Karen Nieves-Lugo, PhD George Washington University

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Effect of chronic pulmonary lung disease on the decline in physical function in HIV infected and uninfected veterans in the Veterans Aging Cohort Study Karen Nieves-Lugo, PhD George Washington University nieveskaren@gwu.edu John Sorkin, MD, PhD 2, Heather Hoffman, PhD 1, Janet Tate, ScD 3, Todd BrowN, MD 4, Kristina CrotherS, MD 5, Stephen Crystal, PhD 6, AdeeL Butt, MD 7, Maria Rodriguez- Barradas, MD 8, Matt Freiberg, MD 9, Amy Justice, MD, PhD 10, Maria Cecilia Zea, PhD 1, Krisann Oursler, MD,ScM 11 1 George Washington University, 2 University of Maryland School of Medicine & Baltimore Veterans Affairs Medical Center Geriatric Research, Education &Clinical Center, 3 Yale University School of Medicine and Public Health &VA Connecticut Healthcare System, 4 Johns Hopkins University, 5 University of Washington, 6 Center for Health Services Research on Pharmacotherapy Chronic Disease Management, and Outcomes, Institute for Health, Rutgers University, 7 VA Pittsburgh Healthcare System & University of Pittsburgh School of Medicine, 8 Michael E. DeBakey VA Medical Center & Department of Medicine, Baylor Collage of 9 Medicine, Vanderbilt University Medical Center, 10 Yale University School of Medicine and Public Health and VA Connecticut Healthcare System, 11 University of Maryland School of Medicine & Salem VA Medical Center

Acknowledgments Veterans Aging Cohort Study (VACS) participants, staff and investigators. http://www.vacohort.org/index.aspx Supported by National Institutes of Health (NIH) 1 F32 MH105293-01 Latino Health Research Center (LHRC), George Washington University District of Columbia Developmental Center for AIDS Research (DC D- CFAR)

Introduction Physical functioning (PF): ability to perform a physical activity without assistance Predicts survival in HIV-positive patients (K. Oursler et al., 2006) Associated with age, medical comorbidities (e.g., chronic pulmonary lung disease) and lifestyle factors among HIVpositive individuals in cross-sectional studies (K. Oursler et al., 2011, K. Oursler et al., 2006; L. Wang et al., 2002; S. Crystal et al., 2000) Research on decline in physical function in HIV-positive patients limited to pre-art era (S. Crystal et al., 1996)

Chronic pulmonary lung disease (CPLD) Include three main conditions emphysema, chronic bronchitis and asthma HIV is a risk factor for CPLD after controlling for age, race/ethnicity, smoking, IDU, alcohol abuse (K. Crothers et al., 2006) CPLD is associated with lower self-reported physical function, which was significantly amplified in the HIV-positive group (K. Oursler, et al. 2011) Lung function (FEV-1) was associated with lower ambulatory performance in HIV-positive participants (Campo, et al., 2014) Drummond et al. (2013) found that decline in lung function did not differ between HIV-positive and negative drug users, except in those with higher viral load and lower CD4.

Objective Examine the effect of baseline chronic pulmonary lung disease on change in selfreported physical function among HIVpositive and negative veterans Controlling for baseline: Demographic characteristics Smoking Common Medical Comorbidities

Methods

Veterans Aging Cohort Study (VACS) Prospective, observational cohort study HIV-positive and matched control group of negative veterans enrolled between 2001 and 2011 from Infectious Disease Clinic and General Medicine Clinics respectively. 8 Veteran Medical Centers (VAMC): Atlanta, Baltimore, The Bronx, Houston, Los Angeles, Manhattan/Brooklyn, Pittsburgh, Washington, D.C. Institutional Review Board (IRB) approval was obtained. More information http://www.vacohort.org/

Analytical Set VACS participants enrolled 2001-2011 (N= 7319) Measures Participants with baseline physical function (PCS) (N=7218) HIV-Positive (N=3573) Infectious Disease clinics Data Collection HIV-Negative (N=3645) General Medicine clinics Patient and provider surveys. Electronic medical record (EMR) Physical Composite Score (PCS) o SF-12 Demographic characteristics Lifestyle factors (smoking) Common Medical Comorbidities: (chronic pulmonary disease, congestive heart failure, coronary artery disease, diabetes, Hepatitis C, Hypertension, Major Depression, peripheral vascular disease and stroke).

Statistical Analyses Summary statistics Comparison of physical function, common medical comorbidities, lifestyle factors and demographic characteristics of HIV positive and negative veterans. Linear mixed model was used to determine the changes in PCS over five-years of follow-up.

Results

Baseline characteristics 60 HIV (+) HIV (-) 50 Percent (%) 40 30 20 10 28.2 (n=1007) 25.4 (n=926) 23.5 21.7 23.1 23.3 (n=827) (n=838) (n=790) (n=848) 25.2 (n=901) 29.7 (n=1081) HIV-positive (n= 3573) Mean=49.2 years-old HIV-negative (n= 3645) Mean=50.5 years-old 0 < 44 45-49 50-54 >55 Age at baseline

Baseline characteristics HIV Positive N=3575 HIV Negative N=3645 Total Sample N=7218 Male 97.40 92.40 94.87 Race* White 19.84 23.32 21.60 Black 66.72 63.02 64.85 Hispanic 9.40 10.18 9.79 Other 4.03 3.48 3.75 Current smoker* 51.73 44.67 48.20 Chronic Pulmonary Lung Disease (CPLD)* 6.80 8.40 7.61 Congestive Heart Failure* 1.68 2.77 2.23 Coronary Artery Disease* 4.34 7.96 6.17 Diabetes Mellitus* 12.03 21.54 16.83 Hepatitis C* 26.56 14.71 20.57 Hypertension* 25.64 46.78 36.31 Major Depression 11.08 12.48 11.79 Peripheral Vascular 1.54 2.80 2.18 Disease* Stroke 0.92 1.45 1.19 α =0.01; *p<0.01

PCS at baseline <36 Mean: 42.3 HIV-Negative Mean: 43.6 HIV-Positive

Multivariable Regression Model 1 Variables Model 1 YRS -0.22 ** HIV 1.66 ** Age at baseline -0.14 ** Race: White 1.63 ** Black 2.45 ** Hispanic 1.63 ** Male 0.93 Current Smoking -1.02 ** Chronic pulmonary lung Disease (CPLD) -3.37 ** Intercept 46.82 *p<0.01, **p<0.001 HIV-uninfected, non-smoking, absence of CPLD were used as reference category

Multivariable Regression Models 2 and 3 Variables Model 2 Model 3 YRS -0.23** -0.32** HIV 1.24** 0.98 Age at baseline -0.08** -0.08** Race: White 1.45** 1.43** Black 2.57** 2.54** Hispanic 1.77** 1.73** Male 1.22* 1.24* Current Smoking -0.95** -0.94** Chronic pulmonary lung Disease (CPLD) -2.50** -1.80** Congestive Heart Failure -4.20** -4.22** Coronary Artery Disease -2.61** -2.64** Diabetes -2.14** -2.14** Hepatitis C -1.97** -1.95** Hypertension -1.13** -1.10** Major Depression -3.12** -3.11** Peripheral Vascular Disease -4.79** -4.76** Stroke -2.65* -2.66* HIV*YRS 0.19* Intercept 45.26 45.37 *p<0.01, **p<0.001 HIV-uninfected, non-smoking, absence of comorbidities were used as reference category

Change in physical function over time HIV-Positive HIV-Negative 33 CPLD (-) CPLD (+) Age=50 years-old 33 CPLD (-) CPLD (+) Age=50 years-old 32 32 PCS Mean 31 30 PCS Mean 31 30 29 29 28 0 1 2 3 4 5 6 Duration of Follow-Up (years) 28 0 1 2 3 4 5 6 Duration of Follow-Up (years)

Conclusions

Smoking and age-related comorbidities are risk factors for decline in physical function. Participants with CPLD at baseline have reduced PCS over time. The decline in function among those with chronic pulmonary disease (βhiv*cpld= -1.53, p=0.07) was not significantly different by HIV group after controlling for demographic characteristics, baseline comorbidities and lifestyle factors. These results highlight the need of optimizing smoking cessation programs and medical comorbidities treatments for both populations to prevent limitation in physical function.

Limitations Participants primarily men and African-American Physical function by self-report Lack of information on severity of lung disease

Future Directions Additional analyses with mental health conditions SF-12 MCS, depression and substance use (alcohol, drug, and tobacco use) Additional analyses in the HIV-infected population CD4, viral load, ART, adherence Longitudinal study with objective assessment of physical function