Abstract

Introduction

The topic of health-related quality of life (HRQoL) has become increasingly significant due to the advancements in antiretroviral therapies and the increase in life expectancy among individuals living with people living with human immunodeficiency virus (PLWH). We aimed to ascertain the levels of anxiety, depression, and HRQoL in PLWH.

Materials and Methods

This study was conducted between March and November 2020 at Mersin University Hospital, a tertiary level hospital in Turkey. The HRQoL was evaluated using the 36-Item Short Form Health Survey (SF-36), while depression and anxiety were assessed using the Beck Depression Scale (BDS) and Beck Anxiety Scale (BAS), respectively. Based on the univariate analysis results, all candidate variables with a p value of<0.25, which may clinically be a risk factor for SF-36 physical component summary (PCS) and mental component summary (MCS), were selected and evaluated using multivariate logistic regression analysis.

Results

The PCS and MCS scores were significantly lower (p<0.05), while the BDS and BAS scores were significantly higher (p<0.05) in the PLWH group. The depression and anxiety rates were 31.7% and 22.1%, respectively. Anxiety and depression adversely affected the quality of life (p<0.05). Multivariate analysis demonstrated that female sex [p=0.040, odds ratios (OR): 3.115, 95% confidence interval (CI): 0.109-0.949 for PCS; p=0.033, OR: 4.200, 95% CI: 0.063-0.893 for MCS], missed outpatient clinic appointments (p=0.025, OR: 2.397, 95% CI: 1.114-5.159 for PCS; p=0.017, OR: 3.407, 95% CI: 1.250-9.282 for MCS), depression (p=0.001, OR: 3.479, 95% CI: 1.612-7.508 for PCS; The risk on MCS could not be calculated), and anxiety (p=0.042, OR: 2.597, 95% CI: 1.035-6.518 for PCS; p=0.001, OR: 6.74, 95% CI: 2.153-21.124 for MCS), were factors related to both low PCS and MCS scores.

Conclusion

High anxiety and depression levels among the PLWH in our study had an adverse impact on their HRQoL.

INTRODUCTION

As of 2021, approximately 38.4 million people worldwide are estimated to be infected with human immunodeficiency virus (HIV). Of these, 1.8 million individuals reside in Eastern Europe and Central Asia, including Turkey^[1]. Although the prevalence of HIV infection in Turkey is low, it is one of the regions that is experiencing an increase in the disease prevalence. According to official data, nearly 34,000 people are currently living with HIV in Turkey, and between January and November 2022, approximately 3,000 new HIV diagnoses have been made^[2].

Advancements in antiretroviral therapy (ART) have transformed acquired immunodeficiency syndrome (AIDS) from a fatal illness into a manageable chronic condition, allowing patients to attain a normal life expectancy^[3]. Consequently, the health-related quality of life (HRQoL) for people living with HIV (PLWH) has become increasingly significant. It is widely acknowledged that optimal treatment outcome objectives should encompass improvements in HRQoL^[4]. Studies report that PLWH typically experience a lower HRQoL compared to the general population^{[5, 6]}. Therefore, the enhancement of HRQoL has been suggested as a key goal in addition to the 90-90-90 targets set by UNAIDS^[7].

The World Health Organization defines quality of life as an individual’s perception of their position in life within the context of their culture and value systems, encompassing their goals, expectations, standards, and concerns^[8]. It is a multidimensional concept that incorporates physiological, psychological, and social aspects. Health-related quality of life specifically assesses the impact of a disease and its treatment on an individual’s quality of life^{[9, 10]}. Measuring HRQoL is valuable as it can help predict behaviors detrimental to health^[11]. Furthermore, identifying HRQoL determinants for PLWH can have a substantial impact on their social and medical well-being.

Sociodemographic and clinical variables are linked to the HRQoL in PLWH. In addition, to physical health challenges, PLWH experience psychological issues, such as depression and anxiety, which are more prevalent in this demographic than in the general public. Depression and anxiety significantly influence the HRQoL in PLWH^{[11, 12]}.

The national multicenter study assessing UNAIDS targets revealed that Turkey has essentially achieved the last two goals of the 90-90-90 targets, but lacks data for the initial 90-target, i.e., 90% of PLWH will know their HIV status^[13]. Similar to the findings of other studies conducted in Turkey, although the 2^nd and 3^rd 90-target were almost achieved, the success rate for the first 90-target was reported as 48-50%^{[14, 15]}.

Although these targets have been nearly achieved, studies on depression, anxiety, and HRQoL among PLWH in Turkey, which could provide valuable insights from a biopsychosocial perspective, are limited^[16-21].

This study aimed to examine and contrast the levels of anxiety, depression, and HRQoL among PLWH and healthy volunteers in Turkey. The objective is to comprehend the impact of HIV infection on these outcomes and to explore the factors that influence HRQoL. The findings of this study are anticipated to optimize comprehensive treatments for PLWH and improve clinical outcomes by offering insights into the specific challenges encountered by PLWH in our country.

Given the limited number of studies on this topic in Turkey, we believe that our findings will be beneficial.

Materials and Methods

Study Design and Population

This single-center, cross-sectional study, conducted between March and November 2020, involved 208 PLWH and 100 healthy volunteers who met the inclusion and exclusion criteria.

Exclusion criteria for PLWH:

- Age under 18.

- Human immunodeficiency virus diagnosis within the first six months of enrollment.

- Patients with cognitive impairment that prevents them from understanding and filling out the study forms.

Exclusion criteria for healthy volunteers:

- Age under 18.

- Those with a chronic disease.

- Those with cognitive impairment that prevents them from understanding and filling out the study forms.

The participants of this study were PLWH who were treated and monitored at at a Mersin University Hospital, a tertiary-level hospital in Turkey between March and November 2020. We aimed to maintain the highest feasible number of HIV-infected patients in this study. Therefore, there was no sampling in the PLWH group. This study included HIV-infected patients older than 18 years who were willing to participate in the current study and who visited the routine outpatient clinic control. Thus, the study included 208 of the 320 patients who had been regularly monitored by the department of infectious diseases.

The study included one hundred healthy volunteers who met the exclusion and inclusion criteria and resided in the city where the study was conducted. The study was approved by the Mersin University of Clinical Research Ethics Committee (protocol number: 2020/168, date: 20.02.2020).

Data Collection

Demographic and epidemiological variables, including age, sex at birth, marital status, educational status, occupation, and monthly income, were requested from participants in both groups on a self-completed form. The sociodemographic characteristics of all participants are outlined in Table 1.

The PLWH group was provided with an additional form detailing the epidemiological and clinical characteristics of the disease. Information regarding sexual orientation, route of transmission, time since diagnosis, duration of HIV treatment, baseline and current HIV RNA levels, and current CD4 counts was included in this form. In addition, data on the presence of comorbidities, smoking and alcohol habits, the quantity of ART tablets, regular ART use, ART adverse effects, and the transition from a multitablet regimen to a single-tablet regimen were evaluated. The definitions of the other queries in this form are as follows:

Outpatient visit attendance: Indicates whether the participant had missed at least two appointments within the past year (yes or no).

Presence of lipodystrophy: The individual’s self-perception and self-report for lipodystrophy was used to ascertain the presence of lipodystrophy in our study participants.

History of psychiatric illness: Determined by whether the participant had been diagnosed with a psychiatric disorder by a psychiatrist prior to the commencement of our study.

Satisfaction with communication with the doctor: assessed by the participant’s feedback regarding their communication experiences with their healthcare provider.

The socioepidemiological data in the form was provided by the participant. The physician who conducted the study completed the medical information by reviewing the medical record. The epidemiological and clinical characteristics of the PLWH are illustrated in Table 2.

The 36-Item Short Form Health Survey (SF-36) scale, the Beck Depression Scale, and the Beck Anxiety Scale were administered to both the PLWH and healthy volunteers to evaluate the quality of life, depression, and anxiety status, respectively.

Assessment Tools

Short Form-36 Scale

This quality-of-life scale was developed by Ware and Sherbourne^[22] and comprises 36 questions that address eight categories: physical functioning, role physical, bodily pain (BP), general health, vitality (VT), social functioning (SF), role emotional, and mental health (MH). This scale evaluates health on a scale of 0 to 100, with higher scores indicating better quality of life. The sub-scales can be combined to generate two summary measures: physical component summary (PCS) and mental component summary (MCS) scores. The SF-36 is an extensively used and validated instrument for HRQoL evaluation. Prior studies have reported equal use of both generic and HIV-specific instruments. Studies that compared PLWH with individuals without HIV were more likely to utilize generic instruments such as the SF-36 scale. Generic instruments were preferred for comparative studies because they effectively capture the differences in HRQoL between those with and without the disease^[23]. Therefore, we used SF-36 in our study.

Several studies have confirmed that individuals with PCS and MCS >50 experience an improved quality of life^[24-26]. In our study, PCS and MCS were classified as ≤50 and >50, respectively, in accordance with the existing literature.

Beck Depression Scale

It is a 21-question, self-assessment scale developed by Beck in which each item is scored between 0 and 3^[27]. Higher scores suggest that depressive symptoms are more severe, with the maximum possible score being 63. Hisli^[28] conducted a validity and reliability investigation for Turkey, and the cutoff point for clinically significant depression in the Turkish language version was established as 17. Beck Depression Scale was utilized because it can be applied to both healthy volunteers and PLWH.

Beck Anxiety Scale

It is a self-assessment scale developed by Beck, consisting of 21 questions, in which each item is scored between 0 and 3^[29]. The maximum attainable score is 63, with higher scores indicating greater severity of anxiety symptoms. A validity and reliability study for the Turkish version was conducted by Ulusoy^[30]. The recommended minimal score for diagnosing clinically significant anxiety in BAS is 16^[31]. Beck Anxiety Scale was used as it can be applied to both healthy volunteers and PLWH.

Statistical Analysis

Statistical analysis was performed using the Statistical Package for the Social Sciences 26 software (trial version). The Kolmogorov-Smirnov test was used to verify the normal distribution of the data. The age was the sole variable summarized in terms of mean±standard deviation. The other numerical variables were summarized using the median (Q₁-Q₃) values. Categorical variables are presented as numbers and percentages (n, %).

The age means were compared using the Student’s t-test. The Mann-Whitney U test was utilized to compare the median of the groups. Box and whisker plots were drawn in accordance with the group’s scores. Categorical variables were compared using the chi-square test. The two ratio Z test was implemented for ratio comparisons in accordance with the results of the chi-square test.

Multivariate logistic regression analysis was conducted using the backward stepwise method to evaluate all candidate variables with p<0.25 and potential clinical risk factors for PCS and MCS, as determined by the univariate analysis results. Odds ratios (ORs) and 95% confidence intervals (CIs) were also calculated. The odds ratio, which did not include a CI of 1, was considered statistically significant.

For all statistical comparisons, a p≤0.05 was considered statistically significant.

Results

The study comprised 308 participants, including 208 PLWH, four of whom were AIDS patients, and 100 healthy volunteers. The mean age of the PLWH group participants was 39.8±13.74 (minimum-maximum: 18-74), while that of the healthy group participants was 40.3±14.3 (minimum-maximum: 18-69). Males comprised 89.9% (n=187) of the PLWH participants, while females comprised 10.1% (n=21). Among the healthy group participants, 91% (n=91) were male and 9% (n=9) were female. The groups demonstrated comparable distribution in terms of age, sex, and educational status, and there were no statistically significant differences between them (p>0.05).

There was a statistically significant correlation between marital status and the groups (p<0.05). The rate differences contributing to this relationship are as follows: The proportion of singles in the PLWH group (51.4%) was significantly higher than that of the healthy individuals’ group (34%); the percentage of married individuals was significantly lower (35.1%) in the PLWH group than in the healthy individuals’s group (55%). The differences between these rates are statistically significant (p<0.05). Conversely, the proportions of widowed/divorced individuals were comparable in both groups (p>0.05).

There was a statistically significant relationship between the groups in terms of the participants’ occupation (p<0.05). In the PLWH group, the proportion of public employees was substantially lower (10.1%) than in the healthy individuals’ group (25%). Conversely, the percentage of participants employed in the private sector was significantly higher (45.2%) in the PLWH group than in the group of healthy individuals (29%).

A statistically significant relationship was observed between the groups in terms of the monthly income of the participants (p<0.05). The PLWH group comprised a significantly lower proportion (11.1%) of individuals with a monthly income above the minimum wage compared to those in the healthy individuals’ group (22%). The percentage of individuals with a monthly income between the minimum wage and the poverty threshold was significantly lower (41.3%) in the PLWH group than in the healthy individuals’ group (54%). However, the proportion of individuals with an income equivalent to the minimum wage and below (≤373 $) was significantly higher (p<0.05) in the PLWH group (47.6%) than in the healthy individuals’s group (24%).

The statistical comparisons of the sociodemographic characteristics of PLWH and healthy volunteers are illustrated in Table 1.

The HRQoL scores among the PLWH group participants ranged from 60 (VT) to 100 (BP). In the PLWH group, the scores were low in all subgroups except for BP. The scores of the seven subgroups of SF-36 (except BP subgroup) and PCS-MCS scores among the PLWH group participants were significantly lower than those of the healthy volunteers. Anxiety and depression scores were higher than those of the healthy volunteers (Figure 1, Table 3). The PLWH group demonstrated higher median scores for depression and anxiety (p<0.0001) than the healthy volunteers group. Depression was diagnosed in 31.7% and anxiety in 22.1% of the patients, and the co-occurence rate of depression and anxiety was revealed to be 15.9%. The depression and anxiety rates were higher in the PLWH group than in the healthy group participants (p<0.05) (Table 3). The univariate analysis results revealed that lipodystrophy, number of tablets, ART adverse effects, missed outpatient clinic appointments, and the presence of depression and anxiety were the factors affecting both PCS and MCS scores among the PLWH group participants. Tables 4 and 5 illustrate the univariate analysis outcomes of the factors that influence PCS and MCS scores among the PLWH group participants.

Multivariate analysis revealed that female sex (p=0.040, OR: 3.115, 95% CI: 0.109-0.949 for PCS; p=0.033, OR: 4.200, 95% CI: 0.063-0.893 for MCS), missed outpatient clinic appointment (p=0.025, OR: 2.397, 95% CI: 1.114-5.159 for PCS; p=0.017, OR: 3.407, 95% CI: 1.250-9.282 for MCS), depression (p=0.001, OR: 3.479, 95% CI: 1.612-7.508 for PCS. The risk on MCS could not be calculated), and anxiety (p=0.042, OR: 2.597 95% CI: 1.035-6.518 for PCS; p=0.001, OR: 6.745 95% CI: 2.153-21.124 for MCS) were factors linked to low PCS and MCS scores.

Table 6 summarizes the association between sociodemographic and clinical factors and PCS and MCS as indicated by the multivariate analysis.

Discussion

In our study, we noted significantly lower scores in all SF-36 subgroup scores (except BP) as well as PCS and MCS scores among the PLWH group participants compared to the healthy volunteers. The HRQoL scores among the PLWH group participants ranged from 60 (VT) to 100 (BP), indicating a general decrease in scores in all subgroups except for BP. This emphasizes the decrease in HRQoL resulting from HIV infection. Various studies have consistently documented similar negative effects of HIV on HRQoL^{[5, 6, 26, 32, 33]}. Similarly, studies in Turkey have discovered lower SF-36 subgroup scores in PLWH than in the general population^{[17, 18]}. Barger et al.^[34] reported that only ~63% of PLWH reported experiencing a good or very good QOL, although they attained the 90-90-90 UNAIDS target in the late 2010s. To summarize, even when viral suppression was achieved and immunity was good, PLWH experienced a poor HRQoL compared with the general population^{[5, 6]}. However, certain studies conducted in countries like the Netherlands, the United Kingdom, Romania, and Spain have reported higher HRQoL among PLWH, indicating that progress has been made in these regions^{[11, 12]}. This is a positive and prospective improvement; however, the HRQoL in many different territories remains low. Due to numerous potential factors, including higher income, easier access to medical facilities, as well as reduced stigma and unemployment concerns, it appears that it is more feasible to achieve a higher HRQoL in patients from developed countries.

Given the variability in HRQoL across various countries and societies, understanding the contributing factors is crucial for developing effective interventions for PLWH. In our study, multivariate analysis identified depression, anxiety, female sex, and missed outpatient clinic appointments as factors influencing both PCS and MCS in PLWH. Additionally, univariate analysis detected lipodystrophy, number of tablets, ART adverse effects, and the presence of depression and anxiety as variables associated with low PCS and MCS scores among PLWH.

We observed higher rates of depression (31.7%) and anxiety (22.1%) among PLWH compared to the control group, with both conditions strongly correlating with lower MCS and PCS scores, respectively. These findings are consistent with the existing literature, which emphasizes the importance of depression and anxiety as significant determinants of HRQoL in PLWH^{[11, 12, 35, 36]}. Popping et al.^[11] reported that anxiety and depression are primary contributors to lower HRQoL, noting a prevalence approximately twice as high among PLWH compared to the general population. Similarly, a collaborative study conducted by Kall et al.^[12] in Romania and Spain highlighted significantly elevated levels of anxiety and depression among PLWH compared to the general population. Anxiety was diagnosed in 25.7% of 307 PLWH in a web-based questionnaire study conducted in Turkey using BAS^[16]. In a study conducted in Turkey using the Hospital Anxiety and Depression Scale, anxiety was identified in 12.9% of the 217 PLWH, while depression was identified in 27.6% of the same group^[20]. Another study using the Hospital Anxiety and Depression Scale found depression in 56% and anxiety in 37% of PLWH^[21]. In our study, the prevalence rates of depression and anxiety among PLWH are in close agreement with the current literature. Although making precise comparisons is challenging, studies conducted from the 1990s on the present report elevated levels of depression and anxiety among PLWH^{[11, 12, 16, 37, 38]}.

However, the reported rates of these MH conditions are subject to significant variation across studies. This may be attributed to diverse factors, including variations in patient clinical profiles, access to treatment, environmental and social contexts, the use of diverse assessment scales for depression and anxiety, and discrepancies in scale scoring methods.

Despite significant advancements in HIV diagnosis and treatment, the persistently high prevalence of anxiety and depression highlights the critical confluence of HIV and psychiatric comorbidities. This emphasizes the ongoing necessity for comprehensive care strategies that encompass both the medical and psychological components of HIV management.

Our study revealed that the female gender was associated with worse PCS and MCS scores in PLWH. In various studies, female sex has been linked to lower HRQoL^{[35, 36, 39]}. It has been reported that there is no relationship between sex and HRQoL in PLWH^[40]. There is no consensus on the effect of sex on HRQoL^[41]. The influence of gender on HRQoL in PLWH remains debated and may differ depending on the social and cultural context.

In our study, missed outpatient clinic appointments were one of the factors associated with poor HRQoL. Optimizing adherence to treatment and improving health outcomes in PLWH necessitates consistent patient follow-up. It is essential to monitor ART adherence, prevent the progression of HIV infection, and identify complications at an early stage. Overall, consistent patient monitoring constitutes a cornerstone of HIV care, contributing substantially to the treatment efficacy and HRQoL in PLWH.

Rodriguez-Penney et al.^[42] used the Charlson index to evaluate the burden of comorbidities and discovered that it negatively affected physical QOL in PLWH. This is in agreement with the results of our research and those of other investigations^[34]. The comorbidities can reduce the quality of life due to the diminished physical capacity, multi-drug use, and related adverse effects.

Poorer HRQoL has been linked to low educational status in numerous studies, similar to our investigation^{[34, 43]}. Conversely, the level of education is not related to the quality of life, according to certain studies^{[12, 26]}. The influence of educational success on PLWH can be multifaceted. Education frequently influences employment opportunities, socioeconomic status, and the extent of one’s understanding of the disease. Higher education levels may improve an individual’s ability to manage HIV, enhance their knowledge about the disease, and consequently improve various domains of HRQoL.

In our study, smokers exhibited a lower QOL. This finding is corroborated by several other studies in the literature^{[34, 44-46]}. Although some studies have reported lower PCS among smokers due to the detrimental effects of smoking on physical health, our research specifically noted a decline in MCS scores^{[34, 46]}. Smoking has a detrimental impact on numerous organs, increases the risk of comorbidities, and diminishes physical capacity. Therefore, while low PCS can be expected, our study highlighted a notable impact on MCS. We hypothesize that smoking may be linked to the notion of coping with the social and psychological problems resulting from the disease.

Study Limitations

There were various limitations of our study. Our study was a single-center, cross-sectional study. The number of study participants was small. The HIV-specific quality of life scale was not employed to ascertain the quality of life. Additionally, the investigation did not address organic conditions, including anemia, hypothyroidism, and vitamin B12 deficiency, which may contribute to psychiatric symptoms, particularly depression.

Conclusion

Improving HRQoL in PLWH is one of the primary therapeutic endpoints. To achieve this goal, detecting factors influencing HRQoL and improving the negative factors should be among the principal objectives.