Living Fit (LivFit) with HIV: Reducing inflammation and improving vascular function among older persons with HIV Open Access

Irwin, Crista (Spring 2023)

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Background: Persons with HIV experience endothelial dysfunction due in part to chronic inflammation that increases their risk for poor vascular function and cardiovascular disease (CVD). Routine moderate to vigorous aerobic exercise intensity has been shown to improve inflammation and vascular function, but the level of exercise adherence required for improvement among older persons with HIV (OPWH) has not been established. In addition, validation studies for the activity monitors to determine exercise intensity was also not established in OPWH. The purpose of this study was to: conduct a systematic review on the validity and accuracy of the FitBit Charge 2 for measuring aerobic exercise intensity level; utilize data from a secondary analysis to test the level of exercise adherence on measures of inflammation, and endothelial vascular function among OPWH.

Methods: Participants (n=115, mean age 55, 65% male, 82% Black) were enrolled in the 2-arm randomized controlled trial (RTC) Healing Hearts and Mending Minds parent study. The intervention group consisted of a progressive walking program (Let’s Move) compared to attention control participants (Let’s Flex) which were evaluated at baseline (BL) for cardiorespiratory fitness using the modified Balke VO2 max test. Inflammatory biomarkers Interleukin-6 (IL6), Tumor necrosis factor (TNF), and soluble C-differential-14 (sCD14) were drawn at BL, 3, 6-, and 12-months. Endothelial vascular function was measured by flow-mediated dilation (FMD) at BL and 6-months. Participants were provided with activity trackers and an exercise prescription based on their individual target heart rate at 60-70 % intensity and progressed to a minimum of 300 minutes per week. T-test were also used to compare the changes in inflammatory values between adherent and non-adherent participants in the exercise intervention group between BL and 3-, 6-, and 12-month timepoints. Change in FMD was examined between both groups from baseline to 6-months. Multilevel linear modeling was performed within the exercise intervention group to examine the incremental change in the biomarker values over time in association with a cumulative adherence level. Cumulative exercise was calculated by adding up whether exercise adherence was met (yes=1, no=0) at each 3-, 6-, and 12- month timepoint (i.e. cumulative adherence values ranged from 0 to 3).

Results: A systematic review of validation studies suggests that the Fitbit Charge2 activity tracker adequately measured HR at moderate intensity exercise levels. Over 60% of the participants in the intervention group maintained adherence to >300 minutes of moderately to vigorous (60-70% HR maximum) exercise throughout the 12-month study duration. Attrition rate was <10% in both groups over the study duration. The change in FMD was not significant between the intervention and attention control groups but was significantly improved among the participants who were adherent to their exercise prescription at least 70% of the time compared to those who were not adherent (adherent = 0.58, not adherent = -1.61, p=0.025) at 6-months. Among the participants in the exercise intervention who were adherent to their exercise prescription at least 70% of the time, sCD14 and TNF values decreased without statistical significance with small to moderate effect sizes (0.42 and 0.35 respectively).

Conclusions: Findings from this study indicated that OPWH were willing to remain engaged in a study over a 12-month period with very low attrition rates observed. Although reductions in the inflammatory markers were minimal, this was likely due to participants being well-controlled on their antiretroviral therapy (ART) with little room for improvement or change. Higher exercise adherence was associated with improved endothelial vascular function among OPWH and may lower CVD risk. Future studies are needed to examine exercise dose and modes on CVD risk reduction among OPWH.

Table of Contents

Chapter I: Introduction                                                                                                          6

Statement of the problem                                                                                                     6

           Inflammation and HIV                                                                                               6

           Endothelial Function and HIV                                                                                   7

           Exercise, inflammation, and endothelial function in HIV                                          8

           Exercise adherence                                                                                                  8

           Exercise and physical activity measurement in HIV                                                9

           Motivation to exercise                                                                                               10

           Purpose                                                                                                                     10

           Specific Aims                                                                                                            11

Manuscript descriptions                                                                                            12

Conceptual Framework                                                                                             12

Figure 1: Concept framework                                                                                   12

Background and Significance                                                                                               13

           Effect of exercise on CVD                                                                                        13

The role of inflammatory biomarkers in CVD etiology and disease

progression in PWH                                                                                     16


           Endothelial vascular function and CVD/HIV                                                            17

           Flow-mediated dilation                                                                                              18

           Exercise and endothelial function                                                                             18

Research Methods and Design                                                                                            19

           Parent Fitbrain Study design                                                                                    19

           Table 1: Exercise prescription                                                                                  19

           Intervention group                                                                                                     19

           Table 2: Fitbit assessment schedule                                                                        20

Control group                                                                                                            20

           Parent FitBrain study recruitment and sample                                                         21

           Human Subjects and informed consent                                                                   21

           Sample size and power calculation                                                                          21

           Table 3: Adherent versus non-adherent sample sizes                                            22

Variables and Measures                                                                                                       22

           Sociodemographic variables                                                                                    22

           Table 4: Demographics                                                                                             23

           Clinical variables                                                                                                       23

           Table 5: Baseline clinical variables                                                                          23

           Parent study data collection                                                                                     23

                       Cardiorespiratory fitness testing                                                                   23

                       AIM 1 data collection: Fitbit tracker validation.                                             24

                       AIM 2 data collection: Flow-mediated dilation                                              24

                       Figure 2: Flow-mediated dilation process                                                    25

                       AIM 3 data collection: Inflammatory biomarker collection                                25

                       Table 6: Variables, measures, and timepoint                                               26

           Data analysis                                                                                                            26

Summary                                                                                                                               28

References                                                                                                                            29

Chapter 2: Systematic Review of Fitbit Charge 2 Validation Studies for Exercise

Tracking                                                                                                                    37


Chapter 3: Higher exercise adherence among older persons with HIV is associated

with improved flow-mediated dilation                                                                       56


Chapter 4: Higher exercise adherence lowers inflammation among older persons

with HIV                                                                                                                    81


Chapter 5: Integrative summary                                                                                           104

           Strengths and limitations                                                                                          107

           Implications and future directions                                                                             108

           Conclusions                                                                                                              109

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