Author
Location
Study design
Setting
Sample size
% Females
Measures of depression symptoms
Validation measure
% depression symptoms
Measure of major depression
% major depression
Association between depression and ART adherence
Adewuya 2008†‡
Nigeria
Cross-sectional
HIV psychosocial support center
N = 87
56.3 % females
15.1 % depression symptoms
Mini international neuropsychiatric interview
NA
11.8 % major depression
NA
Adewuya 2010†§
Nigeria
Cross-sectional
HIV psychosocial support center
N = 182
53 % females
General health questionnaire (12 items)
Cut-off score : ≥ 3
Not locally validated in study population
65.4 % depression symptoms
Depressed patients were less likely to be adherent to ART compared to non-depressed patients
AOR = 0.23; 95% CI (0.09–0.55)
Amberbir 2008†§
Ethiopia
Longitudinal
HIV treatment clinic attached to general hospital
Baseline N = 400
59.8 % females
Becks depression Inventory (21 items)
Cut-off score: ≥10
Not locally validated in study population
55.8 % baseline depression symptoms
Depressed patients were less likely to be adherent to ART compared to non depressed patients
OR = 0.47; 95% CI (0.26–0.90)
Association between alcohol use and adherence was not assessed
Byakika-Tusime 2009§
Uganda
Cross-sectional
Mother-to-child-transmission plus program
N = 177
70.1 % females
Becks Depression Inventory (BDI) (21 items)
Cut-off score : not reported
Not locally validated in study population
Mean BDI score for the sample was 9.74 (SD = 4.6)
Among those who had used ART for less than 6 months, the odds of adherence decreased by 99 % for every unit increase in depression symptom score
AOR = 0.01; 95% CI (0.00–0.77)
Among those “stable” on ART, the odds of adherence decreased by 61 % for every unit increase in depression symptom score
AOR = 0.39; 95% CI (0.11–1.34)
Cohen 2009†
Rwanda
Cross-sectional
HIV psychosocial support center
N = 658
100 % females
Center for epidemiological studies depression scale (20 items)
Cut-off score: ≥16
Not locally validated in study population
81 % depression symptoms
NA
Do 2010†
Botswana
Cross-sectional
HIV treatment clinic attached to general hospital
N = 300
76.3 % females
Becks depression inventory (21 items)
Cut-off score: ≥14
Not locally validated in study population
28.3 % depression symptoms
NA
Etienne 2010§
Kenya, Uganda, Zambia, Nigeria, and Rwanda
Cross-sectional
HIV treatment clinics attached to general hospitals
N = 921
65.4 % females
Factor scores of depression were constructed from three questions of depression (persistent feelings of sadness/hopefulness in the past month, frequency of crying in the past month, and frequency of feeling confused in the past month)
Reliability score 0.67
57.2 % low
depression scores, 22.0 % medium depression scores, 20.8 % high depression scores
Those with high depression scores were less likely to adhere to ART compared to those with low scores AOR = 0.57; 95% CI (0.39–0.84)
Those who never used alcohol were more likely to be adherent to ART than those who used alcohol
AOR = 2.14; 95% CI (1.36–3.37)
Farley 2010†§
Nigeria
Cross-sectional
HIV treatment clinic attached to a general hospital
N = 399
70 % females
Center for epidemiological studies depression scale (20 items)
Cut-off score: ≥21
The Cronbach alpha: 0.86
13 % depression symptoms
Study participants with CES-D scores ≥16 were less likely to be adherent to ART compared to those with scores < 16
OR = 0.23; 95% CI (0.08–0.68)
No association between AUDIT scores and pharmacy refill rate
OR = 1.55; 95% CI (0.19–12.46)
Kagee 2010†
South Africa
Cross-sectional
HIV clinics within primary health care facilities
N = 85
75.3 % females
The Beck Depression Inventory 1(BDI-1)
Cut-off score : ≥18
Cronbach’s alpha: 0.85
37.6 % depression symptoms
NA
Kaharuza 2006†
Uganda
Cross-sectional
HIV psychosocial support center
N = 1,017
77 % females
A modified center for epidemiological studies depression scale (12 items) was computed by removing the CES-D items reflecting somatic complaints
Cut-off score: ≥23
Cronbach’s alpha: 0.85
47 % depression symptoms
NA
Kekwaletswe 2011#§†
South Africa
Cross-sectional
HIV treatment center
N = 304
68 % females
Center for Epidemiological studies Depression scale (20 items)
Cut-off score : ≥16
Cronbach’s alpha: 0.92
59.2 % depression symptoms
Patients with CES-D score of >16 were less likely to be adherent to ART compared to those with scores < 16
OR = 0.43;.95 % CI (0.25–0.72)
Patients with AUDIT score >8 were less likely to be adherent to ART compared to those with scores <8
OR = 0.30; 95 % CI (0.19–0.73)
Lawler 2010†‡
Botswana
Cross-sectional
HIV treatment clinic attached to a general hospital
N = 120
50 % females
Beck Depression Inventory-Fast Screen (BDI-FS)
Cut-off score: ≥4
Cronbach’s alpha: 0.84
38 % depression symptoms
Prime-MD Mood Module (MM)
24 % major depression
NA
Martinez 2008†
Uganda
Cross-sectional
HIV treatment clinic attached to a general hospital
N = 421
63.2 % females
A modified depression section of the Hopkins Symptoms checklist with somatic measures removed.
Cut-off score: ≥1.75
Cronbach’s alpha: 0.74
18.8 % depression symptoms
NA
Marwick 2010‡
Tanzania
Cross-sectional
HIV treatment clinic attached to a general hospital
N = 220
74 % females
Clinic interview schedule –Revised
Previously validated in primary health clinic attendees
Cronbach’s alpha for this sample not reported
15.5 % major depression
NA
Monahan 2009†
Kenya
Cross-sectional
HIV psychosocial support center
N = 347
73 % females
Patient health questionnaire (9 items)
Cut-off score: ≥10
Cronbach’s alpha 0.78
34 % depression symptoms
NA
Myer 2008†‡
South Africa
Cross-sectional
Primary health care facility
N = 465
75 % females
Center for Epidemiological studies Depression scale
Cut-off score : ≥ 6
45 % depression symptoms. Locally validated in study population.
Sensitivity: 79 %
Specificity: 61 %
Mini international neuropsychiatric interview
14 % major depression
NA
Nachega 2011#†
South Africa.
Longitudinal
HIV treatment center
Baseline N = 274
60 % females
Brief Symptom Inventory (BSI) 51 items
Cut-off score: ≥9
Not locally validated in study population
25.4 % baseline depression symptoms
Depression scores were not associated with ART adherence at 12 and 24 month follow-up.
OR =0.5, 95% CI (0.15–1.56) Alcohol abuse was a baseline independent predictor of ART adherence
OR 2.4, 95% CI (1.20–5.0)
Nakasujj 2010†
Uganda
Longitudinal
HIV treatment clinic attached to a general hospital
N = 102(baseline)
72.6 % females
Center for epidemiological studies depression scale (20 items)
Cut-off score: ≥16
Not locally validated in study population
54 % baseline depression symptoms
NA
Nakimuli-Mpungu 2009†§
Uganda
Cross-sectional
HIV treatment clinic attached to a Mental hospital
N = 122
78.% females
Self-reporting questionnaire (20 items)
Cut-off score: ≥6
Not locally validated in study population
30.3 % depression symptoms
Those with significant depression symptoms were less likely to adhere to ART compared to those without significant depression symptoms
AOR = 0.27; 95% CI (0.10–0.72)
Nakimuli-Mpungu 2010†
Uganda
Cross-sectional
HIV treatment clinic attached to a general hospital
N = 244
63.9.% females
DSM-IV symptom checklist
Cut-off score: ≥6
Not locally validated in study population
40 % depression symptoms
NA
Olley 2006‡
South Africa
Longitudinal
HIV treatment clinic attached to a general hospital
N = 149(baseline)
70.5.% females
Mini international neuropsychiatric interview
Not locally validated in study population
34.9 % major depression
Patel 2009
Zimbabwe
Cross-sectional
HIV treatment clinic attached to a general hospital
N = 200
100 % females
Shona symptom questionnaire (14 items)
Cut-off score : not reported
Cronbach’s alpha 0.86
Mean depression score 28.44 (9.28)
NA
Pearson 2009†
Mozambique
Longitudinal
HIV treatment
clinic
N = 277(baseline)
56.3 % female
Center for epidemiological studies depression scale (10 items)
Cut-off score: ≥10
Cronbach’s alpha: 0.74
9.4 % baseline depression symptoms
NA
Peltzer 2010§
South Africa
Cross-sectional
District hospital
N = 519
73.4 % females
Center for epidemiological studies depression scale (10 items)
Cut-off score: not reported
Cronbach’s alpha: 0.54
NA
The odds of adherence decreased by 29 % for every unit increase in depression symptom score
OR = 0.88; 95% CI (0.80–0.96)
Pourpad 2007†
Senegal
Cross-sectional
HIV treatment clinic
N = 200
63.5 % females
Center for epidemiological studies depression scale (20 items)
Cut-off score : ≥16
Not locally validated in study population
18 % depression symptoms
NA
Ramadhani 2007†§
Tanzania
Cross-sectional
HIV treatment clinic
N = 150
63 % females
Hopkins symptom checklist (25 items)
Cut-off score: ≥1.75
Cronbach’s alpha: 0.93
21 % depression symptoms
Those with significant depression symptoms were less likely to adhere to ART compared to those without significant depression symptoms
AOR = 0.48; 95% CI (0.15–1.56)
Simbayi 2007†
South Africa
Cross-sectional
Psychosocial support center
N = 1,063
60.5 % females
Modified center for epidemiological studies depression scale (11 items)
Cut-off score: ≥16
Cronbach’s alpha: 0.93
30 % depression symptoms
NA
Spies 2009‡
South Africa
Cross-sectional
Primary health care HIV treatment facilities
N = 429
76 % females
Kessler-10
Cut-off score: ≥28
Cronbach’s alpha: 0.87
Mini international neuropsychiatric interview
13 % major depression
NA
Wagner 2011†
Uganda
Cross-sectional
HIV treatment clinic attached to a general hospital
N = 602
68 % females
Patient health questionnaire (9 items)
Cut-off score: ≥10
The Cronbach alpha coefficient for the sample not reported
13 % depression symptoms
NA
Weidle 2006†
Uganda
Longitudinal
Psychosocial support center
N = 987
74 % females
Modified center for epidemiological studies depression scale (20 items)
Cut-off score: ≥23
Cronbach’s alpha not reported
45 % baseline depression symptoms
NA
The studies on prevalence of depression in HIV positive populations give variable prevalence estimates of depression; from as high as 81 % in HIV positive individuals attending an HIV treatment program in Rwanda to as low as 0 % in HIV positive individuals in the Democratic Republic of Congo (DRC). If the findings of these studies are to be taken at face value, then eight of ten HIV positive patients in Rwanda has significant depression symptoms and depression is non-existent in DRC. A critical re-evaluation of these studies is required given the variability of findings.
A recent systematic review of studies documenting the prevalence of significant depressive symptoms and major depression among HIV-positive individuals enrolled in ART programs in sub-Saharan Africa, found prevalence estimates of 31 % and 18 %, respectively [17]. These estimates are much higher than prevalence estimates of depressive symptoms and major depression in community studies in Uganda and South Africa [2], suggesting an increased risk of depressive symptoms and major depression in HIV-positive individuals.
Most studies reporting on the prevalence of depression among PLWHA, have not assessed subjects for bipolar disorder [18], an important diagnosis to rule out. Many studies screened or assessed people for depressive symptoms and without further evaluation, no distinction can be made between subclinical depression and other depressive disorders besides major depression [15, 19, 20]. The few studies that have evaluated study participants with a diagnostic interview have neither reported on subclinical depression nor lifetime depressive disorders [13, 21, 22]. Knowledge of the prevalence of specific depressive disorders would allow for better resource allocation to provide required treatments (e.g., pharmacotherapy and psychotherapies) [23, 24] while management of lifetime depression would focus on relapse prevention using psychosocial interventions and maintenance medication.
In Uganda, a recent cross-sectional study of HIV positive individuals in a rural ART program in the southern regions of the country found the prevalence estimates of any depressive disorder, subclinical depression, both current and lifetime major depression, and bipolar depression were 46.4 %, 17.8 %, 25 % and 3.6 % respectively [25]. In comparison to non-depressed patients, those with sub-clinical depression were less likely to have high levels of self-efficacy, more likely to be using ART for less than 1 year, had advanced HIV disease and current alcohol use disorders (AUD’s). Those with both current and lifetime depressive disorders were less likely to be 85 % adherent to antiretroviral therapy (ART), have social support and high levels of self-efficacy, more likely to have tuberculosis and past manic episodes. Those with only lifetime depressive disorders were more likely to have current alcohol use disorder (AUD) and past manic episodes. The large proportion of HIV positive individuals with depressive disorders or significant depressive symptoms in ART programs in Uganda and other developing countries who remain undiagnosed and untreated is indeed a major unmet healthcare need.
Depression and Non-adherence to ART
In 2005, two African studies investigated the association between current significant depression symptoms and adherence to ART. In both studies, the association did not attain statistical significance. Since then, two Ugandan studies, [15, 26]; one study from South Africa [27] Nigeria [28] and Ethiopia [29] have investigated this association. All studies report a statistically significant association between current significant depression symptoms and poor adherence to ART. Qualitative studies in sub-Saharan Africa on barriers to ART adherence echo similar findings [30–32].
Given that depression is a recurrent complex mood disorder with various DSM-5 categories, it is important to investigate the relationship between lifetime depressive disorders and adherence to ART. A recent case-control study among rural HIV positive individuals using anti-retroviral therapy revealed that HIV positive individuals with lifetime depressive disorders had an increased risk of non-adherence to ART after controlling for education status, income, self-efficacy, perceived social support, cognitive impairment and current alcohol use disorders [32]. This association was stronger in females than males. This finding indicates that it would be important to closely monitor and support individuals with a history of lifetime depressive disorders who are initiating ART.
Studies have shown that untreated depressive disorders increase HIV transmission risk behaviors [33, 34], decrease immune status [35, 36] and decrease adherence to antiretroviral therapy (ART) [37–40] which may result in decreased clinical effectiveness and potential development of drug resistance [41, 42]. Thus, depression does pose challenging barriers to effective medical care at multiple points along the continuum of HIV medical care engagement and treatment (i.e. the ‘HIV treatment cascade’) [43]. Untreated depression has been associated with a lower likelihood of receiving anti-retroviral drugs [44, 45], poor adherence [34, 46] and increased morbidity [47–50] and mortality [35]. Depression is a predictor of clinical progression independently of non-adherence behaviors [49]. Depression is frequently under diagnosed and when recognized is often poorly treated, particularly in primary medical settings where most HIV/AIDS patients receive care [7, 51]. Mounting evidence suggests that effective treatment of depression in HIV patients may have benefits for their HIV-treatment retention, ART adherence, and virologic suppression, and, therefore, for community viral load [43].
HIV-Related Secondary Mania
Mania in a patient with HIV/AIDS may occur as a phase of a coexisting bipolar disorder, or it may be secondary to the direct neuronal effects of HIV infection [4, 52], treatments for HIV infection [53–55], or HIV-related secondary infections of the brain [56]. Affected patients appear to present with severe psychopathology [57, 58]. In developed countries, prevalence studies have shown that mania secondary to HIV infection is common [59, 60], and it occurs more among individuals with AIDS than among those with HIV infection alone [57, 60]. Researchers have previously hypothesized that mania occurring in the early stages of HIV infection may represent bipolar disorder in its manic phase, whereas mania in persons with AIDS is secondary mania linked to the pathophysiology of HIV brain infection [59, 61].
The evidence for an etiological association with HIV neuropathy was bolstered by a prospective study of HIV-positive patients with and without mania that demonstrated a protective effect from an antiretroviral agent able to penetrate the central nervous system [62]. However, given the small sample sizes used in these studies, any conclusions drawn from them should be considered tentative. The epidemiology of mania secondary to HIV infection in Uganda and other African countries that have high rates of HIV infection and limited access to highly active antiretroviral therapy remains largely unknown.
A study in Uganda compared the presentation and correlates of primary mania in HIV-negative patients with those of first episode secondary mania in HIV-positive patients [63]. The majority of HIV-positive patients with mania met criteria for first-episode secondary mania. Compared with HIV-negative patients with primary mania, they were predominantly female, age 30–49 years and of low socioeconomic and educational status. A significant number were divorced or had been widowed as a result of losing spouses to AIDS. Clinically, the majority presented in late stages of HIV infection, in WHO clinical stages 3 and 4. They were irritable and had aggressive and disruptive behaviors, decreased need for sleep, over talkativeness, and high rates of cognitive impairment, paranoid delusions, visual hallucinations, and auditory hallucinations as well as high rates of HIV-related signs and symptoms [63].
These findings show that first-episode secondary mania in HIV-positive individuals and primary mania in HIV-negative individuals are clinically and immunologically distinct. The relationship between secondary mania and depressed CD4 counts suggests that in the setting of an AIDS epidemic in poor countries where the costs of measures of immune status, such as CD4 cell counts, are prohibitive, secondary mania maybe used as an indicator to initiate highly active antiretroviral therapy [63]. Knowledge about the presentation of secondary mania in HIV infection may improve its clinical recognition and hence guide the development of early, effective interventions to control symptoms that not only interfere with a patient’s ability to adhere to treatment but also predispose patients to HIV risk behaviors, which may lead to further spread of HIV infection.
Early Onset Versus Late Onset HIV-Related Secondary Mania
A follow –up study compared the demographic and clinical characteristics of HIV-positive patients with early-onset and late-onset first-episode secondary mania in HIV infection, in order to determine whether baseline characteristics might provide insights into appropriate methods of assessment and management [61]. This study showed that among HIV-positive patients who met criteria for secondary mania, patients with early-onset and late-onset mania had comparable socio-demographic characteristics. Clinically, consistent with previous findings [57], patients with late-onset secondary mania had more manic symptoms on the Young Mania Rating Scale, YMRS. They were more irritable and had a more decreased need for sleep than patients with early-onset secondary mania.
Bipolar Disorder Co-morbid with HIV/AIDS
Another study in Uganda revealed that patients with bipolar mania, regardless of HIV status, had a more-or-less similar demographic profile. They had comparable age at onset of first affective symptoms, marital and education status. Generally, these findings are in keeping with previous descriptions of demographic characteristics of patients with bipolar disorder elsewhere [64]. It is interesting to note that, at the time of assessment, HIV-positive patients with bipolar disorder were older than the HIV-negative patients. This indicates that the HIV-positive patients had a longer duration of bipolar illness than the HIV-negative patients. One possible explanation for this finding could be that the lack of routine screening for HIV infection in our psychiatric hospital may have delayed diagnosis of HIV in the majority of these patients. Previous researchers have argued that HIV-positive patients with various bipolar subtypes may have associated impulsive, risk-taking traits that may play a role in HIV risk-behavior such as unprotected sex [65].
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