Adherence to antiretroviral therapy mediates the link between posttraumatic stress disorder symptoms and health-related quality of life

Abstract

Human immunodeficiency virus is one of the trauma-inducing chronic illnesses with attendant-negative impact on health-related quality of life. Substantial literature exists on the association of posttraumatic stress disorder symptoms and health-related quality of life among people living with human immunodeficiency virus, but little is known about the pathways explaining this link. This study therefore examined the mediating role of adherence to antiretroviral therapy in the association between posttraumatic stress disorder symptoms and health-related quality of life among people living with human immunodeficiency virus. Nine hundred and sixty-nine people living with human immunodeficiency virus in Nigeria who were on antiretroviral therapy completed measures of posttraumatic stress disorder symptoms, adherence to antiretroviral therapy, and health-related quality of life. Hayes PROCESS macro for SPSS was used to analyse the data. Adherence to antiretroviral therapy mediated the association between posttraumatic stress disorder symptoms and health-related quality of life in the relationship and treatment impact domains, implying that poor adherence to antiretroviral therapy is a pathway through which posttraumatic stress disorder symptoms exert negative influence on health-related quality of life of people living with human immunodeficiency virus. Interventions aimed at reducing the impact of posttraumatic stress disorder symptoms on quality of life of people living with human immunodeficiency virus should focus on improving clients’ level of adherence to antiretroviral therapy treatment.

Keywords

Adherence antiretroviral therapy health-related quality of life human immunodeficiency virus posttraumatic stress disorder trauma

A World Health Organization (2020) report revealed that more than 70% of the global index cases of human immunodeficiency virus (HIV) are recorded in Africa. This report also showed that there is higher death rate of people living with HIV (PLWH) (61% of death across the globe) in Africa than in other continents. Nigeria ranks second among countries with the largest burden of the disease globally, having about 10% of the global index cases and over 100,000 annual deaths (Joseph Afe et al., 2017; National Agency for the Control of AIDS [NACA], 2017; The Joint United Nations Programme on HIV and AIDS [UNAIDS], 2020). Studies have shown that PLWH have poorer health-related quality of life (HRQoL) than the general population (Lee et al., 2002; Miners et al., 2014). The situation may be worse for Nigeria as the country has a weak health care system arising from inefficiencies and corruption, which impact the quality of care the patients receive (see Onwujekwe et al., 2020). Improving HRQoL of PLWH calls for a holistic management approach (Chu & Selwyn, 2011) and is therefore a priority health concern.

HRQoL is a concept that refers to the subjective evaluation of the impact of a disease and its treatment on life functions of patients (Nilsson, 2012; Schipper et al., 1996). This subjective evaluation is important among people living with various chronic illnesses, such as HIV, because it helps policy makers, researchers, and practitioners to effectively allocate health management resources, monitor HIV progression, and evaluate treatment combinations (Reis et al., 2012; Wu, 2000). It is however important to recognise that the diagnosis of HIV and the consequential management can be a traumatic experience.

Diagnosis, treatment, and progression of chronic and life-threatening health conditions trigger posttraumatic stress disorder (PTSD) symptoms in patients (American Psychiatric Association [APA], 2013). PTSD symptoms include: intrusion (repeated, disturbing, and unwanted memories of the traumatic event), avoidance (avoiding memories, thoughts, or feelings related to the traumatic event), negative alterations in cognition or mood (having trouble remembering important parts of the traumatic event), and arousal/reactivity problems (irritable behaviours, angry outburst, or acting aggressively) (APA, 2013). PLWH have been widely reported to experience PTSD symptoms (Hays et al., 2000; Neigh et al., 2016; Tang et al., 2020). Some researchers, nonetheless refute that the nature of HIV-related distress qualifies as PTSD symptoms. For example, Kagee (2008) queried whether concerns and reactions triggered by HIV diagnosis merit being classified as PTSD symptoms, given that the concerns of PLWH are rather focusing on the future (example, possible death and stigma), unlike victims of other traumatic events whose concerns focus on past traumatic experiences. But Edmondson (2014) has argued that PTSD symptoms can emanate from either acute events that are external to the individual (for example, accident or war) or internal events that are within the individual (for example, life-threatening illnesses) such as HIV and cancer. Survivors of internal traumatic events (such as life-threatening illnesses) experience PTSD symptoms emanating also from the past (disease diagnosis), the present (struggle with the disease), and the future (death threat) (Moye & Rouse, 2014; Onu et al., 2020; Rzeszutek & Gruszczyńska, 2018).

Studies (example, Cohen et al., 2009; Haagsma et al., 2012; Luo et al., 2017; Nadim et al., 2012; Nightingale et al., 2011; Pence et al., 2012; Wintermann et al., 2019) have consistently found PTSD symptoms to be negatively associated with poor HRQoL among patients living with various chronic and trauma-inducing health conditions, including PLWH. However, little is known about the process by which PTSD symptoms are associated with poor HRQoL. Identifying behavioural mechanisms involved in the PTSD symptoms–HRQoL relationship among PLWH will help researchers go beyond explaining that PTSD symptoms are associated with HRQoL to reveal intermediate linkages between PTSD symptoms and HRQoL. Identifying intermediate linkages of the PTSD symptoms–HRQoL link may be helpful to practitioners in managing PLWH. Adherence to antiretroviral therapy (ART) treatment regimen may be one of such behavioural linkages, such that PTSD symptoms are associated with poor adherence to antiretroviral therapy (AtART) which is then linked to poor HRQoL. (See Figure 1 for the conceptual model of the mediation).

Figure 1.

Conceptual model showing the mediating role of adherence to antiretroviral therapy in the PTSD symptoms–HRQoL association.

Although the effectiveness of ART has significantly prolonged the lifespan of PLWH, patients must tolerate potential side effects associated with it (for example, rash, lipodystrophy, and neuropathy) and pill burden (number of ART to be taken per day) to experience improved HRQoL (Jia et al., 2007; Mannheimer et al., 2005). AtART is defined as the extent to which PLWH took their ART as prescribed. A systematic review by Spaan et al. (2018) indicated that about 40% PLWH do not sufficiently adhere to their treatment regimens which has adverse effects on their quality of life. Other studies (example, Alemu et al., 2013; Nyamathi et al., 2018; Onu et al., 2019; Suswani et al., 2018; Vagiri et al., 2018) have found increased AtART to be a strong positive correlate of HRQoL among PLWH. Frazier et al. (2004) observed that strong correlates or predictors of an outcome variable can be good mediators.

On the contrary, studies have found PTSD symptoms to be negatively related to AtART. For instance, Boarts et al. (2006) reported that PLWH who reported more PTSD symptoms were less likely to adhere to ART treatment regimen. Whetten et al. (2013) also found that PLWH who had a history of traumatic experiences and PTSD were less likely to adhere to ART treatment regimen. PTSD symptoms have also been linked to poor adherence to treatment regimen among people living with other health conditions such as rheumatoid arthritis (Subtirelu et al., 2017) and transient ischemic attacks (Kronish et al., 2012).

There is consistent evidence that among PLWH, PTSD symptoms are linked to poor HRQoL and that people who have PTSD symptoms adhere less to ART. In addition, there is evidence that adhering to ART is associated with improved HRQoL of PLWH. These patterns of associations appear to suggest that AtART may be helpful in explaining the PTSD symptoms–HRQoL link. Studies with focus on understanding the potential role of AtART in managing the link between PTSD symptoms and health functions of this vulnerable group would therefore be worthwhile. This justify the need for this study. Among type-2 diabetes patients, Li et al. (2017) reported that adherence to medication mediated the relationship between personality type and health outcome. It is therefore hypothesised that:

Hypothesis 1: PTSD symptoms will be negatively associated with HRQoL.

Hypothesis 2: PTSD symptoms will be negatively associated with AtART.

Hypothesis 3: AtART will be positively associated with HRQoL.

Hypothesis 4: ATART will mediate the relationship between PTSD symptoms and HRQoL (See Figure 1).

Method

Participants

Participants were 969 PLWH (628 males and 341 females) conveniently drawn from four public hospitals in the South Eastern region of Nigeria. With 5% margin of error and HIV prevalence of 1.4% in Nigeria (NACA, 2017), the minimum sample size recommended was 385 PLWH (http://www.raosoft.com/samplesize.html), making the current sample size adequate for this study. All participants had at least completed secondary school education, which meant they could read and understand English. Participants were on ART for at least 6 months. The majority of them (86%) were Christians, 7.4% were of African Traditional Religion, while 6.6% were of Islamic religion (see Table 1 for participants’ demographic characteristics).

Table1.

Showing participants characteristics.

Gender	Male	628 (64.8)
Gender	Female	341 (35.5)
Education	Secondary to ND	664 (68.5)
Education	HND to PhD	305 (31.5)
Religion	Christianity	833 (86.0)
	Islam	64 (6.6)
	Others	72 (7.4)
Marital status	Single	687 (70.9)
	Married	200 (20.6)
	Widow/widower	18 (1.8)
	Separated	64 (6.6)
Occupation	Public/civil servant	290 (29.9)
	Self-employed	501 (52.7)
	Student	118 (12.2)
	Unemployed	50 (5.2)

Education = level of education; ND = national diploma; HND = highest national diploma.

Instruments

PTSD symptoms were assessed using the PTSD Checklist for Diagnostic and Statistical Manual of Mental Disorders (5th ed.; DSM-5; APA, 2013) (PCL-5; Weathers et al., 2013). It is a 20-item, four-domain instrument developed to assess PTSD symptoms. Items on the PCL-5 correspond with DSM-5 (APA, 2013) criteria for PTSD namely: intrusion, avoidance, negative alterations in cognition or mood, arousal, and reactivity. Focusing on their health condition, respondents were asked to rate the extent to which they were worried by traumatic experiences in the past 1 month on a 5-point Likert-type scale ranging from 0 (not at all) to 4 (extremely). Total scores ranged between 0 and 80, with higher scores indicating more severe PTSD symptoms severity. The developers reported Cronbach’s α of .94, while a previous study in Nigeria reported a Cronbach’s α of .93 (Abiama, 2018). In this study, PCL-5 yielded a minimum of .80 alpha reliability coefficient across subscales and a full-scale alpha reliability of .85. Developers recommended the use of either total scale scores to indicate total symptoms severity or the use of subscale scores to indicate the extent of severity in each of the symptom clusters. PCL-5 total scale scores was used to ascertain PTSD symptoms in this study.

AtART was assessed using the Morisky Medical Adherence Scale (MMAS; Morisky et al., 2008). MMAS is an 8-item instrument developed to assess the extent to which a client adheres to professional medical advice. Most items require yes/no response except the eighth item that is rated on a Likert-type format, with the score range of 0 to 8. MMAS scores lower than 6 reflects low AtART, while a score of 6 and above reflect moderate to high AtART. The developers reported a Cronbach’s α of .83. MMAS yielded a Cronbach’s α reliability of .80 in this study.

HRQoL was assessed using the 38-item patient-reported outcome quality of life—HIV (PROQOL-HIV) (Lalanne et al., 2016). It has four subscales as follows: (a) physical health symptoms (PHS), which focuses on patients’ ability to engage in physical activities; (b) relationship health (REL), which measures the extent of patients’ relationship with others; (c) cognitive health symptoms (COG), which examines level of health concern and mental distress (anxiety and depression) of patients; and (d) treatment impact (TRT), which assesses the side effect of ART on patients. Items on the PROQOL-HIV are rated on a 5-point Likert-type scale format ranging from never = 0 to always = 4. A higher score indicates better HRQoL. Lalanne et al. (2016) reported a minimum reliability coefficient of .79 across all domains. PROQOL-HIV has been found to be reliable and valid in previous studies conducted among PLWH in Nigeria (See Onu et al., 2019, 2020). Cronbach’s α of the PROQoL-HIV subscales in this study were as follows: .80 (PHS), .80 (REL), .91 (COG), and (TRT) .81.

Procedure

Data were collected in a questionnaire format with the help of three research assistants (nurses) from each of the four hospitals. Between February and October 2019, PLWH who volunteered to participate in the study and could read and understand English language were invited during clinic hours, upon signing an informed consent form, to respond to the study questionnaires. They responded in the outpatients’ clinic while waiting to see their doctors (response rate = 92.32%). Participants’ medical records were also consulted to ascertain their CD4 count and also verify other demographic information as reported in the questionnaires.

Ethical considerations

The ethical research committee of the Federal Teaching Hospital, Abakiliki, Ebonyi State (FTHA/REC/VOL2/2019/158) approved this study. The purpose of the study was explained to participants and those who consented to participate completed the survey forms. Participants were assured of confidentiality. They were also informed of their freedom to withdraw from the study at any point.

Data analysis

Bivariate correlation was first conducted among the study variables, including the demographics and traditional risk factors (CD4 count and comorbidity of other health conditions). Second Model 4 of Hayes (2018) regression-based PROCESS macro version 3.0 for SPSS was used to estimate the path coefficients in the mediator model and generate bias-corrected bootstrapped confidence intervals (CIs) for total and specific indirect effects (IEs) of PTSD symptoms on HRQoL via AtART. PROCESS macro has become a very useful tool in tests of mediation hypotheses as demonstrated in previous research (for example, Onu et al., 2020; Ugwu et al., 2020).

Results

Details of demographic characteristics of the participants are shown in Table 1. In Table 2, correlation results showed that CD4 count was positively associated with PHS, REL, and TRT domains of HRQoL. Age was positively associated with PHS and REL domains. Gender was negatively associated with PHS and REL. Gender was positively associated with COG. Comorbidity of other diseases was positively associated with HRQoL across domains except COG. PTSD symptoms were negatively associated with HRQoL across domains. PTSD symptoms were negatively associated with AtART. AtART was positively associated with HRQoL across domains.

Table 2.

Correlation of demographics and study variables.

Variables		1	2	3	4	5	6	7	8	9	10
1	CD4	—
2	Length of illness	.31***	—
3	Age	−.28***	−.50***	—
4	Gender	.03	.03	−.31***	—
5	Comorbidity	.15***	.31***	−.61***	−.18***	—
6	PTSD	−.12***	−.12***	.11	−.11**	−.12***	—
7	AtART	.11**	.34***	−.21***	−.01	.10*	−.30***	—
8	PHS	.30***	.36***	−.35***	−.03	.44***	−.32***	.15***	—
9	REL	.21***	.17***	−.23***	−.10	.17***	−.51***	.24***	.53***	—
10	COG	.02	−.15	.12***	−.20***	.03	−.42***	.11**	.24***	.62***
11	TRT	.12***	.01	.02	−.11**	.12***	−.40***	.30***	.17***	.41***	.45***

CD4 below 200 (coded 0); CD4 above 200 (coded 1); gender = male (Coded 0); female (coded1); PTSD = posttraumatic stress disorder symptoms; AtART = adherence to antiretroviral therapy; PHS = physical health symptoms domain of health-related quality of life; REL = relationship health symptoms domain of health-related quality; COG = cognitive health symptoms domain of health-related quality of life; TRT = treatment impact domain of health-related quality of life.

p < .05. **p < .01. ***p < .001.

Table 3 shows the mediating influences of AtART on the domains of HRQoL after controlling for demographic variables and risk factors (CD4 count, length of illness, age, gender, and cormobidity of other diseases). Total effects (TEs) indicate the influence of PTSD symptoms on each domain of HRQoL when the mediator (AtART) was not included. Direct effects (DEs) show the effect of PTSD symptoms on each dimension of HRQoL when AtART is held constant in the model. Indirect effects (IE; the most important part of mediation analysis; Field, 2018) indicate the contributions of AtART in the associations between PTSD symptoms and the domains of HRQoL (i.e., effects achieved through the mediation pathways). Mediation is said to have occurred (at the point of IE) when the upper and lower CIs of the IE coefficients are in the same direction (the CIs’ coefficients did not include zero [0]; Field, 2018). In Table 3, it can be seen that the CIs of the IE of AtART on the association between PTSD symptoms and PHS domain of HRQoL (IE = −.070; effect size = .278; CIs = [−.023, −.221]) were all negative. The CIs of the IE of AtART on the association between PTSD symptoms and REL domain of HRQoL (IE = −.047; effect size = .341; CIs = [−.065, −.031]) were all negative. Again, the CIs of the IE of AtART on the association between PTSD symptoms and COG domain of HRQoL (IE = −.014; effect size = .209; CIs = [−.003, −.001]) were all negative. It was also found that CIs of the IE of AtART on the association between PTSD symptoms and TRT domain of HRQoL (IE = −.054; effect size = .201; CIs = [−.074, −.035]) were all negative. These showed that there were mediations (Field, 2018) across all domains of HRQoL. AtART therefore mediated the association between PTSD symptoms and HRQoL.

Table 3.

Summary of mediating influence of ATART on the four domains of HRQoL.

Type of effect		Coeff.	SE	t	BCa 95% CI [LLCI, ULCI]
PHS as the DV
Total effect	PTSD→PHS	−.291	.001	−10.148**	−.006, −.004
R ² M,X		.224			−.031, −.291
Direct effect	PTSD→PHS	−.221	.001	−7.634**	−.005, −.003
R ² Y,X		.142			−.090, −.051
Indirect Effect	PTSD→ATART→PHS	−.070	.001		−.090, 0.14
R ² Y,MX		.278			−.023, −.221
REL as the DV
Total effect	PTSD→REL	−.480	.001	−17.830**	−.009, −.007
R ² M,X		.317			−.051, −.480
Direct effect	PTSD→REL	−.432	.001	−15.669**	−.010, −.008
R ² Y,X		.142			−.065, −.031
Indirect Effect	PTSD→ATART→REL	−.047	.001		−.065, −.031
R ² Y,MX		.341			−.046, −.432
COG as the DV
Total effect	PTSD→COG	−.421	.001	−13.917**	−.009, −.007
R ² M,X		.206			−.043, −.408
Direct effect	PTSD→COG	−.408	.001	−13.997**	−.009, −.007
R ² Y,X		.133			−.003, .031
Indirect Effect	PTSD→ATART→COG	.014	.001		−.003, −.001
R ² Y,MX		.209			−.037, −.344
TRT as the DV
Total effect	PTSD→TRT	−.398	.001	−13.416**	−.006, −.005
R ² M,X		.169			−.042, −.398
Direct effect	PTSD→TRT	−.344	.001	−11.329**	−.006, −.004
R ² Y,X		.142			−.073, −.034
Indirect Effect	PTSD→AtART→TRT	−.054	.001		−.074, −.035
R ² Y,MX		.201			−.037, −.344

Coeff. = coefficient; SE = standard error; BCa CI = bias-corrected and accelerated confidence interval; LLCI = lower-level confidence interval; ULCI = upper-level confidence interval; PHS = physical health symptoms domain of health-related quality of life; DV = dependent variable; PTSD = posttraumatic stress disorder symptoms; R²_M,X is the proportion of variance in M explained by X; R²_Y,X is the proportion of variance in Y explained by X; AtART = adherence to antiretroviral therapy; R²_Y,MX is the proportion of variance in Y explained by X and M; REL = relationship health symptoms domain of health-related quality; COG = cognitive health symptoms domain of health-related quality of life; TRT = treatment impact domain of health-related quality of life; HRQoL = health-related quality of life.

p < .001

Discussion

The major aim of this study was to investigate whether AtART mediates the association between PTSD symptoms and HRQoL among PLWH. It was found that high PTSD symptoms was associated with experiencing poor HRQoL across all domains. AtART mediated the association between PTSD symptoms and HRQoL in all domains. This suggests that AtART is a pathway through which PTSD symptoms are associated with experiencing poor HRQoL among PLWH. Li et al. (2017) had also reported that AtART mediated the association between personality type and health outcome indicator. This study has contributed in filling the existing gap in the literature vis-a-vis the pathway linking PTSD symptoms and HRQoL. PLWH who experienced high PTSD symptoms following their diagnosis, treatment, and disease progression were more likely to experience poor HRQoL. This finding agrees with Luo et al. (2017), Nightingale et al. (2011), and Pence et al. (2012) who reported similar findings across samples of PLWH. Therefore, the more the PLWH experienced negative mental health aftermath of trauma, the more their HRQoL worsens. Thus, increased experience of PTSD symptoms by PLWH seems to worsen patients’ overall health condition.

Also, poor AtART contributes in worsening the impacts of PTSD symptoms on the HRQoL of PLWH. This is in keeping with other studies (eg. Boarts et al., 2006; Whetten et al., 2013) which found that the more PLWH experienced PTSD symptoms, the less likely they were to adhere to ART treatment regimens. This is also in agreement with other studies (eg. Alemu et al., 2013; Nyamathi et al., 2018; Onu et al., 2019; Suswani et al., 2018; Vagiri et al., 2018) reporting that high AtART was positively associated with improved HRQoL among PLWH. This study therefore suggests that AtART is an important explanatory link through which one can better understand how PTSD symptoms are associated with poor health and well-being in PLWH. This implies that PTSD symptoms are associated with poor AtART treatment regimen among PLWH which then explains the poor HRQoL they experienced. In predicting client’s level of health and well-being through his or her level of PTSD symptoms, there is a need to evaluate the client’s level of AtART treatment regimen. The findings of this study suggest that, in order to improve the health of PLWH, health practitioners and policy-makers need to be aware that efforts to encourage adherence to treatment is important. Client’s education and counselling aimed at ensuring proper AtART are important in efforts aimed at ameliorating the impact of PTSD symptoms on HRQoL. Joseph Afe et al. (2017) have noted the importance of adherence in ensuring success of retroviral therapy among PLWH in Nigeria. This is especially important, given that Nigeria is one of the countries where the poor health care system and other factors (such as stigma) seem to precipitate PTSD symptoms among PLWH (Onu et al., 2019; Onwujekwe et al., 2020).

The cross-sectional design of this study is a major limitation. This prevents making causal inferences. Longitudinal studies would help in reaching more definitive conclusions about causality (Onu et al., 2019). Other factors that may be helpful in explaining the PTSD symptoms-HRQoL link, such as posttraumatic growth were not considered in this study. Future studies may take into account other variables to build more robust models in understanding HRQoL among PLWH. Despite these limitations, this study demonstrated that AtART could explain the link through which PTSD symptoms exert negative impact on the health of PLWH.

Conclusion

This study investigated the mediating influence of ATART on the relationship between PTSD symptoms and HRQoL among PLWH. The findings of this study underscore PTSD symptoms as complex phenomena that impact the health of PLWH through a complex mechanism of processes, which include poor ART adherence. The results therefore highlighted the importance of AtART regimen among PLWH to achieve optimal health functioning despite the chronicity of their health condition. Health practitioners involved in rendering services to PLWH could be more sensitive to the level of ART adherence being maintained by client, recognising that the client’s degree of AtART could substantially influence their overall health functions. Clinicians should therefore be aware that poor AtART tends to contribute in conveying the negative impacts of PTSD on the health of PLWH. Results of this study suggest that PTSD symptoms arising from the adverse experiences associated with HIV may worsen the well-being of PLWH, especially those who do not observe maximum adherence to their treatment regimen.

Footnotes

Declaration of conflicting interests

The author(s) declared no potential conflicts of interest with respect to the research, authorship, and/or publication of this article.

Funding

The author(s) received no financial support for the research, authorship, and/or publication of this article.

ORCID iD

Desmond Uchechukwu Onu

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