Clinical Practice & Epidemiology in Mental Health




ISSN: 1745-0179 ― Volume 16, 2020
REVIEW ARTICLE

Depression and HIV Disease Progression: A Mini-Review



Abdilahi Yousuf 1, Siti Roshaidai Mohd Arifin2, *, Ramli Musa3, Muhammad Lokman Md. Isa4
1 College of Medicine and Health Sciences, Jijiga University , Jijiga,Ethiopia
2 Kulliyah of Nursing, IIUM, Selangor, Malaysia
3 Department of psychiatric, Kulliyah of medicine, IIUM, Selangor, Malaysia
4 Department Basic Medical Sciences, Kulliyah of Nursing, IIUM, Selangor, Malaysia

Abstract

Background:

Depression is the most common mental disorder and a leading cause of disability, which commonly presents unexplained psychological and physical symptoms. Depression and HIV/AIDS are commonly comorbid. This review provides an insight into the effect of depression on disease progression among people living with HIV.

Methods:

A search for relevant articles was conducted using a database like MEDLINE, Scopus, PsycINFO and CINAHL. Peer-reviewed English journals published between 2015 and 2019 were included in the review.

Results:

A total of eight studies conducted in different settings were included in the review. This review has found that psychosocial, neurohormonal and virologic factors associated with depression affect HIV disease progression. Yet, the chronicity of depression, absence of the hormones that have a buffer effect on depression and lack of examination if depression is a predictor, or an outcome of disease progression, were some of the gaps that require further investigation.

Conclusion:

Considerably, more research is needed to better understand the effect of mental disorder, especially depression, on HIV disease progression to AIDS and future interventions should, therefore, concentrate on the integration of mental health screening in HIV clinical setup.

Keywords: Risk factors, Depression, Anxiety, Mental health, Disease progression, HIV, AIDS.


Article Information


Identifiers and Pagination:

Year: 2019
Volume: 15
First Page: 153
Last Page: 159
Publisher Id: CPEMH-15-153
DOI: 10.2174/1745017901915010153

Article History:

Received Date: 08/11/2019
Revision Received Date: 19/11/2019
Acceptance Date: 25/11/2019
Electronic publication date: 31/12/2019
Collection year: 2019

© 2019 Yousuf et al.

open-access license: This is an open access article distributed under the terms of the Creative Commons Attribution 4.0 International Public License [CC-BY 4.0], a copy of which is available at: [https://creativecommons.org/licenses/by/4.0/legalcode]. This license permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.


* Address correspondence to this author at Kulliyah of Nursing, IIUM, Selangor, Malaysia; Tel: +601133505235; E-mails: roshaidai@iium.edu.my





1. INTRODUCTION

Depression is a common mental illness, with constant sadness and loss of interest in things that people normally enjoy, and with an incapacity to perform day-to-day work [1Depression and other common mental disorders global health estimates 2017.-5Bianchini V, Giusti L, Salza A, Cofini V, Cifone MG, Casacchia M, et al. Moderate depression promotes posttraumatic growth [Ptg]: A Young population survey 2 years after the 2009 l ’ aquila earthquake 2017; 10-9.]. Many psychological problems can occur as a direct consequence of HIV infection and treatment disruption since both conditions are typically comorbid [6WHO. Depression, A global public health concern 2012 .http://www.who.int/mental_health/management/depression/who_paper_depression_wfmh_2012.pdf]. Individuals with chronic illnesses are at higher risk of suffering from depression [7Osso LD, Pini S. What did we learn from research on comorbidity. Psychiatry 2012; 180-4. , 8Claudia A, Maia CDO, Braga ADA, Paes F, Machado S, Carta MG, et al. Comorbidity of Depression and Anxiety : Association with Poor Quality of Life in Type 1 and 2 Diabetic Patients 2013; 136-41.].

People living with HIV are more frequently implicated in depression than the rest of the population worldwide [9Mohammed M, Mengistie B, Dessie Y, Godana W. Prevalence of depression and associated factors among hiv patients seeking treatments in art clinics at harar town, eastern ethiopia. J AIDS Clin Res 2015; 6(6): 1-6.-11Gupta R, Dandu M, Packel L, et al. Depression and HIV in Botswana: A population-based study on gender-specific socioeconomic and behavioral correlates. PLoS One 2010; 5(12)e14252
[http://dx.doi.org/10.1371/journal.pone.0014252] [PMID: 21170384]
]. Several studies around the world have found that depression occurs approximately twice as common in women than in men [3Fantahun A, Cherie A, Deribe L. Clin Pract Epidemiol Ment Health 2016; 2018: 196-206., 12Dejesus RS, Angstman KB, Cha SS, Williams MD. Antidepressant Medication Use Among Patients with Depression: Com- parison between Usual Care and Collaborative Care Using Care Managers. Clin Pract Epidemiol Ment Health 2008; 2013: 84-7., 13Antelman G, Kaaya S, Wei R, et al. Depressive symptoms increase risk of HIV disease progression and mortality among women in Tanzania. J Acquir Immune Defic Syndr 2007; 44(4): 470-7.http://journals.lww.com/jaids/Abstract/2007/04010/Depressive_Symptoms_Increase_Risk_of_HIV_Disease.15.aspx [Internet].
[http://dx.doi.org/10.1097/QAI.0b013e31802f1318] [PMID: 17179766]
].

However, in HIV cases, depression remains unnoticed and it is a risky condition that may have a negative consequence not only on treatment adherence, social engagements and quality of life, but also on progression of disease and life expectancy of the HIV patients [14Diminić-Lisica I, Francisković T, Janović S, Popović B, Klarić M, Nemcić-Moro I. Comorbid chronic diseases in depressed and non-depressed patients in family practice. Psychiatr Danub 2010; 22(2): 236-40.
[PMID: 20562753]
, 15Clark K. Evaluation of Depression Screening Practices in Comorbid Patients in the Primary Care Setting 2017.].

Depressive symptoms of people living with HIV are associated with biological, clinical and psychosocial characteristics that affect HIV disease progression [16Steve W. Cole psychosocial influences on hiv-1 disease progression: neural, endocrine and virologic mechanisms 2008., 17Ironson G, O’Cleirigh C, Kumar M, et al. Psychosocial and neurohormonal predictors of HIV disease progression [CD4 cells and viral load]: A 4 year prospective study. AIDS Behav 2015; 19(8): 1388-97.
[http://dx.doi.org/10.1007/s10461-014-0877-x] [PMID: 25234251]
]. Yet, there is an increasing concern in resource-limited developing countries of the world where people living with HIV do not get an early mental health screening, awareness and assistance from mental health service to the same level in the developed countries, and the impact on daily life is still increasing [18Memiah P, Shumba C, Etienne-mesubi M, Agbor S, Hossain MB, Komba P, et al. The effect of depressive symptoms and cd4 count on adherence to highly active antiretroviral therapy in sub-saharan Africa. J Int Assoc Provid AIDS Care 2014; 13(4): 346-52.
[http://dx.doi.org/10.1177/2325957413503368]
].

In fact, evidence from certain studies conducted in high-income countries shows that adherence to highly active antiretroviral therapy decreases depression, cognitive impairment, and other mental illnesses [17Ironson G, O’Cleirigh C, Kumar M, et al. Psychosocial and neurohormonal predictors of HIV disease progression [CD4 cells and viral load]: A 4 year prospective study. AIDS Behav 2015; 19(8): 1388-97.
[http://dx.doi.org/10.1007/s10461-014-0877-x] [PMID: 25234251]
, 19SeyedAlinaghi SeyedAhmad, Sara Jam, Maryam Foroughi, AmirHossein Imani, Minoo Mohraz GED, et al. Black and DS. RCT of Mindfulness-Based Stress Reduction Delivered to HIV+ Patients in Iran: Effects on CD4+ T Lymphocyte Count and Medical and Psychological Symptoms. Psychosom Med 2013; 74(6): 620-7., 20Pecoraro A, Mimiaga M, O’Cleirigh C, et al. Depression, substance use, viral load, and CD4+ count among patients who continued or left antiretroviral therapy for HIV in St. Petersburg, Russian Federation. AIDS Care 2015; 27(1): 86-92.
[http://dx.doi.org/10.1080/09540121.2014.959464] [PMID: 25264710]
].

A prior study in developing countries has also shown that anxiety and depression are associated with an increased risk of disease progression in HIV clinical stage III or IV, regardless of sociodemographic, psycho-social support and health condition during enrolment of the patient to HIV care [18Memiah P, Shumba C, Etienne-mesubi M, Agbor S, Hossain MB, Komba P, et al. The effect of depressive symptoms and cd4 count on adherence to highly active antiretroviral therapy in sub-saharan Africa. J Int Assoc Provid AIDS Care 2014; 13(4): 346-52.
[http://dx.doi.org/10.1177/2325957413503368]
, 21Dianatinasab M, Fararouei M, Padehban V, et al. The effect of a 12-week combinational exercise program on CD4 count and mental health among HIV infected women: A randomized control trial. J Exerc Sci Fit 2018; 16(1): 21-5. [Internet].
[http://dx.doi.org/10.1016/j.jesf.2018.02.001] [PMID: 30662488]
].

There is a large body of studies documenting negative stressful life events on disease progression and the existence of an association between biological vulnerability and psychosocial impacts, which are a core to the pathophysiology mechanism of depression [22Fekete EM, Antoni MH, Lopez C, et al. Stress buffering effects of oxytocin on HIV status in low-income ethnic minority women. Psychoneuroendocrinology 2011; 36(6): 881-90.
[http://dx.doi.org/10.1016/j.psyneuen.2010.12.003] [PMID: 21215526]
, 23Schuster R, Bornovalova M, Hunt E. The influence of depression on the progression of HIV : Direct and Indirect Effects. Behav Modif 2012; 36(2)].

To date, most of the studies carried out around the globe that examined depression among ethnically diverse people living with HIV, have focused on socioeconomic and psychosocial factors [9Mohammed M, Mengistie B, Dessie Y, Godana W. Prevalence of depression and associated factors among hiv patients seeking treatments in art clinics at harar town, eastern ethiopia. J AIDS Clin Res 2015; 6(6): 1-6., 11Gupta R, Dandu M, Packel L, et al. Depression and HIV in Botswana: A population-based study on gender-specific socioeconomic and behavioral correlates. PLoS One 2010; 5(12)e14252
[http://dx.doi.org/10.1371/journal.pone.0014252] [PMID: 21170384]
, 24Lee AM, Lam SK, Sze Mun Lau SM, Chong CSY, Chui HW, Fong DYT. Prevalence, course, and risk factors for antenatal anxiety and depression. Obstet Gynecol 2007; 110(5): 1102-12.
[http://dx.doi.org/10.1097/01.AOG.0000287065.59491.70] [PMID: 17978126]
-40Gaynes BN, O’Donnell J, Nelson E, et al. Psychiatric comorbidity in depressed HIV-infected individuals: Common and clinically consequential. Gen Hosp Psychiatry 2015; 37(4): 277-82.
[http://dx.doi.org/10.1016/j.genhosppsych.2015.03.021] [PMID: 25892152]
]. However, little attention has been paid to clinical and biological aspects influencing depression, including neurological, endocrine and virologic mechanisms.

Although Anti-Retroviral treatment interventions have progressed, and the approaches that promote screening, diagnosis, and rehabilitation have advanced, depression remains largely undetected and untreated [6WHO. Depression, A global public health concern 2012 .http://www.who.int/mental_health/management/depression/who_paper_depression_wfmh_2012.pdf].

Untreated depression may lead to poor adherence and non-compliance with antiretroviral care [18Memiah P, Shumba C, Etienne-mesubi M, Agbor S, Hossain MB, Komba P, et al. The effect of depressive symptoms and cd4 count on adherence to highly active antiretroviral therapy in sub-saharan Africa. J Int Assoc Provid AIDS Care 2014; 13(4): 346-52.
[http://dx.doi.org/10.1177/2325957413503368]
, 34Psychiatry G, Duko B, Geja E, Zewude M, Mekonen S. Prevalence and associated factors of depression among patients with HIV / AIDS in Hawassa. Ethiopia, cross - sectional study 2020;(2018): 1-7., 35Peltzer K, Rodriguez VJ, Jones D. Prevalence of prenatal depression and associated factors among HIV-positive women in primary care in Mpumalanga province, South Africa. SAHARA-J J Soc Asp HIV/AIDS [Internet] 2016; 13(1): 60-7.https://www.tandfonline.com/ doi/full/10.1080/17290376.2016.1189847, 41Wroe EB, Hedt-Gauthier BL, Franke MF, Nsanzimana S, Turinimana JB, Drobac P. Depression and patterns of self-reported adherence to antiretroviral therapy in Rwanda. Int J STD AIDS 2015; 26(4): 257-61.
[http://dx.doi.org/10.1177/0956462414535206] [PMID: 24828554]
-43Gebrezgiabher BB, Abraha TH, Hailu E, Siyum H, Mebrahtu G, Gidey B, et al. Depression among Adult HIV / AIDS Patients Attending ART Clinics at Aksum Town, Aksum. Ethiopia: A Cross-Sectional Study Depress Res Treat 2019; 2019 :3250431]. Therefore, this may have worse effects on people living with HIV, regardless of the cause of this situation [22Fekete EM, Antoni MH, Lopez C, et al. Stress buffering effects of oxytocin on HIV status in low-income ethnic minority women. Psychoneuroendocrinology 2011; 36(6): 881-90.
[http://dx.doi.org/10.1016/j.psyneuen.2010.12.003] [PMID: 21215526]
].

Considering factors that can influence the impact of depression in people living with HIV, one can update psychosocial and clinical interventions that promote mental health and HIV management.

Hence, reviewing studies on the role of psychosocial, neurohormonal and virologic impacts of depression on disease progression among people living with HIV has immediate public health management implications [44Leserman J. Role of Depression, Stress, and Trauma in HIV Disease Progression. Psychomatic Med 2008; (15): 539-45.].

This paper is assumed to fill the gap by providing a review of studies on psychosocial and neurohormonal factors that influence the effect of depression on HIV disease progression.

2. METHODS

The purpose of this review is to provide an insight into the effect of depression on disease progression among people living with HIV and to review the existing body of knowledge in diverse communities around the globe.

2.1. Inclusion and Exclusion Criteria

Eligibility criteria for the inclusion of the paper were; they should be peer-reviewed articles published in the English language and articles that study people with depression and living with HIV were included in the review.

Papers on reviews, case studies, opinions and commentaries, which did not include new data, were excluded.

2.2. Search Strategies

A search for relevant articles was conducted by an electronic database like MEDLINE, Scopus, PsycINFO and CINAHL to identify articles published between 2015 to 2019 that studied HIV and depression comorbidity. To ensure the up-to-datedness of the review and avoid publication lag, only those published for the last five years were included [45Dawid Pieper. Sunya-Lee Antoine, Edmund AM Neugebauer ME Up-to-dateness of reviews is often neglected in overviews: a systematic review 2014; 1302-8.].

The keywords used were HIV, AIDS, Depression, and disease progression. This mini-review adheres to and follows the PRISMA guideline [46Moher D, Liberati A, Tetzlaff J, Altman DG. Preferred reporting items for systematic reviews and meta-analyses: The PRISMA statement. Ann Intern Med 2009; 151(4): 264-9.
[http://dx.doi.org/10.7326/0003-4819-151-4-200908180-00135] [PMID: 19622511]
].

The database searches retrieved a total of 766 papers that were exported to RefWorks database, while 388 duplicates and articles which did not meet the criteria were excluded. After screening the titles, abstracts and year of publication, 324 articles which were not related to depression and HIV were excluded.

On further screening of full texts, 46 papers were excluded because of ineligibility or quality criteria, resulting in 8 papers for inclusion. An outline of the search results and screening criteria are summarized in Fig. (1).

3. RESULTS

3.1. Characteristics of Studies and Participants

The selected studies were published between 2015 and 2019. Articles that examined the association of depressive symptoms on disease progression were reviewed. These studies were conducted in 8 deferent settings: Three studies in the USA, and five studies from Switzerland, South Korea, Thailand, China and East African countries (Kenya, Tanzania, Uganda).

The description of the studies is shown in Table 1.

3.2. Measurement of Depression

Among the reviewed studies, two studies used the Beck Depression Inventory (BDI) for the screening of depression. This tool has been commonly used to assess both somatic and cognitive aspects of depression in people living with HIV. Two studies also used the Center for Epidemiologic Study in Depression scale (CES-D). The remaining studies used the Hospital Anxiety and Depression Scale (HADS), The Generalized Anxiety Disorder 7-item (GAD), and one study used the clinical screening questions as shown in Table 1.

3.3. Depression and Psychosocial Factors

In this review, we emphasized the recent epidemiological findings which deal with the effect of depression on disease progression regarding psychosocial, neurohormonal and virologic factors in people living with HIV.

Fig. (1)
Flowchart of the search process.


Table 1
Summary of study characteristics.


The psychosocial effects of depression on disease progress and life expectancy were particularly noticeable among HIV seropositive people with negative psychosocial related life experience in some of the studies [17Ironson G, O’Cleirigh C, Kumar M, et al. Psychosocial and neurohormonal predictors of HIV disease progression [CD4 cells and viral load]: A 4 year prospective study. AIDS Behav 2015; 19(8): 1388-97.
[http://dx.doi.org/10.1007/s10461-014-0877-x] [PMID: 25234251]
, 47Wang YY, Zhao J, Zhang Q, et al. Prevalence of depressive syndrome and their association with demographic and clinical characteristics in Chinese HIV patients. AIDS Care 2018; 30(11): 1388-92.
[http://dx.doi.org/10.1080/09540121.2018.1465172] [PMID: 29690783]
, 48Taniguchi T, Shacham E, Onen NF, Grubb JR, Overton ET. Depression severity is associated with increased risk behaviors and decreased CD4 cell counts. AIDS Care 2014; 26(8): 1004-12.
[http://dx.doi.org/10.1080/09540121.2014.880399] [PMID: 24479743]
]. People living with HIV especially women with chronic depressive symptoms were about two times more likely to die from AIDS than those who never experienced depression [49Antelman G, Kaaya S, Wei R, et al. Depressive symptoms increase risk of HIV disease progression and mortality among women in Tanzania. J Acquir Immune Defic Syndr 2007; 44(4): 470-7.
[http://dx.doi.org/10.1097/QAI.0b013e31802f1318] [PMID: 17179766]
].

Through the investigation of the number of CD4 cells and viral load, variation in HIV disease progression is mostly contributed by psychosocial factors like hopelessness, depressed mood and lack of coping; regardless of the initiation of medication [17Ironson G, O’Cleirigh C, Kumar M, et al. Psychosocial and neurohormonal predictors of HIV disease progression [CD4 cells and viral load]: A 4 year prospective study. AIDS Behav 2015; 19(8): 1388-97.
[http://dx.doi.org/10.1007/s10461-014-0877-x] [PMID: 25234251]
, 50Carrico AW, Riley ED, Johnson MO, et al. Psychiatric risk factors for HIV disease progression: The role of inconsistent patterns of antiretroviral therapy utilization. J Acquir Immune Defic Syndr 2011; 56(2): 146-50.
[http://dx.doi.org/10.1097/QAI.0b013e318201df63] [PMID: 21116186]
].

Psychosocial factors like social support, a coping mechanism, spirituality and good personal behaviour have a positive impact on the improvement of the lifestyle of people living with HIV and may delay disease progression to AIDs [17Ironson G, O’Cleirigh C, Kumar M, et al. Psychosocial and neurohormonal predictors of HIV disease progression [CD4 cells and viral load]: A 4 year prospective study. AIDS Behav 2015; 19(8): 1388-97.
[http://dx.doi.org/10.1007/s10461-014-0877-x] [PMID: 25234251]
].

Similarly, many studies support the hypothesis that psychosocial factors and depression can affect immune suppression and disease progression in people living with HIV regardless of the occurrence of opportunistic infection [51Prasithsirikul W, Chongthawonsatid S, Ohata PJ, Keadpudsa S, Klinbuayaem V, Rerksirikul P, et al. Depression and anxiety were low amongst virally suppressed, long-term treated HIV- infected individuals enrolled in a public sector antiretroviral program in Thailand. AIDS Care 2016; 29(3): 299-305.
[PMID: 27683949]
, 52Kee MK, Lee SY, Kim NY, et al. Anxiety and depressive symptoms among patients infected with human immunodeficiency virus in South Korea. AIDS Care 2015; 27(9): 1174-82.
[http://dx.doi.org/10.1080/09540121.2015.1035861] [PMID: 26197063]
]. However, to the best of our knowledge, previous reviews did not focus on the social factors and little studies have examined the biological mechanism that is associated with disease progression and depression.

Nevertheless, the mechanism of different neuroendocrine factors and whether they are mediators of the above mentioned psychosocial factors or not, remains uncertain regarding their influence in the disease progression.

3.4. Depression and Neurohormonal Factors

Some reviewed articles have shown that regardless of the antiretroviral medication, an increased level of hormones related to anxiety, stress or depression is mostly a source for CD4 cells decline and viral load increase, which may lead to accelerated disease progression to AIDS and short life expectancy [15Clark K. Evaluation of Depression Screening Practices in Comorbid Patients in the Primary Care Setting 2017., 24Lee AM, Lam SK, Sze Mun Lau SM, Chong CSY, Chui HW, Fong DYT. Prevalence, course, and risk factors for antenatal anxiety and depression. Obstet Gynecol 2007; 110(5): 1102-12.
[http://dx.doi.org/10.1097/01.AOG.0000287065.59491.70] [PMID: 17978126]
, 27Kapetanovic S, Christensen S, Karim R, et al. Correlates of perinatal depression in HIV-infected women. AIDS Patient Care STDS 2009; 23(2):101-8. http://www.liebertonline.com/doi/abs/10.1089/apc.2008.0125
[http://dx.doi.org/10.1089/apc.2008.0125] [PMID: 19196032]
, 29Venkatesh KK, Nadel H, Blewett D, Freeman MP, Kaimal AJ, Riley LE. Implementation of universal screening for depression during pregnancy: Feasibility and impact on obstetric care. Am J Obstet Gynecol 2016; 215(4): 517.e1-8. [Internet].
[http://dx.doi.org/10.1016/j.ajog.2016.05.024] [PMID: 27210067]
].

Among the various findings obtained from these reviews, only one study has shown that hormones such as norepinephrine, cortisol, and catecholamine exacerbate the effect of depression on immune suppression through the influence of CD4 levels and viral load [17Ironson G, O’Cleirigh C, Kumar M, et al. Psychosocial and neurohormonal predictors of HIV disease progression [CD4 cells and viral load]: A 4 year prospective study. AIDS Behav 2015; 19(8): 1388-97.
[http://dx.doi.org/10.1007/s10461-014-0877-x] [PMID: 25234251]
]. In contrast, another study has presented that there is no recorded association between cortisol level and some of the disease progression markers like CD4 level [54Odeniyi IA, Fasanmade OA, Ajala MO, Ohwovoriole AE. CD4 count as a predictor of adrenocortical insufficiency in persons with human immunodeficiency virus infection: How useful? Indian J Endocrinol Metab 2013; 17(6): 1012-7.
[http://dx.doi.org/10.4103/2230-8210.122615] [PMID: 24381877]
].

Even though antiretroviral medication adherence reduces the risk of developing depression by people living with HIv [47Wang YY, Zhao J, Zhang Q, et al. Prevalence of depressive syndrome and their association with demographic and clinical characteristics in Chinese HIV patients. AIDS Care 2018; 30(11): 1388-92.
[http://dx.doi.org/10.1080/09540121.2018.1465172] [PMID: 29690783]
,51Prasithsirikul W, Chongthawonsatid S, Ohata PJ, Keadpudsa S, Klinbuayaem V, Rerksirikul P, et al. Depression and anxiety were low amongst virally suppressed, long-term treated HIV- infected individuals enrolled in a public sector antiretroviral program in Thailand. AIDS Care 2016; 29(3): 299-305.
[PMID: 27683949]
, 55Owora AH. Major depression disorder trajectories and HIV disease progression: Results from a 6-year outpatient clinic cohort. Medicine [Baltimore] 2018; 97(12)e0252
[http://dx.doi.org/10.1097/MD.0000000000010252] [PMID: 29561455]
], some of the treatments may have an impact on the noradrenergic effect and can cause HIV disease progression, whereas beta-blocker drugs that block adrenergic mechanism may slow down disease progression [16Steve W. Cole psychosocial influences on hiv-1 disease progression: neural, endocrine and virologic mechanisms 2008.].

In these reviewed papers, the neurohormones were non-mediators to the association between psychosocial variables and HIV disease progression. Nevertheless, some of the results have shown that both psychosocial and neurohormones predict the progression of the disease.

3.5. Depression and Virologic Factors

The association between depression and high viral load has been reported in many studies [50Carrico AW, Riley ED, Johnson MO, et al. Psychiatric risk factors for HIV disease progression: The role of inconsistent patterns of antiretroviral therapy utilization. J Acquir Immune Defic Syndr 2011; 56(2): 146-50.
[http://dx.doi.org/10.1097/QAI.0b013e318201df63] [PMID: 21116186]
, 51Prasithsirikul W, Chongthawonsatid S, Ohata PJ, Keadpudsa S, Klinbuayaem V, Rerksirikul P, et al. Depression and anxiety were low amongst virally suppressed, long-term treated HIV- infected individuals enrolled in a public sector antiretroviral program in Thailand. AIDS Care 2016; 29(3): 299-305.
[PMID: 27683949]
]. Lack of adherence to antiretroviral therapy, substance abuse and other risky behaviours were mentioned as mediating factors of depression on higher viral loads resulting from poor HIV disease outcomes [56Amanor-Boadu S, Hipolito MS, Rai N, et al. Poor CD4 count is a predictor of untreated depression in human immunodeficiency virus-positive African-Americans. World J Psychiatry 2016; 6(1): 128-35.
[http://dx.doi.org/10.5498/wjp.v6.i1.128] [PMID: 27014603]
].

Some of the effects of HIV on the immune system are a significant decline of CD4 count, which makes HIV seropositive people susceptible to opportunistic infection [21Dianatinasab M, Fararouei M, Padehban V, et al. The effect of a 12-week combinational exercise program on CD4 count and mental health among HIV infected women: A randomized control trial. J Exerc Sci Fit 2018; 16(1): 21-5. [Internet].
[http://dx.doi.org/10.1016/j.jesf.2018.02.001] [PMID: 30662488]
].

CD4 T lymphocytes count are major cell types infected by HIV. These cells, being the producer of cytokines, play a major role in the immune defence system against opportunistic infection [56Amanor-Boadu S, Hipolito MS, Rai N, et al. Poor CD4 count is a predictor of untreated depression in human immunodeficiency virus-positive African-Americans. World J Psychiatry 2016; 6(1): 128-35.
[http://dx.doi.org/10.5498/wjp.v6.i1.128] [PMID: 27014603]
].

Higher average symptomatic depression was predictive for faster degradation in CD4 count [17Ironson G, O’Cleirigh C, Kumar M, et al. Psychosocial and neurohormonal predictors of HIV disease progression [CD4 cells and viral load]: A 4 year prospective study. AIDS Behav 2015; 19(8): 1388-97.
[http://dx.doi.org/10.1007/s10461-014-0877-x] [PMID: 25234251]
, 47Wang YY, Zhao J, Zhang Q, et al. Prevalence of depressive syndrome and their association with demographic and clinical characteristics in Chinese HIV patients. AIDS Care 2018; 30(11): 1388-92.
[http://dx.doi.org/10.1080/09540121.2018.1465172] [PMID: 29690783]
, 55Owora AH. Major depression disorder trajectories and HIV disease progression: Results from a 6-year outpatient clinic cohort. Medicine [Baltimore] 2018; 97(12)e0252
[http://dx.doi.org/10.1097/MD.0000000000010252] [PMID: 29561455]
, 48Taniguchi T, Shacham E, Onen NF, Grubb JR, Overton ET. Depression severity is associated with increased risk behaviors and decreased CD4 cell counts. AIDS Care 2014; 26(8): 1004-12.
[http://dx.doi.org/10.1080/09540121.2014.880399] [PMID: 24479743]
]. The hormones released by the adrenaline gland during depression and anxiety influenced CD4 count, showing the existence of an association between depression and immune suppression [17Ironson G, O’Cleirigh C, Kumar M, et al. Psychosocial and neurohormonal predictors of HIV disease progression [CD4 cells and viral load]: A 4 year prospective study. AIDS Behav 2015; 19(8): 1388-97.
[http://dx.doi.org/10.1007/s10461-014-0877-x] [PMID: 25234251]
].

The severity of symptomatic depression is associated with lower CD4 cell count after adjustment for race, sex and ART adherence [17Ironson G, O’Cleirigh C, Kumar M, et al. Psychosocial and neurohormonal predictors of HIV disease progression [CD4 cells and viral load]: A 4 year prospective study. AIDS Behav 2015; 19(8): 1388-97.
[http://dx.doi.org/10.1007/s10461-014-0877-x] [PMID: 25234251]
, 48Taniguchi T, Shacham E, Onen NF, Grubb JR, Overton ET. Depression severity is associated with increased risk behaviors and decreased CD4 cell counts. AIDS Care 2014; 26(8): 1004-12.
[http://dx.doi.org/10.1080/09540121.2014.880399] [PMID: 24479743]
]. Without controlling medication adherence, findings of measurement scales on the experience of depression and stress also significantly predicted a greater decrease in CD4 cells and an increase in viral load over the same period [17Ironson G, O’Cleirigh C, Kumar M, et al. Psychosocial and neurohormonal predictors of HIV disease progression [CD4 cells and viral load]: A 4 year prospective study. AIDS Behav 2015; 19(8): 1388-97.
[http://dx.doi.org/10.1007/s10461-014-0877-x] [PMID: 25234251]
].

Recently, however, these studies have shown that effective management of depression can have a possible advantage for the decline of viral load and management of HIV disease progression.

4. DISCUSSION AND CONCLUSION

Depression, which is a common psycho-social reaction found in people living with HIV, is a stressful experience and often persistent [57Francesca MM, Efisia LM, Alessandra GM, Marianna A, Giovanni CM. Misdiagnosed Hypomanic Symptoms in Patients with Treatment-Resistant Major Depressive Disorder in Italy : Results from the Improve Study 2014; 42-7.]. As a consequence, depression is the world’s most important source of disability [1Depression and other common mental disorders global health estimates 2017.]. As a consequence, depression is the most common primary cause of disability. To our knowledge, this is the first review examining the effect of depression on disease progression among people living with HIV across different settings.

Among the plausible similar descriptions that all these papers had in common in their findings was the significance of depression as a co-morbid disease observed in HIV patients [50Carrico AW, Riley ED, Johnson MO, et al. Psychiatric risk factors for HIV disease progression: The role of inconsistent patterns of antiretroviral therapy utilization. J Acquir Immune Defic Syndr 2011; 56(2): 146-50.
[http://dx.doi.org/10.1097/QAI.0b013e318201df63] [PMID: 21116186]
, 47Wang YY, Zhao J, Zhang Q, et al. Prevalence of depressive syndrome and their association with demographic and clinical characteristics in Chinese HIV patients. AIDS Care 2018; 30(11): 1388-92.
[http://dx.doi.org/10.1080/09540121.2018.1465172] [PMID: 29690783]
, 51Prasithsirikul W, Chongthawonsatid S, Ohata PJ, Keadpudsa S, Klinbuayaem V, Rerksirikul P, et al. Depression and anxiety were low amongst virally suppressed, long-term treated HIV- infected individuals enrolled in a public sector antiretroviral program in Thailand. AIDS Care 2016; 29(3): 299-305.
[PMID: 27683949]
, 55Owora AH. Major depression disorder trajectories and HIV disease progression: Results from a 6-year outpatient clinic cohort. Medicine [Baltimore] 2018; 97(12)e0252
[http://dx.doi.org/10.1097/MD.0000000000010252] [PMID: 29561455]
].

The studies had also consistently presented that there is a high prevalence of depression among people living with HIV/AIDS [18Memiah P, Shumba C, Etienne-mesubi M, Agbor S, Hossain MB, Komba P, et al. The effect of depressive symptoms and cd4 count on adherence to highly active antiretroviral therapy in sub-saharan Africa. J Int Assoc Provid AIDS Care 2014; 13(4): 346-52.
[http://dx.doi.org/10.1177/2325957413503368]
], and disproportionately, the number of people affected by both HIV and depression is higher than the general population. Furtherly, unlike the other reviewed findings, the study by Prasithsirikul et al. reported that anxiety and prevalence were low in people who are on antiretroviral treatment for long period of time [51Prasithsirikul W, Chongthawonsatid S, Ohata PJ, Keadpudsa S, Klinbuayaem V, Rerksirikul P, et al. Depression and anxiety were low amongst virally suppressed, long-term treated HIV- infected individuals enrolled in a public sector antiretroviral program in Thailand. AIDS Care 2016; 29(3): 299-305.
[PMID: 27683949]
]. The reason could be attributed to the different statistical test used for the analysis of the association between depression and treatment outcomes and not examining the positive effect of counselling on treatment adherence [58Santos V, Paes F, Pereira V, Arias-carrión O, Silva AC, Carta MG, et al. The Role of Positive Emotion and Contributions of Positive Psychology in Depression Treatment : Systematic Review 2013; 221-37.].

In addition, almost all the studies analysed also revealed a strong link between depression and the result of poor adherence to HIV treatment [17Ironson G, O’Cleirigh C, Kumar M, et al. Psychosocial and neurohormonal predictors of HIV disease progression [CD4 cells and viral load]: A 4 year prospective study. AIDS Behav 2015; 19(8): 1388-97.
[http://dx.doi.org/10.1007/s10461-014-0877-x] [PMID: 25234251]
, 47Wang YY, Zhao J, Zhang Q, et al. Prevalence of depressive syndrome and their association with demographic and clinical characteristics in Chinese HIV patients. AIDS Care 2018; 30(11): 1388-92.
[http://dx.doi.org/10.1080/09540121.2018.1465172] [PMID: 29690783]
, 51Prasithsirikul W, Chongthawonsatid S, Ohata PJ, Keadpudsa S, Klinbuayaem V, Rerksirikul P, et al. Depression and anxiety were low amongst virally suppressed, long-term treated HIV- infected individuals enrolled in a public sector antiretroviral program in Thailand. AIDS Care 2016; 29(3): 299-305.
[PMID: 27683949]
, 52Kee MK, Lee SY, Kim NY, et al. Anxiety and depressive symptoms among patients infected with human immunodeficiency virus in South Korea. AIDS Care 2015; 27(9): 1174-82.
[http://dx.doi.org/10.1080/09540121.2015.1035861] [PMID: 26197063]
, 55Owora AH. Major depression disorder trajectories and HIV disease progression: Results from a 6-year outpatient clinic cohort. Medicine [Baltimore] 2018; 97(12)e0252
[http://dx.doi.org/10.1097/MD.0000000000010252] [PMID: 29561455]
, 48Taniguchi T, Shacham E, Onen NF, Grubb JR, Overton ET. Depression severity is associated with increased risk behaviors and decreased CD4 cell counts. AIDS Care 2014; 26(8): 1004-12.
[http://dx.doi.org/10.1080/09540121.2014.880399] [PMID: 24479743]
, 53Meffert S M, Neylan T C, McCulloch C E, et al. C. S. Polyak JAA and VGV. East African HIV care: depression and HIV outcomes. Glob Ment Heal 2019; 6: eg.]. Yet, none of them has remarked the potential interactions of anti-depressants and anti-retroviral treatments and their effects on disease progression of HIV. One of the recent pieces of evidence shows that anti-depressants are a major factor for HIV disease progression and potentially, the interaction between antidepressants and ART may result in dopamine change, which may aggravate the Neuro HIV [59Matt SM, Gaskill PJ. Dopaminergic impact of cART and anti-depressants on HIV neuropathogenesis in older adults. Brain Res 2019; 1723146398
[http://dx.doi.org/10.1016/j.brainres.2019.146398] [PMID: 31442412]
, 60Nagaraja SB, Valikayath A, Jha S, Jadhav B, Ladomirska J. HIV, multidrug-resistant TB and depressive symptoms: when three conditions collide 2014; 9716.].

Similar findings from two of the reviewed studies carried out in a different geographical setting have shown that depression and other psychological disorders are associated with lower cellular immunity [50Carrico AW, Riley ED, Johnson MO, et al. Psychiatric risk factors for HIV disease progression: The role of inconsistent patterns of antiretroviral therapy utilization. J Acquir Immune Defic Syndr 2011; 56(2): 146-50.
[http://dx.doi.org/10.1097/QAI.0b013e318201df63] [PMID: 21116186]
, 49Antelman G, Kaaya S, Wei R, et al. Depressive symptoms increase risk of HIV disease progression and mortality among women in Tanzania. J Acquir Immune Defic Syndr 2007; 44(4): 470-7.
[http://dx.doi.org/10.1097/QAI.0b013e31802f1318] [PMID: 17179766]
]. However, the studies did not highlight whether depression is a predictor or an outcome of disease progression. This might be related to the different methodological limitations of these studies. Hence, their findings require to be interpreted with caution.

The effects of depression on disease progress are investigated mostly from four dimensions including psychosocial, neural, hormonal and virologic factors. As stated in the findings of many studies, a broad range of factors related to psychosocial may affect the underlying viral replication including virologic increment and immune system suppression resulting in HIV disease progression [17Ironson G, O’Cleirigh C, Kumar M, et al. Psychosocial and neurohormonal predictors of HIV disease progression [CD4 cells and viral load]: A 4 year prospective study. AIDS Behav 2015; 19(8): 1388-97.
[http://dx.doi.org/10.1007/s10461-014-0877-x] [PMID: 25234251]
].

This reflects the findings that found endocrine, neural and psychosocial factors as a predictor of HIV disease progression [16Steve W. Cole psychosocial influences on hiv-1 disease progression: neural, endocrine and virologic mechanisms 2008., 17Ironson G, O’Cleirigh C, Kumar M, et al. Psychosocial and neurohormonal predictors of HIV disease progression [CD4 cells and viral load]: A 4 year prospective study. AIDS Behav 2015; 19(8): 1388-97.
[http://dx.doi.org/10.1007/s10461-014-0877-x] [PMID: 25234251]
, 56Amanor-Boadu S, Hipolito MS, Rai N, et al. Poor CD4 count is a predictor of untreated depression in human immunodeficiency virus-positive African-Americans. World J Psychiatry 2016; 6(1): 128-35.
[http://dx.doi.org/10.5498/wjp.v6.i1.128] [PMID: 27014603]
]. However, none of these studies has highlighted the biological and behavioural mediators to the immune mechanism related with the outcome of disease progression.

People with HIV who were also depressed were more likely than people who were not depressed to advance toward AIDS. However, the identified papers for review have shown little about whether chronic or symptomatic depression was associated with disease progression to AIDS. Moreover, some studies have stated that symptomatic depression was not significantly associated with the progression of HIV.

Some of the reviewed articles [17Ironson G, O’Cleirigh C, Kumar M, et al. Psychosocial and neurohormonal predictors of HIV disease progression [CD4 cells and viral load]: A 4 year prospective study. AIDS Behav 2015; 19(8): 1388-97.
[http://dx.doi.org/10.1007/s10461-014-0877-x] [PMID: 25234251]
, 50Carrico AW, Riley ED, Johnson MO, et al. Psychiatric risk factors for HIV disease progression: The role of inconsistent patterns of antiretroviral therapy utilization. J Acquir Immune Defic Syndr 2011; 56(2): 146-50.
[http://dx.doi.org/10.1097/QAI.0b013e318201df63] [PMID: 21116186]
] have similarly presented that some of the neurohormones are predicting factors for HIV disease progression. They have mainly focused on the traditional neurohormonal models of stress and depression in which they examined only Sympathetic Adrenal Medullary (SAM) and Hypothalamic-Pituitary-Adrenal (HPA) axis, which is associated with the increase of cortisol, epinephrine, and norepinephrine [61Pasquini M, Berardelli I, Biondi M. Ethiopathogenesis of Depressive Disorders 2014; 166-71.].

Currently, it is found that these investigations were inadequate as some of the hormonal responses to stress or depression mechanism are not mentioned in these articles like oxytocin, which has a buffering effect on stress and depression and the immune function of people living with HIv [22Fekete EM, Antoni MH, Lopez C, et al. Stress buffering effects of oxytocin on HIV status in low-income ethnic minority women. Psychoneuroendocrinology 2011; 36(6): 881-90.
[http://dx.doi.org/10.1016/j.psyneuen.2010.12.003] [PMID: 21215526]
].

The screening tools, study design, data collection instruments and the language used for the validated questionnaire, are one of the remarkable discrepancies in these reviewed studies. Similarly, differences in the definition regarding whether chronic or symptomatic depression are a source for the predictors for disease progression are debatable.

One of the drawbacks of this study was the limited number of studies meeting the criteria for inclusion in a systematic search.

Considerably, more research is needed to better understand the effect of mental disorder especially depression on HIV disease progression to AIDS and future interventions should, therefore, concentrate on the integration of mental health screening in HIV clinical setup.

AUTHORS' CONTRIBUTION

AY and SR performed literature search, data extraction and analysis, RM and ML contributed substantial input in the analysis, reviewed the manuscript and approved the final draft for submission.

CONSENT FOR PUBLICATION

Not applicable.

FUNDING

None.

CONFLICT OF INTEREST

The authors declare no conflict of interest, financial or otherwise.

ACKNOWLEDGEMENTS

AO performed literature search, data extraction and analyses, AO and OG wrote the first draft of the paper. Both authors approved the final draft for submission.

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Jacques Descotes
(Centre Antipoison-Centre de Pharmacovigilance, France)

"Publishing research articles is the key for future scientific progress. Open Access publishing is therefore of utmost importance for wider dissemination of information, and will help serving the best interest of the scientific community."


Patrice Talaga
(UCB S.A., Belgium)

"Open access journals are a novel concept in the medical literature. They offer accessible information to a wide variety of individuals, including physicians, medical students, clinical investigators, and the general public. They are an outstanding source of medical and scientific information."


Jeffrey M. Weinberg
(St. Luke's-Roosevelt Hospital Center, USA)

"Open access journals are extremely useful for graduate students, investigators and all other interested persons to read important scientific articles and subscribe scientific journals. Indeed, the research articles span a wide range of area and of high quality. This is specially a must for researchers belonging to institutions with limited library facility and funding to subscribe scientific journals."


Debomoy K. Lahiri
(Indiana University School of Medicine, USA)

"Open access journals represent a major break-through in publishing. They provide easy access to the latest research on a wide variety of issues. Relevant and timely articles are made available in a fraction of the time taken by more conventional publishers. Articles are of uniformly high quality and written by the world's leading authorities."


Robert Looney
(Naval Postgraduate School, USA)

"Open access journals have transformed the way scientific data is published and disseminated: particularly, whilst ensuring a high quality standard and transparency in the editorial process, they have increased the access to the scientific literature by those researchers that have limited library support or that are working on small budgets."


Richard Reithinger
(Westat, USA)

"Not only do open access journals greatly improve the access to high quality information for scientists in the developing world, it also provides extra exposure for our papers."


J. Ferwerda
(University of Oxford, UK)

"Open Access 'Chemistry' Journals allow the dissemination of knowledge at your finger tips without paying for the scientific content."


Sean L. Kitson
(Almac Sciences, Northern Ireland)

"In principle, all scientific journals should have open access, as should be science itself. Open access journals are very helpful for students, researchers and the general public including people from institutions which do not have library or cannot afford to subscribe scientific journals. The articles are high standard and cover a wide area."


Hubert Wolterbeek
(Delft University of Technology, The Netherlands)

"The widest possible diffusion of information is critical for the advancement of science. In this perspective, open access journals are instrumental in fostering researches and achievements."


Alessandro Laviano
(Sapienza - University of Rome, Italy)

"Open access journals are very useful for all scientists as they can have quick information in the different fields of science."


Philippe Hernigou
(Paris University, France)

"There are many scientists who can not afford the rather expensive subscriptions to scientific journals. Open access journals offer a good alternative for free access to good quality scientific information."


Fidel Toldrá
(Instituto de Agroquimica y Tecnologia de Alimentos, Spain)

"Open access journals have become a fundamental tool for students, researchers, patients and the general public. Many people from institutions which do not have library or cannot afford to subscribe scientific journals benefit of them on a daily basis. The articles are among the best and cover most scientific areas."


M. Bendandi
(University Clinic of Navarre, Spain)

"These journals provide researchers with a platform for rapid, open access scientific communication. The articles are of high quality and broad scope."


Peter Chiba
(University of Vienna, Austria)

"Open access journals are probably one of the most important contributions to promote and diffuse science worldwide."


Jaime Sampaio
(University of Trás-os-Montes e Alto Douro, Portugal)

"Open access journals make up a new and rather revolutionary way to scientific publication. This option opens several quite interesting possibilities to disseminate openly and freely new knowledge and even to facilitate interpersonal communication among scientists."


Eduardo A. Castro
(INIFTA, Argentina)

"Open access journals are freely available online throughout the world, for you to read, download, copy, distribute, and use. The articles published in the open access journals are high quality and cover a wide range of fields."


Kenji Hashimoto
(Chiba University, Japan)

"Open Access journals offer an innovative and efficient way of publication for academics and professionals in a wide range of disciplines. The papers published are of high quality after rigorous peer review and they are Indexed in: major international databases. I read Open Access journals to keep abreast of the recent development in my field of study."


Daniel Shek
(Chinese University of Hong Kong, Hong Kong)

"It is a modern trend for publishers to establish open access journals. Researchers, faculty members, and students will be greatly benefited by the new journals of Bentham Science Publishers Ltd. in this category."


Jih Ru Hwu
(National Central University, Taiwan)


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