smoking survey data: (a) 6,816 HIV-infected and -uninfected participants in the 8-site Veterans Aging Cohort Study (VACS-8) and (b) a subset of 13,689 participants from the national VACS Virtual Cohort (VACS-VC), who also completed the 1999 Large Health Study (LHS) survey. Sensitivity, specificity, and kappa statistics were used to evaluate agreement of EMR Health Factors smoking data with self-report smoking data.
Results:
For the EMR Health Factors and VACS-8 comparison of current, former, and never smoking categories, the kappa statistic was .66. For EMR Health Factors and VACS-VC/LHS comparison of smoking, the kappa statistic was .61.
Conclusions:
Based on kappa statistics, agreement between the EMR Health Factors and survey sources is substantial. Identification of current smokers nationally within the VHA can be used in future studies to track smoking status over time, to evaluate smoking interventions, and to adjust for smoking status in research. Our methodology may provide insights for other organizations seeking to use EMR data for accurate determination of smoking status.
doi:10.1093/ntr/ntr206
PMCID: PMC3223583  PMID: 21911825
3.  FIB-4 index is associated with hepatocellular carcinoma risk in HIV-infected patients 
Background
Chronic inflammation caused by hepatitis B virus infection, hepatitis C virus infection, and/or heavy alcohol use can lead to fibrosis, cirrhosis, and eventually hepatocellular carcinoma (HCC). FIB-4 is an index score calculated from platelet count, alanine transaminase, aspartate transaminase, and age that predicts fibrosis and cirrhosis. We hypothesized that high FIB-4 would be associated with development of HCC in HIV-infected persons, who are at high risk due to high prevalence of viral hepatitis and alcohol consumption, and possibly due to HIV infection itself.
Methods
Using proportional hazards models, we tested this hypothesis among 22,980 HIV-infected men from the Veterans Aging Cohort Study. We identified incident HCC cases from the VA Central Cancer Registry.
Results
During follow-up, there were 112 incident HCC diagnoses. The age-and race/ethnic group-adjusted HR was 4.2 (95% CI: 2.4, 7.4)for intermediate FIB-4 and 13.0 (95% CI: 7.2, 23.4) for high FIB-4, compared to low FIB-4. After further adjustment for enrollment year, CD4 count, HIV-1 RNA level, antiretroviral therapy use, hepatitis B and C virus infection, alcohol abuse/dependency, and diabetes, FIB-4 remained a strong, significant, independent risk factor for HCC. The multivariate-adjusted HR was 3.6 (95% CI: 2.1, 6.4) for intermediate FIB-4 and 9.6 (95% CI: 5.2, 17.4) for high FIB-4.
Conclusions
Calculated from routine, non-invasive laboratory tests, FIB-4 is a strong, independent HCC risk factor in HIV-infected patients.
Impact
FIB-4 might prove valuable as an easily measured index to identify those at highest risk for HCC, even prior to development of clinical cirrhosis.
doi:10.1158/1055-9965.EPI-11-0582
PMCID: PMC3237927  PMID: 22028407
hepatocellular carcinoma; FIB-4; HIV; liver neoplasms; hepatic fibrosis
4.  IMPACT OF CIGARETTE SMOKING ON MORTALITY IN HIV-POSITIVE AND HIV-NEGATIVE VETERANS 
It is unknown whether smoking confers similar mortality risk in HIV-positive as in HIV-negative patients. We compared overall mortality stratified by HIV and smoking of 1,034 HIV-positive block-matched to 739 HIV-negative veterans, enrolled 2001–2002 in the Veterans Aging Cohort 5 Site Study. Adjusted incidence rate ratios (IRR) for mortality were calculated using Poisson regression. Mortality was significantly increased in HIV-positive veterans according to both smoking status and pack-years in unadjusted and adjusted analyses (adjusted IRR 2.31, 95% confidence interval [CI] 1.53–3.49 for HIV-positive current smokers and IRR 1.32, 95% CI 0.67–2.61 for HIV-negative current smokers). Comorbid diseases were also significantly increased according to smoking status and pack-years. Current smoking is associated with poor outcomes; even lower levels of exposure appear to be detrimental in HIV-infected veterans. These findings support the need for improvements in smoking cessation and for studies of mechanisms and diseases underlying increased mortality in smokers with HIV.
doi:10.1521/aeap.2009.21.3_supp.40
PMCID: PMC3118467  PMID: 19537953
5.  Comparison of Two VA Laboratory Data Repositories Indicates That Missing Data Vary Despite Originating From the Same Source 
Medical care  2009;47(1):121-124.
Background
Assessing accuracy and completeness of data is an important component of conducting research. VA Healthcare System benefits from a highly developed electronic medical information system. The Immunology Case Registry was designed to monitor costs and quality of HIV care. The Decision Support System was developed to monitor utilization and costs of veterans in care. Because these systems extract data from the same source using independent methods, they provide an opportunity to compare the accuracy and completeness of each.
Objective
To compare overlapping laboratory data from the Veterans Affairs Health Information System between 2 data repositories.
Research Design
For hemoglobin, CD4+ lymphocyte counts (CD4), HIV RNA viral load, aspartate aminotransferase, alanine aminotransferase, glycosylated hemoglobin, creatinine, and white blood count, we calculated the percent of individuals with a value from each source. For results in both repositories, we calculated Pearson’s correlation coefficients.
Subjects
A total of 22,647 HIV + veterans in the Virtual Cohort with a visit in fiscal year 2002.
Results
For 6 out of 9 tests, 68% to 72% of the observations overlapped. For CD4, viral load, and glycosylated hemoglobin less than 31% of observations overlapped. Overlapping results were nearly perfectly correlated except for CD4.
Conclusions
Six of the laboratory tests demonstrated remarkably similar amounts of overlap, though Immunology Case Registry and Decision Support System both have missing data. Findings indicate that validation of laboratory data should be conducted before its use in quality and efficiency projects. When 2 databases are not available for comparison, other methods of validation should be implemented.
doi:10.1097/MLR.0b013e31817d69c2
PMCID: PMC3032537  PMID: 19106740
laboratory; DSS; ICR; VA
6.  Adherence, virological and immunological outcomes for HIV-infected veterans starting combination antiretroviral therapies 
AIDS (London, England)  2007;21(12):1579-1589.
Objectives
We aimed to determine adherence, virological, and immunological outcomes one year after starting a first combination antiretroviral therapy (ART) regimen.
Design
Observational; synthesis of administrative, laboratory, and pharmacy data. Antiretroviral regimens were divided into efavirenz, nevirapine, boosted protease inhibitor (PI), and single PI categories. Propensity scores were used to control for confounding by treatment assignment. Adherence was estimated from pharmacy refill records.
Setting
Veterans Affairs Healthcare System, all sites.
Participants
HIV-infected individuals starting combination ART with a low likelihood of previous antiretroviral exposure.
Interventions
None.
Outcomes
The proportion of antiretroviral prescriptions filled as prescribed, a change in log HIV-RNA, the proportion with log HIV-RNA viral suppression, a change in CD4 cell count.
Results
A total of 6394 individuals unlikely to have previous antiretroviral exposure started combination ART between 1996 and 2004, and were eligible for analysis. Adherence overall was low (63% of prescriptions filled as prescribed), and adherence with efavirenz (67%) and nevirapine (65%) regimens was significantly greater than adherence with boosted PI (59%) or single PI (61%) regimens (P < 0.001). Efavirenz regimens were more likely to suppress HIV-RNA at one year (74%) compared with nevirapine (62%), boosted PI (63%), or single PI (53%) regimens (all P < 0.001), and this superiority was maintained when analyses were adjusted for baseline clinical characteristics and propensity for treatment assignment. Efavirenz also yielded more favorable immunological outcomes.
Conclusion
HIV-infected individuals initiating their first combination ART using an efavirenz-based regimen had improved virological and immunological outcomes and greater adherence levels.
doi:10.1097/QAD.0b013e3281532b31
PMCID: PMC3460378  PMID: 17630553
Adherence; resistance; ART; Veterans Affairs Healthcare System
7.  Measuring Performance Directly Using the Veterans Health Administration Electronic Medical Record 
Medical care  2007;45(1):73-79.
Background
Electronic medical records systems (EMR) contain many directly analyzable data fields that may reduce the need for extensive chart review, thus allowing for performance measures to be assessed on a larger proportion of patients in care.
Objective
This study sought to determine the extent to which selected chart review-based clinical performance measures could be accurately replicated using readily available and directly analyzable EMR data.
Methods
A cross-sectional study using full chart review results from the Veterans Health Administration's External Peer Review Program (EPRP) was merged to EMR data.
Results
Over 80% of the data on these selected measures found in chart review was available in a directly analyzable form in the EMR. The extent of missing EMR data varied by site of care (P < 0.01). Among patients on whom both sources of data were available, we found a high degree of correlation between the 2 sources in the measures assessed (correlations of 0.89–0.98) and in the concordance between the measures using performance cut points (kappa: 0.86–0.99). Furthermore, there was little evidence of bias; the differences in values were not clinically meaningful (difference of 0.9 mg/dL for low-density lipoprotein cholesterol, 1.2 mm Hg for systolic blood pressure, 0.3 mm Hg for diastolic, and no difference for HgbA1c).
Conclusions
Directly analyzable data fields in the EMR can accurately reproduce selected EPRP measures on most patients. We found no evidence of systematic differences in performance values among these with and without directly analyzable data in the EMR.
doi:10.1097/01.mlr.0000244510.09001.e5
PMCID: PMC3460379  PMID: 17279023
veterans; quality of care; medical records systems; quality measurement
8.  Incorporating Quality of Evidence into Decision Analytic Modeling 
Annals of internal medicine  2007;146(2):133-141.
Our objective was to illustrate the effects of using stricter standards for the quality of evidence used in decision analytic modeling. We created a simple 10-parameter probabilistic Markov model to estimate the cost-effectiveness of directly observed therapy (DOT) for individuals with newly diagnosed HIV infection. We evaluated quality of evidence on the basis of U.S. Preventive Services Task Force methods, which specified 3 separate domains: study design, internal validity, and external validity. We varied the evidence criteria for each of these domains individually and collectively. We used published research as a source of data only if the quality of the research met specified criteria; otherwise, we specified the parameter by randomly choosing a number from a range within which every number has the same probability of being selected (a uniform distribution). When we did not eliminate poor-quality evidence, DOT improved health 99% of the time and cost less than $100 000 per additional quality-adjusted life-year (QALY) 85% of the time. The confidence ellipse was extremely narrow, suggesting high precision. When we used the most rigorous standards of evidence, we could use fewer than one fifth of the data sources, and DOT improved health only 49% of the time and cost less than $100 000 per additional QALY only 4% of the time. The confidence ellipse became much larger, showing that the results were less precise. We conclude that the results of decision modeling may vary dramatically depending on the stringency of the criteria for selecting evidence to use in the model.
PMCID: PMC3460380  PMID: 17227937
9.  Delayed Presentation for Human Immunodeficiency Virus (HIV) Care Among Veterans 
Medical care  2007;45(11):1105-1109.
Background
Despite the effectiveness of antiretroviral therapy, nearly half of patients entering human immunodeficiency virus (HIV) care have advanced disease. Many attribute this delay to poor access to healthcare. Others argue that delays will persist until routine screening is adopted. The Veterans Health Administration (VA) is a unique laboratory to examine whether access to comprehensive health benefits results in earlier entry into HIV care.
Methods
Retrospective observational study of 4368 HIV-positive patients entering HIV care during 1998–2002 at VA medical centers nationwide. Outcomes of interest: rates of acquired immune deficiency syndrome in year of presentation; duration of VA utilization before HIV presentation; presence of “clinical triggers,” signaling greater risk of HIV infection, before presentation.
Results
Fifty-one percent (n = 2211) of all patients presented with CD4 counts of <200 cells/mm3. Thirty-nine percent (n = 1697) of all patients used other VA services before presentation for HIV care, with median duration of 3.6 years (interquartile range 25–75: 2.2–5.1 year) and 6 physician visits [interquartile range (IQR), 25–75: 2–18 visits] between first utilization and HIV presentation. No difference existed in the percentage presenting with CD4 counts <200 cells/mm3 among those with and without prior VA healthcare (50% vs. 51%, P = 0.76). Only 13% of those with prior VA healthcare demonstrated a clinical trigger before HIV presentation.
Conclusions
More than half of veterans entered HIV care with an acquired immune deficiency syndrome diagnosis at presentation irrespective of whether they had previously established healthcare in the VA. Access to care does not seem to be the primary cause of delayed HIV presentation. Widespread HIV screening is needed to improve rates of early detection.
doi:10.1097/MLR.0b013e3181271476
PMCID: PMC3460382  PMID: 18049352
HIV; AIDS; diagnosis; screening; access to care
10.  A Framework for Tailoring Clinical Guidelines to Comorbidity at the Point of Care 
Archives of internal medicine  2007;167(21):2361-2365.
Background
Evidence is accumulating to suggest that clinical guidelines should be modified for patients with comorbidities, yet there is no quantitative and objective approach that considers benefits together with risks.
Methods
We outline a framework using a payoff time, which we define as the minimum elapsed time until the cumulative incremental benefits of a guideline exceed its cumulative incremental harms. If the payoff time of a guideline exceeds a patient’s comorbidity-adjusted life expectancy, then the guideline is unlikely to offer a benefit and should be modified. We illustrate the frame-work by applying this method to colorectal cancer screening guidelines for 50-year-old men with human immunodeficiency virus (HIV) and 60-year-old women with congestive heart failure (CHF).
Results
We estimated that colorectal cancer screening payoff times for 50-year-old men with HIV would range from 1.9 to 5.0 years and that colorectal cancer screening payoff times for 60-year-old women with CHF would range from 0.7 to 2.9 years. Because the payoff times for 50-year-oldmen with HIV were lower than their life expectancies (12.5–24.0 years), colorectal cancer screening may be beneficial for these patients. In contrast, because payoff times for 60-year-old women with CHF were sometimes greater than their life expectancies (0.6 to > 5 years), colorectal cancer screening is likely to be harmful for some of these patients.
Conclusion
Use of a payoff time calculation may be a feasible framework to tailor clinical guidelines to the comorbidity profiles of individual patients.
doi:10.1001/archinte.167.21.2361
PMCID: PMC3460384  PMID: 18039996
11.  Alcohol Consumption and Depressive Symptoms Over Time: A Longitudinal Study of Patients With and Without HIV Infection 
Drug and alcohol dependence  2011;117(2-3):158-163.
Background
The impact of alcohol consumption on depressive symptoms over time among patients who do not meet criteria for alcohol abuse or dependence is not known.
Objective
To evaluate the impact of varying levels of alcohol consumption on depressive symptoms over time in patients with and without HIV infection.
Design
We used data from the Veterans Aging Cohort Study (VACS). We used generalized estimating equations models to assess the association of alcohol-related categories, as a fixed effect, on the time-varying outcome of depressive symptoms.
Participants
VACS is a prospectively enrolled cohort study of HIV-infected patients and age-, race- and site-matched HIV uninfected patients.
Main Measures
Hazardous, binge drinking, alcohol abuse and alcohol dependence were defined using standard criteria. Depressive symptoms were measured by the Patient Health Questionnaire (PHQ-9).
Key Results
Among the 2446 patients, 19% reported past but not current alcohol use, 50% non-hazardous drinking, 8% hazardous drinking, 14% binge drinking, and 10% met criteria for alcohol or dependence. At baseline, depressive symptoms were higher in hazardous and binge drinkers than in past and non-hazardous drinkers (OR=2.65; CI=1.50/4.69; p<.001) and similar to those with abuse or dependence. There was no difference in the association between alcohol-related category and depressive symptoms by HIV status (OR=0.99; CI=.83/1.18; p=.88). Hazardous drinkers were 2.53 (95% CI = 1.34/4.81) times and binge drinkers were 2.14 (95% CI = 1.49/3.07) times more likely to meet criteria for depression when compared to non-hazardous drinkers. The associations between alcohol consumption and depressive symptoms persisted over three years and were responsive to changes in alcohol-related categories.
Conclusions
HIV-infected and HIV-uninfected hazardous and binge drinkers have depressive symptoms that are more severe than non-hazardous and non-drinkers and similar to those with alcohol abuse or dependence. Patients who switch to a higher or lower level of drinking experience a similar alteration in their depressive symptoms. Interventions to decrease unhealthy alcohol consumption may improve depressive symptoms.
doi:10.1016/j.drugalcdep.2011.01.014
PMCID: PMC3113463  PMID: 21345624
Alcohol drinking; Alcoholism; Depression; Depressive disorder; HIV; Acquired Immunodeficiency Syndrome
12.  Rate and predictors of treatment prescription for hepatitis C 
Gut  2006;56(3):385-389.
Background
The true treatment rate for hepatitis C virus (HCV) in veterans is unknown.
Aim
To determine the treatment prescription rates and predictors of treatment prescription for HCV in a large national population.
Methods
The Department of Veterans Affairs National Patient Care Database (NPCD) was used to identify all HCV‐infected people between the fiscal years 1999 and 2003 using the International classification of diseases, 9th revision codes. Demographic information, medical and psychiatric comorbidities, and drug and alcohol use diagnoses were retrieved. Pharmacy data were retrieved from the Department of Veterans Affairs Pharmacy Benefits Management (PBM) database. Logistic regression analysis was used to determine the predictors of treatment for HCV in HCV.
Results
113 927 veterans in the Department of Veterans Affairs care with a diagnosis of HCV were identified. The treatment prescription rate for HCV was 11.8%. Patients not prescribed treatment were older, more likely to be from minority races, have more alcohol and drug misuse, and have medical and psychiatric comorbid conditions. In a multivariate logistic regression model, the following factors were predictive of non‐treatment for HCV: increasing age (odds ratio (OR) 0.77 for each 5‐year increase in age; 95% confidence interval (CI) 0.76 to 0.78); black race (OR 0.64; 95% CI 0.6 to 0.68); Hispanic race (OR 0.88; 95% CI 0.8 to 0.96); alcohol abuse and dependence (OR 0.62; 95% CI 0.59 to 0.65); drug abuse and dependence (OR 0.78; 95% CI 0.74 to 0.82); anaemia (OR 0.18; 95% CI 0.16 to 0.21); hepatitis B infection (OR 0.72; 95% CI 0.62 to 0.83); coronary artery disease (OR 0.9; 95% CI 0.85 to 0.97); stroke (OR 0.75; 95% CI 0.67 to 0.85); bipolar disorder (OR 0.64; 95% CI 0.58 to 0.70); major depression (OR 0.72; 95% CI 0.67 to 0.77); mild depression (OR 0.56; 95% CI 0.53 to 0.59); and schizophrenia (OR 0.71; 95% CI 0.65 to 0.77). The following factors were associated with a higher likelihood of treatment prescription for HCV: liver cirrhosis (OR 1.6; 95% CI 1.5 to 1.7); and diabetes (OR 1.07; 95% CI 1.02 to 1.12).
Conclusions
A small number of HCV‐infected veterans were prescribed treatment for HCV. Non‐treatment is associated with increasing age, non‐white race, drug and alcohol abuse, and dependence and comorbid illnesses. Reasons for non‐treatment need further study.
doi:10.1136/gut.2006.099150
PMCID: PMC1856823  PMID: 17005764
13.  Critical Illness in HIV-Infected Patients in the Era of Combination Antiretroviral Therapy 
As HIV-infected persons on combination antiretroviral therapy (ART) are living longer and rates of opportunistic infections have declined, serious non–AIDS-related diseases account for an increasing proportion of deaths. Consistent with these changes, non–AIDS-related illnesses account for the majority of ICU admissions in more recent studies, in contrast to earlier eras of the AIDS epidemic. Although mortality after ICU admission has improved significantly since the earliest HIV era, it remains substantial. In this article, we discuss the current state of knowledge regarding the impact of ART on incidence, etiology, and outcomes of critical illness among HIV-infected patients. In addition, we consider issues related to administration of ART in the ICU and identify important areas of future research.
doi:10.1513/pats.201009-060WR
PMCID: PMC3132789  PMID: 21653532
MeSH; intensive care unit; critical illness, human immunodeficiency virus; antiretroviral therapy; aging, quality of life
14.  Non-medical use of prescription opioids and pain in Veterans with and without HIV 
Pain  2011;152(5):1133-1138.
Few studies have systematically evaluated non medical use of prescription opioids (NMU) among United States’ military Veterans, those who report pain, and those with HIV. An increased understanding of the factors associated with NMU may help providers to balance maintaining patient access to prescription opioids for legitimate medical reasons and reducing the risks of addiction. We analyzed self-report data and electronic medical and pharmacy record data from 4,122 participants in the Veterans Aging Cohort Study. Bivariate associations were analyzed using chi-square tests, t-tests, and median tests and multivariable associations were assessed using logistic regression. Median participant age was 52 years; 95% were men; 65% were black, and 53% were HIV infected. NMU was reported by 13% of participants. In multivariable analysis, NMU was associated with being Hispanic (AOR 1.8); aged 40–44 (AOR 1.6); Alcohol Use Disorders Identification Test score ≥20 (AOR 2.0); drug use disorder (AOR 1.9); opioid use disorder (AOR 2.7); past month cigarette use (AOR 1.3); receiving a past-year VHA opioid prescription (AOR 1.9); hepatitis C (AOR 1.5); and pain interference (AOR 1.1). Being overweight (AOR 0.6) or obese (AOR 0.5) and having a higher 12-Item Short-Form Health Survey (SF-12) Mental Component Summary (AOR 0.98) were associated with less NMU. Patients with and without NMU did not differ on HIV status or SF-12 Physical Component Summary. Veterans in care have a high prevalence of NMU that is associated with substance use, medical status, and pain interference, but not HIV status.
doi:10.1016/j.pain.2011.01.038
PMCID: PMC3086805  PMID: 21354703
Analgesics; Opioids; Pain; HIV; Veterans
15.  HIV Infection and Risk for Incident Pulmonary Diseases in the Combination Antiretroviral Therapy Era 
Rationale: In aging HIV-infected populations comorbid diseases are important determinants of morbidity and mortality. Pulmonary diseases have not been systematically assessed in the combination antiretroviral therapy (ART) era.
Objectives: To determine the incidence of pulmonary diseases in HIV-infected persons compared with HIV-uninfected persons.
Methods: We analyzed data from the Veterans Aging Cohort Study Virtual Cohort, consisting of 33,420 HIV-infected veterans and 66,840 age, sex, race and ethnicity, and site-matched HIV-uninfected veterans. Using Poisson regression, incidence rates and adjusted incidence rate ratios were calculated to determine the association of HIV with pulmonary disease. The Virtual Cohort was merged with the 1999 Veterans Large Health Survey to adjust for self-reported smoking in a nested sample (14%).
Measurements and Main Results: Incident chronic obstructive pulmonary disease, lung cancer, pulmonary hypertension, and pulmonary fibrosis, as well as pulmonary infections, were significantly more likely among HIV-infected patients compared with uninfected patients in adjusted analyses, although rates of asthma did not differ by HIV status. Bacterial pneumonia and chronic obstructive pulmonary disease were the two most common incident pulmonary diseases, whereas opportunistic pneumonias were less common. Absolute rates of most pulmonary diseases increased with age, although the relative differences between those with and without HIV infection were greatest in younger persons. Chronic obstructive pulmonary disease and asthma, as well as pulmonary infections, were less likely in those with lower HIV RNA levels and use of ART at baseline.
Conclusions: Pulmonary diseases among HIV-infected patients receiving care within the Veterans Affairs Healthcare System in the combination ART era reflect a substantial burden of non–AIDS-defining and chronic conditions, many of which are associated with aging.
doi:10.1164/rccm.201006-0836OC
PMCID: PMC3266024  PMID: 20851926
HIV; respiratory tract diseases; lung diseases, obstructive; pneumonia; pneumonia, bacterial
16.  Does Clinical Inertia Vary According to Provider Type? 
Despite the well established risks of persistently elevated blood pressure, as well as the benefits of controlling such elevations, hypertension remains underdiagnosed and undertreated. These VA researchers compared the rates of antihypertensive medication intensification between resident physicians, midlevel practitioners, and attending physicians.
PMCID: PMC3255094  PMID: 22247610
17.  Association of Age and Comorbidity with Physical Function in HIV-Infected and Uninfected Patients: Results from the Veterans Aging Cohort Study 
AIDS Patient Care and STDs  2011;25(1):13-20.
Abstract
HIV clinical care now involves prevention and treatment of age-associated comorbidity. Although physical function is an established correlate to comorbidity in older adults without HIV infection, its role in aging of HIV-infected adults is not well understood. To investigate this question we conducted cross-sectional analyses including linear regression models of physical function in 3227 HIV-infected and 3240 uninfected patients enrolled 2002–2006 in the Veterans Aging Cohort Study-8-site (VACS-8). Baseline self-reported physical function correlated with the Short Form-12 physical subscale (ρ = 0.74, p < 0.001), and predicted survival. Across the age groups decline in physical function per year was greater in HIV-infected patients (βcoef −0.25, p < 0.001) compared to uninfected patients (βcoef −0.08, p = 0.03). This difference, although statistically significant (p < 0.01), was small. Function in the average 50-year old HIV-infected subject was equivalent to the average 51.5-year-old uninfected subject. History of cardiovascular disease was a significant predictor of poor function, but the effect was similar across groups. Chronic pulmonary disease had a differential effect on function by HIV status (Δβcoef −3.5, p = 0.03). A 50-year-old HIV-infected subject with chronic pulmonary disease had the equivalent level of function as a 68.1-year-old uninfected subject with chronic pulmonary disease. We conclude that age-associated comorbidity affects physical function in HIV-infected patients, and may modify the effect of aging. Longitudinal research with markers of disease severity is needed to investigate loss of physical function with aging, and to develop age-specific HIV care guidelines.
doi:10.1089/apc.2010.0242
PMCID: PMC3030913  PMID: 21214375
18.  Decreased Serum Antibody Responses to Recombinant Pneumocystis Antigens in HIV-Infected and Uninfected Current Smokers▿  
Serologic studies can provide important insights into the epidemiology and transmission of Pneumocystis jirovecii. Exposure to P. jirovecii can be assessed by serum antibody responses to recombinant antigens from the major surface glycoprotein (MsgC), although factors that influence the magnitude of the antibody response are incompletely understood. We determined the magnitudes of antibody responses to P. jirovecii in comparison to adenovirus and respiratory syncytial virus (RSV) in HIV-infected and uninfected patients and identified predictors associated with the magnitude of the response. We performed a cross-sectional analysis using serum samples and data from 153 HIV-positive and 92 HIV-negative subjects enrolled in a feasibility study of the Veterans Aging Cohort 5 Site Study (VACS 5). Antibodies were measured using an enzyme-linked immunosorbent assay (ELISA). Independent predictors of antibody responses were determined using multivariate Tobit regression models. The results showed that serum antibody responses to P. jirovecii MsgC fragments were significantly and independently decreased in current smokers. Antibodies to P. jirovecii also tended to be lower with chronic obstructive pulmonary disease (COPD), hazardous alcohol use, injection drug use, and HIV infection, although these results were not statistically significant. These results were specific to P. jirovecii and did not correlate with adenovirus. Antibody responses to RSV were in the inverse direction. Thus, current smoking was independently associated with decreased P. jirovecii antibody responses. Whether smoking exerts an immunosuppressive effect that affects the P. jirovecii antibody response, colonization, or subsequent risk for disease is unclear; prospective, longitudinal studies are needed to evaluate these findings further.
doi:10.1128/CVI.00421-10
PMCID: PMC3067379  PMID: 21191078
19.  Patterns of drug use and abuse among aging adults with and without HIV: A latent class analysis of a US Veteran cohort* 
Drug and alcohol dependence  2010;110(3):208-220.
This study characterized the extent and patterns self-reported drug use among aging adults with and without HIV, assessed differences in patterns by HIV status, and examined pattern correlates. Data derived from 6351 HIV infected and uninfected adults enrolled in an eight-site matched cohort, the Veterans Aging Cohort Study (VACS). Using clinical variables from electronic medical records and sociodemographics, drug use consequences, and frequency of drug use from baseline surveys, we performed latent class analyses (LCA) stratified by HIV status and adjusted for clinical and socio-demographic covariates. Participants were, on average, age 50 (range 22–86), primarily male (95%) and African-American (64%). Five distinct patterns emerged: non-users, past primarily marijuana users, past multidrug users, current high consequence multidrug users, and current low consequence primarily marijuana users. HIV status strongly influenced class membership. Non -users were most p revalent among HIV uninfected (36.4%) and current high consequence multidrug users (25.5%) were most prevalent among HIV infected. While problems of obesity marked those not currently u sing drugs, current users experienced higher prevalences of medical or mental health disorders. Multimorbidity was highest among past and current multidrug users. HIV-infected participants were more likely than HIV-uninfected participants to be current low consequence primarily marijuana users. In this sample, active drug use and abuse were common. HIV infected and uninfected Veterans differed on extent and patterns of drug use and on important characteristics within identified classes. Findings have the potential to inform screening and intervention efforts in aging drug users with and without HIV.
doi:10.1016/j.drugalcdep.2010.02.020
PMCID: PMC3087206  PMID: 20395074
aging; Veterans; HIV; substance-related disorders; latent class analysis; illicit drugs; cohort studies
20.  The Burden of Illness in the First Year Home: Do Male and Female VA Users Differ in Health Conditions and Healthcare Utilization 
Background
We sought to describe gender differences in medical and mental health conditions and health care utilization among veterans who used Veterans Health Administration (VA) services in the first year after combat in Iraq and Afghanistan.
Methods
This is an observational study, using VA administrative and clinical data bases, of 163,812 Operation Enduring Freedom/Operation Iraqi Freedom veterans who had enrolled in VA and who had at least one visit within 1 year of last deployment.
Results
Female veterans were slightly younger (mean age, 30 years vs. 32 for men; p <.0001), twice as likely to be African American (30% vs. 15%; p <.0001), and less likely to be married (32% vs. 49%; p < .0001). Women had more visits to primary care (2.6 vs. 2.0; p < .001) and mental health (4.0 vs. 3.6; p < .001) clinics and higher use of community care outside the VA (14% vs. 10%; p < .001). After adjustment for significant demographic differences, women were more likely to have musculoskeletal and skin disorders, mild depression, major depression, and adjustment disorders, whereas men were more likely to have ear disorders and posttraumatic stress disorder. Thirteen percent of women sought care for gynecologic examination, 10% for contraceptive counseling, and 7% for menstrual disorders.
Conclusion
Female veterans had similar rates of physical conditions, but higher rates of some mental health disorders and additionally, used the VA for reproductive health needs. They also had slightly greater rates of health care service use. These findings highlight the complexity of female Veteran health care and support the development of enhanced comprehensive women’s health services within the VA.
doi:10.1016/j.whi.2010.08.001
PMCID: PMC3138124  PMID: 21185994
21.  Virologic and immunologic response to HAART, by age and regimen class 
AIDS (London, England)  2010;24(16):2469-2479.
Objective
To determine the impact of age and initial HAART regimen class on virologic and immunologic response within 24 months after initiation.
Design
Pooled analysis of data from 19 prospective cohort studies in the North American AIDS Cohort Collaboration on Research and Design (NA-ACCORD).
Methods
Twelve thousand, one hundred and ninety-six antiretroviral-naive adults who initiated HAART between 1998 and 2008 using a boosted protease inhibitor-based regimen or a nonnucleoside reverse transcriptase inhibitor (NNRTI)-based regimen were included in our study. Discrete time-to-event models estimated adjusted hazard odds ratios (aHOR) and 95% confidence intervals (CIs) for suppressed viral load (≤500 copies/ml) and, separately, at least 100 cells/μl increase in CD4 cell count. Truncated, stabilized inverse probability weights accounted for selection biases from discontinuation of initial regimen class.
Results
Among 12 196 eligible participants (mean age = 42 years), 50% changed regimen classes after initiation (57 and 48% of whom initiated protease inhibitor and NNRTI-based regimens, respectively). Mean CD4 cell count at initiation was similar by age. Virologic response to treatment was less likely in those initiating using a boosted protease inhibitor [aHOR = 0.77 (0.73, 0.82)], regardless of age. Immunologic response decreased with increasing age [18–<30: ref; 30–<40: aHOR 0.92 (0.85, 1.00); 40–<50: aHOR = 0.85 (0.78, 0.92); 50–<60: aHOR = 0.82 (0.74, 0.90); ≥60: aHOR=0.74 (0.65, 0.85)], regardless of initial regimen.
Conclusion
We found no evidence of an interaction between age and initial anti-retroviral regimen on virologic or immunologic response to HAART; however, decreased immunologic response with increasing age may have implications for age-specific when-to-start guidelines.
doi:10.1097/QAD.0b013e32833e6d14
PMCID: PMC3136814  PMID: 20829678
age; CD4 lymphocyte count; HAART; HIV; viral load
22.  Hepatitis C treatment completion rates in routine clinical care 
Background
Treatment completion rates for hepatitis C virus (HCV) infection in clinical practice settings are unknown.
Methods
We assembled a national cohort of HCV-infected veterans-in-care from 1998 to 2003, using the VA National Patient Care Database for demographical/clinical information, Pharmacy Benefits Management database for pharmacy records and the Decision Support Systems database for laboratory data. We used logistic regression to determine the factors predicting treatment non-completion for HCV.
Results
We identified 134 934 HCV-infected veterans of whom 16 043 [11.9%; 95% confidence interval (CI) 11.7–12.1] were prescribed treatment for HCV. Among the 10 641 veterans with > 1 year of follow-up, 2396 (22.5%; 95% CI 21.7–23.3) completed a 48-week course. Non-completers were more likely to have pre-treatment anaemia, coronary artery disease, depression, substance abuse, used standard interferon, higher comorbidity count, and been treated at a low-volume treatment site (defined as sites initiating HCV treatment for < 200 individuals). In multivariable analyses, treatment completion was positively associated with pegylated interferon use [odds ratio (OR) 1.59, 95% CI 1.40–1.80] and site treatment volume (OR 1.87, 95% CI 1.56–2.24 for sites initiating treatment for > 200 individuals) and negatively associated with pre-treatment anaemia (OR 0.68, 95% CI 0.58–0.80 for haemoglobin 10–14 g/dl) and depression (OR 0.78, 95% CI 0.69–0.89). Human immunodeficiency virus coinfection and minority race were not associated with failing to complete treatment.
Conclusions
Among veterans-in-care with known HCV, 11.9% initiate therapy of whom 22.5% (one in 56 with known HCV infection) complete a 48-week course of treatment. Higher completion rates among higher volume treatment sites suggest that some factors associated with non-completion (pre-treatment depression and anaemia), may be modifiable with experience.
doi:10.1111/j.1478-3231.2009.02156.x
PMCID: PMC3132089  PMID: 19889081
anaemia; depression; hepatitis C; HIV infection; pegylated interferon; practice variation; treatment completion
23.  Workshop on HIV Infection and Aging: What Is Known and Future Research Directions 
Highly active antiretroviral treatment has resulted in dramatically increased life expectancy among patients with HIV infection who are now aging while receiving treatment and are at risk of developing chronic diseases associated with advanced age. Similarities between aging and the courses of human immunodeficiency virus (HIV) infection and acquired immunodeficiency syndrome suggest that HIV infection compresses the aging process, perhaps accelerating comorbidities and frailty. In a workshop organized by the Association of Specialty Professors, the Infectious Diseases Society of America, the HIV Medical Association, the National Institute on Aging, and the National Institute on Allergy and Infectious Diseases, researchers in infectious diseases, geriatrics, immunology, and gerontology met to review what is known about HIV infection and aging, to identify research gaps, and to suggest high priority topics for future research. Answers to the questions posed are likely to help prioritize and balance strategies to slow the progression of HIV infection, to address comorbidities and drug toxicity, and to enhance understanding about both HIV infection and aging.
doi:10.1086/590150
PMCID: PMC3130308  PMID: 18627268
24.  Time to Depression Treatment in Primary Care Among HIV-infected and Uninfected Veterans 
BACKGROUND
Multiple factors, including patient characteristics, competing demands, and clinic type, impact delivery of depression treatment in primary care.
OBJECTIVE
Assess whether depression severity and HIV serostatus have a differential effect on time to depression treatment among depressed patients receiving primary care at Infectious Disease or General Medicine clinics.
DESIGN
Multicenter prospective cohort, (Veterans Aging Cohort Study), comparing HIV-infected to uninfected patients.
PARTICIPANTS AND MEASURES
The total cohort consisted of 3,239 HIV-infected and 3,227 uninfected patients. Study inclusion criteria were untreated depressive symptoms, based on a Patient Health Questionnaire (PHQ-9) score of greater than 9, and no antidepressants or mental health visits in the 90 days prior to PHQ-9 assessment. Treatment was defined as antidepressant receipt or mental health visit within 90 days following PHQ-9 assessment. Depression severity based on PHQ-9 scores was defined as mild-moderate (greater than 9 to 19) and severe (20 or greater). Kaplan-Meier curves were used to estimate time to treatment by depression severity and HIV serostatus. Cox proportional hazards methods adjusted for covariates were used.
KEY RESULTS
Overall, 718 (11%) of the cohort met inclusion criteria, 258 (36%) of whom received treatment. Median time to treatment was 7 days [95% confidence interval (CI) = 4, 13] and was shortest for severely depressed HIV-infected patients (0.5 days; 95% CI = 0.5, 6, p = 0.04). Compared to mildly-moderately depressed uninfected patients, severely depressed HIV-infected patients were significantly more likely to receive treatment [adjusted hazard ratio (HR) 1.67, 95% CI = 1.07, 2.60), whereas mildly-moderately depressed HIV-infected patients (adjusted HR 1.10, 95% CI = 0.79, 1.52) and severely depressed uninfected patients (adjusted HR 0.93, 95% CI = 0.60, 1.44) were not.
CONCLUSIONS
In this large cohort, time to primary care treatment of depression was shortest among severely depressed HIV-infected patients. Regardless of HIV serostatus, if depression was not treated on the assessment day, then it was unlikely to be treated within a 90-day period, leading to the majority of depression being untreated.
doi:10.1007/s11606-010-1323-z
PMCID: PMC2881956  PMID: 20405335
AIDS; antidepressant drugs; HIV; major depression; psychotherapy
25.  Influence of Alternative Thresholds for Initiating HIV Treatment on Life Expectancy and Quality-Adjusted Life Expectancy: A Decision Model 
Annals of internal medicine  2008;148(3):178-185.
Background
The optimal threshold for initiating HIV treatment is unclear.
Objective
To compare different thresholds for initiating HIV treatment.
Design
We used our validated computer simulation to weigh important harms from earlier initiation of antiretroviral therapy (toxicity, side effects, and resistance accumulation) against important benefits (decreased HIV-related mortality).
Data Sources
Veterans Aging Cohort Study (5742 HIV-infected patients and 11 484 matched uninfected controls) and published reports.
Target Population
Individuals with newly diagnosed chronic HIV infection and varying viral loads (10 000, 30 000, 100 000, and 300 000 copies/mL) and ages (30, 40, and 50 years).
Time Horizon
Unlimited.
Perspective
Societal.
Intervention
Alternative thresholds for initiating antiretroviral therapy (CD4 counts of 200, 350, and 500 cells/mm3).
Outcome Measures
Life-years and quality-adjusted life-years (QALYs).
Results of Base-Case Analysis
Although the simulation was biased against earlier treatment initiation because it used an upper-bound assumption for therapy-related toxicity, earlier treatment increased life expectancy and QALYs at age 30 years regardless of viral load (life expectancies with CD4 initiation thresholds of 500, 350, and 200 cells/mm3 were 18.2 years, 17.6 years, and 17.2 years, respectively, for a viral load of 10 000 copies/mL and 17.3 years, 15.9 years, and 14.5 years, respectively, for a viral load of 300 000 copies/mL), and increased life expectancies at age 40 years if viral loads were greater than 30 000 copies/mL (life expectancies were 12.5 years, 12.0 years, and 11.4 years, respectively, for a viral load of 300 000 copies/mL).
Results of Sensitivity Analysis
Findings favoring early treatment were generally robust.
Limitations
Results favoring later treatment may not be valid. The findings may not be generalizable to women.
Conclusions
This simulation suggests that earlier initiation of combination antiretroviral therapy is often favored compared with current recommendations.
PMCID: PMC3124094  PMID: 18252681

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