Abstract
Background and aims
People with HIV (PWH) experience a persistent symptom burden that negatively affects quality of life and daily functioning. Evidence examining modifiable lifestyle behaviors that may mitigate symptoms is limited. We examined longitudinal associations between objectively measured physical activity, diet quality, and symptom burden in PWH.
Methods
PROSPER-HIV enrolled adults with well-controlled HIV receiving care at four Centers for AIDS Research Network of Integrated Clinical Systems sites in the United States. Participants completed annual assessments, including physical activity levels using actigraphy, dietary intake measured with three 24-h recalls generating the Healthy Eating Index-2015 (HEI-2015), and symptom burden with the HIV Symptom Index. Linear mixed models evaluated associations adjusting for age, sex at birth, race/ethnicity, and site.
Results
Among 704 participants (mean age, 52.7 years; 78% male; 52% non-Hispanic Black), symptom burden remained stable over follow-up. Participants averaged 5426 ± 3149 steps/day, 164 (IQR, 67–311) minutes/week of moderate-to-vigorous physical activity (MVPA), and an HEI-2015 score of 48.1 ± 14.6. The most prevalent bothersome symptoms were muscle aches/joint pain, fatigue, sleep disturbance, anxiety, and trouble remembering. More steps/day were associated with fewer bothersome symptoms (β = −0.59 steps; P < .01), whereas more sedentary time was associated with higher symptom burden (β = 0.64; P < .01). Higher diet quality was associated with lower symptom burden (β = −0.20; P = .01). Duration of MVPA and light physical activity were not associated with symptom burden.
Conclusions
Among adults with well-controlled HIV, a higher daily step count, less sedentary time, and better diet quality were associated with lower symptom burden, highlighting critical lifestyle behaviors to support symptom management in HIV care.
Learning points
Among adults with well - controlled HIV, objectively measured higher daily steps and better diet quality, but not weekly moderate - to - vigorous physical activity, were associated with lower symptom burden over three years. Achievable targets to improve persistent, clinically meaningful symptoms in HIV care were identified.
Clinical trial registration number
Keywords: Physical Activity, Symptoms, HIV, Diet Quality
Background
HIV-related symptoms are prevalent, distressing, and limit the ability of people with HIV (PWH) to live their fullest lives. Defined as the physical or mental problems one experiences that may indicate a disease process; symptoms cannot be seen or identified on medical tests. Self-report is the best and often only measure of symptoms [1, 2]. In the general primary care population, 40%–49% of patients (n = 70 085) report at least one unexplained symptom [3]. In comparison, approximately 56% of PWH (n = 5370) report at least one symptom, and 33% report at least four highly burdensome symptoms [4, 5]. PWH experience some of the highest rates of distressing symptoms compared to other common chronic conditions [6], and the consequences are severe [4], including increased healthcare costs [7], reduced productivity [8, 9], and poorer quality of life [10, 11]. Among PWH with well-controlled HIV, increased symptom burden, not HIV infection, is one of the strongest predictors of reduced productivity and quality of life [9, 10].
Yet, there are few treatment options to mitigate symptoms in PWH. Non-pharmacological approaches such as physical activity and dietary intake hold promise, yet the field lacks data and standardization of their measurement, which limits the ability to fully understand their effect on symptoms. Physical activity is defined as any skeletal muscle movement that results in energy expenditure [12] and has shown promise as a multi-symptom self-management strategy [13, 14] and may be more tolerable than medications. In populations without HIV, physical activity reduces pain severity [15], depression [16, 17], fatigue [18], and improves cognitive function [19, 20]. Among PWH, physical activity has been associated with reduced depressive symptoms [21], pain [22], fatigue [23], and less neurocognitive impairment [24]. Yet, systematic reviews report mixed results for this relationship due to small sample sizes, differing measurement tools, and variable underlying study quality [21, 25].
Additionally, access to safe and nutritious foods is a crucial component of HIV care and may enhance symptom management [26, 27]. Individuals without HIV experience a decline in depressive symptoms, fatigue, and pain when a high-fiber, moderate-fat, low-carbohydrate diet is followed. However, PWH in the USA consume diets low in fiber and high in fat and carbohydrates [7, 28, 29], which may exacerbate symptoms. Studies of dietary intake among PWH are typically cross-sectional and focus on obesity and chronic disease risk, rather than symptom burden.
We conducted the PROSPER-HIV study to examine longitudinal associations among objectively measured physical activity patterns and dietary intake with symptom burden and intensity in PWH. A secondary objective was to explore the potential moderating effects of anthropometric and physical fitness variables on the relationships between physical activity, dietary patterns, and symptom burden in PWH. We hypothesized that PWH who (i) have more intense, frequent, and longer physical activity bouts will have reduced symptom burden; (ii) eat better quality diets will have reduced symptom burden; and (iii) that this relationship will also vary by age, sex, anthropometry, and physical fitness.
Methods
Design
The PROSPER-HIV study was a 4-year observational study of 704 participants from the Centers for AIDS Research (CFAR) Network of Integrated Clinical Systems (CNICS) [30], a multi-site clinical research network in the United States. PWH at four CNICS sites (i.e. Birmingham, AL; Boston, MA; Cleveland, OH; Seattle, WA) were recruited. Those who enrolled completed standardized assessments of actigraphy-measured physical activity, dietary intake, and physical fitness approximately once a year for 3 years (Fig. 1). Participants also completed a standard CNICS patient-reported outcome assessment, medical chart abstraction, and clinical assessment procedures [31]. The PROSPER-HIV study was approved (00013048) by the University of Washington Institutional Review Board (IRB); IRBs at the other sites sanctioned the protocol, thereby adhering to a single IRB. The PROSPER-HIV study is registered at ClinicalTrials.gov [NCT03790501].
Figure 1.
PROSPER-HIV study flow and participant retention across visits.
Participants
PROSPER-HIV participants
To be eligible, one had to (i) be living with HIV; (ii) be an active CNICS participant at one of our four sites (i.e. they must have a CNICS consent and have completed the current patient reported outcome assessment); (iii) be at least 18 years of age; (iv) prescribed antiretroviral therapy (ART); and (v) had an HIV viral load less than 200 copies/ml at enrollment. This last criterion was included to minimize the risk of acute symptoms related to uncontrolled viremia. Participants were excluded if they (i) were pregnant, breast-feeding, or planning a pregnancy during the study period; (ii) did not have telephone or internet access to complete 24-h diet recalls; or (iii) planned to move out of the area in the next 36 months.
PROSPER-HIV timeline
The proposed timeline for PROSPER-HIV enrollment and baseline visits was March 2019 to December 2020. However, across sites, COVID-19-related policies limiting access to potential participants were initiated in March 2020 and continued through December 2021. The final PROSPER-HIV participants were enrolled in July 2022, extending the enrollment period by 18 months, and all study visits concluded in November 2024.
Measures
Demographic, clinical, and anthropometric factors
Participant demographic data were self-reported. Clinical data, including the length of time in HIV care, height (to the nearest 0.1 cm), weight (to the nearest 0.1 kg), and current comorbid health conditions, were abstracted from the participant’s electronic medical record using CNICS’ standard operating procedures [32]. Waist and hip circumference were measured using a standardized protocol using a flexible tape measure to the nearest 0.1 cm.
Symptoms
The number and burden of symptoms experienced in the past month were assessed with the HIV Symptom Index [33], which was completed as part of the CNICS patient-reported outcomes protocol. This 20-item, HIV-specific scale assessed the presence and intensity of 20 common symptoms reported by PWH (e.g. pain, anxiety, fatigue) over the past 4 weeks. All symptoms are measured on a 1–5 ordinal scale, where 1 is “I do not have the symptom” and 5 is “I have this symptom and it bothers me a lot.” The reliability of the HIV Symptom Index in the CNICS cohort is 0.92 [4]. To achieve our purpose, we analyzed the following endpoints over time: (i) total symptom count (sum all symptoms reported as having the symptom and it bothers the participant at least a little); and (ii) a total count of symptoms that bother the participant a lot (high symptom distress).
Physical activity
Physical activity was measured with the wGT3X-BT ActiGraph accelerometer (ActiGraph, LLC, Fort Walton Beach, FL). Research staff instructed participants to wear the monitor during waking hours for 7–10 consecutive days on their non-dominant hip. A valid wear cycle was determined as continuous data for a minimum of 10 h per day for at least 4 days, including one weekend day [34]. Participants not meeting wear time standards were asked to re-wear the ActiGraph. Data were sampled at 30 Hz, using 60-s epochs, and the normal frequency filter [34]. Our physical activity endpoints were (i) minutes of moderate-to-vigorous physical activity (MVPA) per week; (ii) number of steps per day; (iii) sedentary time per day; and (iv) light physical activity per week. These endpoints were selected for their established clinical and public health significance (Piercy et al. 2018) and set with the Sasaki et al. adult cut-points for tri-axial accelerometers [35]. Sedentary behavior was defined as 10 or more minutes with 100 or fewer counts per minute. Non-wear time was defined as at least 60 consecutive minutes of zero counts. Actigraphy data were analyzed using the ActiLife software (ActiGraph, LLC, Fort Walton Beach, FL). Physical activity guidelines recommend that adults engage in at least 150 min of MVPA per week, and up to 300 min per week [36].
Dietary intake
Participants completed three 24-h diet recalls via phone with registered dietitians within 30 days of their initial visit [37]. Recall interviews were conducted on two weekdays and one weekend day and the responses were analyzed using the Nutrition Data System for Research. All available interviews were averaged to compute each participant’s Healthy Eating Index 2015 (HEI-2015) score. The HEI-2015, and its components, were assessed as a composite diet quality measure assessing how well dietary intake correlates with recommendations in the 2015–2020 Dietary Guidelines for Americans [38]. It is designed to evaluate the balance of food groups in the diet of specific populations using a density-based scoring method (e.g. amount of food per 1000 kcal). The HEI is scored on a 100-point scale, with scores >80 indicating good adherence, 50–80 suggesting a need for improvement, and <50 reflecting poor adherence to the guidelines [38, 39].
Physical function
Participants completed two measures to assess their current physical function, including the Short Physical Performance Battery (SPPB) and hand grip strength. The SPPB is a brief measure of physical performance that includes a timed walk, repeated chair stands, and balance tests. The SPPB is a valid (test-rest reliability = 0.87), widely-used objective assessment of physical function, particularly lower extremity function, and associated with short-term mortality, disability, and hospitalizations, including among PWH [40, 41]. Each of three measures on the SPPB is assigned a score from 0 to 4, with 0 indicating inability to complete the test, yielding a summary score from 0 (frail) to 12 (not frail) [40]. Hand Grip Strength was assessed with the Jamar hand-held dynamometer. The maximum strength of the dominant hand was the endpoint.
Analyses
To characterize physical activity, physical function, and diet quality in PWH, we analyzed data from PROSPER-HIV participants who had complete data on age, sex at birth, current gender, employment status, physical activity, physical function, and diet quality. MVPA was dichotomized at ≥150 and ≥300 min/week, and step count at ≥7000 steps per day to evaluate activity guidelines overall and at each visit [42]. Descriptive characteristics are reported for the total group and by sex as frequency (%) or median (25%, 75%). Between-group differences in demographics, dietary intake, and physical activity levels were analyzed using chi-squared or t-tests. Symptom burden and prevalence/severity of individual symptoms were summarized using frequency (%) by visit year.
We used linear mixed models to estimate the association between physical activity and dietary pattern with the total number of HIV symptoms that PWH reported experiencing. Models were adjusted for age, sex, race/ethnicity, and clinical site. Measures were scaled for these models to aid in interpretation: MVPA scaled by 150 min/week, light activity scaled by 5000 min/week, sedentary time scaled by 300 min/day, steps scaled by 5000 steps/day, and HEI score scaled by 10 points. Separate models were conducted for each exposure variable. We conducted several sensitivity analyses, including models stratified by [1] sex [2], waist to hip ratio, using a cut-off of ≥0.85 if female, ≥0.90 if male, and [3] SPPB score, using a cut-off of ≥10. We further assessed symptom burden by additionally modelling the trajectory of symptom count (using a term for time*symptom count), and by modeling the change in symptom burden (calculated as the symptom count at a subsequent visit–baseline). Finally, we conducted exploratory models estimating the severity of the most prevalent individual symptoms for muscle aches/joint pain, fatigue, difficulty with sleep, anxiety, trouble remembering, and sadness or depression, which were selected a priori, using scores based off the Likert scale, where higher scores indicate greater severity. Again, we used linear mixed models to estimate the average severity of each symptom associated with each activity or diet measure. An observational longitudinal model is a weaker form of causal inference, but an improvement over past research efforts in that it helps establish temporality of the measures. All missing data were censored from the dataset, and the data were analyzed using Stata version 18 (StataCorp, College Station, Texas, USA) with a significance level of P < .05. Sensitivity analyses including imputed models were conducted.
Results
Across all sites, 704 participants were enrolled in the PROSPER-HIV study. The mean baseline age of participants was 52.7 (11.6) years and most of the participants were male (78%), non-Hispanic black (52%), and worked full time (38%) (Table 1). Participants engaged in an average of 164 min of physical activity per week (IQR: 67, 311), with 53% of the sample engaging in at least 150 min of MVPA per week at baseline. Sedentary time per day was approximately 352 min per day (IQR: 211, 459). Their average step count was 5426 steps per day (±3149) and there were significant differences in most physical activity variables by sex (Table 2), which persisted over time (Table 2). The overall diet quality, as indexed by the HEI-2015, was 48.1 (14.6), indicating poor diet quality (Table 1). The amount of MVPA per week, steps per day, and diet quality were stable over time, with decreases in sedentary time and light physical activity per week over time (Ps < .01).
Table 1.
Demographic Characteristics by Sex among PWH in PROSPER - HIV
| Male | Female | Total | P-value | |
|---|---|---|---|---|
| N (%) unless noted | (N = 548) | (N = 156) | (N = 704) | |
| Age | ||||
| Mean (SD) | 52.7 (11.9) | 52.7 (10.6) | 52.7 (11.6) | .991 |
| Median (IQR) | 55 (44, 62) | 54 (46, 60) | 55 (44, 62) | |
| Race/ethnicity | ||||
| Non-Hispanic White | 254 (46.4%) | 21 (13.5%) | 275 (39.1%) | <.001 |
| Non-Hispanic Black | 237 (43.2%) | 129 (82.7%) | 366 (52.0%) | |
| Latino/a/Hispanic | 38 (6.9%) | 3 (1.9%) | 41 (5.8%) | |
| Other/unknown | 19 (3.5%) | 3 (1.9%) | 22 (3.1%) | |
| Employment status | ||||
| Working, full time | 226 (41.2%) | 41 (26.3%) | 267 (37.9%) | <.001 |
| Working, part time | 68 (12.4%) | 13 (8.3%) | 81 (11.5%) | |
| Temp. laid off, sick leave, or maternity leave | 7 (1.3%) | 2 (1.3%) | 9 (1.3%) | |
| Looking for work, unemployed | 29 (5.3%) | 7 (4.5%) | 36 (5.1%) | |
| Retired | 85 (15.5%) | 17 (10.9%) | 102 (14.5%) | |
| Disabled, permanently or temporarily | 106 (19.3%) | 57 (36.5%) | 163 (23.2%) | |
| Keeping house | 2 (0.4%) | 9 (5.8%) | 11 (1.6%) | |
| Student | 6 (1.1%) | 4 (2.6%) | 10 (1.4%) | |
| Other | 19 (3.5%) | 6 (3.8%) | 25 (3.6%) | |
| Waist to hip ratio | 1.0 (0.1) | 0.9 (0.1) | 1.0 (0.1) | <.001 |
| Grip strength (kg) | 37.2 (13.4) | 24.9 (9.3) | 34.5 (13.6) | <.001 |
| SPPB score | 10.5 (1.7) | 9.8 (2.4) | 10.3 (1.9) | <.001 |
| Total HEI 2015 | .021 | |||
| Mean (SD) | 48.9 (15.0) | 45.6 (12.9) | 48.1 (14.6) | |
| Median (IQR) | 48.4 (37.5, 58.4) | 44.9 (36.3, 54.2) | 47.4 (37.0, 57.3) | |
PWH: People with HIV; SPPB: Short physical performance battery.
Table 2.
Baseline physical activity summary by sex among PWH in PROSPER-HIV.
| Sex |
||||
|---|---|---|---|---|
| Male | Female | Total | P-value | |
| (N = 390) | (N = 107) | (N = 497) | ||
| Moderate/vigorous activity/week (minutes/week) | <.01 | |||
| Mean (SD) | 233.5 (204.8) | 161.4 (176.0) | 218.0 (201.0) | |
| Median (IQR) | 178.2 (81.0, 328.1) | 97.1 (48.0, 199.0) | 164.0 (67.2, 311.0) | |
| ≥150 min/week | 227 (58%) | 39 (36%) | 266 (53%) | <.001 |
| ≥300 min/week | 114 (29%) | 20 (19%) | 134 (27%) | .03 |
| Light activity/week (minutes/week) | .017 | |||
| Mean (SD) | 6138.8 (1406.8) | 6465.5 (1420.2) | 6209.2 (1414.6) | |
| Median (IQR) | 5681.1 | 5934.6 | 5730.2 | |
| (5117.0, 6784.2) | (5433.0, 7651.0) | (5159.0, 6959.2) | ||
| Light activity/week (hours/week) | .03 | |||
| Mean (SD) | 102.3 (23.4) | 107.8 (23.7) | 103.5 (23.6) | |
| Median (IQR) | 94.7 (85.3, 113.1) | 98.9 (90.6, 127.5) | 95.5 (86.0, 116.0) | |
| Avg. time spent sedentary/day (minutes/day) | .896 | |||
| Mean (SD) | 350.6 (176.0) | 348.1 (163.5) | 350.0 (173.3) | |
| Median (IQR) | 324.5 | 325.7 | 325.3 | |
| (211.6, 449.9) | (207.5, 480.0) | (211.6, 458.6) | ||
| Total step count/day | <.001 | |||
| Mean (SD) | 5678.7 (3135.1) | 4506.2 (3040.8) | 5426.3 (3149.2) | |
| Median (IQR) | 5123.2 | 3748.2 | 4848.6 | |
| (3351.1, 7279.9) | (2394.2, 5942.2) | (3108.7, 7010.0) | ||
| ≥7000 steps/day | 108 (28%) | 18 (17%) | 126 (25%) | .02 |
| Physical activity summary by visit year | ||||
| Year 1 | N = 390 | N = 107 | N = 497 | |
| Moderate/vigorous activity/week | ||||
| ≥150 min/week | 227 (58%) | 39 (36%) | 266 (53%) | <.001 |
| ≥300 min/week | 114 (29%) | 20 (19%) | 134 (27%) | .03 |
| Total step count/day | ||||
| ≥7000 steps/day | 108 (28%) | 18 (17%) | 126 (25%) | .02 |
| Year 2 | n = 199 | n = 63 | N = 262 | |
| Moderate/vigorous activity/week | ||||
| ≥150 min/week | 96 (48%) | 20 (32%) | 116 (44%) | .02 |
| ≥300 min/week | 48 (24%) | 5 (8%) | 53 (20%) | .01 |
| Total step count/day | ||||
| ≥7000 steps/day | 43 (22%) | 4 (6%) | 47 (18%) | .01 |
| Year 3 | n = 153 | n = 51 | N = 204 | |
| Moderate/vigorous activity/week | ||||
| ≥150 min/week | 81 (52%) | 15 (29%) | 96 (47%) | <.01 |
| ≥300 min/week | 46 (30%) | 9 (18%) | 55 (27%) | .08 |
| Total step count/day | ||||
| ≥7000 steps/day | 40 (26%) | 8 (16%) | 48 (24%) | .1 |
IQR: Interquartile range; PWH: People with HIV; SD: Standard deviation.
Approximately 60% of participants reported any symptoms in the past month. Of those reporting symptoms, they experienced a mean of four symptoms in the past month (Table 3). Symptom prevalence and burden remained stable over time. Of the 20 symptoms assessed, the most burdensome (endorsed as a little bothersome, bothersome, or a lot bothersome) symptoms over time were muscle aches or joint pain, fatigue, difficulty with sleep, anxiety, trouble remembering, and sadness or depression. Gastrointestinal-related symptoms (e.g. nausea and vomiting, loss of appetite, weight loss/wasting) were the least commonly experienced symptoms across time points.
Table 3.
HIV symptoms by PROSPER-HIV visit.
| Year 1 | Year 2 | Year 3 | |
|---|---|---|---|
| (N = 704) | (N = 499) | (N = 370) | |
| HIV Symptom Index score, mean (SD) | 2.6 (3.4) | 2.4 (3.1) | 2.3 (3.0) |
| HIV Symptom Index score, median (IQR) | 1 (0, 4) | 1 (0, 4) | 1 (0, 4) |
| Presenting with >0 symptoms | 425 (62%) | 259 (59%) | 192 (58%) |
| Score if >0 symptoms, mean (SD) | 4.2 (3.4) | 4.0 (3.1) | 4.0 (3.0) |
| Score if >0 symptoms, median (IQR) | 3 (1, 6) | 3 (1, 6) | 3 (2, 5) |
| Fatigue or loss of energy | |||
| Does not have symptom | 287 (40.8%) | 192 (43.5%) | 148 (44.7%) |
| Has symptom, not bothersome | 107 (15.2%) | 71 (16.1%) | 51 (15.4%) |
| Has symptom, a little bothersome | 163 (23.2%) | 109 (24.7%) | 78 (23.6%) |
| Has symptom, bothersome | 90 (12.8%) | 44 (10.0%) | 33 (10.0%) |
| Has symptom, a lot bothersome | 56 (8.0%) | 25 (5.7%) | 21 (6.3%) |
| Fever, chills, sweats | |||
| Does not have symptom | 540 (76.7%) | 358 (81.0%) | 268 (81.0%) |
| Has symptom, not bothersome | 58 (8.2%) | 29 (6.6%) | 21 (6.3%) |
| Has symptom, a little bothersome | 51 (7.2%) | 30 (6.8%) | 30 (9.1%) |
| Has symptom, bothersome | 29 (4.1%) | 13 (2.9%) | 7 (2.1%) |
| Has symptom, a lot bothersome | 26 (3.7%) | 12 (2.7%) | 5 (1.5%) |
| Feeling dizzy or lightheaded | |||
| Does not have symptom | 487 (69.5%) | 317 (71.7%) | 251 (75.8%) |
| Has symptom, not bothersome | 61 (8.7%) | 33 (7.5%) | 19 (5.7%) |
| Has symptom, a little bothersome | 100 (14.3%) | 56 (12.7%) | 42 (12.7%) |
| Has symptom, bothersome | 38 (5.4%) | 25 (5.7%) | 14 (4.2%) |
| Has symptom, a lot bothersome | 15 (2.1%) | 11 (2.5%) | 5 (1.5%) |
| Pain numbness or tingling in the hands or feet | |||
| Does not have symptom | 384 (54.9%) | 234 (52.9%) | 174 (52.6%) |
| Has symptom, not bothersome | 57 (8.1%) | 44 (10.0%) | 31 (9.4%) |
| Has symptom, a little bothersome | 115 (16.4%) | 72 (16.3%) | 49 (14.8%) |
| Has symptom, bothersome | 71 (10.1%) | 46 (10.4%) | 36 (10.9%) |
| Has symptom, a lot bothersome | 73 (10.4%) | 46 (10.4%) | 41 (12.4%) |
| Trouble remembering | |||
| Does not have symptom | 380 (54.0%) | 246 (55.7%) | 175 (52.9%) |
| Has symptom, not bothersome | 75 (10.7%) | 71 (16.1%) | 46 (13.9%) |
| Has symptom, a little bothersome | 154 (21.9%) | 83 (18.8%) | 65 (19.6%) |
| Has symptom, bothersome | 58 (8.2%) | 27 (6.1%) | 29 (8.8%) |
| Has symptom, a lot bothersome | 37 (5.3%) | 15 (3.4%) | 16 (4.8%) |
| Nausea or vomiting | |||
| Does not have symptom | 572 (81.5%) | 366 (82.8%) | 292 (88.2%) |
| Has symptom, not bothersome | 61 (8.7%) | 35 (7.9%) | 18 (5.4%) |
| Has symptom, a little bothersome | 50 (7.1%) | 24 (5.4%) | 14 (4.2%) |
| Has symptom, bothersome | 11 (1.6%) | 8 (1.8%) | 4 (1.2%) |
| Has symptom, a lot bothersome | 8 (1.1%) | 9 (2.0%) | 3 (0.9%) |
| Diarrhea or loose bowel movements | |||
| Does not have symptom | 488 (69.5%) | 328 (74.2%) | 252 (76.1%) |
| Has symptom, not bothersome | 77 (11.0%) | 37 (8.4%) | 28 (8.5%) |
| Has symptom, a little bothersome | 80 (11.4%) | 52 (11.8%) | 28 (8.5%) |
| Has symptom, bothersome | 30 (4.3%) | 12 (2.7%) | 15 (4.5%) |
| Has symptom, a lot bothersome | 27 (3.8%) | 13 (2.9%) | 8 (2.4%) |
| Felt sad, down, or depressed | |||
| Does not have symptom | 372 (53.1%) | 247 (55.9%) | 194 (58.6%) |
| Has symptom, not bothersome | 88 (12.6%) | 60 (13.6%) | 33 (10.0%) |
| Has symptom, a little bothersome | 135 (19.3%) | 86 (19.5%) | 66 (19.9%) |
| Has symptom, bothersome | 61 (8.7%) | 32 (7.2%) | 16 (4.8%) |
| Has symptom, a lot bothersome | 45 (6.4%) | 17 (3.8%) | 22 (6.6%) |
| Felt nervous or anxious | |||
| Does not have symptom | 394 (56.0%) | 236 (53.4%) | 176 (53.2%) |
| Has symptom, not bothersome | 77 (11.0%) | 53 (12.0%) | 41 (12.4%) |
| Has symptom, a little bothersome | 139 (19.8%) | 97 (21.9%) | 70 (21.1%) |
| Has symptom, bothersome | 61 (8.7%) | 37 (8.4%) | 22 (6.6%) |
| Has symptom, a lot bothersome | 32 (4.6%) | 19 (4.3%) | 22 (6.6%) |
| Difficulty falling or staying asleep | |||
| Does not have symptom | 320 (45.6%) | 221 (50.0%) | 144 (43.5%) |
| Has symptom, not bothersome | 73 (10.4%) | 50 (11.3%) | 34 (10.3%) |
| Has symptom, a little bothersome | 126 (18.0%) | 71 (16.1%) | 70 (21.1%) |
| Has symptom, bothersome | 90 (12.8%) | 45 (10.2%) | 38 (11.5%) |
| Has symptom, a lot bothersome | 92 (13.1%) | 55 (12.4%) | 45 (13.6%) |
| Skin problems, such as rash, dryness, or itching | |||
| Does not have symptom | 454 (64.9%) | 305 (69.0%) | 229 (69.2%) |
| Has symptom, not bothersome | 74 (10.6%) | 40 (9.0%) | 32 (9.7%) |
| Has symptom, a little bothersome | 95 (13.6%) | 57 (12.9%) | 39 (11.8%) |
| Has symptom, bothersome | 47 (6.7%) | 26 (5.9%) | 19 (5.7%) |
| Has symptom, a lot bothersome | 30 (4.3%) | 14 (3.2%) | 12 (3.6%) |
| Cough or trouble catching your breath | |||
| Does not have symptom | 475 (67.8%) | 305 (69.0%) | 233 (70.4%) |
| Has symptom, not bothersome | 63 (9.0%) | 44 (10.0%) | 28 (8.5%) |
| Has symptom, a little bothersome | 97 (13.8%) | 54 (12.2%) | 42 (12.7%) |
| Has symptom, bothersome | 44 (6.3%) | 27 (6.1%) | 19 (5.7%) |
| Has symptom, a lot bothersome | 22 (3.1%) | 12 (2.7%) | 9 (2.7%) |
| Headache | |||
| Does not have symptom | 461 (66.0%) | 314 (71.0%) | 241 (72.8%) |
| Has symptom, not bothersome | 74 (10.6%) | 37 (8.4%) | 25 (7.6%) |
| Has symptom, a little bothersome | 100 (14.3%) | 50 (11.3%) | 39 (11.8%) |
| Has symptom, bothersome | 36 (5.2%) | 24 (5.4%) | 17 (5.1%) |
| Has symptom, a lot bothersome | 28 (4.0%) | 17 (3.8%) | 9 (2.7%) |
| Loss of appetite or a change in the taste of food | |||
| Does not have symptom | 522 (74.7%) | 342 (77.4%) | 258 (77.9%) |
| Has symptom, not bothersome | 63 (9.0%) | 39 (8.8%) | 30 (9.1%) |
| Has symptom, a little bothersome | 72 (10.3%) | 32 (7.2%) | 26 (7.9%) |
| Has symptom, bothersome | 26 (3.7%) | 21 (4.8%) | 11 (3.3%) |
| Has symptom, a lot bothersome | 16 (2.3%) | 8 (1.8%) | 6 (1.8%) |
| Bloating, pain, or gas in your stomach | |||
| Does not have symptom | 448 (64.0%) | 296 (67.0%) | 225 (68.0%) |
| Has symptom, not bothersome | 70 (10.0%) | 45 (10.2%) | 23 (6.9%) |
| Has symptom, a little bothersome | 97 (13.9%) | 49 (11.1%) | 55 (16.6%) |
| Has symptom, bothersome | 46 (6.6%) | 32 (7.2%) | 15 (4.5%) |
| Has symptom, a lot bothersome | 39 (5.6%) | 20 (4.5%) | 13 (3.9%) |
| Muscle aches or joint pain | |||
| Does not have symptom | 311 (44.3%) | 189 (42.8%) | 151 (45.6%) |
| Has symptom, not bothersome | 68 (9.7%) | 44 (10.0%) | 26 (7.9%) |
| Has symptom, a little bothersome | 144 (20.5%) | 103 (23.3%) | 69 (20.8%) |
| Has symptom, bothersome | 96 (13.7%) | 48 (10.9%) | 38 (11.5%) |
| Has symptom, a lot bothersome | 83 (11.8%) | 58 (13.1%) | 47 (14.2%) |
| Problems with having sex, such as loss of interest or lack of satisfaction | |||
| Does not have symptom | 444 (63.2%) | 278 (63.0%) | 224 (67.7%) |
| Has symptom, not bothersome | 74 (10.5%) | 42 (9.5%) | 27 (8.2%) |
| Has symptom, a little bothersome | 70 (10.0%) | 57 (12.9%) | 43 (13.0%) |
| Has symptom, bothersome | 54 (7.7%) | 32 (7.3%) | 19 (5.7%) |
| Has symptom, a lot bothersome | 61 (8.7%) | 32 (7.3%) | 18 (5.4%) |
| Changes in the way your body looks, such as fat deposits or weight gain | |||
| Does not have symptom | 386 (55.1%) | 243 (55.0%) | 189 (57.1%) |
| Has symptom, not bothersome | 71 (10.1%) | 55 (12.4%) | 36 (10.9%) |
| Has symptom, a little bothersome | 112 (16.0%) | 68 (15.4%) | 51 (15.4%) |
| Has symptom, bothersome | 60 (8.6%) | 43 (9.7%) | 23 (6.9%) |
| Has symptom, a lot bothersome | 71 (10.1%) | 33 (7.5%) | 32 (9.7%) |
| Problems with weight loss or wasting | |||
| Does not have symptom | 533 (76.3%) | 337 (76.2%) | 268 (81.0%) |
| Has symptom, not bothersome | 62 (8.9%) | 46 (10.4%) | 22 (6.6%) |
| Has symptom, a little bothersome | 50 (7.2%) | 31 (7.0%) | 17 (5.1%) |
| Has symptom, bothersome | 17 (2.4%) | 10 (2.3%) | 5 (1.5%) |
| Has symptom, a lot bothersome | 37 (5.3%) | 18 (4.1%) | 19 (5.7%) |
| Hair loss or changes in the way your hair looks | |||
| Does not have symptom | 500 (71.3%) | 330 (74.7%) | 253 (76.4%) |
| Has symptom, not bothersome | 87 (12.4%) | 40 (9.0%) | 30 (9.1%) |
| Has symptom, a little bothersome | 58 (8.3%) | 30 (6.8%) | 23 (6.9%) |
| Has symptom, bothersome | 30 (4.3%) | 20 (4.5%) | 10 (3.0%) |
| Has symptom, a lot bothersome | 26 (3.7%) | 22 (5.0%) | 15 (4.5%) |
PWH: People with HIV.
When modelling the relationships between physical activity, diet quality, and symptoms over time, several patterns were observed. Controlling for age, sex, race/ethnicity, and study site, sedentary time per day (β = 0.64, 0.27–1.02), steps per day (β = −0.59, −0.94 to −0.24), and HEI-2025 (β = −0.20, −0.33 to −0.06) were all associated with the number of reported symptoms that were bothersome (Ps ≤ 0.01) (Table 4). To examine these associations over the years, we modeled the trajectories of these relationships over time, and while the original effects persisted, the trajectories revealed that there were no changes in the number of symptoms over time (Ps > .05) (Table S1, see online supplementary material for a color version of this table). We also modeled the association between physical activity and diet quality with change in the symptom burden over time and did not observe any associations (Ps > .05) (Table S2, see online supplementary material for a color version of this table).
Table 4.
Linear mixed model for the association between physical activity and dietary quality with total number of bothersome HIV symptoms.a
| Variable | Average difference in symptom burden (95% CI) | P-value |
|---|---|---|
| MVPA per week (per 150 min) | −0.14 (−0.30, 0.02) | .10 |
| Light activity/week (per 5000 min) | 0.58 (−0.21, 1.37) | .15 |
| Sedentary time per day (per 300) | 0.64 (0.27, 1.02) | <.01 |
| Steps per day (per 5000) | −0.59 (−0.94, −0.24) | <.01 |
| HEI 2015 score (per 10 points) | −0.20 (−0.33, −0.06) | .01 |
Individual models adjusted for age, sex, race/ethnicity, and site.
HEI: Healthy Eating Index; MVPA: Moderate to vigorous physical activity.
When examining the association between physical activity and diet quality on symptom severity among the most common symptoms, several patterns emerged. Higher steps per day were associated with significantly lower fatigue, sleep difficulty, sadness, and anxiety (P < .01). Higher sedentary time was associated with higher fatigue and sadness, and a better diet quality was associated with less sleep difficulty and muscle aches/joint pain (Table 5).
Table 5.
Linear mixed model for the association between physical activity and dietary pattern with severity of individual HIV symptoms.
| Exposure | Average difference in symptom severity (95% CI) | P-value |
|---|---|---|
| MVPA per week (per 150 min) | ||
| Fatigue | −0.07 (−0.14, −0.01) | .03 |
| Muscle aches or joint pain | −0.05 (−0.12, 0.03) | .21 |
| Difficulty with sleep | −0.07 (−0.14, 0.01) | .07 |
| Trouble remembering | −0.05 (−0.11, 0.01) | .13 |
| Sadness or depression | −0.05 (−0.11, 0.01) | .12 |
| Anxiety | −0.03 (−0.09, 0.03) | .28 |
| Light activity/week (per 5000 min) | ||
| Fatigue | 0.14 (−0.19, 0.47) | .40 |
| Muscle aches or joint pain | −0.14 (−0.49, 0.22) | .45 |
| Difficulty with sleep | 0.04 (−0.32, 0.40) | .84 |
| Trouble remembering | 0.16 (−0.14, 0.45) | .30 |
| Sadness or depression | 0.18 (−0.13, 0.48) | .25 |
| Anxiety | −0.09 (−0.39, 0.21) | .56 |
| Sedentary time per day (per 300) | ||
| Fatigue | 0.24 (0.08, 0.39) | <.01 |
| Muscle aches or joint pain | −0.02 (−0.19, 0.15) | .84 |
| Difficulty with sleep | 0.16 (−0.01, 0.33) | .07 |
| Trouble remembering | 0.14 (−0.00, 0.28) | .05 |
| Sadness or depression | 0.20 (0.06, 0.34) | .01 |
| Anxiety | 0.05 (−0.09, 0.19) | .52 |
| Steps per day (per 5000) | ||
| Fatigue | −0.24 (−0.38, −0.09) | <.01 |
| Muscle aches or joint pain | −0.14 (−0.30, 0.02) | .08 |
| Difficulty with sleep | −0.26 (−0.42, −0.10) | <.01 |
| Trouble remembering | −0.16 (−0.29, −0.02) | .02 |
| Sadness or depression | −0.20 (−0.33, −0.06) | <.01 |
| Anxiety | −0.19 (−0.32, −0.06) | <.01 |
| HEI 2015 score (per 10 points) | ||
| Fatigue | −0.04 (−0.10, 0.01) | .12 |
| Muscle aches or joint pain | −0.07 (−0.13, −0.01) | .03 |
| Difficulty with sleep | −0.08 (−0.14, −0.02) | .01 |
| Trouble remembering | −0.03 (−0.08, 0.02) | .29 |
| Sadness or depression | −0.03 (−0.08, 0.02) | .31 |
| Anxiety | −0.01 (−0.06, 0.04) | .69 |
Individual models adjusted for age, sex, race/ethnicity, and site.
To determine the influence of sex, anthropometric measurements, and physical fitness on these relationships, we stratified these models. When stratifying by sex, we observed strong associations between steps per day (β = −1.12, −1.99 to −0.26 vs β = −0.54, −0.91 to −0.17) and diet quality (β = −0.30, −0.62 to −0.03 vs β = −0.17, −0.32 to −0.02) among women (Table S3, see online supplementary material for a color version of this table). Similar patterns were observed for those with high risk waist hip ratio (females ≥0.85, males ≥0.90), with those with high risk WHR experiencing a stronger association between steps per day (β = −0.63, −1.01 to −0.26 vs β = −0.27, −1.20–0.67) and diet quality (β = −0.21, −0.36 to −0.05 vs β = −0.12, −0.46–0.21) than those with low risk WHR (Table S4, see online supplementary material for a color version of this table). No significant relationships were observed when stratifying by SPPB or grip strength (P ≥ .01) (Table S5, see online supplementary material for a color version of this table). Finally, as sensitivity analyses, we repeated primary models using multiple imputations using an approximately rule of 1 imputation per 1% missingness. We ran 25 imputations based on 22% missing physical activity, and findings were materially unchanged (data not shown).
Discussion
To our knowledge, this is the first study to examine the longitudinal association of physical activity and diet quality with symptoms in PWH in the modern ART era. Symptoms are common among PWH, yet understudied, which, up to now, has hindered clinical approaches to help mitigate these symptoms. The PROSPER-HIV study identified several novel findings to help advance this field. First, despite PWH engaging in less than recommended levels of physical activity and diet quality, taking more steps per day and consuming a higher quality diet were associated with a lower symptom burden. Previous research among PWH found associations between physical activity and diet and specific symptoms (e.g. depression, fatigue, forgetfulness) [43, 44]—often using cross-sectional and brief self-report assessments [45–47]. Our findings, coupled with this existing evidence, support our hypotheses and help quantify the thresholds at which PWH can experience clinically meaningful lower symptom burden. An additional 5000 steps per day and a 10-point higher Healthy Eating Index was associated with a lower symptom burden. However, this should be confirmed by intervention research. This is among the first data generated to help quantify this relationship in PWH and can be used by healthcare professionals to help tailor and motivate lifestyle conversations, goals, and interventions for their patients living with HIV.
Second, our data confirms that PWH—even in the modern ART era—have a high symptom burden which remained stable over time. In year 1, 62% of participants reported any symptoms, and among those, they reported an average of three (IQR: 1, 6) symptoms. To date, the few studies examining the longitudinal trajectory of symptoms have often been in highly burdened populations. Among cancer survivors and those with mental health disorders, symptom burden is significant and symptom burden remains stable or declines over time [48, 49].
From the early days of the HIV epidemic, a high symptom burden has characterized the clinical manifestations of HIV infection. However, we have seen a shift in the number and types of symptoms over the past decades. Previously, PWH reported an average of 9–12 symptoms with high levels of psychological symptoms, fatigue, difficulty sleeping, diarrhea, and pain [50, 51]; more recently, these symptoms were mostly muscle aches, fatigue, and poor sleep [52]. In our cohort, muscle aches/joint pain, fatigue, sleep disturbance, trouble remembering, and anxiety were the most prevalent symptoms over time. Compared to earlier studies conducted during periods of more complex ART regimens, contemporary symptoms are fewer in number but remain clinically meaningful and burdensome to PWH.
Third, among this medically stable, older population of adults living with HIV, symptom burden, physical activity, and diet quality were consistent over time. The observational design of PROSPER-HIV allowed us to examine the longitudinal nature of these experiences over time—for the first time in the modern ART era. Among the behavioral factors, except for sedentary time and light physical activity (which decreased), MVPA per week, steps per day, and daily diet quality remained constant over the 3 years of observation. Longitudinal cohort studies of older adults generally reported either stable or trending toward decline in moderate and vigorous physical activity and increased sedentary time—which may be exacerbated with progressive chronic diseases [53, 54]. Yet, many of these studies assessed physical activity with self-report measures [54]. Diet quality measured over time improves slightly from adolescence to adulthood—but remains relatively stable in adulthood [55, 56]. Taken together, the implication of these data is that without intentional interventions, physical activity and diet quality persist at similar levels over time in adults. These lifestyle behaviors may be amenable to behavioral interventions to improve them, provided the stimulus is tailored and strong enough. Importantly, these behavioral targets associated with lower symptom burden in PROSPER-HIV are pragmatic and reinforceable within routine HIV care. Modest increases in daily physical activity, reducing prolonged sedentary time, and improving dietary quality through small, sustainable dietary changes may represent feasible symptom-management strategies for adults aging with HIV.
However, we note that this is among the first literature examining these natural variations over time in PWH, using gold-standard assessment tools. These trajectories should be confirmed across diverse PWH populations, settings, and time periods, and the PROSPER-HIV data can provide a valuable baseline for future comparison.
These data benefit from several strengths, including the longitudinal design; rigorous, gold standard measures of physical activity and diet quality; geographically diverse sample, and a significant proportion of women and non-white PWH—all of which increase the validity of these findings and advance the field of symptom science. However, there are also limitations that may limit the generalizability of these findings. First, PROSPER-HIV was an observational study, which precludes causal inference regarding the relationships between physical activity, diet quality, and symptom burden. Although analytic models were rigorously adjusted, residual confounding of the observed relationships from unmeasured behavioral, psychosocial, or clinical factors cannot be excluded. The relationship between symptom burden and physical activity and diet remains complex, and likely bidirectional, in that participants with higher symptom burden may have been less able to engage in physical activity or maintain healthier dietary behaviors. Our model estimates focus specifically on the direction of how physical activity and diet impact symptoms; however, the reverse remains an important question to fully understand this relationship.
Second, the cohort comprised adults with well-controlled HIV who were engaged in regular HIV care in the United States, potentially limiting generalizability to individuals with uncontrolled HIV viremia, limited healthcare access, differing sociodemographic characteristics, or those outside of the USA. Future randomized and pragmatic interventional studies across settings are needed to determine whether targeted improvements in physical activity and diet quality lead to clinically meaningful reductions in symptom burden among people with HIV.
In conclusion, in our large, longitudinal cohort of PWH, more daily steps and better diet quality were consistently associated with lower symptom burden over 3 years of follow-up, whereas more sedentary time was associated with a higher symptom burden. These findings underscore the clinical relevance of pragmatic, attainable lifestyle behaviors that can be assessed and supported in routine HIV care. Even modest increases in daily walking and incremental improvements in diet quality are achievable behavioral targets to support symptom management in routine HIV care. By identifying concrete, patient-centered targets linked to symptom improvement, PROSPER-HIV provides actionable evidence to inform symptom management strategies, guide clinician counseling, and support the full integration of lifestyle approaches into comprehensive HIV care for people aging with HIV.
Supplementary Material
Contributor Information
Allison Webel, School of Medicine, University of Washington, WA, 98195, United States.
Stephanie Ruderman, School of Medicine, University of Washington, WA, 98195, United States.
Christine Horvat Davey, Frances Payne Bolton School of Nursing, Case Western Reserve University, Cleveland, OH, 44106, United States.
Vitor H F Oliveira, School of Nursing, University of Washington, Seattle, WA, 98105, United States.
Heidi M Crane, School of Medicine, University of Washington, WA, 98195, United States.
Thomas W Buford, Birmingham/Atlanta VA GRECC, Birmingham VA Medical Center, 35294, United States.
Barbara M Gripshover, University Hospitals, Case Western Reserve University, Cleveland, OH, 44106, United States.
Greer A Burkholder, University of Alabama at Birmingham, 35294, United States.
Julia G Fleming, Fenway Health, Boston, MA, 02215, United States.
Josepha A Delaney, School of Medicine, University of Washington, WA, 98195, United States.
Michael S Saag, University of Alabama at Birmingham, 35294, United States.
Amanda L Willig, TW Education, Dallas, TX, 75201, United States.
Author contributions
Allison R. Webel (Conceptualization [lead], Funding acquisition [lead], Investigation [lead], Methodology [lead], Project administration [lead], Supervision [equal], Writing—original draft [lead], Writing—review & editing [lead]), Stephanie Ruderman (Formal analysis [equal], Investigation [equal], Methodology [equal], Visualization [equal], Writing—original draft [equal], Writing—review & editing [equal]), Christine Horvat Davey (Data curation [equal], Investigation [equal]), Vitor H.F. Oliveira (Data curation [equal], Investigation [equal], Project administration [equal], Writing—review & editing [equal]), Heidi M. Crane (Conceptualization [equal], Investigation [equal], Supervision [equal]), Thomas W. Buford (Conceptualization [equal], Investigation [equal], Writing—review & editing [equal]), Barbara M. Gripshover (Investigation [equal], Writing—review & editing [equal]), Greer A. Burkholder (Investigation [equal]), Julia G. Fleming (Data curation [equal], Investigation [equal], Writing—review & editing [equal]), Joseph A. Delaney (Data curation [equal], Formal analysis [equal], Methodology [equal], Visualization [equal], Writing—review & editing [equal]), Michael S. Saag (Conceptualization [equal], Funding acquisition [equal], Investigation [equal], Supervision [equal], Writing—review & editing [equal]), and Amanda L. Willig (Conceptualization [equal], Funding acquisition [equal], Investigation [equal], Methodology [equal], Project administration [equal], Writing—review & editing [equal])
Supplementary material
Supplementary material is available at Research Connections online.
Conflicts of interest
None declared.
Funding
Funding for this study was provided by different agencies: (i) the National Institute of Nursing Research under grant # R01NR018391 to A.R.W. and A.L.W. & grant # R21AG082537 to V.H.F.O.; (ii) the National Institute of Allergy and Infectious Disease CNICS Research Network under grant # R24-AI06703 to M.S.S. and H.M.C.; (iii) the National Institute of Allergy and Infectious Disease for the Centers for AIDS Research at the University of Washington (P30 AI027757) to M.S.S. and H.M.C.
Ethical approval
Study procedures adhered to the Helsinki Declaration, and all procedures were approved by Institutional Review Boards.
Data Availability
The data underlying this article will be shared on reasonable request to the corresponding author.
Patient consent
All participants provided written informed consent prior to initiating any study activities.
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Data Availability Statement
The data underlying this article will be shared on reasonable request to the corresponding author.