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1.  Association of COPD with risk for pulmonary infections requiring hospitalization in HIV-infected Veterans 
Background
Pulmonary infections remain more common in HIV-infected (HIV+) compared to uninfected individuals. The increase in chronic lung diseases among aging HIV+ individuals may contribute to this persistent risk. We sought to determine whether chronic obstructive pulmonary disease (COPD) is an independent risk factor for different pulmonary infections requiring hospitalization among HIV+ patients.
Methods
We analyzed data from 41,993 HIV+ Veterans in the nationwide Veterans Aging Cohort Study Virtual Cohort (VACS-VC) from 1996–2009. Using ICD-9 codes, we identified baseline comorbid conditions, including COPD, and incident community-acquired pneumonia (CAP), pulmonary tuberculosis (TB) and Pneumocystis jirovecii pneumonia (PCP) requiring hospitalization within two years after baseline. We used multivariable Poisson regression to determine incidence rate ratios (IRR) associated with COPD for each type of pulmonary infection, adjusting for comorbidities, CD4+ cell count, HIV viral load, smoking status, substance use, vaccinations and calendar year at baseline.
Results
Unadjusted incidence rates of CAP, TB and PCP requiring hospitalization were significantly higher among persons with COPD compared to those without COPD (CAP: 53.9 vs. 19.4 per 1,000 person-years; TB: 8.7 vs. 2.8; PCP: 15.5 vs. 9.2; p ≤0.001). In multivariable Poisson regression models, COPD was independently associated with increased risk of CAP, TB and PCP (IRR 1.94, 95% CI 1.64–2.30; IRR 2.60, 95% CI 1.70–3.97; and IRR 1.48, 95% CI 1.10–2.01, respectively).
Conclusions
COPD is an independent risk factor for CAP, TB and PCP requiring hospitalization among HIV+ individuals. As the HIV+ population ages, the growing burden of COPD may confer substantial risk for pulmonary infections.
doi:10.1097/QAI.0000000000000751
PMCID: PMC4607625  PMID: 26181820
COPD; pulmonary infection; pneumonia; HIV; comorbidities
2.  Proceedings of the 13th annual conference of INEBRIA 
Watson, Rod | Morris, James | Isitt, John | Barrio, Pablo | Ortega, Lluisa | Gual, Antoni | Conner, Kenneth | Stecker, Tracy | Maisto, Stephen | Paroz, Sophie | Graap, Caroline | Grazioli, Véronique S | Daeppen, Jean-Bernard | Collins, Susan E | Bertholet, Nicolas | McNeely, Jennifer | Kushnir, Vlad | Cunningham, John A. | Crombie, Iain K | Cunningham, Kathryn B | Irvine, Linda | Williams, Brian | Sniehotta, Falko F | Norrie, John | Melson, Ambrose | Jones, Claire | Briggs, Andrew | Rice, Peter | Achison, Marcus | McKenzie, Andrew | Dimova, Elena | Slane, Peter W | Grazioli, Véronique S. | Collins, Susan E. | Paroz, Sophie | Graap, Caroline | Daeppen, Jean-Bernard | Baggio, Stéphanie | Dupuis, Marc | Studer, Joseph | Gmel, Gerhard | Magill, Molly | Grazioli, Véronique S. | Tait, Robert J. | Teoh, Lucinda | Kelty, Erin | Geelhoed, Elizabeth | Mountain, David | Hulse, Gary K. | Renko, Elina | Mitchell, Shannon G. | Lounsbury, David | Li, Zhi | Schwartz, Robert P. | Gryczynski, Jan | Kirk, Arethusa S. | Oros, Marla | Hosler, Colleen | Dusek, Kristi | Brown, Barry S. | Finnell, Deborah S. | Holloway, Aisha | Wu, Li-Tzy | Subramaniam, Geetha | Sharma, Gaurav | Wallhed Finn, Sara | Andreasson, Sven | Dvorak, Robert D. | Kramer, Matthew P. | Stevenson, Brittany L. | Sargent, Emily M. | Kilwein, Tess M. | Harris, Sion K. | Sherritt, Lon | Copelas, Sarah | Knight, John R. | Mdege, Noreen D | McCambridge, Jim | Bischof, Gallus | Bischof, Anja | Freyer-Adam, Jennis | Rumpf, Hans-Juergen | Fitzgerald, Niamh | Schölin, Lisa | Toner, Paul | Böhnke, Jan R. | Veach, Laura J. | Currin, Olivia | Dongre, Leigh Z. | Miller, Preston R. | White, Elizabeth | Williams, Emily C. | Lapham, Gwen T. | Bobb, Jennifer J. | Rubinsky, Anna D. | Catz, Sheryl L. | Shortreed, Susan | Bensley, Kara M. | Bradley, Katharine A. | Milward, Joanna | Deluca, Paolo | Khadjesari, Zarnie | Watson, Rod | Fincham-Campbell, Stephanie | Drummond, Colin | Angus, Kathryn | Bauld, Linda | Baumann, Sophie | Haberecht, Katja | Schnuerer, Inga | Meyer, Christian | Rumpf, Hans-Jürgen | John, Ulrich | Gaertner, Beate | Barrault-Couchouron, Marion | Béracochéa, Marion | Allafort, Vincent | Barthélémy, Valérie | Bonnefoi, Hervé | Bussières, Emmanuel | Garguil, Véronique | Auriacombe, Marc | Saint-Jacques, Marianne | Dorval, Michel | M’Bailara, Katia | Segura-Garcia, Lidia | Ibañez-Martinez, Nuria | Mendive-Arbeloa, Juan Manuel | Anoro-Perminger, Manel | Diaz-Gallego, Pako | Piñar-Mateos, Mª Angeles | Colom-Farran, Joan | Deligianni, Marianthi | Yersin, Bertrand | Adam, Angeline | Weisner, Constance | Chi, Felicia | Lu, Wendy | Sterling, Stacy | Kraemer, Kevin L. | McGinnis, Kathleen A. | Fiellin, David A. | Skanderson, Melissa | Gordon, Adam J. | Robbins, Jonathan | Zickmund, Susan | Korthuis, P. Todd | Edelman, E. Jennifer | Hansen, Nathan B. | Cutter, Christopher J. | Dziura, James | Fiellin, Lynn E. | O’Connor, Patrick G. | Maisto, Stephen A. | Bedimo, Roger | Gilbert, Cynthia | Marconi, Vincent C. | Rimland, David | Rodriguez-Barradas, Maria | Simberkoff, Michael | Justice, Amy C. | Bryant, Kendall J. | Berman, Anne H | Shorter, Gillian W | Bray, Jeremy W | Barbosa, Carolina | Johansson, Magnus | Hester, Reid | Campbell, William | Souza Formigoni, Maria Lucia O. | Andrade, André Luzi Monezi | Sartes, Laisa Marcorela Andreoli | Sundström, Christopher | Eék, Niels | Kraepelien, Martin | Kaldo, Viktor | Fahlke, Claudia | Hernandez, Lynn | Becker, Sara J. | Jones, Richard N. | Graves, Hannah R. | Spirito, Anthony | Diestelkamp, Silke | Wartberg, Lutz | Arnaud, Nicolas | Thomasius, Rainer | Gaume, Jacques | Grazioli, Véronique | Fortini, Cristiana | Malan, Zelra | Mash, Bob | Everett-Murphy, Katherine | Grazioli, Véronique S. | Studer, Joseph | Mohler-Kuo, M. | Bertholet, Nicolas | Gmel, Gerhard | Doi, Lawrence | Cheyne, Helen | Jepson, Ruth | Luna, Vanesa | Echeverria, Leticia | Morales, Silvia | Barroso, Teresa | Abreu, Ângela | Aguiar, Cosma | Stewart, Duncan | Abreu, Angela | Brites, Riany M. | Jomar, Rafael | Marinho, Gerson | Parreira, Pedro | Seale, J. Paul | Johnson, J. Aaron | Henry, Dena | Chalmers, Sharon | Payne, Freida | Tuck, Linda | Morris, Akula | Gonçalves, Cátia | Besser, Bettina | Casajuana, Cristina | López-Pelayo, Hugo | Balcells, María Mercedes | Teixidó, Lídia | Miquel, Laia | Colom, Joan | Hepner, Kimberly A. | Hoggatt, Katherine. J. | Bogart, Andy | Paddock, Susan. M. | Hardoon, Sarah L | Petersen, Irene | Hamilton, Fiona L | Nazareth, Irwin | White, Ian R. | Marston, Louise | Wallace, Paul | Godfrey, Christine | Murray, Elizabeth | Sovinová, Hana | Csémy, Ladislav
doi:10.1186/s13722-016-0062-9
PMCID: PMC5032602  PMID: 27654147
3.  Human Immunodeficiency Virus Type 1 Monoclonal Antibodies Suppress Acute Simian-Human Immunodeficiency Virus Viremia and Limit Seeding of Cell-Associated Viral Reservoirs 
Journal of Virology  2016;90(3):1321-1332.
ABSTRACT
Combination antiretroviral therapy (cART) administered shortly after human immunodeficiency virus type 1 (HIV-1) infection can suppress viremia and limit seeding of the viral reservoir, but lifelong treatment is required for the majority of patients. Highly potent broadly neutralizing HIV-1 monoclonal antibodies (MAbs) can reduce plasma viremia when administered during chronic HIV-1 infection, but the therapeutic potential of these antibodies during acute infection is unknown. We tested the ability of HIV-1 envelope glycoprotein-specific broadly neutralizing MAbs to suppress acute simian-human immunodeficiency virus (SHIV) replication in rhesus macaques. Four groups of macaques were infected with SHIV-SF162P3 and received (i) the CD4-binding-site MAb VRC01; (ii) a combination of a more potent clonal relative of VRC01 (VRC07-523) and a V3 glycan-dependent MAb (PGT121); (iii) daily cART, all on day 10, just prior to expected peak plasma viremia; or (iv) no treatment. Daily cART was initiated 11 days after MAb administration and was continued for 13 weeks in all treated animals. Over a period of 11 days after a single administration, MAb treatment significantly reduced peak viremia, accelerated the decay slope, and reduced total viral replication compared to untreated controls. Proviral DNA in lymph node CD4 T cells was also diminished after treatment with the dual MAb. These data demonstrate the virological effect of potent MAbs and support future clinical trials that investigate HIV-1-neutralizing MAbs as adjunctive therapy with cART during acute HIV-1 infection.
IMPORTANCE Treatment of chronic HIV-1 infection with potent broadly neutralizing HIV-1 MAbs has been shown to significantly reduce plasma viremia. However, the antiviral effect of MAb treatment during acute HIV-1 infection is unknown. Here, we demonstrate that MAbs targeting the HIV-1 envelope glycoprotein both suppress acute SHIV plasma viremia and limit CD4 T cell-associated viral DNA. These findings provide support for clinical trials of MAbs as adjunctive therapy with antiretroviral therapy during acute HIV-1 infection.
doi:10.1128/JVI.02454-15
PMCID: PMC4719604  PMID: 26581981
4.  Short Communication: Coronary Heart Disease Risk by Framingham Risk Score in Hepatitis C and HIV/Hepatitis C-Coinfected Persons 
Abstract
We compared the Framingham risk score (FRS) for 10-year coronary heart disease (CHD) risk in age- and race-matched hepatitis C virus (HCV)-infected and HCV-uninfected persons: 114,073 HCV-infected (111,436 HCV-monoinfected and 2,637 HIV/HCV-coinfected) and 122,996 HCV-uninfected (121,380 HIV and HCV-uninfected and 1,616 HIV-monoinfected) males without cardiovascular disease, diabetes, or hepatitis B. In unadjusted analyses, FRS was similar between the HCV-infected and HCV-uninfected groups [median (interquartile range, IQR) risk points 13 (10–14) vs. 13 (10–14), p=0.192]. Cholesterol levels were lower and current smoking more prevalent in the HCV groups (both HCV and HIV/HCV) compared with the uninfected groups (p<0.001 for both). Prevalence of non-FRS CHD risk factors, such as substance abuse and chronic kidney disease, in the cohort was high, and differed by HCV and HIV status. Adjusting for age, race/ethnicity, body mass index, chronic kidney disease, drug and alcohol use, and HIV status, HCV infection was associated with minimally lower FRS (β=−0.095 risk points, p<0.001), suggesting a small but significant difference in 10-year CHD risk estimation in HCV-infected as compared to HCV-uninfected persons when measuring risk by FRS. Given the complex relationship between HCV, HIV, and CHD risk factors, some of which are not captured by the FRS, the FRS may underestimate CHD risk in HCV-monoinfected and HIV/HCV-coinfected persons. HCV- and HIV/HCV-specific risk scores may be needed to optimize CHD risk stratification.
doi:10.1089/aid.2014.0284
PMCID: PMC4505770  PMID: 25858663
5.  HIV status and the risk of ischemic stroke among men 
Neurology  2015;84(19):1933-1940.
Objective:
Given conflicting data regarding the association of HIV infection and ischemic stroke risk, we sought to determine whether HIV infection conferred an increased ischemic stroke risk among male veterans.
Methods:
The Veterans Aging Cohort Study–Virtual Cohort consists of HIV-infected and uninfected veterans in care matched (1:2) for age, sex, race/ethnicity, and clinical site. We analyzed data on 76,835 male participants in the Veterans Aging Cohort Study–Virtual Cohort who were free of baseline cardiovascular disease. We assessed demographics, ischemic stroke risk factors, comorbid diseases, substance use, HIV biomarkers, and incidence of ischemic stroke from October 1, 2003, to December 31, 2009.
Results:
During a median follow-up period of 5.9 (interquartile range 3.5–6.6) years, there were 910 stroke events (37.4% HIV-infected). Ischemic stroke rates per 1,000 person-years were higher for HIV-infected (2.79, 95% confidence interval 2.51–3.10) than for uninfected veterans (2.24 [2.06–2.43]) (incidence rate ratio 1.25 [1.09–1.43]; p < 0.01). After adjusting for demographics, ischemic stroke risk factors, comorbid diseases, and substance use, the risk of ischemic stroke was higher among male veterans with HIV infection compared with uninfected veterans (hazard ratio 1.17 [1.01–1.36]; p = 0.04).
Conclusions:
HIV infection is associated with an increased ischemic stroke risk among HIV-infected compared with demographically and behaviorally similar uninfected male veterans.
doi:10.1212/WNL.0000000000001560
PMCID: PMC4433456  PMID: 25862803
6.  Food Insecurity and Health: Data from the Veterans Aging Cohort Study 
Public Health Reports  2015;130(3):261-268.
Objective
Food insecurity may be a modifiable and independent risk factor for worse control of medical conditions, but it has not been explored among veterans. We determined the prevalence of, and factors independently associated with, food insecurity among veterans in the Veterans Aging Cohort Study (VACS).
Methods
Using data from VACS from 2002–2008, we determined the prevalence of food insecurity among veterans who have accessed health care in the Veterans Health Administration (VA) as defined by “concern about having enough food for you or your family in the past month.” We used multivariable logistic regression to determine factors independently associated with food insecurity and tests of trend to measure the association between food insecurity and control of hypertension, diabetes, HIV, and depression.
Results
Of the 6,709 veterans enrolled in VACS, 1,624 (24%) reported being food insecure. Food insecurity was independently associated with being African American, earning <$25,000/year, recent homelessness, marijuana use, and depression. Being food insecure was also associated with worse control of hypertension, diabetes, HIV, and depression (p<0.001).
Conclusion
Food insecurity is prevalent and associated with worse control of medical conditions among veterans who have accessed care in the VA.
PMCID: PMC4388224  PMID: 25931630
7.  Number of Drinks to "Feel a Buzz" by HIV Status and Viral Load in Men 
AIDS and behavior  2016;20(3):504-511.
The impact of HIV and its treatment on the effects of alcohol remain unclear. Blood alcohol concentrations have been noted to be higher in HIV infected individuals prior to antiretroviral initiation.
Our goal was to compare number of drinks to “feel a buzz or high” among HIV infected and uninfected men, stratified by viral load (VL) suppression.
Data includes 1,478 HIV infected and 1,170 uninfected men in the Veterans Aging Cohort Study who endorsed current drinking. Mean (SD) number of drinks to feel a buzz was 3.1 (1.7) overall. In multivariable analyses, HIV infected men reported a lower mean number of drinks to feel a buzz compared to uninfected men (coef = −0.14 for VL<500; −0.34 for VL>500; p<.05).
Men with HIV, especially those with a detectable viral load, reported fewer drinks to feel a buzz. Future research on the relationship between alcohol and HIV should consider the role of VL suppression.
doi:10.1007/s10461-015-1053-7
PMCID: PMC4780364  PMID: 26936030
HIV; Alcohol Intoxication; Alcohol Use; Alcohol-Related Disorders; Buzz
8.  Drinking Trajectories among HIV-Infected Men Who Have Sex With Men: A Cohort Study of United States Veterans* 
Background
Although high rates of alcohol consumption and related problems have been observed among HIV-infected men who have sex with men (MSM), little is known about the long-term patterns of and factors associated with hazardous alcohol use in this population. We sought to identify alcohol use trajectories and correlates of hazardous alcohol use among HIV-infected MSM.
Methods
Sexually active, HIV-infected MSM participating in the Veterans Aging Cohort Study were eligible for inclusion. Participants were recruited from VA infectious disease clinics in Atlanta, Baltimore, New York, Houston, Los Angeles, Pittsburgh, and Washington, DC. Data from annual self-reported assessments and group-based trajectory models were used to identify distinct alcohol use trajectories over an eight-year study period (2002–2010). We then used generalized estimate equations (GEE) to examine longitudinal correlates of hazardous alcohol use (defined as an AUDIT-C score ≥4).
Results
Among 1,065 participants, the mean age was 45.5 (SD=9.2) and 606 (58.2%) were African American. Baseline hazardous alcohol use was reported by 309 (29.3%). Group-based trajectory modeling revealed a distinct group (12.5% of the sample) with consistently hazardous alcohol use, characterized by a mean AUDIT-C score of >5 at every time point. In a GEE-based multivariable model, hazardous alcohol use was associated with earning <$6,000 annually, having an alcohol-related diagnosis, using cannabis, and using cocaine.
Conclusions
More than 1 in 10 HIV-infected MSM US veterans reported consistent, long-term hazardous alcohol use. Financial insecurity and concurrent substance use were predictors of consistently hazardous alcohol use, and may be modifiable targets for intervention.
doi:10.1016/j.drugalcdep.2014.12.023
PMCID: PMC4330114  PMID: 25596785
alcohol; men who have sex with men; veterans; HIV infection; trajectories; trends
9.  Comparison of Risk and Age at Diagnosis of Myocardial Infarction, End-Stage Renal Disease, and Non-AIDS-Defining Cancer in HIV-Infected Versus Uninfected Adults 
Although HIV-infected veterans had a higher risk of myocardial infarction, end-stage renal disease, and non-AIDS-defining cancer, diagnosis with these conditions were occurring at similar ages compared with HIV-uninfected veterans.
Background. Although it has been shown that human immunodeficiency virus (HIV)-infected adults are at greater risk for aging-associated events, it remains unclear as to whether these events happen at similar, or younger ages, in HIV-infected compared with uninfected adults. The objective of this study was to compare the median age at, and risk of, incident diagnosis of 3 age-associated diseases in HIV-infected and demographically similar uninfected adults.
Methods. The study was nested in the clinical prospective Veterans Aging Cohort Study of HIV-infected and demographically matched uninfected veterans, from 1 April 2003 to 31 December 2010. The outcomes were validated diagnoses of myocardial infarction (MI), end-stage renal disease (ESRD), and non-AIDS-defining cancer (NADC). Differences in mean age at, and risk of, diagnosis by HIV status were estimated using multivariate linear regression models and Cox proportional hazards models, respectively.
Results. A total of 98 687 (31% HIV-infected and 69% uninfected) adults contributed >450 000 person-years and 689 MI, 1135 ESRD, and 4179 NADC incident diagnoses. Mean age at MI (adjusted mean difference, −0.11; 95% confidence interval [CI], −.59 to .37 years) and NADC (adjusted mean difference, −0.10 [95% CI, −.30 to .10] years) did not differ by HIV status. HIV-infected adults were diagnosed with ESRD at an average age of 5.5 months younger than uninfected adults (adjusted mean difference, −0.46 [95% CI, −.86 to −.07] years). HIV-infected adults had a greater risk of all 3 outcomes compared with uninfected adults after accounting for important confounders.
Conclusions. HIV-infected adults had a higher risk of these age-associated events, but they occurred at similar ages than those without HIV.
doi:10.1093/cid/ciu869
PMCID: PMC4318916  PMID: 25362204
HIV infection; aging; myocardial infarction; end-stage renal disease; non-AIDS-defining cancers
10.  Comparing Alcohol Screening Measures Among HIV Infected and Uninfected Men 
Background
Brief measures of unhealthy alcohol use have not been well-validated among people with HIV. We compared the Alcohol Use Disorders Identification Test (AUDIT) to reference standards for unhealthy alcohol use based on 30 day Timeline Follow Back (TLFB) and Composite International Diagnostic Interview - Substance Abuse Module (CIDI-SAM), among 873 male HIV infected and uninfected patients in the Veterans Aging Cohort Study.
Methods
Three reference standards were: 1)Risky drinking - based on TLFB: >14 drinks over 7 consecutive days or >4 drinks on one day; 2)Alcohol dependence - based on a CIDI-SAM diagnosis; and 3)Unhealthy alcohol use - risky drinking or a CIDI-SAM diagnosis of abuse or dependence. Various cutoffs for the AUDIT, AUDIT-C, and heavy episodic drinking were compared to the reference standards.
Results
Mean age of patients was 52 years, 53% (444) were HIV infected, and 53% (444) were African-American. Among HIV infected and uninfected patients, the prevalence of risky drinking (14% vs. 12% respectively), alcohol dependence (8% vs. 7%), and unhealthy alcohol use (22% vs. 20%) was similar. For risky drinking and alcohol dependence, multiple cutoffs of AUDIT, AUDIT-C, and heavy episodic drinking provided good sensitivity (>80%) and specificity (>90%). For unhealthy alcohol use, few cutoffs provided sensitivity >80%; however, many cutoffs provided good specificity. For all three alcohol screening measures, sensitivity improved when heavy episodic drinking was included with the cutoff. Sensitivity of measures for risky drinking and unhealthy alcohol use were lower in HIV infected than in uninfected patients.
Conclusions
For identifying risky drinking, alcohol dependence, and unhealthy alcohol use, AUDIT-C performs as well as AUDIT and similarly in HIV infected and uninfected patients. Cutoffs should be based on the importance of specific operating characteristics for the intended research or clinical use. Incorporating heavy episodic drinking increased sensitivity for detecting alcohol dependence and unhealthy alcohol use.
doi:10.1111/j.1530-0277.2012.01937.x
PMCID: PMC4492202  PMID: 23050632
11.  Incarceration and Health Outcomes in HIV-Infected Patients: The Impact of Substance Use, Primary Care Engagement, and Antiretroviral Adherence 
Background and Objectives
One in seven HIV-infected individuals is incarcerated each year. We used data from the Veterans Aging Cohort Study (VACS) to explore the relationship between incarceration and HIV disease outcomes and evaluate potential mediators of this relationship.
Methods
HIV disease outcomes included: low CD4 counts (<200 cells/mL), detectable viral RNA loads (>500 copies/mL), and the VACS Index score. We performed a mediation analysis among 1,591 HIV-infected patients to examine whether unhealthy alcohol use, drug use, primary care engagement, or antiretroviral adherence mediated observed associations.
Results
Among 1,591 HIV-infected patients, 47% reported having a history of incarceration. In multivariate analyses, a history of incarceration was associated with a higher VACS Index score (β 2.47, 95% CI 0.52–4.43). Mediation analysis revealed that recent drug use attenuated the association by 22% (β 1.93, 95% CI −0.06, 3.91) while other proposed mediators did not.
Conclusions and Scientific Significance
Improving access to drug treatment when incarcerated and upon release may be an important target to improving the health of HIV-infected individuals with a history of incarceration.
doi:10.1111/ajad.12177
PMCID: PMC4397180  PMID: 25662297
12.  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.
doi:10.1093/cid/cit652
PMCID: PMC3864500  PMID: 24065316
blood pressure; prehypertension; HIV; myocardial infarction
13.  HIV Infection is associated with reduced pulmonary diffusing capacity 
Journal of acquired immune deficiency syndromes (1999)  2013;64(3):10.1097/QAI.0b013e3182a9215a.
Rationale:
Prior studies comparing abnormalities in pulmonary function between HIV-infected and HIV-uninfected persons in the current era are limited.
Objectives:
To determine the pattern and severity of impairment in pulmonary function in HIV-infected compared to HIV-uninfected individuals.
Methods:
Cross-sectional analysis of 300 HIV-infected and 289 HIV-uninfected men enrolled from 2009-2011 in two clinical centers of the Lung HIV Study. Participants completed pre- and post-bronchodilator spirometry, diffusing capacity (DLCO) measurement, and standardized questionnaires.
Results:
Most participants had normal airflow; 18% of HIV-infected and 16% of HIV-uninfected men had airflow obstruction. The mean percent predicted DLCO was 69% in HIV-infected vs. 76% in HIV-uninfected men (p<0.001). A moderately to severely reduced DLCO of ≤60% was observed in 30% of HIV-infected compared to 18% of HIV-uninfected men (p<0.001), despite the fact that 89% of those with HIV were on antiretroviral therapy. A reduced DLCO was significantly associated with HIV and CD4 cell count in linear regression adjusting for smoking and other confounders. The DLCO was lowest in HIV-infected men with CD4 cell counts <200 compared to those with CD4 cell counts ≥200 and to HIV-uninfected men. Respiratory symptoms of cough, phlegm and dyspnea were more prevalent in HIV-infected patients particularly those with abnormal pulmonary function compared to HIV-uninfected patients.
Conclusions:
HIV infection is an independent risk factor for reduced DLCO, particularly in individuals with a CD4 cell count below 200. Abnormalities in pulmonary function among HIV-infected patients manifest clinically with increased respiratory symptoms. Mechanisms accounting for the reduced DLCO require further evaluation.
doi:10.1097/QAI.0b013e3182a9215a
PMCID: PMC3845879  PMID: 23979001
Pulmonary function; FEV1; DLCO; gas exchange; COPD; HIV/AIDS
14.  Risk factors for hospitalization and medical intensive care unit (MICU) admission among HIV infected Veterans 
Objective
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.
Methods
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.
Results
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.
Conclusions
The VACS Index predicted hospitalization and MICU admission as did current smoking, hazardous alcohol use, and AIDS and certain non-AIDS diagnoses.
doi:10.1097/QAI.0b013e318278f3fa
PMCID: PMC4182723  PMID: 23111572
HIV; hospitalization; medical intensive care unit (MICU); aging; VACS Index; comorbidity
15.  HIV Infection and Cardiovascular Disease in Women 
Background
HIV infection is associated with increased risk of cardiovascular disease (CVD) in men. Whether HIV is an independent risk factor for CVD in women has not yet been established.
Methods and Results
We analyzed data from the Veterans Aging Cohort Study on 2187 women (32% HIV infected [HIV+]) who were free of CVD at baseline. Participants were followed from their first clinical encounter on or after April 01, 2003 until a CVD event, death, or the last follow‐up date (December 31, 2009). The primary outcome was CVD (acute myocardial infarction [AMI], unstable angina, ischemic stroke, and heart failure). CVD events were defined using clinical data, International Classification of Diseases, Ninth Revision, Clinical Modification codes, and/or death certificate data. We used Cox proportional hazards models to assess the association between HIV and incident CVD, adjusting for age, race/ethnicity, lipids, smoking, blood pressure, diabetes, renal disease, obesity, hepatitis C, and substance use/abuse. Median follow‐up time was 6.0 years. Mean age at baseline of HIV+ and HIV uninfected (HIV−) women was 44.0 versus 43.2 years (P<0.05). Median time to CVD event was 3.1 versus 3.7 years (P=0.11). There were 86 incident CVD events (53%, HIV+): AMI, 13%; unstable angina, 8%; ischemic stroke, 22%; and heart failure, 57%. Incident CVD/1000 person‐years was significantly higher among HIV+ (13.5; 95% confidence interval [CI]=10.1, 18.1) than HIV− women (5.3; 95% CI=3.9, 7.3; P<0.001). HIV+ women had an increased risk of CVD, compared to HIV− (hazard ratio=2.8; 95% CI=1.7, 4.6; P<0.001).
Conclusions
HIV is associated with an increased risk of CVD in women.
doi:10.1161/JAHA.114.001035
PMCID: PMC4323817  PMID: 25324353
AIDS; CVD risk factors; Women
16.  Unhealthy Alcohol and Illicit Drug Use are Associated with Decreased Quality of HIV Care 
Background
HIV-infected patients with substance use experience suboptimal health outcomes, possibly to due to variations in care.
Objectives
To assess the association between substance use and the quality of HIV care (QOC) received.
Research Design
Retrospective cohort study.
Subjects
HIV-infected patients enrolled in the Veterans Aging Cohort Study.
Measures
We collected self-report substance use data and abstracted 9 HIV quality indicators (QIs) from medical records. Independent variables were unhealthy alcohol use (AUDIT-C score ≥4) and illicit drug use (self-report of stimulants, opioids, or injection drug use in past year). Main outcome was the percentage of QIs received, if eligible. We estimated associations between substance use and QOC using multivariable linear regression.
Results
The majority of the 3,410 patients were male (97.4%) and Black (67.0%) with a mean age of 49.1 years (SD 8.8). Overall, 25.8% reported unhealthy alcohol use, 22% illicit drug use, and participants received 81.5% (SD=18.9) of QIs. The mean percentage of QIs received was lower for those with unhealthy alcohol use vs. not (59.3% vs. 70.0%, p<.001) and those using illicit drugs vs. not (57.8% vs. 70.7%, p<.001). In multivariable models, unhealthy alcohol use (adjusted β −2.74; 95% CI −4.23, −1.25) and illicit drug use (adjusted β −3.51 95% CI −4.99, −2.02) remained inversely associated with the percentage of QIs received.
Conclusions
Though the overall QOC for these HIV-infected Veteran patients was high, gaps persist for those with unhealthy alcohol and illicit drug use. Interventions that address substance use in HIV-infected patients may improve the QOC received.
doi:10.1097/QAI.0b013e31826741aa
PMCID: PMC3460799  PMID: 22820808
Alcohol; Quality of Health Care; HIV; Quality Indicators; Health Care; Opioid-Related Disorders
17.  HIV Status, Burden of Comorbid Disease, and Biomarkers of Inflammation, Altered Coagulation, and Monocyte Activation 
We investigated the association between human immunodeficiency virus (HIV) and prevalence of elevated biomarkers of inflammation, altered coagulation, and monocyte activation in a cohort of HIV-infected and uninfected veterans who had a comparable burden of comorbid conditions.
Background. Biomarkers of inflammation, altered coagulation, and monocyte activation are associated with mortality and cardiovascular disease (CVD) in the general population and among human immunodeficiency virus (HIV)–infected people. We compared biomarkers for inflammation, altered coagulation, and monocyte activation between HIV-infected and uninfected people in the Veterans Aging Cohort Study (VACS).
Methods. Biomarkers of inflammation (interleukin-6 [IL-6]), altered coagulation (d-dimer), and monocyte activation (soluble CD14 [sCD14]) were measured in blood samples from 1525 HIV-infected and 843 uninfected VACS participants. Logistic regression was used to determine the association between HIV infection and prevalence of elevated (>75th percentile) biomarkers, adjusting for confounding comorbidities.
Results. HIV-infected veterans had less prevalent CVD, hypertension, diabetes, obesity, hazardous drinking, and renal disease, but more dyslipidemia, hepatitis C, and current smoking than uninfected veterans. Compared to uninfected veterans, HIV-infected veterans with HIV-1 RNA ≥500 copies/mL or CD4 count <200 cells/µL had a significantly higher prevalence of elevated IL-6 (odds ratio [OR], 1.54; 95% confidence interval [CI],1.14–2.09; OR, 2.25; 95% CI, 1.60–3.16, respectively) and d-dimer (OR, 1.97; 95% CI, 1.44–2.71, OR, 1.68; 95% CI, 1.22–2.32, respectively) after adjusting for comorbidities. HIV-infected veterans with a CD4 cell count <200 cells/µL had significantly higher prevalence of elevated sCD14 compared to uninfected veterans (OR, 2.60; 95% CI, 1.64–4.14). These associations still persisted after restricting the analysis to veterans without known confounding comorbid conditions.
Conclusions. These data suggest that ongoing HIV replication and immune depletion significantly contribute to increased prevalence of elevated biomarkers of inflammation, altered coagulation, and monocyte activation. This contribution is independent of and in addition to the substantial contribution from comorbid conditions.
doi:10.1093/cid/cis406
PMCID: PMC3493182  PMID: 22534147
18.  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
19.  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
20.  Food Insecurity is Associated with Poor Virologic Response among HIV-Infected Patients Receiving Antiretroviral Medications 
Journal of General Internal Medicine  2011;26(9):1012-1018.
ABSTRACT
BACKGROUND AND OBJECTIVE
Food insecurity negatively impacts HIV disease outcomes in international settings. No large scale U.S. studies have investigated the association between food insecurity and severity of HIV disease or the mechanism of this possible association. The objective of this study was to examine the impact of food insecurity on HIV disease outcomes in a large cohort of HIV-infected patients receiving antiretroviral medications.
DESIGN
This is a cross-sectional study.
PARTICIPANTS AND SETTING
Participants were HIV-infected patients enrolled in the Veterans Aging Cohort Study between 2002–2008 who were receiving antiretroviral medications.
MAIN MEASUREMENTS
Participants reporting “concern about having enough food for you or your family in the past 30 days” were defined as food insecure. Using multivariable logistic regression, we explored the association between food insecurity and both low CD4 counts (<200 cells/μL) and unsuppressed HIV-1 RNA (>500 copies/mL). We then performed mediation analysis to examine whether antiretroviral adherence or body mass index mediates the observed associations.
KEY RESULTS
Among 2353 HIV-infected participants receiving antiretroviral medications, 24% reported food insecurity. In adjusted analyses, food insecure participants were more likely to have an unsuppressed HIV-1 RNA (AOR 1.37, 95% CI 1.09, 1.73) compared to food secure participants. Mediation analysis revealed that neither antiretroviral medication adherence nor body mass index contributes to the association between food insecurity and unsuppressed HIV-1 RNA. Food insecurity was not independently associated with low CD4 counts.
CONCLUSIONS
Among HIV-infected participants receiving antiretroviral medications, food insecurity is associated with unsuppressed viral load and may render treatment less effective. Longitudinal studies are needed to test the potential causal association between food insecurity, lack of virologic suppression, and additional HIV outcomes.
doi:10.1007/s11606-011-1723-8
PMCID: PMC3157515  PMID: 21573882
food insecurity; HIV; patients; antiretrovirals
21.  A Comparison of Treatment Eligibility for Hepatitis C Virus in HCV-Monoinfected Versus HCV/HIV-Coinfected Persons in Electronically Retrieved Cohort of HCV-Infected Veterans 
Abstract
Treatment rates for hepatitis C virus (HCV) are low in actual clinical settings. However, the proportion of patients eligible for treatment, especially among those coinfected with HIV, is not well known. Our aim was to determine and compare the rates for HCV treatment eligibility among HCV and HCV-HIV-coinfected persons. We assembled a national cohort of HCV-infected veterans in care from 1998–2003, using the VA National Patient Care Database for demographic/clinical information, the Pharmacy Benefits Management database for pharmacy records, and the Decision Support Systems database for laboratory data. We compared the HCV-monoinfected and HCV-HIV-coinfected subjects for treatment indications and eligibility using current treatment guidelines. Of the 27,452 subjects with HCV and 1225 with HCV-HIV coinfection, 74.0% and 84.6% had indications for therapy and among these, 43.9% of HCV-monoinfected and 28.4% of HCV-HIV-coinfected subjects were eligible for treatment. Anemia, decompensated liver disease (DLD), chronic obstructive pulmonary disease (COPD), recent alcohol abuse, and coronary artery disease were the most common contraindications in the HCV, and anemia, DLD, renal failure, recent drug abuse, and COPD in the HCV-HIV-coinfected group. Among those eligible for treatment, only 23% of the HCV-monoinfected and 15% of the HCV-HIV-coinfected subjects received any treatment for HCV. Most veterans with HCV are not eligible for treatment according to the current guidelines. Even for those who are eligible for treatment, only a minority is prescribed treatment. Several contraindications are modifiable and aggressive management of those may improve treatment prescription rates.
doi:10.1089/aid.2011.0004
PMCID: PMC3719436  PMID: 21338329
22.  The Risk of Incident Coronary Heart Disease Among Veterans with and without HIV and Hepatitis C 
Background
Whether hepatitis C (HCV) confers additional coronary heart disease (CHD) risk among Human Immunodeficiency Virus (HIV) infected individuals is unclear. Without appropriate adjustment for antiretroviral therapy, CD4 count, and HIV-1 RNA, and substantially different mortality rates among those with and without HIV and HCV infection, the association between HIV, HCV, and CHD may be obscured.
Methods and Results
We analyzed data on 8579 participants (28% HIV+, 9% HIV+HCV+) from the Veterans Aging Cohort Study Virtual Cohort who participated in the 1999 Large Health Study of Veteran Enrollees. We analyzed data collected on HIV and HCV status, risk factors for and the incidence of CHD, and mortality from 1/2000–7/2007. We compared models to assess CHD risk when death was treated as a censoring event and as a competing risk. During the median 7.3 years of follow-up, there were 194 CHD events and 1186 deaths. Compared with HIV−HCV− Veterans, HIV+ HCV+ Veterans had a significantly higher risk of CHD regardless of whether death was adjusted for as a censoring event (adjusted hazard ratio (HR)=2.03, 95% CI=1.28–3.21) or a competing risk (adjusted HR=2.45, 95% CI=1.83–3.27 respectively). Compared with HIV+HCV− Veterans, HIV+ HCV+ Veterans also had a significantly higher adjusted risk of CHD regardless of whether death was treated as a censored event (adjusted HR=1.93, 95% CI=1.02–3.62) or a competing risk (adjusted HR =1.46, 95% CI=1.03–2.07).
Conclusions
HIV+HCV+ Veterans have an increased risk of CHD compared to HIV+HCV−, and HIV−HCV− Veterans.
doi:10.1161/CIRCOUTCOMES.110.957415
PMCID: PMC3159506  PMID: 21712519
viruses; coronary disease; mortality; multi morbidity
24.  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
25.  An Experimental Study of the Agreement of Self-Administration and Telephone Administration of the Timeline Followback Interview* 
Objective
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.
Method
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.
Results
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.
Conclusions
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

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