Physical Activity,Anxiety,Depression,and Adherence to Antiretroviral Therapy in People with HIV

Abstract

Physical activity (PA) levels, as well as symptoms of anxiety and depression, can affect adherence to antiretroviral therapy (ART) impacting people's health. This study aimed to evaluate the association between PA levels, clinical symptoms of anxiety and depression, and adherence to ART in people living with HIV (PLHIV). A cross-sectional study, including 125 PLHIV was conducted. Adherence to ART was assessed using the Simplified Medication Adherence Questionnaire (SMAQ). For anxiety and depression, the Hospital Anxiety and Depression Scale was applied. The level of PA was assessed using the short version of the International Physical Activity Questionnaire. SPSS version 22.0 was used for statistical analysis. The prevalence of clinical levels of anxiety and depression symptoms was 53.6% and 37.6%, respectively. Fifty-three percent presented clinical levels of depression and anxiety symptoms. Sixty-one people (48.8%) had vigorous PA levels, 36 people (28.8%) had moderate PA levels, and 28 people (22.4%) had low PA levels. According to the SMAQ, 34.5% of the patients were adherent to ART. People who performed low PA levels had more risk to develop clinical levels of depression symptoms. Clinical level of anxiety, depression, and psychological distress (PD) symptoms was found to increase the risk of nonadherence to ART.

Introduction

Physical activity (PA), defined as “any body movement produced by the skeletal muscles, with the consequent consumption of energy,”¹ can be a low-cost, nonpharmacological intervention that can improve the health status of people living with HIV (PLHIV). Several studies have suggested that structured and planned PA improves some aspects of cardiovascular and metabolic health, anxiety and/or depression symptoms, antiretroviral therapy (ART) success, and quality of life in PLHIV.^2

–5

The most common mental disorders in PLHIV are anxiety and depression.⁶ Generalized anxiety disorder is associated with poor socioeconomic status, depression, comorbid somatic health conditions, and unhealthy lifestyle choices such as physical inactivity.⁷ Depressive symptoms are consistently associated with nonadherence to ART, with a decreased quality of life, and have also been linked to worse HIV health outcomes causing decreased life expectancy.^8,9

Since the introduction of ART, the quality of life and life expectancy of PLHIV has improved.^10,11 In Mexico, ART has been accessible since 2003.¹² However, to obtain the desired results, strict adherence is necessary. Various studies have shown that lack of adherence can lead to therapeutic failure, viral resistance, and disease.^13,14 Several factors that affect adherence to ART have been described, among which socioeconomic factors such as age, sex, employment status, cognitive factors, and presence of adverse events stand out.¹⁰ Mental health disorders can disrupt a patient's ability to comply with ART. Likewise, anxiety and/or depression symptoms have been related to a decrease in adherence to ART.¹⁵ In Mexico, a prevalence of anxiety and depression of 56% and 33%, respectively, in the PLHIV population have been reported.¹⁶ Adherence to ART ranging from 50% to 78% has also been described.^17,18

Few studies in Mexico report the levels of PA and adherence to ART in this population, and it is also unknown whether symptoms of anxiety and depression are associated with PA and adherence to ART. Therefore, this work aimed to evaluate the levels of PA, symptoms of anxiety, depression, psychological distress (PD), adherence to ART, and the relationship between them.

Methods

Participants

A cross-sectional, descriptive, and correlational study was designed and conducted at the Outpatient Centre for the Prevention and Care of HIV/AIDS and Sexually Transmitted Infections (CAPASITS) in the city of Cuernavaca in México. CAPASITS offers medical, dental, psychological, laboratory, pharmaceutical, nutritional, and social work services to PLHIV older than 18 years of age. CAPASITS launched these services on July 2003, and on January 2019 a total of 1,735 PLHIV had received assistance. Using convenience sampling, between January and June 2019, the 800 people who attended their CD4 cell count and viral load routine laboratory tests were invited in person to participate by CAPASITS medical and laboratory staff while they were in the waiting room.

From the 800 people who were invited, 650 refused and 150 agreed to participate and signed an informed consent form. However, by the time the questionnaires began, 12 people changed their minds and withdrew. Seven people had not started ART yet and six people who did not adequately fill in the questionnaire were excluded. Thus, the final sample consisted of 125 people. The questionnaires were applied by trained personnel.

Pregnant women, imprisoned people, and those without ART were excluded from the study. The following parameters were used to calculate the sample size: total population of 1,735 CAPASITS patients, physical inactivity frequencies previously reported by Medina et al.¹⁹ for a Mexican population 16.5%, and 95% confidence interval (CI) with a marginal error of 10%.

The project was approved by the Bioethics Committee of the Henry Dunant Hospital in Cuernavaca. Everyone who agreed to participate signed an informed consent form. Subsequently, a questionnaire on sociodemographic factors was administered to them, and laboratory results of HIV viral load, CD4 lymphocyte count, and blood chemistry were obtained.

Anthropometric measurements

Anthropometric measurements for weight (kg) and height (cm) were obtained. Height was measured with a mobile stadiometer (Seca 213, Germany), with an accuracy of 0.5 cm, with the subject's head in the Frankfurt plane. Body weight was determined to the nearest 100 g using a digital scale (Seca 354). Measurements were taken three times, and the average was obtained. All measurements were taken with the individual barefoot and wearing light clothing. They were taken by trained personnel and standardized. Once the anthropometric data were obtained, the following parameters were calculated: body mass index (BMI, kg/m²), percentage of body fat, and percentage of muscle mass.

Assessment of PA levels

To assess the level of PA in the study population, the short version of the International Physical Activity Questionnaire (IPAQ) was used. This version has been validated in Spanish in Mexico²⁰ and consists of seven open-ended questions referring to the activities carried out by people in the last 7 days. The data processing and scoring of the IPAQ-short form (IPAQ-SF) were conducted as per the guidelines.²¹ An Excel spreadsheet that enables automatic scoring of the IPAQ-SF was used.²² The metabolic equivalent (MET) values were used for measurements. The subject's total PA (MET-min/week) was used as a continuous variable. Also, the IPAQ score was categorized as low, moderate, and vigorous according to guidelines.²¹

Instrument to determine anxiety and depression

To determine anxiety and depression, the Hospital Anxiety and Depression Scale (HADS), validated in Mexico, was applied.¹⁶ The HADS is a questionnaire with 14 items, made up of 2 subscales of 7 items each, 1 for anxiety (HADS-A, odd items) and the other 1 for depression (HADS-D, even items). The response options are Likert-type from 0 to 3, with a minimum score of 0 and a maximum of 21 for each subscale. A score of 0 to 7 for either subscale could be regarded as being in the normal range (noncases), a score of 8 to 10 being just suggestive of the presence of the respective state (doubtful cases), and a score of 11 or higher indicating probable presence (“caseness”) of the anxiety/depression disorder.²³

It is difficult to empirically distinguish both constructs which are closely correlated, particularly in PLHIV. Hence, there is a new construct named PD, which has been suggested as an indicator of mental health defined as an emotional state of suffering characterized by anxious and depressive symptoms.¹⁶

To assess psychological distress globally, both subscales were combined to produce a total (HADS-T) score. A higher score indicates higher levels of psychological distress (PD) and a HADS-T score ≥13 indicates PD symptoms (96% sensibility and 82% specificity).^24,25

Adherence to ART

To assess treatment adherence, the Simplified Medication Adherence Questionnaire (SMAQ) was used. The SMAQ is a previously validated instrument in Spanish that consists of six items.²⁶ The person was classified as being adherent if they responded adequately to the first four questions and if response 5 was ≤2 and response 6 was ≤2 days.²⁶

Statistical analysis

The normality of the continuous variables was evaluated using the Kolmogorov–Smirnov test. Comparisons between the means of variables with normal distribution were made using Student's t-test or analysis of variance. For comparing the means of the non-normal variables, the Mann–Whitney or Kruskal–Wallis U test was used.

To evaluate the association between different variables, a multiple logistic regression analysis was performed. Sex, age, schooling years, BMI status, viral load, CD4 cells, PA levels, and adherence to ART were used as independent variables. Anxiety, depression, and PD were used as dependent variables.

The dependent variables were grouped as follows: all those people who had a score of <8 was reclassified as subclinical symptoms and those with a score of ≥8 as clinical levels of depressive or anxiety symptoms. The cutoff score of ≥8 on the HADS-D, yielded a sensitivity of 0.63 and higher specificity (0.94). Also, we used the same cutoff (≥8) for HADS-A, being the most frequently recommended. The HADS-T score ≥13 indicates PD.^25,27 The adjusted odds ratios (aOR) and 95% CI were calculated. A p-value of .05 was considered statistically significant.

The data were analyzed with the statistical program SPSS version 20 for Windows™ (SPSS, Inc., Chicago, IL).

Results

The median age was 34 years (standard deviation = 16.5). Men had more years of schooling than women (68% vs. 28%, respectively, p < .001). Table 1 shows the general and clinical characteristics of the population.

Table 1.

General and Clinical Characteristics of the Population

	Total (n = 125), n (%)	Female (n = 25), n (%)	Male (n = 100) n (%)	p
Age, years^a	34 (16.5)	38.0 (20)	33.0 (14)	.022
<34	66 (52.8)	10 (40)	56 (56)
≥34	59 (47.2)	15 (60)	44 (44)
Schooling, years
≤9	50 (40)	18 (72)	32 (32)	<.001^*
>9	75 (60)	7 (28)	68 (68)
BMI, kg/m^{2 a}	24.8 (4.4)	25.1 (6.9)	24.5 (5.5)	.073
BMI status
Underweight	5 (4)	0	5 (5)
Normal	63 (50.4)	12 (48)	51 (51)	.246
Overweigh	44 (35.2)	8 (32)	36 (36)
Obese	13 (10.4)	5 (20)	8 (8)
Plasma HIV-RNA, copies/mL
<40	108 (86.4)	22 (88)	86 (86)	.814
≥40	17 (13.6)	3 (12)	14 (14)
CD4, cell/mm³
<350	22 (17.6)	4 (16)	82 (82)
≥350	103 (82.4)	21 (84)	18 (18)
PA level
Vigorous	61 (48.8)	10 (40)	51 (51)
Moderate	36 (28.8)	9 (36)	27 (27)	.579
Low	28 (22.4)	6 (14)	22 (22)
Adherence
Yes	38 (30.4)	7 (28)	31 (31)	.771
No	87 (67.9)	18 (72)	69 (69)
Anxiety
HADS-A score^a	8 (5)	9 (5)	7.5 (5)	.111
Non-cases	58 (46.4)	8 (32)	50 (50)
Doubtful cases	37 (29.6)	9 (36)	28 (28)	.264
Caseness	30 (24.0)	8 (32)	22 (22)
Depression
HADS-D score^a	7 (5)	7 (5)	6 (5)	.680
Non-cases	78 (62.4)	15 (60)	63 (63)
Doubtful cases	28 (22.4)	8 (32)	20 (20)	.304
Caseness	19 (15.2)	2 (8)	17 (17)
Psychological distress
HADS-T score^b	14.9 (6.6)	16.1 (5.1)	14.6 (6.9)	.323
HADS-T score <13	48 (38.4)	6 (24)	42 (42)	.098
HADS-T score ≥13	77 (61.6)	19 (76)	58 (58)

Data are expressed as the medians (interquartile range).

Data are expressed as the arithmetic means (±SD).

p-Values were obtained by comparing male versus female.

BMI, body mass index; HADS, Hospital Anxiety and Depression Scale; HADS-A, Hospital Anxiety and Depression Scale-Anxiety subscale; HADS-D, Hospital Anxiety and Depression Scale-Depression subscale; HADS-T, Hospital Anxiety and Depression Scale Distress-Total score; PA, physical activity; SD, standard deviation.

PA levels and the percentage of people adherent to ART and with doubtful cases and caseness of anxiety and depression were similar in both sexes. Anxiety caseness appeared more frequently with respect to depression caseness (24% vs. 15.2%, respectively). Women showed higher PD than men. An overall 67.9% of the population was classified as nonadherent (Table 1).

When conducting a multivariate regression analysis to determine whether there was an association between PA levels, adherence to ART, and clinical and sociodemographic variables (independent variables) with clinical levels of depressive or anxiety symptoms and PD symptoms, it was found that nonadherence to ART and ≤9 schooling years are a risk factor for clinical levels of depressive symptoms (aOR = 3.4, 95% CI = 1.39–8.6; p = .008 and aOR = 2.49; 95% CI = 1.07–5.79; p = .034, respectively) (Table 2).

Table 2.

Factors Associated with Anxiety, Depression, and General Psychological Distress from Logistic Regression Models

	HADS-A ≥8, aOR (95% CI)	p	HADS-D ≥8, aOR (95% CI)	p	HADS-T ≥13, aOR (95% CI)	p
Gender
Female	1.00 (ref.)		1.00 (ref.)		1.00 (ref.)
Male	0.653 (0.23–1.85)	.425	1.039 (0.378–2.85)	.941	0.603 (1.96–1.85)	.378
Age, years
<37	1.00 (ref.)		1.00 (ref.)		1.00 (ref.)
≥37	1.17 (0.513–2.70)	.699	1.025 (0.450–2.33)	.953	1.09 (0.46–2.57)	.836
Schooling, years
>9	1.00 (ref.)		1.00 (ref.)		1.00 (ref.)
≤9	2.49 (1.07–5.79)	.034	1.10 (0.47–2.54)	.819	2.3 (0.96–5.51)	.061
BMI
Underweight+normal	1.00 (ref.)		1.00 (ref.)		1.00 (ref.)
Overweight+obesity	0.43 (0.183–1.02)	.056	1.16 (0.510–2.67)	.570	0.21 (0.23–1.37)	.210
Plasma HIV1-RNA, copies/mL
<40	1.00 (ref.)		1.00 (ref.)		1.00 (ref.)
≥40	1.58 (0.450–5.61)	.472	1.06 (0.318–3.53)	.925	1.22 (0.34–4.33)	.754
CD4, cells/mm³
≥350	1.00 (ref.)		1.00 (ref.)		1.00 (ref.)
< 350	1.17 (0.397–3.49)	.767	1.46 (0.50–4.25)	.480	0.836 (0.27–2.5)	.753
PA level
Vigorous	1.00 (ref.)		1.00 (ref.)		1.00 (ref.)
Moderate	1.33 (0.536–3.30)	.537	2.0 (0.85–5.15)	.106	1.7 (0.67–4.48)	.257
Low	2.64 (0.954–7.34)	.061	3.2 (1.19–8.70)	.020	2.8 (0.97–8.11)	.056
Adherence
Yes	1.00 (ref.)		1.00 (ref.)		1.00 (ref.)
No	3.4 (1.39–8.60)	.008	2.3 (0.93–5.84)	.069	4.2 (1.73–10.35)	.002

Multivariate logistic regression was adjusted for sex, age, schooling years, BMI status, viral load, CD4 cells, PA, and adherence to antiretroviral.

aOR, adjusted odds ratios; CI, confidence interval.

When stratified by sex, it was observed that nonadherence to ART was associated with clinical levels of anxiety symptoms (aOR = 3.5; 95% CI = 1.29–9.74; p = .029) and with PD (aOR = 4.25; 95% CI = 1.55–11.64; p = .01), while low and moderate levels of PA were associated with clinical levels of depressive symptoms in men (aOR = 3.3; 95% CI = 1.59–9.74; p = .026 and aOR = 4.0; 95% CI = 1.3–12.34; p = .016, respectively) (data not shown). When the adherence variable (yes/no) is placed as dependent variable and clinical levels of depressive, anxiety, or PD symptoms as independent variables, it is observed that clinical levels of anxiety symptoms (aOR = 2.6; 95% CI = 1.17–6.10; p = .02) and PD symptoms (aOR = 2.8; 95% CI = 1.65–8.91; p = .002) were associated with nonadherence to ARV therapy (data not shown).

In a similar way, placing the variable PA (low+moderate vs. intense) as dependent, it was found that men with clinical levels of depressive symptoms were associated to low+moderate PA levels (aOR = 7.8, 85% CI = 2.0–29.7; p = .003). No association was observed with any of the variables in the group of women (data not shown).

The correlation between the HADS-A score and HADS-D score subscales was 0.497 (p < .001), while the correlation between the HADS-A subscale and the HADS-T scale was 0.908 (p < .001); for the HADS-D and the HADS-T scale, it was 0.814 (p < .001). The correlation between HADS-D score and PA evaluated by METs/min/week was −0.200 (p = .025). No correlation was found between HADS-A and HADS-T with PA (data not shown).

Discussion

PA levels

This is the first report describing the levels of PA in outpatient PLHIV from a first-level care clinic in Mexico. The results of the 2018–2019 National Health and Nutrition Survey (ENSANUT) showed that 71% of Mexicans older than 20 years of age perform vigorous PA.²⁸ However, in this population, the percentage of people with vigorous PA was 48.8%, these data suggest that PLHIV are less active than the rest of the population. Previous studies comparing PA levels between PLHIV and a population without HIV found that PLHIV are less active.²⁹

The WHO recommends that people with chronic diseases should do physical activities for at least 150–300 min or intense aerobic physical activities for at least 75–150 min/week.³⁰ These activities will help prevent and combat chronic noncommunicable diseases. Therefore, it is very important to understand why people with HIV/AIDS are less active since this will allow the implementation of strategies that favor the performance of PA, which will bring a better physical and mental healthy life.

Anxiety and depression frequencies

The mean HADS-A, HADS-D, and HADS-T scores were in agreement to those found by Orozco et al. for a population of PLHIV from Mexico (7.61, 4.89 and 12.5, respectively).¹⁶ In this population, anxiety and depression symptoms occurred in 53.6% and 37.6%, respectively. Alderete-Aguilar et al. reported a frequency of 23.5% and 13.9% for anxiety and depression, respectively, for a Mexican population of PLHIV at the time of hospital admission.³¹ In both studies, the same assessment instrument and cutoff were used. Different factors could have influenced these differences; for example, feeling that their clinical symptoms would improve during their stay in the hospital or that the required drug therapy would be well supervised.

Likewise, the prevalence of depressive and anxiety symptoms in this study was higher than the observed in a recent study of men who have sex with men (MSM) living with HIV in the Philippines (anxiety 37.3% and depression 21.8%), but similar to Chinese MSM living with HIV (36% for depression and 42% for anxiety).³² Sociodemographic differences could be one of the reasons of these differences.

Adherence frequency

Nonadherence to ART has been associated with high viral replication,¹³ however, in this population, although poor adherence was found, the viral replication, measurement by viral load, was below the detection limit in 86.5% of the subjects. The poor adherence found in these subjects is likely due to the restrictive characteristics of the SMAQ since people who declared having missed a dose are classified as nonadherent. However, these patients may be at higher risk of developing viral resistance. It would be important to invite them to adherence programs to prevent increase in viral replication and probable progression of the disease.

Factors associated with level of activity, clinical symptoms of anxiety, and depression

Participants who performed low PA levels were 3.2 times more likely to have clinical levels of depressive symptoms. Similarly, participants with low PA levels have a higher risk of clinical levels of anxiety symptoms and PD symptoms (marginal significance p = .056 and p = .061, respectively). Not engaging in physical activities may lead to social isolation. A current study described that high perceived isolation was linked to increased depression and anxiety symptoms.³³ Conversely, clinical levels of depression symptoms were associated with PA levels (OR = 2.5, p = .02). This association has been previously described in other populations,^7,34 which suggests that people with depression symptoms are less inclined to engage in PA.

Our data suggest that clinical levels of anxiety and PD symptoms could cause not taking your medications on time. It is crucial to consider the fact that anxiety and depression can worsen without effective intervention and make adherence to treatment more difficult over time. This situation can lead to virological and immunological failure with adverse consequences on the person's clinical status.

This study only shows the association with some of the variables analyzed, however, more research is required to determine the impact on physical and mental health of simple and economic interventions such as those that promote PA.

When reviewing the information that is available on the PLHIV population that attends CAPASITS in the State of Morelos, it was found that there are no significant differences in relationship to the percentage of males (81%) aged ≥34 years (48.4%) or undetectable viral load (VL) levels (89%) between the total population of CAPASITS^35,36 and the population of this study.

This study has several limitations, the first being that the results are not representative of all PLHIV users at CAPASITS-Cuernavaca since the sampling used was not probabilistic. Second, it is likely that people with severe depressive and/or anxiety symptoms who do not usually attend health services are left out. Third, it is not possible to speak of a causal relationship between the variables under study because the analysis carried out was descriptive and correlational in scope.

Finally, the reasons why users refused to participate in the research were not recorded or systematized, which would have provided relevant information for future studies, given the high number of people who refused to participate. However, recovering the observations of the personnel who made the invitation, the most frequent reason expressed by the people was that they did not have time to respond to the questionnaires because they had to leave quickly since they had to get to work or school.

Conclusions

Our study indicates that low PA levels were associated with the presence of clinical levels of depression symptoms in this population and vice versa. Likewise, clinical levels of anxiety, depression, and PD symptoms were associated with nonadherence to ART.

It is important to promote and implement simple and inexpensive interventions, such as well-structured physical exercise, to reduce levels of depression and anxiety to have a positive impact on adherence to ART.

Footnotes

Acknowledgments

The authors thank all the participants in this study, and the medical, laboratory, and administrative staff of CAPASITS Cuernavaca.

Authors' Contributions

M.F.M.-S. designed the study, conducted the statistical analysis, and drafted the article. Formal analyses, writing review, and editing were done by P.H.-S. and N.B.G.F. M.A.O.-R. oversaw survey activities and revised the article. All authors have read and agreed to the published version of the article.

Author Disclosure Statement

No competing financial interests exist.

Funding Information

No funding was received for this article.

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