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1.  Hepatitis C Viremia and the Risk of Chronic Kidney Disease in HIV-Infected Individuals 
Lucas, Gregory M. | Jing, Yuezhou | Sulkowski, Mark | Abraham, Alison G. | Estrella, Michelle M. | Atta, Mohamed G. | Fine, Derek M. | Klein, Marina B. | Silverberg, Michael J. | Gill, M. John | Moore, Richard D. | Gebo, Kelly A. | Sterling, Timothy R. | Butt, Adeel A. | Kirk, Gregory D. | Benson, Constance A. | Bosch, Ronald J. | Collier, Ann C. | Boswell, Stephen | Grasso, Chris | Mayer, Ken | Hogg, Robert S. | Harrigan, Richard | Montaner, Julio | Cescon, Angela | Brooks, John T. | Buchacz, Kate | Gebo, Kelly A. | Moore, Richard D. | Carey, John T. | Rodriguez, Benigno | Horberg, Michael A. | Silverberg, Michael J. | Horberg, Michael A. | Thorne, Jennifer E. | Goedert, James J. | Jacobson, Lisa P. | Klein, Marina B. | Rourke, Sean B. | Burchell, Ann | Rachlis, Anita R. | Rico, Puerto | Hunter-Mellado, Robert F. | Mayor, Angel M. | Gill, M. John | Deeks, Steven G. | Martin, Jeffrey N. | Patel, Pragna | Brooks, John T. | Saag, Michael S. | Mugavero, Michael J. | Willig, James | Eron, Joseph J. | Napravnik, Sonia | Kitahata, Mari M. | Crane, Heidi M. | Justice, Amy C. | Dubrow, Robert | Fiellin, David | Sterling, Timothy R. | Haas, David | Bebawy, Sally | Turner, Megan | Gange, Stephen J. | Anastos, Kathryn | Moore, Richard D. | Saag, Michael S. | Gange, Stephen J. | Kitahata, Mari M. | McKaig, Rosemary G. | Justice, Amy C. | Freeman, Aimee M. | Moore, Richard D. | Freeman, Aimee M. | Lent, Carol | Kitahata, Mari M. | Van Rompaey, Stephen E. | Crane, Heidi M. | Webster, Eric | Morton, Liz | Simon, Brenda | Gange, Stephen J. | Althoff, Keri N. | Abraham, Alison G. | Lau, Bryan | Zhang, Jinbing | Jing, Jerry | Golub, Elizabeth | Modur, Shari | Hanna, David B. | Rebeiro, Peter | Wong, Cherise | Mendes, Adell
The Journal of Infectious Diseases  2013;208(8):1240-1249.
Background. The role of active hepatitis C virus (HCV) replication in chronic kidney disease (CKD) risk has not been clarified.
Methods. We compared CKD incidence in a large cohort of HIV-infected subjects who were HCV seronegative, HCV viremic (detectable HCV RNA), or HCV aviremic (HCV seropositive, undetectable HCV RNA). Stages 3 and 5 CKD were defined according to standard criteria. Progressive CKD was defined as a sustained 25% glomerular filtration rate (GFR) decrease from baseline to a GFR < 60 mL/min/1.73 m2. We used Cox models to calculate adjusted hazard ratios (HRs) and 95% confidence intervals (CIs).
Results. A total of 52 602 HCV seronegative, 9508 HCV viremic, and 913 HCV aviremic subjects were included. Compared with HCV seronegative subjects, HCV viremic subjects were at increased risk for stage 3 CKD (adjusted HR 1.36 [95% CI, 1.26, 1.46]), stage 5 CKD (1.95 [1.64, 2.31]), and progressive CKD (1.31 [1.19, 1.44]), while HCV aviremic subjects were also at increased risk for stage 3 CKD (1.19 [0.98, 1.45]), stage 5 CKD (1.69 [1.07, 2.65]), and progressive CKD (1.31 [1.02, 1.68]).
Conclusions. Compared with HIV-infected subjects who were HCV seronegative, both HCV viremic and HCV aviremic individuals were at increased risk for moderate and advanced CKD.
PMCID: PMC3778973  PMID: 23904290
HIV; hepatitis C virus; chronic kidney disease; hepatitis C RNA; cohort study; glomerular filtration rate; injection drug use
2.  Trends and Disparities in Antiretroviral Therapy Initiation and Virologic Suppression Among Newly Treatment-Eligible HIV-Infected Individuals in North America, 2001–2009 
Hanna, David B. | Buchacz, Kate | Gebo, Kelly A. | Hessol, Nancy A. | Horberg, Michael A. | Jacobson, Lisa P. | Kirk, Gregory D. | Kitahata, Mari M. | Korthuis, P. Todd | Moore, Richard D. | Napravnik, Sonia | Patel, Pragna | Silverberg, Michael J. | Sterling, Timothy R. | Willig, James H. | Lau, Bryan | Althoff, Keri N. | Crane, Heidi M. | Collier, Ann C. | Samji, Hasina | Thorne, Jennifer E. | Gill, M. John | Klein, Marina B. | Martin, Jeffrey N. | Rodriguez, Benigno | Rourke, Sean B. | Gange, Stephen J. | Benson, A. | Bosch, Ronald J. | Collier, Ann C. | Boswell, Stephen | Grasso, Chris | Mayer, Ken | Hogg, Robert S. | Harrigan, Richard | Montaner, Julio | Cescon, Angela | Brooks, John T. | Buchacz, Kate | Gebo, Kelly A. | Moore, Richard D. | Rodriguez, Benigno | Horberg, Michael A. | Silverberg, Michael J. | Thorne, Jennifer E. | Goedert, James J. | Jacobson, Lisa P. | Klein, Marina B. | Rourke, Sean B. | Burchell, Ann | Rachlis, Anita R. | Hunter-Mellado, Robert F. | Mayor, Angel M. | Gill, M. John | Deeks, Steven G. | Martin, Jeffrey N. | Saag, Michael S. | Mugavero, Michael J. | Willig, James | Eron, Joseph J. | Napravnik, Sonia | Kitahata, Mari M. | Crane, Heidi M. | Justice, Amy C. | Dubrow, Robert | Fiellin, David | Sterling, Timothy R. | Haas, David | Bebawy, Sally | Turner, Megan | Gange, Stephen J. | Anastos, Kathryn | Moore, Richard D. | Saag, Michael S. | Gange, Stephen J. | Kitahata, Mari M. | McKaig, Rosemary G. | Justice, Amy C. | Freeman, Aimee M. | Moore, Richard D. | Freeman, Aimee M. | Lent, Carol | Platt, Aaron | Kitahata, Mari M. | Van Rompaey, Stephen E. | Crane, Heidi M. | Webster, Eric | Morton, Liz | Simon, Brenda | Gange, Stephen J. | Abraham, Alison G. | Lau, Bryan | Althoff, Keri N. | Zhang, Jinbing | Jing, Jerry | Golub, Elizabeth | Modur, Shari | Hanna, David B. | Rebeiro, Peter | Wong, Cherise | Mendes, Adell
In the last decade, timely initiation of antiretroviral therapy and resulting virologic suppression have greatly improved in North America concurrent with the development of better tolerated and more potent regimens, but significant barriers to treatment uptake remain.
Background. Since the mid-1990s, effective antiretroviral therapy (ART) regimens have improved in potency, tolerability, ease of use, and class diversity. We sought to examine trends in treatment initiation and resulting human immunodeficiency virus (HIV) virologic suppression in North America between 2001 and 2009, and demographic and geographic disparities in these outcomes.
Methods. We analyzed data on HIV-infected individuals newly clinically eligible for ART (ie, first reported CD4+ count <350 cells/µL or AIDS-defining illness, based on treatment guidelines during the study period) from 17 North American AIDS Cohort Collaboration on Research and Design cohorts. Outcomes included timely ART initiation (within 6 months of eligibility) and virologic suppression (≤500 copies/mL, within 1 year). We examined time trends and considered differences by geographic location, age, sex, transmission risk, race/ethnicity, CD4+ count, and viral load, and documented psychosocial barriers to ART initiation, including non–injection drug abuse, alcohol abuse, and mental illness.
Results. Among 10 692 HIV-infected individuals, the cumulative incidence of 6-month ART initiation increased from 51% in 2001 to 72% in 2009 (Ptrend < .001). The cumulative incidence of 1-year virologic suppression increased from 55% to 81%, and among ART initiators, from 84% to 93% (both Ptrend < .001). A greater number of psychosocial barriers were associated with decreased ART initiation, but not virologic suppression once ART was initiated. We found significant heterogeneity by state or province of residence (P < .001).
Conclusions. In the last decade, timely ART initiation and virologic suppression have greatly improved in North America concurrent with the development of better-tolerated and more potent regimens, but significant barriers to treatment uptake remain, both at the individual level and systemwide.
PMCID: PMC3657490  PMID: 23315317
antiretroviral therapy; healthcare disparities; HIV; time factors; viral load
3.  Medicare and Medicaid enrollment and outside hospitalizations among HIV-infected and uninfected veterans engaged in VA care: a retrospective cohort study 
Many veterans engaged in care with the Veterans Administration (VA) health system are also enrolled in Medicare and/or Medicaid and may receive care both inside and outside of the VA. Use of dual health systems has been associated with worse outcomes. Veterans with HIV may have different rates of Medicare and Medicaid enrollment and may be at greater risk of poor outcomes related to non-VA use. This study compares the frequency and factors associated with Medicare and/or Medicaid enrollment and non-VA use in an HIV-infected and uninfected population of veterans.
We used data from the VA and Center for Medicare & Medicaid Services from 2004 and 2005 to determine the frequency of Medicare and/or Medicaid enrollment among a cohort of HIV-infected and uninfected veterans engaged in VA care. We then restricted the cohort to veterans enrolled in fee-for-service (FFS) Medicare and/or Medicaid with at least one hospitalization and identified characteristics associated with non-VA hospital admissions.
HIV-infected veterans had higher rates of Medicare and/or Medicaid enrollment than uninfected veterans (38% vs. 33%, p < 0.01), though the opposite was true when our sample was limited to veterans 65 years and older (53% vs. 70%, p < 0.0 1). Among veterans enrolled in the VA and FFS Medicare and/or Medicaid, veterans with HIV had greater illness severity and more frequent hospitalizations, but were less likely to be hospitalized outside the VA (48% vs. 54%, p < 0.01). HIV infection was associated with lower odds of outside hospitalization (OR = 0.76 [95% CI: 0.68, 0.85]).
Veterans with HIV have higher rates of Medicare and/or Medicaid enrollment, but lower odds of non-VA hospitalization. The VA integrated model of HIV care may discourage outside use among HIV-infected veterans.
PMCID: PMC4307747  PMID: 25608566
HIV; AIDS; Veterans; Medicare; Medicaid; Fragmentation
4.  CD8+ T-Cells Count in Acute Myocardial Infarction in HIV Disease in a Predominantly Male Cohort 
BioMed Research International  2015;2015:246870.
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 < 0.001, 95% CI: 1.46 to 2.28). There was evidence that the effect of CD8+ T-cell tertiles on AMI risk differed by CD4+ T-cell level: compared to uninfected people, HIV-infected people with CD4+ T-cell counts ≥200 cells/mm3 had increased AMI risk with high CD8+ T-cell count, while those with CD4+ T-cell counts <200 cells/mm3 had increased AMI risk with low CD8+ T-cell count. CD8+ T-cell counts may add additional AMI risk stratification information beyond that provided by CD4+ T-cell counts alone.
PMCID: PMC4320893
5.  Cancer Incidence in HIV-Infected Versus Uninfected Veterans: Comparison of Cancer Registry and ICD-9 Code Diagnoses 
Given the growing interest in the cancer burden in persons living with HIV/AIDS, we examined the validity of data sources for cancer diagnoses (cancer registry versus International Classification of Diseases, Ninth Revision [ICD-9 codes]) and compared the association between HIV status and cancer risk using each data source in the Veterans Aging Cohort Study (VACS), a prospective cohort of HIV-infected and uninfected veterans from 1996 to 2008.
We reviewed charts to confirm potential incident cancers at four VACS sites. In the entire cohort, we calculated cancer-type-specific age-, sex-, race/ethnicity-, and calendar-period-standardized incidence rates and incidence rate ratios (IRR) (HIV-infected versus uninfected). We calculated standardized incidence ratios (SIR) to compare VACS and Surveillance, Epidemiology, and End Results rates.
Compared to chart review, both Veterans Affairs Central Cancer Registry (VACCR) and ICD-9 diagnoses had approximately 90% sensitivity; however, VACCR had higher positive predictive value (96% versus 63%). There were 6,010 VACCR and 13,386 ICD-9 incident cancers among 116,072 veterans. Although ICD-9 rates tended to be double VACCR rates, most IRRs were in the same direction and of similar magnitude, regardless of data source. Using either source, all cancers combined, most viral-infection-related cancers, lung cancer, melanoma, and leukemia had significantly elevated IRRs. Using ICD-9, eight additional IRRs were significantly elevated, most likely due to false positive diagnoses. Most ICD-9 SIRs were significantly elevated and all were higher than the corresponding VACCR SIR.
ICD-9 may be used with caution for estimating IRRs, but should be avoided when estimating incidence or SIRs. Elevated cancer risk based on VACCR diagnoses among HIV-infected veterans was consistent with other studies.
PMCID: PMC4285627  PMID: 25580366
Neoplasms; Registries; International Classification of Diseases; HIV Infections
6.  An internationally generalizable risk index for mortality after one year of antiretroviral therapy 
AIDS (London, England)  2013;27(4):563-572.
Despite the success of antiretroviral therapy (ART), excess mortality continues for those with HIV infection. A comprehensive approach to risk assessment, addressing multiorgan system injury on ART, is needed. We sought to develop and validate a practical and generalizable mortality risk index for HIV-infected individuals on ART.
Design and methods
The Veterans Aging Cohort Study (VACS) was used to develop the VACS Index, based on age, CD4 cell count, HIV-1 RNA, hemoglobin, aspartate and alanine transaminase, platelets, creatinine and hepatitis C status, and a Restricted Index based on age, CD4 cell count and HIV-1 RNA with an outcome of death up to 6 years after ART initiation. Validation was in six independent cohorts participating in the ART Cohort Collaboration (ART-CC).
In both the development (4932 patients, 656 deaths) and validation cohorts (3146 patients, 86 deaths) the VACS Index had better discrimination than the Restricted Index (c-statistics 0.78 and 0.72 in VACS, 0.82 and 0.78 in ART-CC). The VACS Index also demonstrated better discrimination than the Restricted Index for HIV deaths and non-HIV deaths, in men and women, those younger and older than 50 years, with and without detectable HIV-1 RNA, and with or without HCV coinfection.
Among HIV-infected patients treated with ART, the VACS Index more accurately discriminates mortality risk than traditional HIV markers and age alone. By accounting for multiorgan system injury, the VACS Index may prove a useful tool in clinical care and research.
PMCID: PMC4283204  PMID: 23095314
anemia; cohort study; comorbidity; FIB-4; HIV; mortality; prognostic index
7.  Medical ICU Admission Diagnoses and Outcomes in Human Immunodeficiency Virus–Infected and Virus–Uninfected Veterans in the Combination Antiretroviral Era 
Critical care medicine  2013;41(6):1458-1467.
Human 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.
Observational data analyses (Veterans Aging Cohort Study).
Eight Veterans Affairs medical centers nationwide.
HIV infected and uninfected with a medical ICU admission between 2002 and 2010.
Measurements and Main Results
Medical 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.
Medical 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.
PMCID: PMC4283206  PMID: 23507717
30-day mortality; comorbidity; human immunodeficiency virus; medical ICU; Veterans Aging Cohort Study Index
8.  Prehypertension, Hypertension, and the Risk of Acute Myocardial Infarction in HIV-Infected and -Uninfected Veterans 
We found increased acute myocardial infarction risk among hypertensive and prehypertensive HIV-infected veterans compared to normotensive uninfected veterans, independent of confounding comorbidities.
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 (<140/90 or <130/80 mm Hg) as their uninfected counterparts. Whether HIV-infected people with elevated BP have excess AMI risk compared to uninfected people is not known. This study examines whether the association between elevated BP and AMI risk differs by HIV status.
Methods. The Veterans Aging Cohort Study Virtual Cohort (VACS VC) consists of HIV-infected and -uninfected veterans matched 1:2 on age, sex, race/ethnicity, and clinical site. For this analysis, we analyzed 81 026 people with available BP data from VACS VC, who were free of cardiovascular disease at baseline. BP was the average of the 3 routine outpatient clinical measurements performed closest to baseline (first clinical visit after April 2003). BP categories used in the analyses were based on criteria of the Seventh Report of the Joint National Committee on Prevention, Detection, Evaluation, and Treatment of High Blood Pressure. Analyses were performed using Cox proportional hazards regression.
Results. Over 5.9 years (median), 860 incident AMIs occurred. Low/high prehypertensive and untreated/treated hypertensive HIV-infected individuals had increased AMI risk compared to uninfected, untreated normotensive individuals (hazard ratio [HR], 1.60 [95% confidence interval {CI}, 1.07–2.39]; HR, 1.81 [95% CI, 1.22–2.68]; HR, 2.57 [95% CI, 1.76–3.76]; and HR, 2.76 [95% CI, 1.90–4.02], respectively).
Conclusions. HIV, prehypertensive BP, and hypertensive BP were associated with an increased risk of AMI in a cohort of HIV-infected and -uninfected veterans. Future studies should prospectively investigate whether HIV interacts with BP to further increase AMI risk.
PMCID: PMC3864500  PMID: 24065316
blood pressure; prehypertension; HIV; myocardial infarction
9.  Hepatic Decompensation in Antiretroviral-Treated HIV/Hepatitis C-Coinfected Compared to Hepatitis C-Monoinfected Patients: A Cohort Study 
Annals of internal medicine  2014;160(6):369-379.
The incidence and determinants of hepatic decompensation have been incompletely examined among HIV/hepatitis C virus (HCV)-coinfected patients in the antiretroviral therapy (ART) era, and few studies have compared rates of outcomes to those of patients with chronic HCV alone.
To compare the incidence of hepatic decompensation between antiretroviral-treated HIV/HCV-coinfected and HCV-monoinfected patients, and evaluate factors associated with decompensation among coinfected patients on ART.
Retrospective cohort study.
Veterans Health Administration.
4,280 HIV/HCV-coinfected patients who initiated ART and 6,079 HCV-monoinfected patients receiving care between 1997 and 2010. All patients had detectable HCV RNA and were HCV treatment-naïve.
Incident hepatic decompensation, determined by diagnoses of ascites, spontaneous bacterial peritonitis, or esophageal variceal hemorrhage.
The incidence of hepatic decompensation was greater among coinfected than monoinfected patients (at 10 years: 7.4% versus 4.8%; p<0.001). Compared to HCV-monoinfected patients, antiretroviral-treated HIV/HCV-coinfected patients had a higher rate of hepatic decompensation (hazard ratio [HR] accounting for competing risks, 1.56 [95% confidence interval (CI), 1.31–1.86]). Coinfected patients who maintained HIV RNA levels <1,000 copies/mL still had higher rates of decompensation than HCV-monoinfected patients (HR, 1.44 [95% CI, 1.05–1.99]). Baseline advanced hepatic fibrosis (FIB-4 >3.25; HR, 5.45 [95% CI, 3.79–7.84]), baseline hemoglobin <10 g/dL (HR, 2.24 [CI, 1.20–4.20]), diabetes mellitus (HR, 1.88[95% CI, 1.38–2.56]), and non-black race (HR, 2.12 [95% CI, 1.65–2.72]) were each associated with higher rates of decompensation among coinfected patients on ART.
Observational study of predominantly male patients.
Despite ART, HIV/HCV-coinfected patients had higher rates of hepatic decompensation than HCV-monoinfected individuals. Rates of decompensation were higher for coinfected patients with advanced liver fibrosis, severe anemia, diabetes, and non-black race.
PMCID: PMC4254786  PMID: 24723077
hepatic decompensation; end-stage liver disease; HIV/HCV coinfection; HIV; hepatitis C
10.  Acetaminophen Receipt Among HIV-Infected Patients with Advanced Hepatic Fibrosis 
Pharmacoepidemiology and drug safety  2013;22(12):1352-1356.
HIV-infected patients may be at particular risk for acetaminophen-induced hepatotoxicity, but acetaminophen use in the context of liver injury has been incompletely examined among HIV-infected patients. Among a sample of HIV-infected patients, we aimed to determine acetaminophen exposure; assess the cross-sectional association between acetaminophen exposure and advanced hepatic fibrosis; and determine whether factors associated with acetaminophen exposure varied by HCV status.
We conducted a cross-sectional analysis of the Veterans Aging Cohort Study. Advanced hepatic fibrosis was defined as a FIB-4 > 3.25, a composite score calculated based on age, alanine aminotransferase, aspartate aminotransferase and platelet count. Multivariable ordered polytomous logistic regression was used to determine the association between FIB-4 status and acetaminophen exposure stratified by HCV status.
Among HIV-infected patients (n=14,885), 31% received at least one acetaminophen prescription. Among those receiving acetaminophen, acetaminophen overuse was common among both HIV-monoinfected and HIV/HCV-coinfected patients (846 [31%] vs. 596[32%], p=0.79). After stratifying by HCV status, those with evidence of advanced liver fibrosis were equally likely to be exposed to acetaminophen. Further, HIV-monoinfected patients with an alcohol use disorder were more likely to have acetaminophen overuse (OR [95% CI]=1.56 [1.21, 2.02]).
Strategies to minimize acetaminophen exposure, especially for HIV-monoinfected patients, are warranted.
PMCID: PMC4164158  PMID: 24285468
acetaminophen; HIV; Hepatitis C; Veterans; medication
11.  Risk factors for hospitalization and medical intensive care unit (MICU) admission among HIV infected Veterans 
With 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.
We analyzed data from the Veterans Aging Cohort Study (VACS), a prospective study of HIV-infected Veterans receiving care between 2002–2008. 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.
1141/3410 (33.5%) patients were hospitalized within 2 years; 203/1141 (17.8%) included a 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.
The VACS Index predicted hospitalization and MICU admission as did current smoking, hazardous alcohol use, and AIDS and certain non-AIDS diagnoses.
PMCID: PMC4182723  PMID: 23111572
HIV; hospitalization; medical intensive care unit (MICU); aging; VACS Index; comorbidity
12.  Mortality in Patients with HIV-1 Infection Starting Antiretroviral Therapy in South Africa, Europe, or North America: A Collaborative Analysis of Prospective Studies 
PLoS Medicine  2014;11(9):e1001718.
Analyzing survival in HIV treatment cohorts, Andrew Boulle and colleagues find mortality rates in South Africa comparable to or better than those in North America by 4 years after starting antiretroviral therapy.
Please see later in the article for the Editors' Summary
High early mortality in patients with HIV-1 starting antiretroviral therapy (ART) in sub-Saharan Africa, compared to Europe and North America, is well documented. Longer-term comparisons between settings have been limited by poor ascertainment of mortality in high burden African settings. This study aimed to compare mortality up to four years on ART between South Africa, Europe, and North America.
Methods and Findings
Data from four South African cohorts in which patients lost to follow-up (LTF) could be linked to the national population register to determine vital status were combined with data from Europe and North America. Cumulative mortality, crude and adjusted (for characteristics at ART initiation) mortality rate ratios (relative to South Africa), and predicted mortality rates were described by region at 0–3, 3–6, 6–12, 12–24, and 24–48 months on ART for the period 2001–2010. Of the adults included (30,467 [South Africa], 29,727 [Europe], and 7,160 [North America]), 20,306 (67%), 9,961 (34%), and 824 (12%) were women. Patients began treatment with markedly more advanced disease in South Africa (median CD4 count 102, 213, and 172 cells/µl in South Africa, Europe, and North America, respectively). High early mortality after starting ART in South Africa occurred mainly in patients starting ART with CD4 count <50 cells/µl. Cumulative mortality at 4 years was 16.6%, 4.7%, and 15.3% in South Africa, Europe, and North America, respectively. Mortality was initially much lower in Europe and North America than South Africa, but the differences were reduced or reversed (North America) at longer durations on ART (adjusted rate ratios 0.46, 95% CI 0.37–0.58, and 1.62, 95% CI 1.27–2.05 between 24 and 48 months on ART comparing Europe and North America to South Africa). While bias due to under-ascertainment of mortality was minimised through death registry linkage, residual bias could still be present due to differing approaches to and frequency of linkage.
After accounting for under-ascertainment of mortality, with increasing duration on ART, the mortality rate on HIV treatment in South Africa declines to levels comparable to or below those described in participating North American cohorts, while substantially narrowing the differential with the European cohorts.
Please see later in the article for the Editors' Summary
Editors' Summary
AIDS has killed about 36 million people since the first recorded case of the disease in 1981, and a similar number of people (including 25 million living in sub-Saharan Africa) are currently infected with HIV, the virus that causes AIDS. HIV destroys immune system cells (including CD4 cells, a type of lymphocyte), leaving infected individuals susceptible to other serious infections. Early in the AIDS epidemic, HIV-positive people usually died within 10 years of becoming infected. In 1996, effective antiretroviral therapy (ART) became available and, for people living in high-income countries, HIV infection became a chronic condition. But ART was expensive, so HIV/AIDS remained largely untreated and fatal in resource-limited countries. Then, in 2003, the international community began to work towards achieving universal access to ART. By the end of 2012, nearly two-thirds of HIV-positive people (nearly 10 million individuals) living in low- and middle-income countries who were eligible for treatment because their CD4 cell count had fallen below 350/mm3 blood or because they had developed an AIDS-defining condition were receiving treatment.
Why Was This Study Done?
It is known that a larger proportion of HIV-positive patients starting ART die during the first year of treatment in sub-Saharan Africa than in Europe and North America. This difference arises in part because patients in resource-limited settings tend to have lower CD4 counts when they start treatment than patients in wealthy countries. However, the lack of reliable data on mortality (death) in resource-limited settings has made it hard to compare longer-term outcomes in different settings. Information on the long-term outcomes of HIV-positive patients receiving ART in resource-limited countries is needed to guide the development of appropriate health systems and treatment regimens in these settings. In this collaborative analysis of prospective cohort studies, the researchers compare mortality up to 4 years on ART in South Africa, Europe, and North America. A prospective cohort study follows a group of individuals over time to see whether differences in specific characteristics at the start of the study affect subsequent outcomes. A collaborative analysis combines individual patient data from several studies.
What Did the Researchers Do and Find?
The researchers combined data from four South Africa cohorts of HIV-positive patients starting ART included in the International Epidemiologic Databases to Evaluate AIDS South African (IeDEA-SA) collaboration with data from six North American cohorts and nine European cohorts included in the ART Cohort Collaboration (ART-CC). The South African cohorts were chosen because unusually for studies undertaken in countries in sub-Saharan Africa the vital status of patients (whether they had died) who had been lost to follow-up in these cohorts could be obtained from the national population register. Patients in South Africa began treatment with more advanced disease (indicated by a lower average CD4 count) than patients in Europe or North America. Notably, high early mortality after starting ART in South Africa occurred mainly in patients starting ART with a CD4 count below 50 cells/mm3. The cumulative mortality after 4 years of ART was 16.6%, 4.7%, and 15.3% in South Africa, Europe, and North America, respectively. After adjusting for patient characteristics at ART initiation, the mortality rate among patients beginning ART was initially lower in Europe and North American than in South Africa. However, although the adjusted mortality rate in Europe remained lower than the rate in South Africa, the rate in North America was higher than that in South Africa between 24 and 48 months on ART.
What Do These Findings Mean?
Although the linkage to national vital registration systems (databases of births and deaths) undertaken in this collaborative analysis is likely to have greatly reduced bias due to under-ascertainment of mortality, the accuracy of these findings may still be limited by differences in how this linkage was undertaken in different settings. Nevertheless, these findings suggest that mortality among HIV-infected patients receiving ART in South Africa, although initially higher than in Europe and North America, rapidly declines with increasing duration on ART and, after 4 years of treatment, approaches the rate seen in high-income settings. Intriguingly, these findings also highlight the relatively higher late mortality in North America compared to either Europe or South Africa, a result that needs to be investigated to explore the extent to which differences in mortality ascertainment, patient characteristics and comorbidities, or health systems and treatment regimens contribute to variations in outcomes among HIV-positive patients in various settings.
Additional Information
Please access these websites via the online version of this summary at
This study is further discussed in a PLOS Medicine Perspective by Agnes Binagwaho and colleagues
Information is available from the US National Institute of Allergy and Infectious Diseases on HIV infection and AIDS
NAM/aidsmap provides basic information about HIV/AIDS, and summaries of recent research findings on HIV care and treatment
Information is available from Avert, an international AIDS charity, on many aspects of HIV/AIDS, including information on universal access to ART, on HIV and AIDS in sub-Saharan Africa, and on HIV and AIDS in South Africa (in English and Spanish)
The World Health Organization provides information on all aspects of HIV/AIDS (in several languages); its 2013 Consolidated guidelines on the use of antiretroviral drugs for treating and preventing HIV infections: recommendations for a public health approach are available
The 2013 UNAIDS World AIDS Day Report provides up-to-date information about the AIDS epidemic and efforts to halt it
Information about the International Epidemiologic Databases to Evaluate AIDS South African (IeDEA-SA) collaboration and about the ART Cohort Collaboration is available
Personal stories about living with HIV/AIDS are available through Avert, Nam/aidsmap, and Healthtalkonline
PMCID: PMC4159124  PMID: 25203931
13.  Association of the Veterans Aging Cohort Study Index with Exercise Capacity in HIV-Infected Adults 
AIDS Research and Human Retroviruses  2013;29(9):1218-1223.
Physical disability is a major priority in aging, affecting morbidity, mortality, and quality of life. Despite the large number of adults aging with HIV, our understanding of the physiologic and clinical risk factors for disability is limited. Our goal is to determine whether the Veterans Aging Cohort Study (VACS) Index, based on routine clinical blood tests, could serve as a point of care screening tool to identify HIV-infected adults at high risk for physical disability. HIV-infected adults enrolled in the VACS participated in a cross-sectional exercise study with established measures of strength and endurance. The VACS Index was calculated using recent clinical laboratory values and age; a higher score reflects greater mortality risk. Statistical analyses included correlation and linear regression models adjusted for muscle mass. Fifty-five HIV-infected adults, predominantly African-American men, were included with age mean±SD of 52±7 years. Median (IQR) CD4 cell count was 356 cells/mm3 (212–527). The VACS Index was inversely correlated with quadriceps strength (r=−0.45, p<0.01), grip strength (r=−0.28, p=0.04), and 6-min walk distance (r=−0.27, p=0.05). A 20-point increase in VACS Index score was associated with a 10% lower leg strength (p<0.01), which remained significant after adjustment for muscle cross-sectional area (p=0.02). The VACS Index explained 31% of the variance in specific leg strength. In this group of middle-aged adults with well-controlled HIV infection the VACS Index was significantly associated with upper and lower extremity strength. The VACS Index may be valuable for identification of patients at high risk for disability due to muscle weakness.
PMCID: PMC3749694  PMID: 23705911
14.  Validation of an Algorithm to Identify Antiretroviral-Naïve Status at Time of Entry into a Large, Observational Cohort of HIV-infected Patients 
Pharmacoepidemiology and drug safety  2013;22(9):10.1002/pds.3476.
Large, 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.
We 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.
Among 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 <400 copies/ml. Sensitivity analysis revealed that PPV would be maximized by increasing the viral load threshold, whereas sensitivity would be maximized by lowering the viral load threshold.
A prediction algorithm using available laboratory data can be used to accurately identify ART-naïve patients in large, observational HIV cohorts. Use of this algorithm will allow investigators to accurately limit analyses to ART-naïve patients when studying the contribution of ART to outcomes and adverse events.
PMCID: PMC3831617  PMID: 23836591
HIV-1; Antiretroviral Therapy, Highly Active; Cohort Studies; HIV infections/epidemiology; HIV infections/drug therapy
15.  Does social isolation predict hospitalization and mortality among HIV+ and uninfected older Veterans? 
Background and Objectives
Aging, HIV, and social isolation may affect acute care utilization and outcomes. Our objectives were to compare levels of social isolation in aging Veterans with and without HIV and determine associations with hospital admission and mortality.
Study Design, Participants, and Setting
The Veterans Aging Cohort Study (VACS) is a longitudinal study of HIV+ and uninfected Veterans at eight VA Medical Centers nationally. We analyzed data for 1,836 Veterans age ≥55 enrolled in VACS from 2002–2008.
We created a Social Isolation Score (SIS) using baseline survey responses about: relationship status, number of friends/family and frequency of visits, and involvement in volunteer work, religious or self-help groups, or other community activities. We compared scores by age and HIV status and used multivariable regression to assess effects of social isolation scores on hospital admission and all-cause mortality.
Mean SIS was higher for HIV+ patients with increasing difference by age (p=.01 for trend). Social isolation was also more prevalent for HIV+ (59%) compared to uninfected patients (51%; p<.001). In multivariable regression analysis of HIV+ and uninfected groups combined, adjusted for demographic and clinical features, isolation was independently associated with increased risk of incident hospitalization (HR=1.25, 95% CI=1.09–1.42) as well as risk of all-cause mortality (HR=1.28, 95% CI=1.06–1.54). Risk estimates calculated for HIV+ and uninfected groups separately were not significantly different.
Social isolation is associated with increased risk of hospitalization and death among both HIV+ and uninfected older Veterans. Despite similar effects in both groups, the population level impact of social isolation may be greater in those who are HIV+ because of the higher prevalence of social isolation, particularly among the oldest patients.
PMCID: PMC3773301  PMID: 23927911
Social isolation; aging; HIV/AIDS; hospitalization; mortality; outcomes of care
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.
PMCID: PMC3118467  PMID: 19537953
17.  An Experimental Study of the Agreement of Self-Administration and Telephone Administration of the Timeline Followback Interview* 
The Timeline Followback (TLFB) interview has become state-of-the-science for the collection of retrospective self-reports of daily alcohol consumption. Such data are especially useful for addressing questions of the co-occurrence of quantity of alcohol consumption and other behaviors, such as HIV-related risky sex, on the event level. The purpose of this study was to determine if the TLFB could be used effectively by self-administration compared with the more costly telephone interview in a large, multisite observational study of HIV-positive and HIV-negative adults.
An experimental design was used to compare self-administered and telephone-administered TLFB modes in a subsample (N = 70) of the Veterans Aging Cohort Study, an ongoing longitudinal study of more than 6,000 HIV-positive and HIV-negative men and women presenting for treatment at eight Department of Veterans Affairs Infectious Disease or General Medicine clinics. Participants were randomly assigned to one of four experimental groups defined by mode and sequence of a TLFB administration on two occasions occurring within 1 week: telephone-telephone, telephone-self, self-telephone, and self-self.
Analyses showed no differences in median total number of drinks reported between modes of TLFB administration or sequence of mode of administration. The same findings held for classification of participants as “hazardous” drinkers. Additional analyses showed good-to-excellent test-retest reliability of self-reports for both modes of TLFB administration.
The data derived from this study provide strong experimental evidence for the utility of the self-administered, 30-day TLFB in collecting daily alcohol consumption in large observational studies of HIV-positive and HIV-negative individuals.
PMCID: PMC3115624  PMID: 18432391
18.  Veterans Aging Cohort Study (VACS) 
Medical care  2006;44(8 Suppl 2):S13-S24.
The Veterans Aging Cohort Study (VACS) is a study of human immunodeficiency virus (HIV) infected and uninfected patients seen in infectious disease and general medical clinics. VACS includes the earlier 3 and 5 site studies (VACS 3 and VACS 5) as well as the ongoing 8 site study.
We sought to provide background and context for analyses based upon VACS data, including study design and rationale as well as its basic protocol and the baseline characteristics of the enrolled sample.
Research Design
We undertook a prospectively consented multisite observational study of veterans in care with and without HIV infection.
Data were derived from patient and provider self report, telephone interviews, blood and DNA samples, focus groups, and full access to the national VA “paperless” electronic medical record system.
More than 7200 veterans have been enrolled in at least one of the studies. The 8 site study (VACS) has enrolled 2979 HIV-infected and 3019 HIV-uninfected age–race–site matched comparators and has achieved stratified enrollment targets for race/ethnicity and age and 99% of its total target enrollment as of October 30, 2005. Participants in VACS are similar to other veterans receiving care within the VA. VACS participants are older and more predominantly black than those reported by the Centers for Disease Control.
VACS has assembled a rich, in-depth, and representative sample of veterans in care with and without HIV infection to conduct longitudinal analyses of questions concerning the association between alcohol use and related comorbid and AIDS-defining conditions.
PMCID: PMC3049942  PMID: 16849964
HIV/AIDS; alcohol; aging veterans; data management/research design
19.  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.
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.
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.
A total of 22,647 HIV + veterans in the Virtual Cohort with a visit in fiscal year 2002.
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.
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.
PMCID: PMC3032537  PMID: 19106740
laboratory; DSS; ICR; VA
20.  Physiologic Frailty and Fragility Fracture in HIV-Infected Male Veterans 
Frailty, as measured by the Veterans Aging Cohort Study Index, is an important predictor of fragility fracture in the context of established fracture risk factors. Anemia and increasing age drive this association in a male veteran population.
Background. The Veterans Aging Cohort Study (VACS) Index is associated with all-cause mortality in individuals infected with human immunodeficiency virus (HIV). It is also associated with markers of inflammation and may thus reflect physiologic frailty. This analysis explores the association between physiologic frailty, as assessed by the VACS Index, and fragility fracture.
Methods. HIV-infected men from VACS were included. We identified hip, vertebral, and upper arm fractures using ICD-9-CM codes. We used Cox regression models to assess fragility fracture risk factors including the VACS Index, its components (age, hepatitis C status, FIB-4 score, estimated glomerular filtration rate, hemoglobin, HIV RNA, CD4 count), and previously identified risk factors for fragility fractures.
Results. We included 40 115 HIV-infected male Veterans. They experienced 588 first fragility fractures over 6.0 ± 3.9 years. The VACS Index score (hazard ratio [HR], 1.15; 95% confidence interval [CI], 1.11–1.19), white race (HR, 1.92; 95% CI, 1.63–2.28), body mass index (HR, 0.94; 95% CI, .92–.96), alcohol-related diagnoses (HR, 1.65; 95% CI, 1.26–2.17), cerebrovascular disease (HR, 1.95; 95% CI, 1.14–3.33), proton pump inhibitor use (HR, 1.87; 95% CI, 1.54–2.27), and protease inhibitor use (HR, 1.25; 95% CI, 1.04–1.50) were associated with fracture risk. Components of the VACS Index score most strongly associated with fracture risk were age (HR, 1.40; 95% CI, 1.27–1.54), log HIV RNA (HR, 0.91; 95% CI, .88–.94), and hemoglobin level (HR, 0.82; 95% CI, .78–.86).
Conclusions. Frailty, as measured by the VACS Index, is an important predictor of fragility fractures among HIV-infected male Veterans.
PMCID: PMC3634308  PMID: 23378285
HIV; frailty; fragility fractures; Veterans
21.  Adjudicated Morbidity and Mortality Outcomes by Age among Individuals with HIV Infection on Suppressive Antiretroviral Therapy 
PLoS ONE  2014;9(4):e95061.
Non-AIDS conditions such as cardiovascular disease and non-AIDS defining cancers dominate causes of morbidity and mortality among persons with HIV on suppressive combination antiretroviral therapy. Accurate estimates of disease incidence and of risk factors for these conditions are important in planning preventative efforts.
With use of medical records, serious non-AIDS events, AIDS events, and causes of death were adjudicated using pre-specified criteria by an Endpoint Review Committee in two large international trials. Rates of serious non-AIDS which include cardiovascular disease, end-stage renal disease, decompensated liver disease, and non-AIDS cancer, and other serious (grade 4) adverse events were determined, overall and by age, over a median follow-up of 4.3 years for 3,570 participants with CD4+ cell count ≥300 cells/mm3 who were taking antiretroviral therapy and had an HIV RNA level ≤500 copies/mL. Cox models were used to examine the effect of age and other baseline factors on risk of a composite outcome of all-cause mortality, AIDS, or serious non-AIDS.
Five-year Kaplan-Meier estimates of the composite outcome, overall and by age were 8.3% (overall), 3.6% (<40), 8.7% (40–49) and 16.1% (≥50), respectively (p<0.001). In addition to age, smoking and higher levels of interleukin-6 and D-dimer were significant predictors of the composite outcome. The composite outcome was dominated by serious non-AIDS events (overall 65% of 277 participants with a composite event). Most serious non-AIDS events were due to cardiovascular disease and non-AIDS cancers.
To date, few large studies have carefully collected data on serious non-AIDS outcomes. Thus, reliable estimates of event rates are scarce. Data cited here, from a geographically diverse cohort, will be useful for planning studies of interventions aimed at reducing rates of serious non-AIDS events among people with HIV.
PMCID: PMC3984283  PMID: 24728071
22.  Rate and predictors of treatment prescription for hepatitis C 
Gut  2006;56(3):385-389.
The true treatment rate for hepatitis C virus (HCV) in veterans is unknown.
To determine the treatment prescription rates and predictors of treatment prescription for HCV in a large national population.
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.
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).
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.
PMCID: PMC1856823  PMID: 17005764
23.  The VACS Index Accurately Predicts Mortality and Treatment Response among Multi-Drug Resistant HIV Infected Patients Participating in the Options in Management with Antiretrovirals (OPTIMA) Study 
PLoS ONE  2014;9(3):e92606.
The VACS Index is highly predictive of all-cause mortality among HIV infected individuals within the first few years of combination antiretroviral therapy (cART). However, its accuracy among highly treatment experienced individuals and its responsiveness to treatment interventions have yet to be evaluated. We compared the accuracy and responsiveness of the VACS Index with a Restricted Index of age and traditional HIV biomarkers among patients enrolled in the OPTIMA study.
Using data from 324/339 (96%) patients in OPTIMA, we evaluated associations between indices and mortality using Kaplan-Meier estimates, proportional hazards models, Harrel’s C-statistic and net reclassification improvement (NRI). We also determined the association between study interventions and risk scores over time, and change in score and mortality.
Both the Restricted Index (c = 0.70) and VACS Index (c = 0.74) predicted mortality from baseline, but discrimination was improved with the VACS Index (NRI = 23%). Change in score from baseline to 48 weeks was more strongly associated with survival for the VACS Index than the Restricted Index with respective hazard ratios of 0.26 (95% CI 0.14–0.49) and 0.39(95% CI 0.22–0.70) among the 25% most improved scores, and 2.08 (95% CI 1.27–3.38) and 1.51 (95%CI 0.90–2.53) for the 25% least improved scores.
The VACS Index predicts all-cause mortality more accurately among multi-drug resistant, treatment experienced individuals and is more responsive to changes in risk associated with treatment intervention than an index restricted to age and HIV biomarkers. The VACS Index holds promise as an intermediate outcome for intervention research.
PMCID: PMC3965438  PMID: 24667813
24.  Agreement Between Electronic Medical Record-based and Self-Administered Pain Numeric Rating Scale: Clinical and Research Implications 
Medical care  2013;51(3):245-250.
Pain screening may improve the quality of care by identifying patients in need of further assessment and management. Many healthcare systems use the numeric rating scale (NRS) for pain screening, and record the score in the patients’ electronic medical record (EMR).
Determine level of agreement between EMR and patient survey NRS, and whether discrepancies vary by demographic and clinical characteristics.
We linked survey data from a sample of Veterans receiving care in eight Veterans Affairs (VA) medical facilities, to EMR data including an NRS collected on the day of the survey in order to compare responses to the NRS question from these two sources. We assessed correlation, agreement on clinical cut-points (e.g. severe), and, using the survey as the gold standard, whether patient characteristics were associated with a discrepancy on moderate-severe pain.
A total of 1,643 participants had a survey and EMR NRS score on the same day. The correlation was 0.56 (95% CI 0.52/0.59), but the mean EMR score was significantly lower than the survey score (1.72 vs. 2.79; p<0.0001). Agreement was moderate (kappa=0.35). Characteristics associated with a increased odds of a discrepancy included: diabetes (adjusted odds ratio (AOR)=1.48), post traumatic stress disorder (AOR=1.59), major depressive disorder (AOR=1.81), other race vs. white (AOR=2.29), and facility in which care was received.
The underestimation of pain using EMR data, especially clinically actionable levels of pain, has important clinical and research implications. Improving the quality of pain care may require better screening.
PMCID: PMC3572341  PMID: 23222528
Veterans; pain measurement; electronic medical records
25.  Receipt of Opioid Analgesics by HIV-Infected and Uninfected Patients 
Opioids are increasingly prescribed, but there are limited data on opioid receipt by HIV status.
To describe patterns of opioid receipt by HIV status and the relationship between HIV status and receiving any, high-dose, and long-term opioids.
Cross-sectional analysis of the Veterans Aging Cohort Study.
HIV-infected (HIV+) patients receiving Veterans Health Administration care, and uninfected matched controls.
Pain-related diagnoses were determined using ICD-9 codes. Any opioid receipt was defined as at least one opioid prescription; high-dose was defined as an average daily dose ≥120 mg of morphine equivalents; long-term opioids was defined as ≥90 consecutive days, allowing a 30 day refill gap. Multivariable models were used to assess the relationship between HIV infection and the three outcomes.
Among the HIV+ (n = 23,651) and uninfected (n = 55,097) patients, 31 % of HIV+ and 28 % of uninfected (p < 0.001) received opioids. Among patients receiving opioids, HIV+ patients were more likely to have an acute pain diagnosis (7 % vs. 4 %), but less likely to have a chronic pain diagnosis (53 % vs. 69 %). HIV+ patients received a higher mean daily morphine equivalent dose than uninfected patients (41 mg vs. 37 mg, p = 0.001) and were more likely to receive high-dose opioids (6 % vs. 5 %, p < 0.001). HIV+ patients received fewer days of opioids than uninfected patients (median 44 vs. 60, p < 0.001), and were less likely to receive long-term opioids (31 % vs. 34 %, p < 0.001). In multivariable analysis, HIV+ status was associated with receipt of any opioids (AOR 1.40, 95 % CI 1.35, 1.46) and high-dose opioids (AOR 1.22, 95 % CI 1.07, 1.39), but not long-term opioids (AOR 0.94, 95 % CI 0.88, 1.01).
Patients with HIV infection are more likely to be prescribed opioids than uninfected individuals, and there is a variable association with pain diagnoses. Efforts to standardize approaches to pain management may be warranted in this highly complex and vulnerable patient population.
PMCID: PMC3539026  PMID: 22895747
opioid; pain; HIV; narcotics; veterans

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