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AMEABRA International Virtual Conference on Environment-Bahaviour Studies, 1stSeries
cE-Bs, FSPU, Universiti Teknologi MARA, Shah Alam, 24-25 Jun 2020

Factors Contributing to Depressive Disorder among

Patients with Retroviral Disease

Nor Hidayah Jaris1, Suresh Kumar Chidambaram2, Mohd Razali Salleh1, Salmi Razali1,3
1 Departmentof Psychiatry, Faculty of Medicine, Universiti Teknologi MARA, Malaysia
2 Department of Medicine, 3Institute of Pathology, Laboratory and Forensic Medicine (I-PPerForM)
Universiti Teknologi MARA, 47000 Sungai Buloh, Selangor, Malaysia
[email protected], [email protected], [email protected], [email protected]
Tel.: +603-61265000

Abstract
Major depressive disorder (MDD) increases further morbidity and mortality of patients with retroviral disease (RVD) or human immunodeficiency virus
(HIV) infection. This study aimed to determine the prevalence of MDD and its contributing factors among them. Depressive symptoms were screened
using the Hospital Anxiety Depression Scale (HADS), and MDD was diagnosed with the Mini International Neuropsychiatric Interview (MINI). Of the
total 210 RVD patients, 27(12.9%) had MDD. The contributing factors for MDD include amphetamine-type stimulants use, social support system, and
CD4 count. Interventions for RVD patients should include counselling for those abusing drugs, increasing support system and adherence to treatment.

Keywords: Retroviral Disease, Human Immunodeficiency Virus, Depression, Support system

eISSN: 2398-4287© 2020. The Authors. Published for AMER ABRA cE-Bs by e-International Publishing House, Ltd., UK. This is an open access article under the CC
BYNC-ND license (http://creativecommons.org/licenses/by-nc-nd/4.0/). Peer–review under responsibility of AMER (Association of Malaysian Environment-Behaviour
Researchers), ABRA (Association of Behavioural Researchers on Asians) and cE-Bs (Centre for Environment-Behaviour Studies), Faculty of Architecture, Planning &
Surveying, Universiti Teknologi MARA, Malaysia.
DOI: https://doi.org/10.21834/ebpj.v5i14.2336

1.0 Introduction
Major depressive disorder (MDD) is a disease of a mind manifested with symptoms of feeling depressed, lack of appetite, weight
reduction, sleep difficulties, feeling hopeless, useless, excessive guilt feelings and having negative thoughts as outlined by the
Diagnostic and Statistical Manual of Mental Disorders Fifth Edition (DSM-5). MDD among patients with the retroviral disease (RVD) or
human immunodeficiency virus (HIV) infection is prevalent. To date, 39% of them have been identified to have depression (Tran et al.,
2019). MDD is a debilitating mental illness that may increase further morbidity and mortality of RVD patients (Todd et al., 2017). RVD
patients with MDD have poor adherence to Highly Active Antiretroviral Therapy (HAART) (Tull, Berghoff, Bardeen, Schoenleber, &
Konkle-Parker, 2018) increasing their susceptibility for symptoms of Acquired immunodeficiency syndrome (AIDS) and other
complications. Moreover, MDD also predispose RVD patients to devastating psychological complications such as psychosis, early
dementia and suicide (Tyree, Vaida, Zisook, Mathews, & Grelotti, 2019). Given significant negative consequences of depression among
RVD patients, it is crucial that this mental illness to be detected and treated early so that RVD patients are able to have the optimum
quality of life while experiencing various challenges having this stigmatising illness.

eISSN: 2398-4287© 2020. The Authors. Published for AMER ABRA cE-Bs by e-International Publishing House, Ltd., UK. This is an open access article under the CC
BYNC-ND license (http://creativecommons.org/licenses/by-nc-nd/4.0/). Peer–review under responsibility of AMER (Association of Malaysian Environment-Behaviour
Researchers), ABRA (Association of Behavioural Researchers on Asians) and cE-Bs (Centre for Environment-Behaviour Studies), Faculty of Architecture, Planning &
Surveying, Universiti Teknologi MARA, Malaysia.
DOI: https://doi.org/10.21834/ebpj.v5i14.2336
 Jaris, N.H., et.al. / AIVCE-BS-1, 2020ShahAlam, cE-Bs, FSPU, Universiti Teknologi MARA, Shah Alam, Malaysia, 24-25 Jun 2020/ E-BPJ, 5(14), Jul 2020 (pp.83-89)

2.0 Literature review

Feeling depressed comes in a spectrum from normal sadness to feeling low because of a stressful event, and to severe depression
which occurs as part of the manifestation of mental illness. Mental health professionals only considered those who have feelings of
depression as a ‘case’ of MDD when patients fulfilled the criteria of depression in DSM-5. RVD or HIV infections attack the immune
system and weakens the mechanisms of defence against diseases and other forms of cancer in people. Infected individuals slowly
become immunodeficient as the virus kills and impairs the role of the immune cells. Usually, immune activity is calculated by the count
of cells CD4 (Word Health Organization (WHO), 2019). Co-morbidity of MDD or depression among RVD patients is prevalent. Previous
researchers have suggested several factors that may contribute to depression among RVD patients. In terms of sociodemographic
factors, it has been shown that younger RVD patients have a higher tendency for MDD (Deshmukh, Borkar, & Deshmukh, 2017). Female
RVD patients may have a higher risk to develop depression in comparison to men (Ngum, Fon, Ngu, Verla, & Luma, 2017). Other crucial
contributing factors for depression were low educational level, unemployment and marital status of being a widow or widower and not
living with a spouse (Zeng et al., 2019).
Clinically, an important parameter that indicates the strength of the immune system, i.e. CD4 count is a crucial predictor for
depression in RVD patients. Scientists indicated that the level of CD4 count of less than 200 cells/ul might lead to depression among
RVD patients (Tesfaye & Bune, 2014). Moreover, the number of HIV viral particles or viral load has also been documented as one of
the essential predictors for depression (Radzniwan et al., 2016). Another factor which is vital to increase their risk for depression is
concomitant drug misuse. A cohort study conducted in AIDS Centre in the United States found that the use of amphetamine within three
months by the RVD patients led to significant depressive symptoms while the use of cannabis alone increased risk of depression
(Mimiaga et al., 2013).
Acting in concert with sociodemographic and clinical factors in predisposing RVD patients to depression is the social support
system. Patients with RVD experience challenges in career and relationship that may increase the vulnerability to develop depression
and affecting their daily activities (Tuan Abdullah et al., 2019). Thus, having good support was found to be an essential coping
mechanism for adjustment and act as a buffer towards stress in mental and physical health (Hostinar & Gunnar, 2015). Positive social
support lowered the risk of getting depression and in contrast, less support associated with a higher score of depressive symptoms
(Fawzi et al., 2012; Seffren et al., 2018).
While substantial studies have been carried out to investigate contributing factors for depression among RVD patients, there are
still gaps of knowledge that need to be fulfilled to inform effective intervention of RVD. Given the feelings of sadness or depression is
very subjective, accurate diagnosis, i.e. Major depressive disorder or MDD is crucial so that correct treatment can be offered. Many
previous researchers have evaluated depression among RVD patients by screening for the illness only, but yet to diagnose this mental
illness properly. Hence, the findings of those studies only informed the results of ‘caseness’, not the ‘case’ of depression (Østergaard
et al., 2010). Furthermore, locally, there is sparse of data and research investigating illicit substance use and social support system
among RVD patients. Previous studies in Malaysia found that female gender, financial support and alcohol consumption were the
factors that contribute to common psychological disorders in patients with HIV (Yee et al., 2009). Shane and Koh’s research
postulated an association between CD4 counts and Hepatitis B co-infection with depression (Shane et al., 2010). A high perceived
social support was identified by Terence et al. to lower the risk of depressive disorder among this vulnerable group (Terence et al.,
2017). Thus, this study aimed to determine the prevalence of the diagnosis of Major depressive disorder (MDD) among RVD patients
and investigate its contributing factors including the sociodemographic factors, clinical factors, adherence to treatment as well as the
level of support by family, friends and significant others given to RVD patients.

3.0 Methodology

3.1 Study design, setting and data collection

This was a cross-sectional study to determine the prevalence of the Major depressive disorder (MDD) among RVD patients receiving
Highly Active Antiretroviral Therapy (HAART) and its associated factors. It was carried out in the Infectious Disease Clinic, Hospital
Sungai Buloh is one of the public hospitals in Selangor, which provides specialised treatment for infectious disease in Malaysia. It is
tertiary and a reference for infectious disease cases from the north region of Selangor. There were about 1000 patients receiving HAART
in a month attending this infectious disease clinic.

3.2 Data collection and assessment tools

Participants were selected using systematic random sampling. The inclusion criteria include RVD patients aged 18 years old and above,
attending an outpatient clinic and receiving HAART, was able to communicate in English or Bahasa Malaysia. Those who had been
diagnosed with severe mental illness and had underlying malignancy were excluded from the study. Only RVD patients who gave
informed consent voluntarily without coercion were enrolled in the study.
The feelings of depression were screened with the Hospital Anxiety Depression Scale (HADS)(Yahya & Othman, 2015). The
participants who scored eight and above for HADS was ‘caseness’ of depression and considered as ‘probable depression’. This group
of participants were interviewed further using the Mini International Neuropsychiatric Interview (MINI) to confirm the ‘case’ of MDD. The
MINI has been used worldwide and validated locally as a structured diagnostic interview instrument. It follows the criteria of the
Diagnostic and Statistical Manual of Mental Disorders Fifth Edition (DSM-5)(Mukhtar et al., 2012). Sociodemographic characteristics
(including age, gender, ethnicity, level of education, employment status, occupation, total household income, marital status and living
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companion) and clinical factors (including viral load, CD4 count, adherence to medication, treatment regime, side effects of medications,
co-morbid substance and duration of illness) were assessed directly from face-to-face interviews with the RVD patients or retrieval of
medical records from the hospital electronic record system. Furthermore, the visual analogue scale (VAS) and the Multidimensional
Scale of Perceived Social Support (MSPSS) were used to measure adherence to treatment and level of social support from family,
friends and significant others) respectively.

3.3 Statistical Analysis

Data were analysed using the Statistical Package for the Social Sciences (SPSS) version 23. The factors associated with MDD among
RVD patients were analysed with simple logistic regression (SLogR) followed by multiple logistic regression (MLogR) as the data
consisted of categorical variables. The sociodemographic factors, clinical factors, adherence to treatment and level of supports from
family, friends and significant others were the independent variables entered into the SLogR. Variables with a p-value of less than 0.05
from the SLogR were then included in the MLogR analysis. A p-value of less than 0.05 was considered statistically significant in the
MLogR. Model fitness was checked using Hosmer-Lemeshow goodness of fit test. Confounders were adjusted; interactions,
multicollinearity and assumptions were also checked. The p-value of less than 0.05 with a confidence interval of 95% was taken as
statistically significant.

3.4 Ethics
Ethical approval was obtained from the Medical and Research Ethics Committee of National Clinical Research Center (CRC) Ministry
of Health, Medical and Research Ethics Committee (Protocol no NMRR-18-3891-44221), Faculty of Medicine Universiti Teknologi
MARA Research Committee, Medical and Research Ethics Committee, Universiti Teknologi MARA, 600-IRMI 5/1/6, REC/47/19
Medical and Research Ethics Committee of the Clinical Research Center (CRC) of the respective hospital prior to commencing the
study.

4.0 Findings

4.1 Background of participants

Of the total 210 participants, the mean age of the participants was 29.72 ± 9.98 years and more than three-quarter of the participants
were male (186; 88.6%). More than a half of the participants (116; 55.2%) were Malay, and others were Chinese (71; 33.8%), Indian
(21; 10%) and others (2; 1%). Most of the participants received tertiary education (113; 53.8%) and completed secondary school (86;
41%). Less than 10% went to primary school only (11; 5.2%). Among the participants, 134 were employed, and 16(7.6%) were
unemployed. More than half of participants (134; 63.8%) were in Bottom 40 group (B40) with total household income less than RM 3860,
less than one-third (45; 21.4%) were in the Middle 40 group (M40) with household income between RM 3860 and RM 8319 and others
(31; 14.8%) were in the Top 20 group (T20) with the income of more than RM 8319. They were mostly single (134; 63.8%) and others
had a spouse (76; 36.8%) (Table 1).

4.2 Prevalence of Major depressive disorder

There were 47 (22%) probable depression, and among these 27 participants were established to have MDD. Figure 1 shows the different
level of severity with 31 (14.8%) of RVD patients had mild depression, 14 (6.7%) had moderate, and 2(1%) had a severe level of
depression.

14.8%

6.7%

1.0%

Mild Moderate Severe

Fig 1: Severity of Depression in Patients with Retroviral Disease

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4.3 Sociodemographic factors and Major Depressive Disorder

There was no variable of sociodemographic characteristics that had a statistically significant association with MDD among RVD patients
receiving HAART. However, an almost significant result was found for marital status; more than half of the RVD (89%) were single and
less than 50% of them were living alone. Refer Table 1 for further information.

4.4 Contributing factors to Major Depressive Disorder

The significant associations between independent variables and MDD among RVD patients analysed using SLogR include
amphetamine-type stimulant (ATS) use for the past three months, history of taking an illicit substance, receiving low to moderate support
from family, friends, and significant others, and overall support, CD4 counts (≥ 350 cells/ul), side effects of medications and viral load
(≥ 20 copies/ml)(Table 2). Multiple logistic regression (MLogR) indicated the four significant predictors for MDD among RVD patients
including ATS use for the past three months, receiving low to moderate support from family and significant others, and level of CD4
counts (≥ 350 cells/ul). The use of ATS for the past three months markedly increased the odds of having MDD by 40.23 times (AOR=
40.23; p=0.01; 95% CI=3.61-447.86). RVD patients who received only low to moderate social support from family and significant others
had about 5.65 and 4.36 odds of having RVD (AOR= 5.65; p=0.01; 95% CI=1.43-22.38 and AOR=4.36; p=0.02; 95% CI=1.22-15.64)
respectively. Furthermore, having the level of CD4 count of more than 350 cells/ul protected RVD patients from MDD (AOR=0.31;
p=0.03; 95% CI= 0.11-0.86). The Omnibus test for model coefficient showed that the model was significant (X2 (5) = 46.08; p<0.001;
the Nagelkerke R2=0.368; Cox & Snell R2=0.197) and the predictive accuracy of the model for the training sample was 85.10%. There
was no multicollinearity exist between independent variables; the values for tolerance were more than 0.1, and VIF was less than 10 for
each variable.

Table 1. Background Socio-demography of Patients with RVD and Major Depressive Disorder
Sociodemographic Major depressive disorder
Factors No (n=183) Yes(n=27) B p-value OR (95% CI)
Age
<45 years old 125(68.3%) 21(77.8%) 0.49 0.32 1.62(0.62-4.23)
≥45 years old 58(31.7%) 6(22.2%)
Gender
Male 160(87.4%) 26(96.3%) -1.32 0.21 3.737(0.48-28.88)
Female 23(12.6%) 1(3.7%)
Ethnicity
Malay 98(53.6%) 18(66.7%) 0.55 0.21 1.74(0.74-4.06)
Non-Malay 85(46.4%) 9(33.3%)
Religion
Islam 102(55.7%) 18(66.7%) 0.46 0.29 1.59(0.68-3.72)
Others 81(44.3%) 9(33.3%)
Education
Primary school 8(4.4%) 3(11.1%) 1.01 0.16 2.73(0.68-11.02)
Secondary to tertiary 175 (95.6%) 24 (88.9%)
Employment
Employed 161(87.0%) 22(81.5%) -0.51 0.35 0.60(0.20-1.75)
Unemployed 22(12.0%) 5(18.5%)
Total Household income
B40 & M40 154(84.2%) 25(92.6%) 0.86 0.26 2.35(0.53-10.49)
T20 29(15.8%) 2(7.4%)
Marital Status
Single/ Widow/Separated/Divorce 128(69.9%) 24(88.9%) 1.24 0.05 3.44(0.99-11.89)
Married 55(30.1%) 3(11.1%)
Living companion
With companion 142(77.6%) 19(70.4%) -0.38 0.41 0.69(0.28-1.68)
Alone 41(22.4%) 8(29.6%)
The Bottom 40 group (B40) = total household income less than RM 3860; the Middle 40 group (M40) = total household income between RM 3860 and RM
8319; the Top 20 group (T20) = total household income of more than RM 8319. Univariate analysis used simple logistic regression; B-beta value; p value;
OR-Odds Ratio; CI-confidence interval; *significant p value <0.05; **significant p value <0.01

Table 2. Multiple Logistic Regression of Factors Associated with Major Depressive Disorder
Variables Simple Logistic Regressions Multiple Logistic Regressions
B(df) p-value ORa 95% CI B(df) p-value AORb 95% CI

ATS use for the past three months 3.13(1) 0.008 22.75 2.27 227.56 5.16(1) 0.001* 40.23 3.61 447.86
LMSS from family 2.07(1) 0.000 7.92 2.63 23.83 1.73(1) 0.01* 5.65 1.43 22.38
LMSS from significant others 1.94(1) 0.000 6.94 2.51 19.16 1.47(1) 0.02* 4.36 1.22 15.64
CD4 counts ≥ 350 cells/ul -1.26(1) 0.003 0.28 0.12 0.65 -1.19(1) 0.03* 0.31 0.11 0.86
Side effects of medications 1.61(1) 0.002 4.99 1.76 14.12 1.10(1) 0.09 3.03 0.86 10.57
LMSS overall 1.53(1) 0.002 4.61 1.78 11.95 0.49(1) 0.59 1.63 0.27 9.91
Viral load ≥ 20 copies/ml 1.42(1) 0.001 4.15 1.74 9.94 1.10(1) 0.59 3.01 0.96 9.49
History of taking illicit substance 0.89(1) 0.04 2.45 1.01 5.96 0.34(1) 0.63 1.36 0.39 4.62
LMSS from friends 1.02(1) 0.03 2.78 1.07 7.21 0.32(1) 0.70 1.38 0.26 7.19
aSimple logistic regression; bMultiple logistic regression; B=beta value; CI=confidence interval; df- degree of freedom; AOR=adjusted odds ratio; OR=Odds Ratio;

*significant p value <0.05; **significant p value <0.01; ATS=Amphetamine-type stimulant; LMSS=Low and moderate social support

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5.0 Discussion
The main contributing factors of MDD are the use of ATS for the past three months, the low and moderate social support from family
and significant others as well as a CD4 count less than 350 cells/ul. ATS drugs include amphetamine, methamphetamine and ecstasy
or 3,4-methylenedioxyethylamphetamine (MDMA) (Massaro et al., 2017). The ATS recent use increases about 40-fold of chances for
RVD patients to get MDD. Researchers indicated that ATS directly damages the brain, suppresses the immune system and increases
cytokine levels of RVD patients (Schuster & Gonzalez, 2012). Its neurotoxicity increases the risk of depression among the RVD
patients (Zeng et al., 2018). Furthermore, abstinent from ATS among those who had already dependent on this drug can manifest with
symptoms of MDD, including a dysphoric state and low motivation (Amiri et al., 2016). In view of that, the awareness of the
consequences of taking illicit substances must be emphasised continuously as well as the encouragement of living a healthy lifestyle
without drugs.
Our study indicated the importance of the support system in particular, support from family and other significant people in the life of
RVD patients. The complimentary messages and perceptions from the family could reduce the rumination of hopelessness and improve
self-esteem in continuing the treatment among patients with chronic illness (Pernice-Duca, 2010). The patients with RVD face multiple
challenges in their life, including career, relationship with family and others. An individual needs support from family as a source of
security, acceptance and worthiness; hence this group of patients feel fear of rejection and being labelled by the family members (Tuan
Abdullah et al., 2019). Therefore, lack of rejection and adequate support from the family could lessen the pessimism and encourage
RVD patients to cope well with the stress as well as reduce the risk of having psychological disorder which leads to proper treatment
adherence (Dejman et al., 2015). Higher perceived social support from family, especially emotional or informational, reduce the risk of
having depression among RVD patients (Matsumoto et al., 2017). The significant others are one's closest and most trusted individual
that could be mothers, fathers, relatives and friends (Cheng & Starks, 2002). RVD is a manageable chronic disease exposed to
numerous psychosocial challenges. Thus, RVD patients need countless support from others, especially the close one. It starts from the
first moment when they received the bad news informing that they are infected by HIV.
CD4 is a type of white blood cells, named T-cells which is also known as regulatory T cells which acts by reducing the excessive
immune response and regulate immune tolerance (Workman, Szymczak-Workman, Collison, Pillai, & Vignali, 2009). CD4 stimulates
the production of anti-inflammatory cytokines such as interleukin-10 and subsequently regulate inflammatory responses (Miyara et al.,
2009). Our study indicated that the level of CD4 is a crucial determinant for MDD among RVD patients. Those who have CD4 counts
more than 350 cells/ul are protected from having MDD. This result supported the findings of other researchers elsewhere (Terloyeva et
al., 2018). HIV may infect and kill CD4 cells which cause the failure of the immune system (Aavani & Allen, 2019). Therefore, CD4 cells
play a critical role to inhibit the worsening of the inflammatory process before developing depression that occurs during stressful
experiences. On the other hand, when the immune system is low due to reduced CD4 counts, it may lead to abnormality in the cascade
of neurohormonal changes at the Hypothalamus-Pituitary-Adrenal Gland (HPA) resulted in depletion of the precursor of serotonin which
can lead to depression (Masih & J.M.I. Verbeke, 2018). The level of CD4 count is negatively correlated with MDD among RVD patients,
therefore, it is recommended that the physicians to strengthen the education on adherence of HAART to achieve the optimal CD4 counts
more than 350 cells/ul and to ensure optimum immunity in reducing the risk of getting depression.

6.0 Conclusion and Recommendations

This study indicated that the use of ATS for the past three months, receiving only low to moderate social support from family and
significant others as well as having CD4 count less than 350 cells/ul increase the risk of RVD patients for MDD. The findings may inform
clinicians on the needs for early intervention, including counselling for RVD patients who are abusing drugs and increasing support
system for them. Addressing these psychological aspects is essential so that the detrimental effects of MDD such as premature
dementia, psychosis and suicide can be prevented early. Minimising the psychological consequences of this chronic and stigmatising
illness can help them to have optimum quality of life. Moreover, enhancing their adherence to the HAART may improve the CD4 counts
to ≥350 cells/ul, which could lessen the odds of getting MDD. This study provides insights to the contributing factors of MDD among the
RVD patients; nevertheless, we would like to inform that the study was limited by its design and suggest a more robust prospective
study, and larger sample sizes to determine the causal factors for MDD among the RVD patients. We are aware that many other physical,
personal and environmental factors that could influence MDD among them.

Acknowledgement
We would like to thank the Director-General of Health Malaysia for his permission to publish this article and to express our appreciation
to all the study participants who had volunteered to participate in this study. We would like to express our gratitude to the senior lecturer
and consultant of public health medicine, Dr Ikhsan Selamat, and Dr Semran Kaur, a psychiatrist in Hospital Sungai Buloh who were
directly involved in this study. The authors received no financial support for the research, authorship or publication of this article and
declared no conflict of interest.

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