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1.  Comparative Effectiveness of Diabetic Oral Medications Among HIV-Infected and HIV-Uninfected Veterans 
Diabetes Care  2016;40(2):218-225.
Type 2 diabetes is increasingly common in HIV-infected individuals. The objective of this study was to compare the glycemic effectiveness of oral diabetic medications among patients with and without HIV infection.
A longitudinal cohort study was conducted among HIV-infected and uninfected veterans with type 2 diabetes initiating diabetic medications between 1999 and 2010. Generalized estimating equations were used to compare changes in hemoglobin A1c (HbA1c) through the year after medication initiation, adjusting for baseline HbA1c level and clinical covariates. A subanalysis using propensity scores was conducted to account for confounding by indication.
A total of 2,454 HIV-infected patients and 8,892 HIV-uninfected patients initiated diabetic medications during the study period. The most commonly prescribed medication was metformin (n = 5,647, 50%), followed by a sulfonylurea (n = 5,554, 49%) and a thiazolidinedione (n = 145, 1%). After adjustment for potential confounders, there was no significant difference in the change in HbA1c level among the three groups of new users. HIV infection was not significantly associated with glycemic response (P = 0.24). Black and Hispanic patients had a poorer response to therapy compared with white patients, with a relative increase in HbA1c level of 0.16% (95% CI 0.08, 0.24) [1.7 mmol/mol (0.9, 2.6)] (P < 0.001) and 0.25% (0.11, 0.39) [2.7 mmol/mol (1.2, 4.3)] (P = 0.001), respectively.
We found that glycemic response was independent of the initial class of diabetic medication prescribed among HIV-uninfected and HIV-infected adults with type 2 diabetes. The mechanisms leading to poorer response among black and Hispanic patients, who make up a substantial proportion of those with HIV infection and type 2 diabetes, require further investigation.
PMCID: PMC5250696  PMID: 27634393
2.  Immunological and infectious risk factors for lung cancer in US veterans with HIV: a longitudinal cohort study 
The lancet. HIV  2016;4(2):e67-e73.
HIV infection is independently associated with risk of lung cancer, but few data exist for the relation between longitudinal measurements of immune function and lung-cancer risk in people living with HIV.
We followed up participants with HIV from the Veterans Aging Cohort Study for a minimum of 3 years between Jan 1, 1998, and Dec 31, 2012, and used cancer registry data to identify incident cases of lung cancer. The index date for each patient was the later of the date HIV care began or Jan 1, 1998. We excluded patients with less than 3 years’ follow-up, prevalent diagnoses of lung cancer, or incomplete laboratory data. We used Cox regression models to investigate the relation between different time-updated lagged and cumulative exposures (CD4 cell count, CD8 cell count, CD4/CD8 ratio, HIV RNA, and bacterial pneumonia) and risk of lung cancer. Models were adjusted for age, race or ethnicity, smoking, hepatitis C virus infection, alcohol use disorders, drug use disorders, and history of chronic obstructive pulmonary disease and occupational lung disease.
We identified 277 cases of incident lung cancer in 21 666 participants with HIV. In separate models for each time-updated 12 month lagged, 24 month simple moving average cumulative exposure, increased risk of lung cancer was associated with low CD4 cell count (p trend=0·001), low CD4/CD8 ratio (p trend=0·0001), high HIV RNA concentration (p=0·004), and more cumulative bacterial pneumonia episodes (12 month lag only; p trend=0·0004). In a mutually adjusted model including these factors, CD4/CD8 ratio and cumulative bacterial pneumonia episodes remained significant (p trends 0·003 and 0·004, respectively).
In our large HIV cohort in the antiretroviral therapy era, we found evidence that dysfunctional immune activation and chronic inflammation contribute to the development of lung cancer in the setting of HIV infection. These findings could be used to target lung-cancer prevention measures to high-risk groups.
US National Institutes of Health.
PMCID: PMC5444465  PMID: 27916584
3.  Association of serum albumin and AST with 5-year all-cause mortality in HIV/HCV Coinfection and HIV Monoinfection 
AIDS (London, England)  2017;31(1):71-79.
Liver disease markers have been associated with mortality in HIV-infected individuals, in the modern era of effective antiretroviral therapy. Our objective was to determine which markers are most predictive of mortality in HIV-monoinfected and HIV/HCV-coinfected persons.
Research Design and Methods
We measured serum albumin, total protein, calculated globulin, aspartate transaminase (AST), and alanine transaminase (ALT) in 193 HIV/HCV-coinfected and 720 HIV-monoinfected persons in the study of Fat Redistribution and Metabolic Change in HIV Infection. We evaluated associations of each marker with five-year, all-cause mortality, adjusting for cardiovascular, HIV-related factors, inflammation, renal disease, muscle, and adiposity.
After 5 years of follow-up, overall mortality was 21% in HIV/HCV-coinfected and 12% in HIV-monoinfected participants. After multivariable adjustment, lower albumin and higher AST were independently associated with increased mortality. Lower albumin was associated with 49% increased odds of mortality overall (per 0.5g/dL decrease, 95%CI:1.2–1.9); the association was stronger in HIV/HCV-coinfected (OR=2.1, 95%CI:1.4–3.2) versus HIV-monoinfected (OR=1.3, 95%CI:1.0–1.7; HCV-by-albumin interaction: p=0.038). Higher AST was associated with 41% increased odds of mortality (per AST doubling; 95%CI:1.1–1.8); associations were much stronger among HIV/HCV-coinfected (OR=2.5, 95%CI:1.5–4.1) than HIV-monoinfected (OR=1.1, 95%CI:0.8–1.5; HCV-by-AST interaction: p=0.0042).
Lower serum albumin and higher AST appear to be important mortality risk factors in HIV/HCV-coinfection, but much less so in HIV-monoinfected individuals. The association of low albumin with mortality may reflect its role as a negative acute phase response protein. AST levels do not appear to be useful in predicting mortality in HIV-monoinfection, and should be considered primarily in the context of HCV-coinfection.
PMCID: PMC5127775  PMID: 27677166
HIV infection; HCV infection; mortality; albumin; globulin; total protein; liver enzymes
4.  The Starting Treatment for Ethanol in Primary care Trials (STEP Trials): Protocol for Three Parallel Multi-Site Stepped Care Effectiveness Studies for Unhealthy Alcohol Use in HIV-Positive Patients 
Unhealthy alcohol use is common among HIV-positive patients, yet effective evidence-based treatments are rarely provided in clinical settings providing HIV care. Further, given patient variability in response to initial treatments, stepped care approaches may be beneficial. We describe the rationale, aims and study design for the current Starting Treatment for Ethanol in Primary care Trials (STEP Trials); three parallel randomized controlled effectiveness trials being conducted in five Infectious Disease Clinics. Participants meeting criteria for: 1) at-risk drinking, 2) moderate alcohol use with liver disease (MALD), or 3) alcohol use disorder (AUD) are randomized to integrated stepped care versus treatment as usual. For those with at-risk drinking or MALD, integrated stepped care starts with a one session brief intervention and follow-up 2-week telephone booster. Based on pre-specified nonresponse criteria, participants may be “stepped up” at week 4 to receive four sessions of motivational enhancement therapy (MET) and “stepped up” again at week 12 for addiction physician management (APM) and consideration of alcohol pharmacotherapy. For those with AUD, integrated stepped care begins with APM. Non-responders may be “stepped up” at week 4 to receive MET and again at week 12 for a higher level of care (e.g. intensive outpatient program). The primary outcome is alcohol consumption assessed at 24 weeks, and secondary outcome is the VACS Index, a validated measure of HIV morbidity and mortality risk. Results from the STEP Trials should inform future research and the implementation of interventions to address unhealthy alcohol use among HIV-positive individuals.
PMCID: PMC5253227  PMID: 27876616
Multicenter study; Randomized controlled trial; Algorithms; HIV; Alcohol
5.  Baseline, Time-Updated, and Cumulative HIV Care Metrics for Predicting Acute Myocardial Infarction and All-Cause Mortality 
Six human immunodeficiency virus (HIV) care metrics predicted acute myocardial infarction (AMI) and mortality among HIV-infected individuals. Time-updated Veterans Aging Cohort Study Index provided the best prediction for both AMI and mortality.
Background. After adjustment for cardiovascular risk factors and despite higher mortality, those with human immunodeficiency virus (HIV+) have a greater risk of acute myocardial infarction (AMI) than uninfected individuals.
Methods. We included HIV+ individuals who started combination antiretroviral therapy (cART) in the Veterans Aging Cohort Study (VACS) from 1996 to 2012. We fit multivariable proportional hazards models for baseline, time-updated and cumulative measures of HIV-1 RNA, CD4 counts, and the VACS Index. We used the trapezoidal rule to build the following cumulative measures: viremia copy-years, CD4-years, and VACS Index score-years, captured 180 days after cART initiation until AMI, death, last clinic visit, or 30 September 2012. The primary outcomes were incident AMI (Medicaid, Medicare, and Veterans Affairs International Classification of Diseases-9 codes) and death.
Results. A total of 8168 HIV+ individuals (53 861 person-years) were analyzed with 196 incident AMIs and 1710 deaths. Controlling for known cardiovascular risk factors, 6 of the 9 metrics predicted AMI and all metrics predicted mortality. Time-updated VACS Index had the lowest Akaike information criterion among all models for both outcomes. A time-updated VACS Index score of 55+ was associated with a hazard ratio (HR) of 3.31 (95% confidence interval [CI], 2.11–5.20) for AMI and a HR of 31.77 (95% CI, 26.17–38.57) for mortality.
Conclusions. Time-updated VACS Index provided better AMI and mortality prediction than CD4 count and HIV-1 RNA, suggesting that current health determines risk more accurately than prior history and that risk assessment can be improved by biomarkers of organ injury.
PMCID: PMC5106607  PMID: 27539575
acute myocardial infarction; HIV; mortality; VACS Index
6.  Incarceration History and Uncontrolled Blood Pressure in a Multi-Site Cohort 
Journal of General Internal Medicine  2016;31(12):1496-1502.
Incarceration is associated with increased risk of hypertension and cardiovascular disease mortality. We used data from the Veterans Aging Cohort Study (VACS) to explore the impact of incarceration on blood pressure (BP) control.
Among hypertensive VACS participants, we measured the association between self-reported recent incarceration or past (not recent) history of incarceration and BP control in the year following the survey. To analyze the association between incarceration and BP control, we used logistic regression models adjusted for sociodemographic characteristics, clinical factors (HIV status and body mass index), and behavioral factors (history of smoking, unhealthy alcohol use, illicit drug use). We explored potential mediators including post-traumatic stress disorder (PTSD), depression, primary care engagement, and adherence to antihypertensive medications.
Among the 3515 eligible VACS participants, 2304 participants met the inclusion criteria. Of these, 163 (7 %) reported recent incarceration, and 904 (39 %) reported a past history of incarceration. Participants with recent or past history of incarceration were more likely to have uncontrolled BP than those without a history of incarceration (67 % vs. 56 % vs. 51 %, p < 0.001). In multivariable analysis, recent incarceration (adjusted odds ratio [AOR] = 1.57 95 % confidence interval [CI]: 1.09–2.26), but not a past history of incarceration (AOR = 1.08 95 % CI: 0.90–1.30), was associated with uncontrolled BP compared with those who were never incarcerated.
Among patients with a history of hypertension, recent incarceration is associated with having uncontrolled BP following release. Interventions are needed for recently released individuals to improve hypertension outcomes.
Electronic supplementary material
The online version of this article (doi:10.1007/s11606-016-3857-1) contains supplementary material, which is available to authorized users.
PMCID: PMC5130961  PMID: 27619934
hypertension/epidemiology; hypertension/therapy; prisoners; socioeconomic factors; chronic disease/epidemiology; chronic disease/therapy; incarceration
7.  The Effect of Substance Use Disorders on the Association Between Guideline-Concordant Long-Term Opioid Therapy and All-Cause Mortality 
Journal of addiction medicine  2016;10(6):418-428.
Patients with substance use disorders (SUDs) prescribed long-term opioid therapy (LtOT) are at risk for overdose and mortality. Prior research has shown that receipt of LtOT in accordance with clinical practice guidelines has the potential to mitigate these outcomes. Our objective was to determine whether the presence of a SUD modifies the association between guideline-concordant care and 1-year all-cause mortality among patients receiving LtOT for pain.
Among HIV+ and HIV- patients initiating LtOT (≥ 90d opioids) between 2000 and 2010 as part of the Veterans Aging Cohort Study, we used time-updated Cox regression and propensity-score matching to examine—stratified by SUD status—the association between 1-year all-cause mortality and 3 quality indicators derived from national opioid prescribing guidelines. Specifically, we examined whether patients received: psychotherapeutic co-interventions (≥ 2 outpatient mental health visits), benzodiazepine co-prescriptions (≥ 7d), and SUD treatment (≥ 1 inpatient day or outpatient visit). These indicators were among those found in a previous study to have a strong association with mortality.
Among 17,044 patients initiating LtOT, there were 1,048 (6.1%) deaths during one year of follow-up. Receipt of psychotherapeutic co-interventions was associated with lower mortality in the sample overall and was more protective in patients with SUDs (adjusted hazard ratio [AHR] 0.43, 95% confidence interval [CI] 0.33–0.56 vs. AHR 0.65, 95% CI 0.53–0.81; P for interaction = .002). Benzodiazepine co-prescribing was associated with higher mortality in the sample overall (AHR 1.41; 95% CI 1.22–1.63), but we found no interaction by SUD status (P for interaction = .11). Among patients with SUDs, receipt of SUD treatment was associated with lower mortality (AHR 0.43; 95% CI 0.33–0.57).
For clinicians prescribing LtOT to patients with untreated SUDs, engaging patients with psychotherapeutic and SUD treatment services may reduce mortality. Clinicians should also avoid, when possible, prescribing opioids with benzodiazepines.
PMCID: PMC5083184  PMID: 27610580
Opioid analgesics; practice guideline; quality of healthcare; mortality; substance use disorders
8.  White Blood Count, Albumin, and BMI Enhance VACS Index Prognostic Model, but Nadir CD4 and CD8 Metrics Do Not 
Open Forum Infectious Diseases  2017;4(Suppl 1):S210.
People living with HIV frequently achieve long-term viral suppression necessitating better metrics of disease burden for clinical management and research. The Veterans Aging Cohort Study (VACS) Index predicts hospitalization, mortality, and other outcomes, using routinely available clinical data. We sought to enhance the index by evaluating whether nadir CD4, CD8, CD4/CD8 ratio, white blood count (WBC) or absolute neutrophil count (ANC), albumin, and body mass index (BMI) enhanced prediction. The original index categorized predictors for ease of understanding and calculation of a risk score. We also sought to expand categories and develop a continuous variable model, suitable for use with automated calculation, to provide higher resolution.
VACS, includes all HIV infected patients in VA Care. Among those who initiated ART 1996–2013, (excluding any treated for HCV infection), we obtained laboratory values from a randomly selected visit 2000–2014, at least one year after ART initiation. Patients were followed for 5-year, all cause mortality until September 30, 2016. We fit Cox models starting with currently used predictors (age, CD4, HIV-1 RNA, hemoglobin, FIB4, eGFR and HCV status) and decided to include new variables based on model fit, chi-square, strength and significance of individual levels and c-statistic. Functional form for continuous variables was determined graphically. Adequacy of final models was assessed with Kaplan-Meier plots by deciles of risk.
Among 28,390 patients there were 7,293 deaths (7.2 per 100 person-years) in median 4.1 years of follow-up. Nadir CD4, CD8, CD4:CD8 did not improve prediction. WBC and ANC performed equally but WBC was more widely available. C-statistics improved from 0.776 for the original VACS Index (in this sample) to 0.805.
Addition of WBC, albumin, and BM enhances utility of the VACS Index as a measure of overall severity of disease both as an outcome for research and for patient monitoring in the clinical setting. Validation in external cohorts is in progress.
All authors: No reported disclosures.
PMCID: PMC5631891
9.  Weight Gain and Incident Diabetes among HIV Infected-Veterans Initiating Antiretroviral Therapy Compared to Uninfected Individuals 
The health implications of weight gain after antiretroviral therapy (ART) for HIV infection are not well characterized and may differ from weight gain among uninfected individuals. We use data from the Veterans Aging Cohort Study (VACS) to determine whether weight gain after ART has a similar association with incident type-2 diabetes mellitus (DM) as weight gained among HIV-uninfected (uninfected) individuals.
We explored associations of weight gain and incident diabetes (A1c ≥ 6.5 %), in VACS, a national observational study of HIV infected (HIV+) individuals demographically matched 1:2 to uninfected controls. From 2000 to 2011, weight change was assessed in the year following ART initiation for HIV+ individuals and date of first available BMI for uninfected individuals. We estimated hazard ratios (HR) and 95% CI adjusted for baseline BMI using Cox regression.
HIV+ individuals had lower prevalence of DM at baseline (12%, HIV+, 23% uninfected) and lower incident diabetes (5% HIV+, 11% uninfected). The association of weight gain with risk of DM was linear for HIV+ and uninfected but the slope of the association was steeper for HIV+. For each 5 pounds of weight gained, HIV+ had 14% increased risk of DM (HR, 1.14; 95% CI, 1.10–1.17) and uninfected individuals had 8% increased risk (HR: 1.08; 95% CI, 1.07–1.10) (p<0.01 for interaction).
Weight gained in the first year after ART initiation is associated with greater risk of DM than that among uninfected individuals. HIV+ individuals initiating ART who are not underweight should avoid substantial weight gain.
PMCID: PMC5023454  PMID: 27171741
Diabetes; HIV; weight gain; obesity; Veterans; Inflammation
10.  Association Between Depressive Disorders and Incident Acute Myocardial Infarction in Human Immunodeficiency Virus–Infected Adults 
JAMA cardiology  2016;1(8):929-937.
With the advent of highly effective antiretroviral therapy and improved survival, human immunodeficiency virus (HIV)–infected people are living longer and are now at an increased risk for cardiovascular disease (CVD). There is an urgent need to identify novel risk factors and primary prevention approaches for CVD in HIV. Although depression is prevalent in HIV-infected adults and is associated with future CVD in the general population, its association with CVD events has not been examined in the HIV-infected population.
To examine whether depressive disorders are prospectively associated with incident acute myocardial infarction (AMI) in a large cohort of adults with HIV.
Included in this cohort study were 26 144 HIV-infected veterans without CVD at baseline (1998–2003) participating in the US Department of Veterans Affairs Veterans Aging Cohort Study from April 1, 2003, through December 31, 2009. At baseline, 4853 veterans (19%) with major depressive disorder (MDD; International Classification of Diseases, Ninth Revision [ICD-9] codes 296.2 and 296.3) and 2296 (9%) with dysthymic disorder (ICD-9 code 300.4) were identified. The current analysis was conducted from January 2015 to November 2015.
Incident AMI (defined by discharge summary documentation, enzyme/electrocardiography evidence of AMI, inpatient ICD-9 code for AMI (410), or AMI as underlying cause of death [International Statistical Classification of Diseases and Related Health Problems, Tenth Revision code 121]) between the enrollment date and December 31, 2009.
The mean (SD) age of those with MDD was 47.3 (7.9) years and for those without MDD was 48.2 (9.7) years. During 5.8 years of follow-up, 490 AMI events (1.9%) occurred. Baseline MDD was associated with incident AMI after adjusting for demographics (hazard ratio [HR], 1.31; 95% CI, 1.05–1.62), CVD risk factors (HR, 1.29; 95% CI, 1.04–1.60), and HIV-specific factors (HR, 1.30; 95% CI, 1.05–1.62). Further adjustment for hepatitis C, renal disease, substance abuse, and hemoglobin level (HR, 1.25; 95% CI, 1.00–1.56) and antidepressant use (HR, 1.12; 95% CI, 0.87–1.42) attenuated associations. Baseline dysthymic disorder was not associated with incident AMI.
We report novel evidence that HIV-infected adults with MDD have a 30% increased risk for AMI than HIV-infected adults without MDD after adjustment for many potential confounders. Our findings raise the possibility that MDD may be independently associated with incident atherosclerotic CVD in the HIV-infected population.
PMCID: PMC5621480  PMID: 27557332
11.  Proceedings of the 14th annual conference of INEBRIA 
Holloway, Aisha S. | Ferguson, Jennifer | Landale, Sarah | Cariola, Laura | Newbury-Birch, Dorothy | Flynn, Amy | Knight, John R. | Sherritt, Lon | Harris, Sion K. | O’Donnell, Amy J. | Kaner, Eileen | Hanratty, Barbara | Loree, Amy M. | Yonkers, Kimberly A. | Ondersma, Steven J. | Gilstead-Hayden, Kate | Martino, Steve | Adam, Angeline | Schwartz, Robert P. | Wu, Li-Tzy | Subramaniam, Geetha | Sharma, Gaurav | McNeely, Jennifer | Berman, Anne H. | Kolaas, Karoline | Petersén, Elisabeth | Bendtsen, Preben | Hedman, Erik | Linderoth, Catharina | Müssener, Ulrika | Sinadinovic, Kristina | Spak, Fredrik | Gremyr, Ida | Thurang, Anna | Mitchell, Ann M. | Finnell, Deborah | Savage, Christine L. | Mahmoud, Khadejah F. | Riordan, Benjamin C. | Conner, Tamlin S. | Flett, Jayde A. M. | Scarf, Damian | McRee, Bonnie | Vendetti, Janice | Gallucci, Karen Steinberg | Robaina, Kate | Clark, Brendan J. | Jones, Jacqueline | Reed, Kathryne D. | Hodapp, Rachel M. | Douglas, Ivor | Burnham, Ellen L. | Aagaard, Laura | Cook, Paul F. | Harris, Brett R. | Yu, Jiang | Wolff, Margaret | Rogers, Meighan | Barbosa, Carolina | Wedehase, Brendan J. | Dunlap, Laura J. | Mitchell, Shannon G. | Dusek, Kristi A. | Gryczynski, Jan | Kirk, Arethusa S. | Oros, Marla T. | Hosler, Colleen | O’Grady, Kevin E. | Brown, Barry S. | Angus, Colin | Sherborne, Sidney | Gillespie, Duncan | Meier, Petra | Brennan, Alan | de Vargas, Divane | Soares, Janaina | Castelblanco, Donna | Doran, Kelly M. | Wittman, Ian | Shelley, Donna | Rotrosen, John | Gelberg, Lillian | Edelman, E. Jennifer | Maisto, Stephen A. | Hansen, Nathan B. | Cutter, Christopher J. | Deng, Yanhong | Dziura, James | Fiellin, Lynn E. | O’Connor, Patrick G. | Bedimo, Roger | Gibert, Cynthia | Marconi, Vincent C. | Rimland, David | Rodriguez-Barradas, Maria C. | Simberkoff, Michael S. | Justice, Amy C. | Bryant, Kendall J. | Fiellin, David A. | Giles, Emma L. | Coulton, Simon | Deluca, Paolo | Drummond, Colin | Howel, Denise | McColl, Elaine | McGovern, Ruth | Scott, Stephanie | Stamp, Elaine | Sumnall, Harry | Vale, Luke | Alabani, Viviana | Atkinson, Amanda | Boniface, Sadie | Frankham, Jo | Gilvarry, Eilish | Hendrie, Nadine | Howe, Nicola | McGeechan, Grant J. | Ramsey, Amy | Stanley, Grant | Clephane, Justine | Gardiner, David | Holmes, John | Martin, Neil | Shevills, Colin | Soutar, Melanie | Chi, Felicia W. | Weisner, Constance | Ross, Thekla B. | Mertens, Jennifer | Sterling, Stacy A. | Shorter, Gillian W. | Heather, Nick | Bray, Jeremy | Cohen, Hildie A. | McPherson, Tracy L. | Adam, Cyrille | López-Pelayo, Hugo | Gual, Antoni | Segura-Garcia, Lidia | Colom, Joan | Ornelas, India J. | Doyle, Suzanne | Donovan, Dennis | Duran, Bonnie | Torres, Vanessa | Gaume, Jacques | Grazioli, Véronique | Fortini, Cristiana | Paroz, Sophie | Bertholet, Nicolas | Daeppen, Jean-Bernard | Satterfield, Jason M. | Gregorich, Steven | Alvarado, Nicholas J. | Muñoz, Ricardo | Kulieva, Gozel | Vijayaraghavan, Maya | Adam, Angéline | Cunningham, John A. | Díaz, Estela | Palacio-Vieira, Jorge | Godinho, Alexandra | Kushir, Vladyslav | O’Brien, Kimberly H. M. | Aguinaldo, Laika D. | Sellers, Christina M. | Spirito, Anthony | Chang, Grace | Blake-Lamb, Tiffany | LaFave, Lea R. Ayers | Thies, Kathleen M. | Pepin, Amy L. | Sprangers, Kara E. | Bradley, Martha | Jorgensen, Shasta | Catano, Nico A. | Murray, Adelaide R. | Schachter, Deborah | Andersen, Ronald M. | Rey, Guillermina Natera | Vahidi, Mani | Rico, Melvin W. | Baumeister, Sebastian E. | Johansson, Magnus | Sinadinovic, Christina | Hermansson, Ulric | Andreasson, Sven | O’Grady, Megan A. | Kapoor, Sandeep | Akkari, Cherine | Bernal, Camila | Pappacena, Kristen | Morley, Jeanne | Auerbach, Mark | Neighbors, Charles J. | Kwon, Nancy | Conigliaro, Joseph | Morgenstern, Jon | Magill, Molly | Apodaca, Timothy R. | Borsari, Brian | Hoadley, Ariel | Scott Tonigan, J. | Moyers, Theresa | Fitzgerald, Niamh M. | Schölin, Lisa | Barticevic, Nicolas | Zuzulich, Soledad | Poblete, Fernando | Norambuena, Pablo | Sacco, Paul | Ting, Laura | Beaulieu, Michele | Wallace, Paul George | Andrews, Matthew | Daley, Kate | Shenker, Don | Gallagher, Louise | Watson, Rod | Weaver, Tim | Bruguera, Pol | Oliveras, Clara | Gavotti, Carolina | Barrio, Pablo | Braddick, Fleur | Miquel, Laia | Suárez, Montse | Bruguera, Carla | Brown, Richard L. | Capell, Julie Whelan | Paul Moberg, D. | Maslowsky, Julie | Saunders, Laura A. | McCormack, Ryan P. | Scheidell, Joy | Gonzalez, Mirelis | Bauroth, Sabrina | Liu, Weiwei | Lindsay, Dawn L. | Lincoln, Piper | Hagle, Holly | Wallhed Finn, Sara | Hammarberg, Anders | Andréasson, Sven | King, Sarah E. | Vargo, Rachael | Kameg, Brayden N. | Acquavita, Shauna P. | Van Loon, Ruth Anne | Smith, Rachel | Brehm, Bonnie J. | Diers, Tiffiny | Kim, Karissa | Barker, Andrea | Jones, Ashley L. | Skinner, Asheley C. | Hinman, Agatha | Svikis, Dace S. | Thacker, Casey L. | Resnicow, Ken | Beatty, Jessica R. | Janisse, James | Puder, Karoline | Bakshi, Ann-Sofie | Milward, Joanna M. | Kimergard, Andreas | Garnett, Claire V. | Crane, David | Brown, Jamie | West, Robert | Michie, Susan | Rosendahl, Ingvar | Andersson, Claes | Gajecki, Mikael | Blankers, Matthijs | Donoghue, Kim | Lynch, Ellen | Maconochie, Ian | Phillips, Ceri | Pockett, Rhys | Phillips, Tom | Patton, R. | Russell, Ian | Strang, John | Stewart, Maureen T. | Quinn, Amity E. | Brolin, Mary | Evans, Brooke | Horgan, Constance M. | Liu, Junqing | McCree, Fern | Kanovsky, Doug | Oberlander, Tyler | Zhang, Huan | Hamlin, Ben | Saunders, Robert | Barton, Mary B. | Scholle, Sarah H. | Santora, Patricia | Bhatt, Chirag | Ahmed, Kazi | Hodgkin, Dominic | Gao, Wenwu | Merrick, Elizabeth L. | Drebing, Charles E. | Larson, Mary Jo | Sharma, Monica | Petry, Nancy M. | Saitz, Richard | Weisner, Constance M. | Young-Wolff, Kelly C. | Lu, Wendy Y. | Blosnich, John R. | Lehavot, Keren | Glass, Joseph E. | Williams, Emily C. | Bensley, Kara M. | Chan, Gary | Dombrowski, Julie | Fortney, John | Rubinsky, Anna D. | Lapham, Gwen T. | Forray, Ariadna | Olmstead, Todd A. | Gilstad-Hayden, Kathryn | Kershaw, Trace | Dillon, Pamela | Weaver, Michael F. | Grekin, Emily R. | Ellis, Jennifer D. | McGoron, Lucy | McGoron, Lucy
PMCID: PMC5606215
12.  Hepatic safety of buprenorphine in HIV-infected and uninfected patients with opioid use disorder: The role of HCV-infection 
Individuals with HIV and hepatitis C (HCV) infection, alcohol use disorder, or who are prescribed potentially hepatotoxic medications may be at increased risk for buprenorphine (BUP) associated hepatotoxicity.
Materials and methods
We examined a cohort of HIV-infected and uninfected patients receiving an initial BUP prescription between 2003 and 2012. We compared changes in alanine and aspartate aminotransferases (ALT and AST) and total bilirubin (TB) stratified by HIV status. We identified cases of liver enzyme elevation (LEE), TB elevation (TBE), and conducted chart review to assess for cases of drug induced liver injury (DILI) and death. We examined associations between age, sex, race, HIV-infection, HCV-infection, alcohol use disorder, and prescription of other potentially heptatotoxic medications with the composite endpoint of LEE, TBE, and DILI.
Of 666 patients prescribed BUP, 36% were HIV-infected, 98% were male, 60% had RNA-confirmed HCV infection, 50% had a recent diagnosis of alcohol use disorder, and 64% were prescribed other potentially hepatotoxic medications. No clinically significant changes were observed in median ALT, AST and TB and these changes did not differ between HIV-infected and uninfected patients. Compared with uninfected patients, HIV-infected (OR 7.3, 95% CI 2.1-26.1, p=0.002), HCV-infected (OR 4.9 95% CI 1.6-15.2, p=0.007) or HIV/HCV co-infected patients (OR 6.9, 95%CI 2.1-22.2, p=0.001) were more likely to have the composite endpoint of LEE, TB elevation or DILI, in analyses that excluded 60 patients with evidence of pre-existing liver injury. 31 patients had LEE, 14/187 HIV-infected and 17/340 uninfected (p = 0.25); 11 had TBE, including 9/186 HIV-infected and 2/329 uninfected (p = 0.002); 8 experienced DILI, 4/202 HIV-infected and 2/404 uninfected (p = 0.45). There were no significant associations with alcohol use disorder or prescription of other potentially hepatotoxic medications after adjustment for HIV/HCV status.
Liver enzymes and TB are rarely elevated in HIV-infected and uninfected patients receiving BUP. Risk of hepatotoxicity was greater in individuals infected with HIV, HCV, or HIV/HCV co-infection, who may benefit from increased monitoring.
PMCID: PMC4976086  PMID: 27431048
buprenorphine; HIV; Hepatitis C; drug induced liver injury
13.  Fracture prediction with modified-FRAX in older HIV-infected and uninfected men 
FRAX® is a validated, computer-based clinical fracture risk calculator that estimates 10-year risk of major osteoporotic (clinical spine, forearm, hip or shoulder) fracture, and hip fracture alone. It is widely used for decision-making in fracture prevention, but may underestimate risk in HIV-infected individuals. Some experts recommend considering HIV a cause of secondary osteoporosis when calculating FRAX in HIV-infected individuals.
From the Veterans Aging Study Virtual Cohort (VACS-VC), we included 24451 HIV-infected and uninfected 50-70 year old men with complete data in year 2000 to approximate all but two factors (i.e. history of secondary osteoporosis and parental hip fracture) for modified-FRAX calculation without bone density and 10-year observational data for incident fragility fracture. Accuracy of the modified-FRAX calculation was compared by observed/estimated (O/E) ratios of fracture by HIV status.
Accuracy of modified-FRAX was less for HIV-infected (O/E=1.62, 95%CI: 1.45, 1.81) than uninfected men (O/E=1.29, 95%CI: 1.19, 1.40), but improved when HIV was included as a cause of secondary osteoporosis (O/E=1.20, 95%CI: 1.08, 1.34). However, only 3-6% of men with incident fractures were correctly identified by the modified-FRAX using accepted FRAX thresholds for pharmacologic therapy.
Modified-FRAX underestimated fracture rates more in older HIV-infected than otherwise similar uninfected men. Accuracy improved when HIV was included as a cause of secondary osteoporosis, but it still performed poorly for case-finding. Further studies are necessary to determine how to use FRAX or define an HIV-specific index to risk stratify for screening and treatment in older HIV-infected individuals.
PMCID: PMC4942335  PMID: 27003493
fracture incidence; HIV; men; FRAX
14.  Association Between HIV Infection and the Risk of Heart Failure With Reduced Ejection Fraction and Preserved Ejection Fraction in the Antiretroviral Therapy Era 
JAMA cardiology  2017;2(5):536-546.
With improved survival, heart failure (HF) has become a major complication for individuals with human immunodeficiency virus (HIV) infection. It is unclear if this risk extends to different types of HF in the antiretroviral therapy (ART) era. Determining whether HIV infection is associated with HF with reduced ejection fraction (HFrEF), HF with preserved ejection fraction (HFpEF), or both is critical because HF types differ with respect to underlying mechanism, treatment, and prognosis.
To investigate whether HIV infection increases the risk of future HFrEF and HFpEF and to assess if this risk varies by sociodemographic and HIV-specific factors.
This study evaluated 98 015 participants without baseline cardiovascular disease from the Veterans Aging Cohort Study, an observational cohort of HIV-infected veterans and uninfected veterans matched by age, sex, race/ethnicity, and clinical site, enrolled on or after April 1, 2003, and followed up through September 30, 2012. The dates of the analysis were October 2015 to November 2016.
Human immunodeficiency virus infection.
Outcomes included HFpEF (EF≥50%), borderline HFpEF (EF 40%–49%), HFrEF (EF<40%), and HF of unknown type (EF missing).
Among 98 015 participants, the mean (SD) age at enrollment in the study was 48.3 (9.8) years, 97.0% were male, and 32.2% had HIV infection. During a median follow-up of 7.1 years, there were 2636 total HF events (34.6% were HFpEF, 15.5% were borderline HFpEF, 37.1% were HFrEF, and 12.8% were HF of unknown type). Compared with uninfected veterans, HIV-infected veterans had an increased risk of HFpEF (hazard ratio [HR], 1.21; 95% CI, 1.03–1.41), borderline HFpEF (HR, 1.37; 95% CI, 1.09–1.72), and HFrEF (HR, 1.61; 95% CI, 1.40–1.86). The risk of HFrEF was pronounced in veterans younger than 40 years at baseline (HR, 3.59; 95% CI, 1.95–6.58). Among HIV-infected veterans, time-updated HIV-1 RNA viral load of at least 500 copies/mL compared with less than 500 copies/mL was associated with an increased risk of HFrEF, and time-updated CD4 cell count less than 200 cells/mm3 compared with at least 500 cells/mm3 was associated with an increased risk of HFrEF and HFpEF.
Individuals who are infected with HIV have an increased risk of HFpEF, borderline HFpEF, and HFrEF compared with uninfected individuals. The increased risk of HFrEF can manifest decades earlier than would be expected in a typical uninfected population. Future research should focus on prevention, risk stratification, and identification of the mechanisms for HFrEF and HFpEF in the HIV-infected population.
PMCID: PMC5541383  PMID: 28384660
15.  Time trends in cancer incidence in persons living with HIV/AIDS in the antiretroviral therapy era: 1997–2012 
AIDS (London, England)  2016;30(11):1795-1806.
Utilizing the Veterans Aging Cohort Study, the largest HIV cohort in North America, we conducted one of the few comprehensive comparisons of cancer incidence time trends in HIV-infected (HIV+) versus uninfected persons during the antiretroviral therapy (ART) era.
Prospective cohort study.
We followed 44,787 HIV+ and 96,852 demographically-matched uninfected persons during 1997–2012. We calculated age-, sex-, and race/ethnicity-standardized incidence rates (IR) and incidence rate ratios (IRR, HIV+ versus uninfected) over four calendar periods with IR and IRR period trend p-values for cancer groupings and specific cancer types.
We observed 3,714 incident cancer diagnoses in HIV+ and 5,760 in uninfected persons. The HIV+ all cancer crude IR increased between 1997–2000 and 2009–2012 (p-trend=0.0019). However, after standardization, we observed highly significant HIV+ IR declines for all cancer (25% decline; p-trend<0.0001), AIDS-defining cancers (ADC; 55% decline; p-trend<0.0001), non-AIDS-defining cancers (NADC; 15% decline; p-trend=0.0003), and non-virus-related NADC (20% decline; p-trend<0.0001); significant IRR declines for all cancer (from 2.0 to 1.6; p-trend<0.0001), ADC (from 19 to 5.5; p-trend<0.0001), and non-virus-related NADC (from 1.4 to 1.2; p-trend=0.049); and borderline significant IRR declines for NADC (from 1.6 to 1.4; p-trend=0.078) and virus-related NADC (from 4.9 to 3.5; p-trend=0.071).
Improved HIV care resulting in improved immune function most likely contributed to the HIV+ IR and the IRR declines. Further promotion of early and sustained ART, improved ART regimens, reduction of traditional cancer risk factor (e.g., smoking) prevalence, and evidence-based screening could contribute to future cancer incidence declines among HIV+ persons.
PMCID: PMC4925286  PMID: 27064994
acquired immunodeficiency syndrome; HIV infections; neoplasms; cancer; Veterans
16.  Do Biomarkers Of Inflammation, Monocyte Activation And Altered Coagulation Explain Excess Mortality Between HIV Infected and Uninfected People? 
HIV infection and biomarkers of inflammation (measured by interleukin-6 [IL-6]), monocyte activation (soluble CD14 [sCD14]), and coagulation (D-dimer) are associated with morbidity and mortality. We hypothesized that these immunologic processes mediate (explain) some of the excess risk of mortality among HIV infected (HIV+) versus uninfected people independently of co-morbid diseases.
Among 2350 (1521 HIV+) participants from the Veterans Aging Cohort Study Biomarker Cohort (VACS BC) we investigated whether the association between HIV and mortality was altered by adjustment for IL-6, sCD14 and D-dimer, accounting for confounders. Participants were followed from date of blood draw for biomarker assays (baseline) until death or 7/25/2013. Analyses included ordered logistic regression and Cox Proportional Hazards regression.
During 6·9 years (median), 414 deaths occurred. The proportional odds of being in a higher quartile of IL-6, sCD14 or D-dimer was 2-3 fold higher for viremic HIV+ versus uninfected people. Mortality rates were higher among HIV+ compared to uninfected people (incidence rate ratio (95% CI): 1·31 (1·06-1·62). Mortality risk increased with increasing quartiles of IL-6, sCD14 and D-dimer regardless of HIV status. Adjustment for IL-6, sCD14 and D-dimer partially attenuated mortality risk among HIV+ people with unsuppressed viremia (HIV-1 RNA≥10000 copies/mL) compared to uninfected people – hazard ratio (95% CI) decreased from 2·18 (1·60-2·99) to 2·00 (1·45-2·76).
HIV infection is associated with elevated IL-6, sCD14 and D-dimer, which are in turn associated with mortality. Baseline measures of these biomarkers partially mediate excess mortality risk among HIV+ versus uninfected people.
PMCID: PMC4867134  PMID: 26885807
HIV; mortality; inflammation; monocyte activation; coagulation
17.  The Association Between Receipt of Guideline-Concordant Long-Term Opioid Therapy and All-Cause Mortality 
For patients receiving long-term opioid therapy (LtOT), the impact of guideline-concordant care on important clinical outcomes—notably mortality—is largely unknown, even among patients with a high comorbidity and mortality burden (e.g., HIV-infected patients). Our objective was to determine the association between receipt of guideline-concordant LtOT and 1-year all-cause mortality.
Among HIV-infected and uninfected patients initiating LtOT between 2000 and 2010 through the Department of Veterans Affairs, we used Cox regression with time-updated covariates and propensity-score matched analyses to examine the association between receipt of guideline-concordant care and 1-year all-cause mortality.
Of 17,044 patients initiating LtOT between 2000 and 2010, 1048 patients (6%) died during 1 year of follow-up. Patients receiving psychotherapeutic co-interventions (hazard ratio [HR] 0.62; 95% confidence interval [CI] 0.51–0.75; P < 0.001) or physical rehabilitative therapies (HR 0.81; 95% CI 0.67–0.98; P = 0.03) had a decreased risk of all-cause mortality compared to patients not receiving these services, whereas patients prescribed benzodiazepines concurrent with opioids had a higher risk of mortality (HR 1.39; 95% CI 1.12–1.66; P < 0.001). Among patients with a current substance use disorder (SUD), those receiving SUD treatment had a lower risk of mortality than untreated patients (HR 0.47; 95% CI 0.32–0.68; P = < 0.001). No association was found between all-cause mortality and primary care visits (HR 1.12; 95% CI 0.90–1.26; P = 0.32) or urine drug testing (HR 0.96; 95% CI 0.78–1.17; P = 0.67).
Providers should use caution in initiating LtOT in conjunction with benzodiazepines and untreated SUDs. Patients receiving LtOT may benefit from multi-modal treatment that addresses chronic pain and its associated comorbidities across multiple disciplines.
Electronic supplementary material
The online version of this article (doi:10.1007/s11606-015-3571-4) contains supplementary material, which is available to authorized users.
PMCID: PMC4835362  PMID: 26847447
Opioid analgesics; practice guideline; quality of health care; mortality; pain
18.  Isolated Hepatitis B Core Antibody is Associated with Advanced Hepatic Fibrosis in HIV/HCV Infection but not in HIV infection alone 
HIV+/HCV+ persons with isolated HBcAb have a higher prevalence of advanced fibrosis than persons who are non-immune to HBV, who have resolved HBV, or who are HbsAb+ only.
PMCID: PMC4837046  PMID: 26829660
Hepatitis B Core Antibody; HIV; hepatitis C
We evaluated the utility of the World Health Organization Fracture Risk Assessment Tool (FRAX) in assessing fracture risk in patients with human immunodeficiency virus (HIV) and vitamin D deficiency.
This was a retrospective study of HIV-infected patients with co-existing vitamin D deficiency at the Atlanta Veterans Affairs Medical Center. Bone mineral density (BMD) was assessed by dual-energy X-ray absorptiometry (DEXA), and the 10-year fracture risk was calculated by the WHO FRAX algorithm. Two independent radiologists reviewed lateral chest radiographs for the presence of subclinical vertebral fractures.
We identified 232 patients with HIV and vitamin D deficiency. Overall, 15.5% of patients met diagnostic criteria for osteoporosis on DEXA, and 58% had low BMD (T-score between −1 and −2.5). The median risk of any major osteoporotic and hip fracture by FRAX score was 1.45 and 0.10%, respectively. Subclinical vertebral fractures were detected in 46.6% of patients. Compared to those without fractures, those with fractures had similar prevalence of osteoporosis (15.3% versus 15.7%; P>.999), low BMD (53.2% versus 59.3%; P = .419), and similar FRAX hip scores (0.10% versus 0.10%; P = .412). While the FRAX major score was lower in the nonfracture group versus fracture group (1.30% versus 1.60%; P = .025), this was not clinically significant.
We found a high prevalence of subclinical vertebral fractures among vitamin D–deficient HIV patients; however, DEXA and FRAX failed to predict those with fractures. Our results suggest that traditional screening tools for fragility fractures may not be applicable to this high-risk patient population.
PMCID: PMC5369646  PMID: 26684149
HIV; Vitamin D; osteoporosis; FRAX; fractures; veterans
20.  Alcohol-Related Diagnoses and All-Cause Hospitalization Among HIV-Infected and Uninfected Patients: A Longitudinal Analysis of United States Veterans from 1997 to 2011 
AIDS and behavior  2016;20(3):555-564.
Individuals with HIV infection are living substantially longer on antiretroviral therapy, but hospitalization rates continue to be relatively high. We do not know how overall or diagnosis-specific hospitalization rates compare between HIV-infected and uninfected individuals or what conditions may drive hospitalization trends. Hospitalization rates among United States Veterans were calculated and stratified by HIV serostatus and principal diagnosis disease category. Because alcohol-related diagnoses (ARD) appeared to have a disproportional effect, we further stratified our calculations by ARD history. A multivariable Cox proportional hazards model was fitted to assess the relative risk of hospitalization controlling for demographic and other comorbidity variables. From 1997–2011, 46,428 HIV-infected and 93,997 uninfected patients were followed for 1,497,536 person-years. Overall hospitalization rates decreased among HIV-infected and uninfected patients. However, cardiovascular and renal insufficiency admissions increased for all groups while gastrointestinal and liver, endocrine, neurologic, and non-AIDS cancer admissions increased among those with an alcohol-related diagnosis. After multivariable adjustment, HIV-infected individuals with an ARD had the highest risk of hospitalization (hazard ratio 3.24, 95%CI 3.00, 3.49) compared to those free of HIV infection and without an ARD. Still, HIV alone also conferred increased risk (HR 2.08, 95%CI 2.04, 2.13). While decreasing overall, risk of all-cause hospitalization remains higher among HIV-infected than uninfected individuals and is strongly influenced by the presence of an ARD.
PMCID: PMC4550577  PMID: 25711299
inpatient care; HIV; substance abuse; clinical epidemiology; aging
21.  Quality of HIV Care and Mortality Rates in HIV-Infected Patients 
Links between human immunodeficiency virus (HIV) care quality indicators (QIs) and mortality rates are not well established. We assessed HIV-infected patients' baseline QIs; mortality rates during 24 805–person-years of follow-up were lower among patients receiving ≥80% of baseline HIV QIs.
Background. The Patient Protection and Affordable Care Act encourages healthcare systems to track quality-of-care measures; little is known about their impact on mortality rates. The objective of this study was to assess associations between HIV quality of care and mortality rates.
Methods. A longitudinal survival analysis of the Veterans Aging Cohort Study included 3038 human immunodeficiency virus (HIV)–infected patients enrolled between June 2002 and July 2008. The independent variable was receipt of ≥80% of 9 HIV quality indicators (QIs) abstracted from medical records in the 12 months after enrollment. Overall mortality rates through 2014 were assessed from the Veterans Health Administration, Medicare, and Social Security National Death Index records. We assessed associations between receiving ≥80% of HIV QIs and mortality rates using Kaplan–Meier survival analysis and adjusted Cox proportional hazards models. Results were stratified by unhealthy alcohol and illicit drug use.
Results. The majority of participants were male (97.5%) and black (66.8%), with a mean (standard deviation) age of 49.0 (8.8) years. Overall, 25.9% reported past-year unhealthy alcohol use and 28.4% reported past-year illicit drug use. During 24 805 person-years of follow-up (mean [standard deviation], 8.2 [3.3] years), those who received ≥80% of QIs experienced lower age-adjusted mortality rates (adjusted hazard ratio, 0.75; 95% confidence interval, .65–.86). Adjustment for disease severity attenuated the association.
Conclusions. Receipt of ≥80% of select HIV QIs is associated with improved survival in a sample of predominantly male, black, HIV-infected patients but was insufficient to overcome adjustment for disease severity. Interventions to ensure high-quality care and address underlying chronic illness may improve survival in HIV-infected patients.
PMCID: PMC4690479  PMID: 26338783
alcohol; quality of health care; HIV; health care; opioid-related disorders
22.  Cost-effectiveness of Collaborative Care for Depression in Human Immunodeficiency Virus Clinics 
To examine the cost-effectiveness of the HITIDES intervention.
Randomized controlled effectiveness and implementation trial comparing depression collaborative care with enhanced usual care.
Three Veterans Health Administration (VHA) HIV clinics in the Southern US.
249 HIV-infected patients completed the baseline interview; 123 were randomized to the intervention and 126 to usual care.
HITIDES consisted of an off-site HIV depression care team that delivered up to 12 months of collaborative care. The intervention used a stepped-care model for depression treatment and specific recommendations were based on the Texas Medication Algorithm Project and the VA/Department of Defense Depression Treatment Guidelines.
Main outcome measure(s)
Quality-adjusted life years (QALYs) were calculated using the 12-Item Short Form Health Survey, the Quality of Well Being Scale, and by converting depression-free days to QALYs. The base case analysis used outpatient, pharmacy, patient, and intervention costs. Cost-effectiveness was calculated using incremental cost effectiveness ratios (ICERs) and net health benefit (NHB). ICER distributions were generated using nonparametric bootstrap with replacement sampling.
The HITIDES intervention was more effective and cost-saving compared to usual care in 78% of bootstrapped samples. The intervention NHB was positive and therefore deemed cost-effective using an ICER threshold of $50,000/QALY.
In HIV clinic settings this intervention was more effective and cost-saving compared to usual care. Implementation of off-site depression collaborative care programs in specialty care settings may be a strategy that not only improves outcomes for patients, but also maximizes the efficient use of limited healthcare resources.
PMCID: PMC4626259  PMID: 26102447
23.  Association of COPD with risk for pulmonary infections requiring hospitalization in HIV-infected Veterans 
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.
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.
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).
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.
PMCID: PMC4607625  PMID: 26181820
COPD; pulmonary infection; pneumonia; HIV; comorbidities
24.  Depression and HIV Infection are Risk Factors for Incident Heart Failure Among Veterans: Veterans Aging Cohort Study 
Circulation  2015;132(17):1630-1638.
Both HIV and depression are associated with increased heart failure (HF) risk. Depression, a common comorbidity, may further increase the risk of HF among HIV+ adults. We assessed the association between HIV, depression and incident HF.
Methods and Results
Veterans Aging Cohort Study (VACS) participants free from cardiovascular disease at baseline (N = 81,427; 26,908 HIV+, 54,519 HIV-) were categorized into four groups: HIV- without major depressive disorder (MDD) [reference]; HIV- with MDD; HIV+ without MDD; and HIV+ with MDD. ICD-9 codes from medical records were used to determine MDD and the primary outcome, HF. After 5.8 follow-up years, HF rates per 1000 person-years were highest among HIV+ participants with MDD (9.32; 95% CI, 8.20–10.6). In Cox proportional hazards models, HIV+ participants with MDD had significantly higher risk of HF [adjusted hazard ratio (aHR) = 1.68; 95% CI, 1.45–1.95] compared to HIV- participants without MDD. MDD was associated with HF in separate fully adjusted models for HIV- and HIV+ participants (aHR = 1.21; 1.06–1.37 and 1.29; 1.11–1.51, respectively). Among those with MDD, baseline antidepressant use was associated with lower risk of incident HF events (aHR = 0.76; 0.58–0.99).
Our study is the first to suggest MDD is an independent risk factor for HF in HIV+ adults. These results reinforce the importance of identifying and managing MDD among HIV+ patients. Future studies must clarify mechanisms linking HIV, MDD, antidepressants, and HF; and identify interventions to reduce HF morbidity and mortality in those with both HIV and MDD.
PMCID: PMC4624488  PMID: 26358261
HIV infection; depression; psychiatric comorbidity; heart failure; epidemiology
25.  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
PMCID: PMC5032602  PMID: 27654147

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