Order 932343: Does exercise and fitness affect cognitive health

ORIGINAL PAPER

The Effect of a Community-Based Exercise Program on Inflammation, Metabolic Risk, and Fitness Levels Among Persons Living with HIV/AIDS

Stacy E. Cutrono1,2 • John E. Lewis3 • Arlette Perry1 • Joseph Signorile1 •

Eduard Tiozzo3 • Kevin A. Jacobs1

Published online: 25 November 2015

� Springer Science+Business Media New York 2015

Abstract The human immunodeficiency virus (HIV)

pandemic remains a top national health priority. Chronic

inflammation may be a critical component in the disease

course of HIV as C-reactive protein (CRP) is elevated and

associated with increased mortality. This study examined

the effect of 3 months of combined aerobic and resistance

exercise training among a diverse cohort of HIV-infected

men and women. The fixed effect of time for CRP was

found to be non-significant (F[1,57.3] = 1.7, p = 0.19).

There was a significant fixed effect for time for upper body

(F[1,51.6] = 18.1, p \ 0.05) and lower body strength (F[1,48.0] = 15.7, p \ 0.05) and significant declines in diastolic blood pressure (p = 0.002) and waist circumfer-

ence (p = 0.027). Though levels of CRP were not impac-

ted after 3 months training, participants demonstrated a

significant increase in muscular strength as well as bene-

ficial changes in metabolic risk factors. Future studies

should focus on determining the optimal exercise inter-

vention length and mode to reduce inflammation among

individuals living with HIV.

Keywords Human immunodeficiency virus � Aerobic exercise � Resistance training � C-reactive protein � Inflammation � Metabolic risk

Introduction

Globally, the rate of new human immunodeficiency virus

(HIV) infections has fallen by 33 % since 2001 [1], but has

held steady in the United States (U.S.) at an estimated

50,000 new cases per year [2]. As such, the HIV/acquired

immune deficiency syndrome (AIDS) pandemic continues

to affect millions worldwide and remains a top health

priority in the U.S. Recent reports indicate that the state of

Florida has one of the highest rates of newly reported HIV

infections and newly reported AIDS cases in the country

[3]. Furthermore, the burden of HIV/AIDS continues to

disproportionately affect individuals of minority race/eth-

nicity, such as African Americans and Hispanics who

represent 44 and 20 % of new HIV infections, respectively,

as well as individuals with lower socioeconomic status

(SES) and reduced access to quality health care [2].

The use of combination antiretroviral therapy (ART) has

significantly reduced the risk of mortality and morbidity in

persons living with HIV (PLWH) since its introduction in

the mid-1990s [4–7]. However, the extensive use of ART

has given rise to serious and adverse side effects including

hyperlipidemia, insulin resistance, and lipodystrophy thus

increasing the risk for non-AIDS events such as cardio-

vascular disease and the development of metabolic syn-

drome (MetS) [8, 9]. The pathogenic mechanism for

metabolic changes secondary to combination ART have yet

to be fully elucidated, however, current investigations

indicate a greater risk of negative side effects are associ-

ated with use of drug combinations containing protease

& Stacy E. Cutrono [email protected]

1 Department of Kinesiology and Sports Sciences, School of

Education and Human Development, University of Miami,

Coral Gables, FL, USA

2 Sylvester Comprehensive Cancer, University of Miami,

Miller School of Medicine, 1475 NW 12th Avenue, Suite

C-021, Miami, FL 33136, USA

3 Department of Psychiatry & Behavioral Sciences, University

of Miami, Miller School of Medicine, Miami, FL, USA

123

AIDS Behav (2016) 20:1123–1131

DOI 10.1007/s10461-015-1245-1

inhibitors or nucleoside reverse transcriptase inhibitors

[10]. The risks associated with widespread and prolonged

use of ART may be managed through effective lifestyle

interventions incorporating exercise and weight

management.

Current research suggests that chronic inflammation

may be a critical component in the course of disease states.

The American Heart Association and the Centers for Dis-

ease Control and Prevention support the use of C-reactive

protein (CRP), an acute, non-specific inflammatory bio-

marker, as an independent predictor of increased coronary

risk and recommends using 3.0 mg/L as the minimum

threshold for high risk classification [11]. In healthy young

adults the median level of CRP is 0.8 mg/L [12]. However,

among PLWH, CRP levels are elevated [9, 13] with

reported ranges of 1.94–4.80 mg/L [14–16] and are asso-

ciated with opportunistic infections, progression to AIDS,

and mortality. Individuals enrolled in the Multicenter AIDS

Cohort Study with CRP levels B1.2 mg/L were found to

have a 47 % reduction in time to AIDS progression com-

pared to those with [2.3 mg/L [17]. Individuals in the Strategies for Management of Anti-Retroviral Therapy trial

with CRP levels C5 mg/L had 7.6-fold higher odds of

developing an opportunistic infection than those with

CRP B 1.0 mg/L [18]. Thus, interventions that reduce

CRP levels may improve the cardiovascular risk profiles

and disease prognosis among PLWH.

The physiological and psychological benefits of regular

exercise are numerous and well established. The available

literature supports the therapeutic use of aerobic and

resistance exercise for improving health and fitness out-

comes among PLWH [19, 20]. For this reason, the Amer-

ican College of Sports Medicine (ACSM) recommends that

PLWH engage in a regular exercise program consisting of

aerobic exercise and resistance exercise on most days of

the week [21]. A reduction in systemic inflammation may

be one of the mechanisms driving the protective effects of

regular exercise for chronic disease risk [22], though the

specific mechanisms by which exercise training may

reduce systemic inflammation has not yet been established.

Recent research examining the effects of exercise inter-

ventions on circulating inflammatory biomarkers has pro-

duced inconsistent results. The third National Health and

Nutrition Examination Survey found that 21 % of seden-

tary individuals had elevated CRP levels compared to 13 %

of moderately active individuals [23]. Several other studies

have reported significant declines in CRP levels after aer-

obic exercise interventions among older individuals [24],

obese women [25] and breast cancer survivors [22]. Yet, a

recent meta-analysis of randomized controlled trials

reported a non-significant decrease in CRP levels among

subjects in aerobic exercise interventions [26]. The pro-

inflammatory changes secondary to treatment with ART

are accepted as a necessary risk in an effort to reduce

progression to AIDS and AIDS mortality, yet inflammatory

changes measured by elevated CRP increase the risk of

non-AIDS events, cardiovascular mortality, as well as

progression to AIDS. Interventions with potential to man-

age treatment side effects and reduce inflammation are

necessary among PLWH. The effect of exercise on CRP

levels has not been well examined among PLWH, how-

ever, given the severity of treatment side effects its

potential beneficial impact warrants further investigation.

The purpose of this study was to determine the effect of

combined aerobic and resistance exercise training

(CARET) on inflammation, metabolic risk profile, and

aerobic and muscular fitness among PLWH after 3 months

of training using data collected from the Healthy Living for

Better Days program. We hypothesized that 3 months of

CARET would significantly improve aerobic and muscular

fitness, and metabolic risk profile and to a lesser extent

systemic inflammation.

Methods

Study Design

The Healthy Living for Better Days was a 12-month,

community exercise program conducted by research staff

at the University of Miami to improve the health of low

SES individuals with HIV residing in Miami-Dade. This

study specifically analyzed baseline and 3-month data.

Program outcome variables measured at baseline and 3

months included: (1) physical characteristics (body weight,

body mass index, waist and hip circumferences, blood

pressure), (2) non-lipid blood markers (high sensitivity

CRP, fasting blood glucose, and insulin), (3) blood lipid

profile (total cholesterol, low-density lipoprotein choles-

terol, high-density lipoprotein cholesterol, and total

triglycerides), and (4) physical fitness variables (estimated

VO2max and one-repetition maximum for upper and lower

body strength).

Participants

Ninety male and female participants were enrolled in

Healthy Living for Better Days through referrals from the

Adult HIV clinic at the University of Miami/Jackson

Health System and other local HIV clinics. Program eli-

gibility criteria included: [1] confirmed HIV infection as

established by external laboratory reports, [2] men or

women C18 years of age, [3] currently receiving

antiretroviral treatment, and [4] ability to attend weekly

exercise sessions at the UHealth Fitness and Wellness

Center. Program exclusion criteria included any medical

1124 AIDS Behav (2016) 20:1123–1131

123

condition or situation for which unsupervised exercise

would be contraindicated. The Institutional Review Board

of the University of Miami approved Healthy Living for

Better Days and all participants gave written informed

consent.

Exercise Program

All exercise sessions for Healthy Living for Better Days

were held at the UHealth Fitness and Wellness Center at

the University of Miami Medical campus. Each participant

was required to swipe an electronic badge to gain admit-

tance to the wellness center allowing attendance to be

recorded and tracked electronically. Participants were

encouraged to attend the supervised exercise sessions held

four times a week, but were also given open access to the

wellness center. Study personnel directed each supervised

session and were available to advise participants on their

exercise intensity and progression. Each supervised exer-

cise session was 40–60 min in length and consisted of at

least 30 min of aerobic exercise completed on a treadmill,

elliptical machine, or stationary bike and resistance exer-

cises completed on stacked weight machines (bench press,

shoulder press, biceps curl, triceps extension, leg extension,

leg curls, leg press, squat, lateral raises, lat pull downs,

back extension, and abdominal crunches). Aerobic exercise

was performed at 60–80 % of each individual’s age-pre-

dicted maximum heart rate (HRmax). The duration of

exercise sessions progressed from 40 to 60 min over the

first 2 weeks of the program. Two to four sets of 8 to 15

repetitions were performed for each upper and lower body

exercise.

Physical Characteristics

Research staff used standard techniques to obtain anthro-

pometric measurements. Weight and height were recorded

to the nearest 0.1 kg and 0.1 cm, respectively, to calculate

body mass index (BMI). Waist circumference was mea-

sured in inches at the narrowest portion between the lowest

rib and the iliac crest. Systolic blood pressure (SBP) and

diastolic blood pressure (DBP) were measured by use of

the automatic oscillometric device (Omron HEM-712CN2,

Omron Healthcare, Inc., Bannockburn, Illinois).

Blood Sampling and Analyses

Blood samples were drawn from participants in the

morning in a fasted condition and processed by the Dia-

betes Research Institute Clinical Laboratory. Chemistry

and immunoassays were performed by automated analyzer

(Roche Cobas-6000; Roche Diagnostics, Indianapolis, IN)

utilizing the manufacturer’s reagents and following the

manufacturer’s instructions. High sensitivity CRP (hsCRP)

was quantified in serum by a high sensitivity latex-particle

enhanced immunoturbidimetric assay with a detection limit

of 0.1 mg/L with an intra- and inter-assay coefficients of

variation (CV) of 1.1 and 2.2 %, respectively. Fasting

glucose (FG) was measured by the hexokinase method with

intra- and inter-assay CVs of 1.9 and 2.7 %, respectively.

Total cholesterol and triglycerides were determined in

serum or plasma by enzymatic, colorimetric assay with

intra- and inter-assay CVs are 0.7 and 1.8 %, respectively

for total cholesterol and 0.9 and 2.3 %, respectively for

triglycerides. High density lipoprotein cholesterol (HDL-

C) was measured using a third generation homogenous

enzymatic colorimetric assay with intra- and inter-assay

CVs of 0.6 and 1.9 %, respectively. Low density lipopro-

tein cholesterol (LDL-C) was calculated using the Friede-

wald equation.

Physical Fitness

Cardiorespiratory fitness was measured using a Rockport

One-Mile Fitness Walking Test [21], which has been val-

idated in healthy adults aged 30–69 years [27] and been

used in other clinical populations [28]. The test was

modified for use indoors with participants performing the

one-mile walk on a treadmill rather than on an outdoor

track. Participants were instructed to walk for one mile on

the treadmill as quickly as possible and were allowed to

modify speed at their discretion throughout the test. Heart

rate was measured for 10 s immediately upon completion

by palpating the radial artery. Age, gender, body weight,

and walk time were also recorded and used in a regression

equation to predict maximal oxygen consumption

(VO2max).

Muscular strength was measured using the ACSM pro-

tocol for one-repetition maximum (1-RM) testing [21].

Program participants completed a maximum of four trials

of 10, 8, 6, and 3 repetitions with rest periods between 2

and 4 min between trials. The initial weight was selected

within the subject’s perceived capacity (50–70 % of

capacity) and resistance was progressively increased until

the participants reached their maximum. The final maxi-

mum weight lifted successfully one time for bench press

and leg press was recorded as the 1-RM.

Metabolic syndrome was defined using ATPIII criteria

[29]. Three or more criteria had to be met to be classified as

having MetS: (1) high fasting serum triglycerides(C150 mg/

dL), (2) abnormal waist circumference ([102 cm for men and[88 cm for women), (3) low HDL-C level (\40 mg/dL for men and\50 mg/dL for women), (4) high blood pressure (BP) (C130/85 mmHg), and (5) high FG level (C110 mg/

dL). Participants who self-reported being diagnosed with

diabetes or who were receiving treatment for diabetes were

AIDS Behav (2016) 20:1123–1131 1125

123

classified as having a high FG level. The same criteria were

used for high BP.

Statistical Analysis

Statistical analyses were performed with the Statistical

Package for Social Sciences (SPSS) version 22 for Win-

dows (IBM Inc., Chicago, IL, USA). Statistical analyses

included descriptive statistics and frequencies for each

variable. Linear Mixed Modeling (LMM) was used to

assess the fixed effect of time on changes in the outcome

variables (hsCRP, estimated VO2max, 1-RM bench press,

and 1-RM leg press) from baseline to 3-months follow

up. The significance level of all analyses was a \ 0.05. LMM with heterogeneous compound symmetry covariance

allowed us to account for missing values, subject attrition,

inter-correlated responses between time points, and non-

constant variability. Changes in hsCRP from baseline to

3-months follow up were further examined controlling for

potential confounders, specifically body mass index, waist

circumference, aerobic fitness, and individuals with

hsCRP [ 3 mg/L classified as high risk at baseline. Paired t tests were used to assess changes in metabolic risk factors

(BP, BMI, FG, HDL-C, LDL-C, waist circumference and

triglycerides) from baseline to 3-months follow up. Chi

square analysis was used to assess the change in MetS

prevalence from baseline to 3-months follow up.

Given that the exercise program consisted of four ses-

sions per week, participants were stratified into exercise

compliance groups based on average exercise sessions

attended as follows: (a) Non-compliant (average of \19/ week for 3 months), (b) Somewhat compliant (average

1–29/week for 3 months), and (c) Compliant (C29/week

for 3 months), where compliant individuals completed at

least 50 % of the prescribed exercise. Comparisons

between groups from baseline to 3 months were analyzed

using LMM for outcome variables.

Results

Demographic data are presented in Table 1. Ninety PLWH

were enrolled in Healthy Living for Better Days. The

majority of participants were women (53.9 %), Black/

African American (65.2 %), and unemployed or disabled at

the time of participation (83.1 %). Nearly one-third of

participants were classified as having MetS at baseline.

Fifty-five percent of total participants were non-compliant

(49/89), 20.2 % were somewhat compliant (18/89), and

24.7 % were compliant (22/89) with the prescribed exer-

cise. After 3 months participation in Healthy Living for

Better Days, nearly one-quarter (24.7 %) of our partici-

pants were meeting physical activity recommendations

defined as a combination of moderate- and vigorous-in-

tensity aerobic exercise at least 75 min/week and resistance

training twice per week.

The fixed effect of time for hsCRP was found to be non-

significant (F[1,57.3] = 1.7, p = 0.19) (Fig. 1). Mean

hsCRP at baseline was 5.75 ± 7.62 mg/L (median 2.30)

and 7.54 ± 14.19 mg/L (median 2.95) at 3-months follow

up. Comparing hsCRP across categories of exercise com-

pliance groups (see Fig. 1) revealed non-significant fixed

effects for time (F[1,55.5] = 2.4, p = 0.13), exercise

compliance (F[2,62.1] = 0.06, p = 0.94) and exercise

compliance 9 time (F[2,55.5] = 0.99, p = 0.38). When

examining the effect of the exercise intervention on

changes in hsCRP from baseline to 3-months follow up

only among individuals classified as high risk

(hsCRP [ 3 mg/dL) at baseline, the fixed effect for time was still found to be non-significant (F[1,30.3] = 0.20

p = 0.657). Comparing hsCRP levels by gender group

revealed a significant fixed effect for gender

(F[1,68.6] = 4.08, p \ 0.05]), with women displaying an overall higher mean hsCRP (8.50 ± 12.69 mg/L) than men

(4.46 ± 13.65 mg/L). The fixed effect for time

(F[1,57.4] = 1.75, p = 0.19]) and gender 9 time was non-

significant (F[1,57.4] = 0.06, p = 0.80]). The fixed effect

of time on changes in CRP from baseline to 3-months

follow up controlling for the use of protease inhibitors

(F[1,55.6] = 1.7, p = 0.200), BMI (F[1,53.2] = 1.7,

p = 0.199), aerobic fitness (F[1,50.1] = 1.1, p = 0.304),

and sleep duration (F[1,56.1] = 2.4, p = 0.129) was found

to be non-significant.

Changes in participant’s metabolic risk profile can be

found in Table 2. Diastolic BP (t(52) = 3.247, 95 % CI

1.55–6.58, p = 0.002) and waist circumference

(t(58) = 2.268, 95 % CI 0.06–1.02, p = 0.027) signifi-

cantly decreased from baseline to 3 months. There were no

significant changes from baseline to 3 months for body

weight (t(58) = 0.405, 95 % CI -1.24 to 1.86, p = 0.687),

SBP (t(52) = 1.796, 95 % CI -0.41 to 7.31, p = 0.078),

BMI (t(58) = 0.196, 95 % CI -0.24 to 0.29, p = 0.845),

triglycerides (t(61) = 0.806, 95 % CI -9.69 to 22.79,

p = 0.423), total cholesterol (t(61) = 0.065, 95 % CI

-7.22 to 7.70, p = 0.948), HDL-C (t(61) = 1.875, 95 %

CI -0.17 to 5.37, p = 0.066), VLDL-C (t(61) = 0.845,

95 % CI -1.87 to 4.62, p = 0.401), LDL-C

(t(61) = -1.186, 95 % CI -10.01 to 2.55, p = 0.240), or

FG (t(61) = 1.226, 95 % CI -3.49 to 14.56, p = 0.225).

There was a non-significant decline in individuals with

MetS from baseline to 3 months (32 vs. 19 %, v2(1, Nbaseline = 89, N3months = 63) = 3.43, p = 0.06).

The fixed effect of time for changes in VO2max was

found to be non-significant (F[1,36.3] = 3.5, p = 0.07)

(Table 3). For upper body 1-RM, a significant fixed

effect was found for time (F[1,51.6] = 18.1, p \ 0.05)

1126 AIDS Behav (2016) 20:1123–1131

123

and the parameter estimate between baseline and 3

months follow up was also significant (t[51.6] = -4.3,

p \ 0.05). Likewise, for lower body 1-RM a significant fixed effect was found for time (F[1,48.0] = 15.7,

p \ 0.05) and the parameter estimate between baseline and 3 month follow up was also significant

(t[48.0] = -4.0, p \ 0.05).

Discussion

Among our participants, changes in hsCRP were not

impacted by 3 months of CARET, even among individuals

with high hsCRP levels at baseline. The number of indi-

viduals classified as having MetS declined from baseline to

3-months, however these results were found to be non-

Table 1 Demographic and baseline population

characteristics by gender

Overall (n = 89) Men (n = 41) Women (n = 48)

Age (years) 48 ± 7 48.7 ± 7 47.8 ± 7.6

Body mass index (kg/m 2 ) 31.2 ± 7.8 28.7 ± 5.2 33.4 ± 8.9

Duration of HIV (years) 17.6 ± 12.7 15.3 ± 7.6 19.5 ± 15.7

Ethnic, n (%)

Non-Hispanic White 9 (10.1) 7 (17.1) 2 (4.2)

African-American 58 (65.2) 21 (51.2) 37 (77.1)

Hispanic 20 (22.5) 12 (29.3) 8 (16.7)

Current smoker, n (%) 32 (36.0) 16 (39.0) 16 (33.3)

Antiretroviral therapy, n (%)

Protease inhibitors 46 (51.7) 22 (53.7) 24 (50.0)

Non-protease inhibitors 36 (40.4) 16 (39.0) 20 (41.7)

Employment, n (%)

Unemployed 74 (83.1) 30 (73.2) 44 (91.7)

Employed (part or full time) 14 (15.7) 11 (26.8) 3 (6.3)

Yearly household income, n (%)

\$5000 27 (30.3) 11 (26.8) 16 (33.3) $5000–$14,999 38 (42.7) 20 (48.7) 18 (37.6)

$15,000–$39,999 12 (13.4) 6 (14.7) 6 (12.5)

Data are mean ± SD or n (%)

0

5

10

15

20

25

30

35

40

Baseline 3-Months

M ea

n CR

P (m

g/ L)

Non-compliant Somewhat Compliant Compliant

Fig. 1 Changes in levels of C-reactive protein across

exercise compliance groups.

Data are mean ± SD. Non-

compliant, average exercise

session of \19/week for 3 months; Somewhat

Compliant, average exercise

session of 1–29/week for

3 months; Compliant, average

exercise session of C29/week

for 3 months; hsCRP, high

sensitivity C-reactive protein

AIDS Behav (2016) 20:1123–1131 1127

123

significant. Participants did significantly increase muscular

strength of the upper and lower body and displayed a trend

for improved aerobic capacity.

Disappointingly, a majority of participants (55 %) were

not compliant with the prescribed exercise regime. Previ-

ous literature has documented barriers and challenges to

appointment adherence or research participation among

PLWH [31, 32]. Though few studies have specifically

assessed challenges to participating in exercise programs,

there have been reports of moderate withdrawals (range

3–44 %) and low compliance (range 24–82 %) in other

exercise interventions [19]. Macarthur et al. [33], reported

transportation and difficulty exercising as challenges to

completing exercise testing and training. Similarly, Neidig

et al. [34], reported changes in employment, unreliable

transportation, and family responsibilities as contributors to

withdrawal from an aerobic exercise trial. Nevertheless,

Healthy Living for Better Days was designed as a com-

munity-based exercise program in an effort to expand

access to a variety of participants. The program was well

received by most participants (data not reported); however,

the low compliance highlights the challenge of engaging

this population in exercise programs.

Mean levels of hsCRP were elevated at baseline

(5.75 ± 0.82 mg/L, Fig. 1) and 40 % of our participants

had hsCRP values that would be classified as high coronary

risk ([3 mg/L) under AHA and CDC guidelines [11]. Median levels of hsCRP at baseline and 3-months follow

up were greater than values previously reported in the lit-

erature among PLWH (1.20–2.83 mg/L) [14, 17]. Elevated

CRP has been associated with metabolic risk factors such

as obesity, hypertension, and dyslipidemia [35]. Among

our participants BMI and waist circumference were ele-

vated at baseline and additionally a few of our participants

displayed very high CRP values perhaps reflective of the

disease course of the HIV infection. Thus, it is possible that

our cohort had more severe inflammation than the general

population of PLWH. Women in our sample were found to

have significantly higher hsCRP levels than men. This is

consistent with data from the third National Health and

Nutrition Examination Survey that found that the odds of

having elevated CRP levels is twofold higher among

women than men [35].

Participants showed a trend for an increase in VO2max of

2.2 mL/kg/min with 3 months of training (Table 3).

Although this trend was not significant, our results were

consistent with previously reported changes in VO2max (range ?2.6 to ?4.7 mL/kg/min) after 3 months of training

among PLWH [8, 36]. Exercise adherence did not appear

to be a contributing factor as even the compliant cohort of

subjects showed no significant improvement in hsCRP. In

contrast to our 3-month program consisting of CARET,

Lindegaard et al. [37] found that hsCRP levels declined in

a small sample (n = 18) of HIV-positive men who per-

formed 35 min of endurance training 39/week for

16 weeks (baseline hsCRP, 2.42 mg/L [1.01–5.80],

16-week hsCRP, 1.82 mg/L [0.76–4.36]; p \ 0.0001). However, the effect of exercise on inflammatory

biomarkers was not the primary variable studied by Lin-

degaard et al. [37]. Nonetheless, we cannot rule out the

possibility that a longer intervention or higher sustained

intensity of aerobic exercise is needed to impact systemic

inflammation.

Table 2 Changes in metabolic risk profile after 3-months of CARET

Baseline 3 months p value

Total body weight (lbs) 191.9 ± 46.5 191.6 ± 46.6 0.687

Systolic BP (mmHg) 127 ± 12 124 ± 11 0.078

Diastolic BP (mmHg) 82 ± 9 78 ± 8 0.002*

Body mass index (kg/m 2 ) 30.7 ± 7.4 30.7 ± 7.4 0.845

Waist circumference (inch) 41.2 ± 7.0 40.7 ± 7.4 0.027*

Total triglycerides (mg/dL) 125.4 ± 72.6 118.8 ± 55.7 0.423

Total cholesterol (mg/dL) 186.7 ± 35.0 186.5 ± 42.0 0.948

HDL cholesterol (mg/dL) 52.3 ± 16.1 49.7 ± 13.7 0.066

VLDL cholesterol (mg/dL) 25.1 ± 14.5 23.7.1 ± 11.2 0.401

LDL cholesterol (mg/dL) 109.4 ± 30.2 113.1 ± 38.1 0.240

Fasting glucose (mg/dL) 95.7 ± 35.1 90.2 ± 16.5 0.225

Data are mean ± SD

CARET combined aerobic and resistance exercise training, BP blood

pressure, VLDL very low density lipoprotein, LDL low density

lipoprotein, HDL high density lipoprotein

* Significant difference from baseline to 3 months (p \ 0.05, paired t test)

Table 3 Changes in cardiorespiratory fitness and

muscular strength

Baseline 3 months Statistic

VO2max (mL/kg/min) 27.2 ± 8.9 29.4 ± 10.0 F[1,36.3] = 3.5, p = 0.07

Upper body 1-RM (lbs) 114 ± 51 125 ± 46 F[1,51.6] = 18.1, *p \ 0.001 Lower body 1-RM (lbs) 225 ± 81 250 ± 96 F[1,48.0] = 15.7, *p \ 0.001

Data are mean ± SD

VO2max maximal volume of oxygen consumed, 1-RM one-repetition maximum

* Significant fixed effect on time (p \ 0.05)

1128 AIDS Behav (2016) 20:1123–1131

123

Participants significantly increased both upper and lower

body strength after 3 months of CARET as has been shown

in other studies that involved resistance training among

PLWH [20, 38, 39]. The improvements in strength in our

study, however, were not associated with a significant

improvement in hsCRP levels from baseline to the 3-month

follow up (Fig. 1). Likewise, Lindegaard et al., [37] found

that despite a 30 % improvement in strength after

16 weeks of resistance training, there was no significant

change in CRP levels (baseline CRP: 1.54 mg/L

[1.0–2.37], 16-week CRP: 1.65 mg/L [1.07–2.54];

p = 0.44) among HIV-positive men. Similarly, among

older adults assigned to 10-months of strength and flexi-

bility training serum CRP levels were not improved com-

pared to those in an aerobic exercise arm [24]. These

results may indicate that aerobic exercise rather than

resistance training may be the primary mode of exercise by

which systemic inflammation is impacted.

It has been suggested that reduction in systemic

inflammation may be the mechanism driving the pro-

tective effects of regular physical activity and exercise

for chronic disease risk [22]. Yet, a meta-analysis by

Kelley et al., [26] of randomized controlled trials among

adult subjects reported a non-significant 3 % decrease in

CRP levels in aerobic exercise interventions ranging

from 8 weeks to 6 years. On the other hand, CRP levels

were reported to significantly decline in aerobic exercise

trials among older adults [24] and postmenopausal obese

women [25] after 10- and 12-months of training,

respectively. Thus, greater gains in aerobic fitness as

measured by VO2max may be necessary to affect hsCRP

levels in PLWH. Future studies examining the role of

exercise interventions on systemic inflammation should

incorporate randomization to an aerobic-only comparison

arm.

The presence of one or more cardiovascular risk fac-

tors, specifically those which contribute to the classifica-

tion of MetS, are associated with a pro-inflammatory

state. Data from the third National Health and Nutrition

Examination Survey indicated that the presence of at least

one abnormal cardiovascular risk factor was associated

with a threefold higher prevalence of elevated CRP [35].

Among PLWH metabolic changes secondary to the

extensive use of ART, such as insulin resistance, adiposity

and poor lipid profiles, has contributed to an elevated

cardiovascular risk profile [40–42]. In our cohort nearly

one-third of participants had MetS at baseline. After 3

months of CARET we observed a significant decrease in

DBP and waist circumference. Loss of abdominal sub-

cutaneous fat and therefore reduced central obesity could

have been indicative of HIV-associated lipoatrophy [43].

Further investigation of body composition and body fat

distribution may be warranted to fully understand the

relationship between metabolic risk factors and inflam-

mation. Though not significant, we observed a trend

towards decreased SBP, total triglycerides, FG, and the

number of individuals with MetS. We did not observe

changes in total body weight or BMI. Several studies have

reported a rapid progression to MetS after initiation of

ART [44–47]. Given the deleterious impact of ART on

metabolic risk factors and the rate of change reported in

previous studies among PLWH, it appears that our pro-

gram may have been effective in delaying a worsening of

these side effects. A longer intervention, in combination

with changes in total body weight, may be necessary to

reduce metabolic risk factors and potentially impact

hsCRP levels.

A strength of the Health Living for Better Days pro-

gram was its enrollment of a sample of participants

comprised mainly of minorities ([85 %). African Amer- icans and Hispanics continue to bear a disproportionate

burden of new HIV cases despite only representing 13.1

and 16.9 % of the general U.S. population, respectively

[30]. For this reason our results may be more generaliz-

able to the larger population of PLWH. A majority of

participants were of low SES as evidenced by high rates

of unemployment (83.1 %) and low household income

(73 %), defined as earning less than $15,000 annually.

Over half of the sample was comprised of women, who

according to the CDC accounted for one in four new HIV

infections in 2010 [2]. Our program included a compre-

hensive assessment of fitness and obtained extensive

information on metabolic risk factors. Furthermore, while

several other protocols have utilized a 6–8 h fast for

blood sampling, we utilized a 12-h fast, thus avoiding

exaggerated triglycerides and eliminating serum chy-

lomicrons which could overestimate triglyceride and

MetS rates.

In addition to the strengths of our study, several limi-

tations were present. Our study design was not a ran-

domized controlled trial and did not include a non-

exercise control arm, though all analyses were conducted

as intent-to-treat. We did not obtain HIV ribonucleic acid

(RNA) levels or information pertaining to secondary

infections, which limits our ability to examine the effect

of CARET on systemic inflammation independent of

changes in the disease course. Similarly, while we did

ascertain the type of ART used among our participants we

did not obtain the total duration of exposure to combi-

nation ART. Extended exposure to combination ART

regimes has been found to increase the risk of myocardial

infarction [48, 49] and thus has the potential to impact

both metabolic risk profile and systemic inflammation.

Further, we cannot rule out the impact of diet and overall

nutritional status on cardiovascular risk reduction and

systemic inflammation.

AIDS Behav (2016) 20:1123–1131 1129

123

Conclusion

In conclusion, our study enrolled a diverse cohort of HIV-

infected individuals receiving ART, who were of pre-

dominantly low SES. Overall mean levels of hsCRP were

elevated in our cohort of HIV-infected individuals receiv-

ing ART. Though levels of hsCRP were not impacted after

3 months of CARET, participants demonstrated a signifi-

cant increase in upper and lower body muscular strength as

well as beneficial changes in waist circumference and

diastolic blood pressure. Although low compliance to the

prescribed exercise limits our ability to make definitive

conclusions about the impact of exercise on systemic

inflammation, it is possible that a longer intervention or

greater intensity is necessary to induce improvements in

aerobic fitness and metabolic profiles and thus impact

systemic inflammation. Future studies should focus on

effective ways of engaging and retaining HIV-infected

minorities in structured exercise interventions and dis-

cerning the optimal dose and duration of exercise to reduce

inflammation.

Acknowledgments This material is based on work supported by AstraZeneca HealthCare Foundation’s Connections for Cardiovas-

cular HealthSM (CCH) program. The CCH program funds charita-

ble work, not research that addresses cardiovascular health issues

within the United States and its territories. Any opinions, findings,

and conclusions or recommendations expressed in this material are

those of the authors and have not been reviewed for approval by the

AstraZeneca HealthCare Foundation.

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