Mental disorder and the outcome of HIV/AIDS in low-income and middle-income countries: a systematic review
Mayston, Rosiea; Kinyanda, Eugeneb; Chishinga, Nathanielc,d; Prince, Martina; Patel, Vikrame
aCentre for Global Mental Health and Health Service & Population Research Department, Institute of Psychiatry, King's College London, UK
bMRC/UVRI Uganda research Unit on AIDS, Entebbe, Uganda & Senior EDCTP Fellowship, Cape Town, South Africa
cZambia AIDS-related TB Project, School of Medicine, Ridgeway Campus, Lusaka, Zambia
dDepartment of Clinical Research
eCentre for Global Mental Health, London School of Hygiene & Tropical Medicine, London, UK.
Correspondence to Rosie Mayston, PO Box 30, Health Service & Population Research Department, Institute of Psychiatry, King's College London, De Crespigny Park, London SE5 8AF.
Received 13 December, 2011
Accepted 25 October, 2012
Objectives: To conduct a systematic review of the literature to examine the interrelationship between mental health and treatment outcomes in low-income and middle-income settings; to update the work of Collins et al. (2006).
Design: Systematic review of peer-reviewed articles that examined one of the following: the effects of mental disorders (including cognitive impairment) upon engagement with treatment and/or adherence; their influence upon HIV-related clinical outcomes; and the impact of interventions for mental disorder.
Methods: Articles about mental health and HIV/AIDS were included if they were published after 2005 and addressed one of the areas of interest described above. Systematic methods were used for searching, screening, and data extraction. Studies employing quantitative measures of exposures and outcomes wherein all participants had a diagnosis of HIV/AIDS were included.
Results: This review found ample and moderately consistent evidence that adverse mental health and alcohol consumption are associated with reduced adherence. Variation in measurement and the relative paucity of work meant that interpretation of studies examining engagement with care and other clinical outcomes was difficult. Evidence on the efficacy and effectiveness of mental health interventions in low-income and middle-income settings was very limited.
Conclusion: This review suggests that psychosocial factors, namely, depression and alcohol may have adverse effects upon HIV-related outcomes. However, further large, high-quality studies examining outcomes other than adherence are needed. There is also an urgent need for randomized controlled trials of interventions for mental disorder and a need to investigate their impact upon HIV-related outcomes.
In high-income, low HIV prevalence settings, research has shown that the prevalence of mental disorder among people living with HIV/AIDS is high (i.e., [1,2]) and that poor mental health has adverse effects upon disease progression and mortality , as well as on adherence to antiretroviral therapy (ART) . This has led to the widespread provision of specialist mental health services for people at-risk or living with the disease, with the implicit aim of improving mental health as well as HIV-related outcomes.
Despite its potential importance in HIV care, the role of mental illness in the lives of people living with HIV/AIDS in low-income and middle-income country (LMIC) settings remains unclear. Systematic review by Collins et al. (2006)  presented an overview of mental health and HIV/AIDS research carried out in LMIC between 1990 and 2005. This wide-ranging review covered research into the following areas: mental health risk factors for HIV, comorbidity with mental and cognitive disorders, the impact of comorbidity on adherence and other health behaviours, and the impact of psychosocial and specific mental illness-focussed interventions on mental health and HIV outcomes. Collins et al. (2006) found 39 relevant studies. Only four studies examined the association between mental illness and poor adherence and just two evaluated the impact of mental health interventions in HIV-affected populations.
In this review, we aim to update the work of Collins et al. (2006), focussing on three areas of the interrelationship between HIV/AIDS and mental health which we believe to be most relevant to treatment outcomes in LMIC today: the effects of mental disorders (including cognitive impairment) upon engagement with treatment and/or adherence; their influence upon HIV-related clinical outcomes; and the impact of interventions that aimed to address mental disorder in people living with HIV/AIDS. Our goal is to synthesize this evidence to generate findings relevant to policy and practice for implementation of mental healthcare within HIV/AIDS programs in LMIC.
We employed a two-stage search strategy. First, we used broad search criteria, in order to identify all English language empirical studies published since 2005 about mental health and HIV/AIDS in LMIC. We used the following search terms to ensure we captured studies measuring three key aspects of mental ill-health: mental illness (mental, psycho*); alcohol and substance use (alcohol, substance use); and HIV-associated neurocognitive disorders (HIV-associated neurocognitive disorders OR HIV neurological symptoms, cognit*, dementia). These search terms were combined with LMIC regional names: Africa, Caribbean, Central America, Latin America, Asia, Pacific Islands, Eastern Europe, and Russia and terms relating to HIV/AIDS (HIV infections OR AIDS). We searched PubMed, MEDLINE, EMBASE, and PsycINFO databases (last searched on 24 March 2011). Search 1 resulted in 5123 references, search 2 resulted in 1275 references, and search 3 resulted in 290 references.
In the second stage, having read abstracts and papers wherein indicated, we refined these results, selecting only papers that met the following criteria:
1. all participants had a diagnosis of HIV/AIDS
2. quantitative measures of exposures and outcomes were used
3. the studies focussed upon the effects of mental disorders (including cognitive impairment) upon engagement with treatment and/or adherence; their influence upon HIV-related clinical outcomes, and the impact of interventions that aimed to address mental disorder in people living with HIV/AIDS.
Search results were reviewed by two independent reviewers, results were compared, and differences in selection were discussed and then resolved through the involvement of a third reviewer.
Study populations, sampling, and measurement
Table 1 describes the principal characteristics of observational studies included in this review. Samples for studies examining the effects of mental ill-health upon adherence and HIV-related clinical outcomes usually comprised general outpatient treatment clinic attendees. Two women-only samples were identified [6,7]; two studies were carried out among people with a history of injection drug use (IDU) [8,35], whereas one study compared outcomes between those with MSM and IDU transmission categories .
Table 1-a Details of...Image Tools
There was heterogeneity in measures of adherence and mental health exposures across studies. Fifteen out of 18 studies measuring depression or anxiety used a range of different structured instruments [such as the Beck's Depression Inventory or the Center for Epidemiologic Studies Depression Scale (CES-D)] to measure symptoms, whereas one study used the MINI International Neuropsychiatric Interview. The remaining two studies asked participants simple questions relating to their mental state (current/over past month) [10,11]. There was much heterogeneity in the measure of alcohol use; four out of 17 studies used a standardized instrument (Alcohol Use Disorders Identification Test) [12–15], whereas in other studies, participants were asked about either the frequency or the quantity of their consumption during a specified period of time or vaguer questions such as whether they drank alcohol ‘never’, ‘sometimes’, or ‘most of the time’.
There was heterogeneity both in the method of measuring adherence, and the time period over which adherence was assessed. In most studies, the assessment was by self-report. In the two studies that used clinical records to measure adherence, 10.4% Nigerian participants were found to have missed medication refills , whereas 13.6% of Ethiopian participants had missed more than two clinical appointments . In another Ethiopian study, 11.9% participants were found to have less than 95% adherence (as measured by unannounced pill-count) . In studies using self-report to measure adherence, taking 90–95% of doses was generally considered the cut-off for good/poor adherence. For the six studies in which short-term adherence was assessed (between 3 and 7 days), the proportion non-adherent ranged from 6.9 to 37.2% [12,17–21]. Nonadherence ranged from 17.2 to 37.2% among studies that measured medium-term to long-term self-reported adherence (missed doses during last month/ever) [10,22–26]. Among the three studies that measured 30-day adherence using a Visual Analogue Scale, nonadherence ranged from 2 to 50% [13,27,28]. Although most studies focussed upon adherence to HAART medication, nonadherence to scheduling and dietary instructions (29.1%) was also assessed in a South African study .
Mental disorder and adherence to antiretroviral therapy
Eight studies were prospective. The effects of depression upon adherence were assessed in six of these studies, with significant associations reported in five. In an Ethiopian cohort, after adjusting for confounders, those without depression were twice as likely to be adherent at baseline [adjusted odds ratio (AOR) = 2.13, 1.18–3.85] . However, this relationship was not significant at 3-month follow-up. Among participants who had just initiated ART in a South African study, after adjusting for confounders, depression was associated with two measures of nonadherence (AOR = 1.14, 1.04–1.25; AOR = 1.41, 1.25–1.61) . In a Ugandan sample, depression was found to be associated with poor adherence (AOR = 3.13, 1.08–9.09) . Studies carried out in Nigeria and Peru reported crude associations between depression and nonadherence (multivariate analysis was not carried out) [15,22]. In an urban Brazilian sample of those who had just initiated ART, although after adjusting for confounders severe anxiety was found to be associated with poor adherence at 7-month follow-up (AOR = 1.87, 1.27–2.73), there was no evidence of any association between depression and adherence .
The effects of alcohol use upon adherence were assessed in three prospective studies. In a Brazilian sample, after adjusting for confounders, alcohol use was found to be associated with nonadherence (AOR = 1.87, 1.27–2.73) , and in a Nigerian study, a crude association between hazardous alcohol use and nonadherence was reported . However, in a study carried out in South Africa, no evidence of any association between alcohol use or hazardous alcohol use and adherence was identified . Both Latin American studies reporting on substance use found it was associated with nonadherence in bivariate analysis [18,22]. In Brazil, lifetime IDU (but not drug use in the last month) was associated with nonadherence [odds ratio (OR) = 2.20, 1.18–4.11] ; however, in multivariate analysis, this association did not persist. In Peru, substance use was associated with greatly increased odds of nonadherence (OR = 5.75, 1.36–24.39) . Among an Indonesian sample, no association was found between a history of IDU and nonadherence .
Among the South African sample, quality of life (QoL) was associated with adherence, based on 4-day recall (AOR for nonadherence = 0.49, 0.25–0.93) ; in the same study, no association between QoL and 30-day adherence was found. Similarly, among Peruvian and Chinese samples, those with good adherence had higher QoL scores [22,19].
Twelve cross-sectional studies were identified. Seven studies examined the relationship between depression and nonadherence. In three out of four studies, multivariate analysis found evidence to support an association between depression and nonadherence: among a sample from Botswana , in Uganda, AOR = 3.66 (1.39–9.78) , in a multisite study with participants from five African countries, AOR = 1.75 (1.19–2.56) , and among a sample in South India AOR = 3.32 (1.19–9.26) . In another study from India, high reported distress was associated with poor adherence . Among Nigerian and Ethiopian samples, crude associations between depression and nonadherence were reported [29,30].
The association between alcohol use and adherence was assessed in nine cross-sectional studies. All of these found that alcohol was associated with nonadherence. This included seven studies in which multivariate analyses were carried out: two were multisite, with participants from four west African countries (association found between ‘some’ consumption of alcohol and hazardous drinking and nonadherence, AOR = 1.40, 1.1–2.0; AOR = 4.70, 2.6–8.6, respectively) ; and five other African countries, wherein ‘never’ consuming alcohol was associated with reduced odds of nonadherence (AOR = 0.47, 0.30–0.74) . Particularly strong associations with nonadherence were reported from two Ethiopian studies, AOR = 4.76 (1.61–14.29)  and AOR = 3.57 (1.78–7.14) ; in the second study, an association was identified between consuming alcohol ‘most of the time’ and nonadherence; no evidence to support association between ‘sometimes’ consuming alcohol and nonadherence was found. Similarly, in India, multivariate analysis showed that alcohol use was associated with nonadherence, AOR = 5.68 (2.10–15.32). In Botswana, alcohol use was found to be associated with nonadherence . Two studies reported crude associations between alcohol use and nonadherence [23,25]. Among an Ethiopian sample, ‘hard drugs’ use was associated with increased odds of nonadherence (AOR = 0.04, 0.01–0.32) .
Mental illness and other indicators of engagement with HIV services
Six cross-sectional studies were identified. Two studies examined the relationship between mental health and late presentation to care after initial diagnosis of HIV/AIDS. Late presentation was defined by WHO disease stage III/VI or CD4 cell count of less than 200 at time of arrival at treatment services. Among an Ethiopian sample, reporting alcohol use ‘most of the time’ (but not ‘some of the time’) was associated with late presentation (AOR = 3.60, 1.63–7.71) . Contrastingly, in Uganda, both moderate and hazardous alcohol use were found to be associated with early presentation at care (AOR = 0.49, 0.33–0.78 and AOR = 0.60, 0.46–0.78, respectively) . In Cameroon, binge-drinking was associated with increased odds of unplanned treatment interruptions (AOR = 2.87, 1.39–5.91) . In Uganda, those who were abstinent from alcohol were more likely to be receiving ART (AOR = 2.27, 1.30–3.98) ; in the same study, no association was found between depression and receipt of ART. In Iran, being on ART was not associated with depression . Contrastingly, among a Chinese sample, those not receiving ART were more likely to be depressed  (Table 2).
Table 2-a Details of...Image Tools
Mental illness and HIV-related clinical outcomes
Table 2-b Details of...Image Tools
Five studies were identified, of which two were prospective. In South Africa, investigators found that among those initiating ART in a community-based treatment programme, consumption of more than 21 units of alcohol per week was associated with poor treatment outcomes (high viral load/discontinuation; AOR = 15.36, 3.22–73.27) . This association was not found among participants from a workplace treatment programme sampled in the same study. In their analysis of four datasets containing information about all Brazilians with a HIV-positive diagnosis between 2000 and 2006, researchers found that IDU was associated with higher AIDS-related mortality (AOR = 1.94, 1.84–2.05) . In an Indonesian study, drug use was associated with a need for antiretroviral substitutions . Otherwise, in this and two other studies carried out in Brazil and Vietnam, no association was found between factors associated with drug and alcohol use and indicators of clinical status [8,35,21] (Table 3).
Table 3-a Details of...Image Tools
HIV clinical status as predictors of mental health outcomes
Table 3-b Details of...Image Tools
Nine studies were identified; two of these were prospective. Among a small South African sample, although there was evidence of an association between a declining CD4 cell count and major depression after 6 months of follow-up in bivariate analyses, this association did not persist in multivariate analysis . In a large study carried out in Uganda, baseline high viral load, low CD4 cell count, and depression were found to be associated with poor mental health QoL score at 12 months .
Seven studies were cross-sectional. Of these, four examined the effects of clinical factors upon QoL. Among an Ethiopian sample, in multivariate analysis, longer duration of treatment was associated with increased QoL (there was no association between CD4 and QoL) . In Uganda, neither CD4 cell count nor duration of treatment was found to be associated with mental health summary score . In a sample of women from Zimbabwe, out of a range of clinical indicators, only CD4 cell category was found to be associated with mental health summary score . Lastly, in a small North Indian sample, having HIV symptoms but not an AIDS diagnosis was associated with lower QoL . Three studies examined the effects of clinical factors upon depression. Among a sample of those undergoing ART eligibility screening in Uganda, having a CD4 cell count of less than 50 or between 50 and 99 was associated with increased odds of depression (AOR = 2.02, 1.22–3.36 and AOR = 2.34, 1.39–3.93, respectively) . In a Chinese sample, no association was found between time since diagnosis, being symptomatic, and depression . In the same study, no associations were identified between any of the clinical variables and anxiety or stress. Among a Brazilian sample, being symptomatic was associated with depression .
Mental health interventions
Of the seven trials of mental health interventions, only two were properly randomized controlled trials. In Uganda, investigators studied the effect of computer-based cognitive rehabilitation therapy or usual care on cognitive outcomes among HIV-positive children . Among a Chinese sample, researchers studied the effect of home visits and telephone support provided by nurses on QoL and adherence among participants with a history of heroin use . A trial conducted in Nigeria to examine the impact of four weekly psychoeducation sessions upon mental health outcomes is best considered controlled but not randomized, as allocation to intervention and waiting list control arms was consecutive . In a South African trial of a peer mentoring and cognitive behavioural intervention, the mental health of HIV-positive mothers accessing Prevention of Mother to Child Transmission (PMTCT) services at sites where the intervention was available was compared with that of HIV-positive women receiving normal PMTCT services at a different site; hence, this trial was also controlled but not randomized. None of the interventions blinded researchers to allocation or outcome measurement . Other than this, the relevant literature comprises two small case series evaluations of cognitive behavioural therapy (CBT), one for major depression in South Africa  and the other for alcohol use disorder in Kenya , and a large-scale nonrandomized and noncontrolled evaluation of a programme designed to improve adherence and outcomes among paediatric patients on ART in Kenya  (Table 4).
In the Chinese randomized controlled trial of nurse home visits and telephone support, outcomes among participants with a history of heroin use were assessed after 8 months . Those allocated to the intervention group were more likely to have complete adherence (47 versus 30% among controls, P < 0.01). The intervention also had significant positive effects upon depression and physical, social, and environmental domains of QoL. Among HIV-positive children in Uganda randomly allocated to receive computer-based cognitive rehabilitation therapy or usual care, researchers found that those in the intervention arm showed greater improvement in cognitive test scores after 10 sessions .
For those trials that were controlled but not randomized, the research team in Nigeria report significantly greater reduction in depression and neurotic symptom scores at 4 weeks among those with recently diagnosed HIV assigned to four weekly psychoeducation sessions compared to wait list controls, and significantly greater increases in safe sex practices and disclosure to significant others . In South Africa, researchers report that for pregnant women living with HIV, those receiving care at sites where peer mentoring and cognitive behavioural intervention was provided when compared to those receiving care at other sites, reported greater availability of social support (9.32 point difference with control group, SE = 3.53) and lower depression scores (−4.43 point difference, SE = 1.62; although there was no difference in scores for those women who scored >16 on the CES-D) .
In the two small CBT case series, in South Africa it was shown that five out of six participants taking part in individual CBT for major depression showed a reduction in depressive symptoms , whereas in Kenya, there was an increase in number of days abstinent among 27 drinkers who took part in a pilot study to evaluate the effectiveness of individualized CBT for reducing consumption of alcohol . In Kenya, researchers described an evaluation of a programme designed to improve adherence and outcomes among paediatric patients on ART, of which psychosocial support activities including support groups and art therapy for patients and their carers were key components. A total of 95.27% of programme participants were alive after 12 months of receipt of ART .
The large number of observational studies included in this review attests to the increasing recognition of the potential relevance of mental disorders and related psychosocial factors to the management of HIV/AIDS and other chronic conditions . In a review published in 2006 , only four studies were identified that examined the relationship between psychological factors and adherence to ART. In the current review, we identified 20 studies investigating the effects of mental health upon adherence, and a further six studies that assessed impact upon other indicators of engagement with HIV services.
There is now ample and quite consistent evidence from observational studies conducted in LMIC treatment settings that adverse mental health and alcohol consumption are associated with reduced adherence to antiretroviral treatment. Ten out of 12 studies reported that symptoms of depression were associated with poor adherence, whereas 10 out of 11 studies presented evidence to suggest that those who used alcohol were less likely to achieve good adherence. However, limitations of study design and measurement limit the reliability and generalizability of these findings. Heterogeneity in prevalence of adherence is likely to reflect true differences between settings and populations as well as being a manifestation of variation in measurement. The range of prevalence was similarly broad among studies that measured short-term adherence (7–37%) and long-term adherence (2–50%), but more consistent among the three studies that checked clinical records or conducted an unannounced pill-count (10.4–13.6%). In most cases, small samples led to a high degree of uncertainty as to the true effect size of mental health exposures upon adherence. Lack of detailed standardized assessments of alcohol use meant that it was difficult to ascertain what it is about consuming alcohol that may inhibit adherence. It is unclear whether any consumption of alcohol is a matter for concern, or only consumption at levels that would normally be considered ‘hazardous’ or ‘harmful’. Likewise the impact of binge-drinking patterns of consumption (particularly common in some LMIC cultures), and alcohol dependence is unclear. Six studies examined the relationship between mental disorder and engagement with HIV services, and similar methodological difficulties pertain. Although three studies found alcohol use to be associated with negative outcomes (unplanned treatment interruptions, late presentation, nonreceipt of ART), a Ugandan study found alcohol use was associated with early presentation at care . One out of three studies found evidence of an association between depression and receipt of ART.
Much less research has been carried out into the impact of mental and cognitive comorbidity upon HIV clinical outcomes. The large national Brazilian cohort study provides compelling evidence of increased mortality on ART for those with a history of IDU , and a South African study found alcohol use was associated with poor clinical outcomes among those enrolled in a community-based treatment programme . Several studies look for evidence to support associations in the opposite direction, with adverse HIV clinical status leading to depression and impaired QoL, but as most of these were cross-sectional in design, the direction of causality could not be established, and results were somewhat inconsistent. Bidirectional effects are plausible.
The contribution of alcohol use and depression to reduced adherence and clinical outcomes is now relatively well established in high-income settings. Two recent systematic reviews have confirmed the relationship between alcohol use disorders  and alcohol use and poor adherence in high-income settings . Frequent alcohol use has also been found to be associated with poor clinical outcomes in longitudinal research (AOR for CD4 cell count of less than 200 comparing frequent drinkers with nondrinkers = 2.91) . Alongside social support, knowledge of treatment, quality of relationship with healthcare provider, side-effects and dosage burden, depression has been recognized as one of a range of psychosocial factors found to inhibit adherence . The findings of this review indicate that it is plausible that depression plays a similar role in LMIC. Although, due to a paucity of research, little is known about the direction of any association, this review provides some evidence to suggest that depression may be linked to negative outcomes in LMIC. In high-income settings, depression has been found to be associated with disease progression , even after controlling for the effects of adherence .
The very limited evidence from LMIC on the efficacy and effectiveness of mental health interventions in the context of HIV care stands in stark contrast to the growth of the evidence base from observational studies. Just two small randomized controlled trials were identified, both providing some evidence of positive benefits, for nurse visits and telephone support on adherence and QoL among heroin users in China, and for cognitive rehabilitation on cognitive test scores among children in South Africa.
Research carried out in high income countries (HIC) indicates that psychological interventions among people living with HIV/AIDS are generally effective in producing small-to-moderate improvements in depressive symptoms. A review of eight randomized, double-blinded trials of group psychotherapy interventions to reduce depressive symptoms found a moderate pooled effect size of 0.38 (0.23–0.53) . Reviews of 35 randomised controlled trials (RCTs) of stress management interventions  and 15 trials of CBT for depression and anxiety identified similar moderate improvements in symptoms . Comparatively fewer trials of mental health interventions to improve adherence or clinical outcomes have been carried out. In a two-arm, randomized, controlled, cross-over trial comparing CBT to improve adherence with treatment as usual, investigators found a large difference in adherence improvement (d = 1.00), maintained at 6-month and 12-month follow-up . However, fostering long-term improvements in adherence is challenging: another RCT that examined the effects of CBT upon adherence found that 10–13% relative improvements between the intervention and the control arm at 15 months had dissipated by 20 and 25 months .
Recent research carried out in the UK highlights the importance of health and treatment-related beliefs in determining adherence behaviours. Perceptions of need (which tend to be driven by persistence of symptoms) and concerns about adverse effects (such as treatment side-effects) have been found to predict adherence to ART over time . In order to maximize the impact of interventions designed to improve mental health and HIV-related treatment outcomes, it will be important to ensure that there is clear understanding of the HIV disease model (and how measures of disease progression such as CD4 cell counts relate to this) . Integration of effective management of treatment side-effects into interventions is also likely to be important.
This review provides tentative evidence to suggest that psychosocial factors, in particular, consumption of alcohol and depression may contribute to adverse HIV-related outcomes, namely, poor adherence to HAART, suboptimal engagement with HIV services, and worse HIV clinical outcomes. Consistency with findings from research carried out in HIC suggests that these associations are plausible. However, there is an urgent need for further large, high-quality observational studies in LMIC, in order to test the generalizability of these associations, to measure the size of any effects more precisely, and to seek to understand mechanisms underlying the associations. Longitudinal research will be important to elucidate the relationship between mental health and HIV-related outcomes over time. A key question for future research is how does mental health interact with health perceptions and behaviours, including traditional beliefs and the use of traditional medicines, symptoms, and biomedical treatments? Given the links between cognitive impairment and HIV/AIDS and the evidence from HIC to suggest that cognitive impairment may be associated with poor adherence , it will also be important to investigate the role of cognitive impairment in adherence and engagement with treatment in LMIC.
Despite evidence to suggest that treatment interruption and discontinuation may be a significant problem in treatment programmes in LMIC [64,65], leading to increased morbidity and mortality, it is interesting to note that only two of the studies included in this review examined the relationship between mental health and discontinuation/unplanned treatment interruptions. Recent research in the United States showed that depression and stimulant use predicted disease progression and mortality, and that these associations were mediated by interruption of ART . Therefore, future research should consider the wider effects of mental health upon the different components of the continuum of care, rather than limiting the scope of research questions to a narrow focus upon adherence.
Lastly, in settings in which the links between poor mental health and poor treatment outcomes are confirmed, there is an urgent need for properly randomized controlled trials of mental health interventions, aiming to improve mental health, engagement with care (including adherence), and enhance treatment outcomes. The most important research questions in this area are as follows: what treatments are effective for mental disorder among people living with HIV/AIDS in low-income settings and what is the impact of these interventions upon HIV-related outcomes? Reviewing the evidence of successful interventions from HIC settings may be important in aiding the design of interventions for trial in LMIC. However, apart from the obvious considerations about the relevance of these findings in culturally and sociodemographically different settings (trials carried out in HIC tend to be dominated by white men), it is imperative that interventions introduced in resource-poor settings are cost-effective and well integrated into HIV care delivery systems in which they are based. Given that there are insufficient mental health specialists to close the enormous treatment gap for mental disorders in resource poor settings, ‘task-shifting’ (training and supporting nonspecialist health workers to deliver mental healthcare) will be an essential element of these packages of care . Ensuring that interventions have a broad focus, taking account of symptoms, side-effects, and health beliefs as well as mental health may improve their effectiveness and increase the sustainability of any positive behavioural changes.
V.P. is supported by a Wellcome Trust Senior Research Fellowship in Clinical Science
Conflicts of interest
The authors have no conflicts of interest to declare.
1. Ciesla JA, Roberts JE. Meta-analysis of the relationship between HIV infection and risk for depressive disorders. Am J Psychiatry 2001; 158:725–730.
2. Bing EG, Burnam MA, Longshore D, Fleishman JA, Sherbourne CD, London AS, et al. Psychiatric disorders and drug use among human immunodeficiency virus-infected adults in the United States. Arch Gen Psychiatry 2001; 58:721–728.
3. Ickovics JR, Hamburger ME, Vlahov D, Schoenbaum EE, Schuman P, Boland RJ, Moore J. HIV Epidemiology Research Study GroupMortality, CD4 cell count decline, and depressive symptoms among HIV-seropositive women: longitudinal analysis from the HIV Epidemiology Research Study. JAMA 2001; 285:1466–1474.
4. Ammassari A, Trotta MP, Murri R, Castelli F, Narciso P, Noto P, et al. AdICoNA Study GroupCorrelates and predictors of adherence to highly active antiretroviral therapy: overview of published literature. J Acquir Immune Defic Syndr 2002; 31 (Suppl 3):S123–S127.Review.
5. Collins PY, Holman AR, Freeman MC, Patel V. What is the relevance of mental health to HIV/AIDS care and treatment programs in developing countries? A systematic review. AIDS 2006; 20:1571–1582.Review.
6. Mello VA, Segurado AA, Malbergier A. Depression in women living with HIV: clinical and psychosocial correlates. Arch Womens Ment Health 2010; 13:193–199.Epub 2009 Sep 16.
7. Patel R, Kassaye S, Gore-Felton C, Wyshak G, Kadzirange G, Woelk G, Katzenstein D. Quality of life, psychosocial health, and antiretroviral therapy among HIV-positive women in Zimbabwe. AIDS Care 2009; 21:1517–1527.
8. Báez Feliciano DV, Gómez MA, Fernández-Santos DM, Quintana R, Rios-Olivares E, Hunter-Mellado RF. Profile of Puerto Rican HIV/AIDS patients with early and nonearly initiation of injection drug use. Ethn Dis 2008; 18 (2 Suppl 2):S2-99–S2-104.
9. Malta M, Bastos FI, da Silva CM, Pereira GF, Lucena FF, Fonseca MG, Strathdee SA. Differential survival benefit of universal HAART access in Brazil: a nation-wide comparison of injecting drug users versus men who have sex with men. J Acquir Immune Defic Syndr 2009; 52:629–635.
10. Etienne M, Hossain M, Redfield R, Stafford K, Amoroso A. Indicators of adherence to antiretroviral therapy treatment among HIV/AIDS patients in 5 African countries. J Int Assoc Physicians AIDS Care (Chic) 2010; 9:98–103.Epub 2010 Mar.
11. Deribe K, Hailekiros F, Biadgilign S, Amberbir A, Beyene BK. Defaulters from antiretroviral treatment in Jimma University Specialized Hospital, Southwest Ethiopia. Trop Med Int Health 2008; 13:328–333.Epub 2008 Feb 21.
12. Jaquet A, Ekouevi DK, Bashi J, Aboubakrine M, Messou E, Maiga M, et al. Alcohol use and nonadherence to antiretroviral therapy in HIV-infected patients in West Africa. Addiction 2010; 105:1416–1421.Epub 2010 Jun 7.
13. Peltzer K, Friend-du Preez N, Ramlagan S, Anderson J. Antiretroviral treatment adherence among HIV patients in KwaZulu-Natal, South Africa. BMC Public Health 2010; 10:111.
14. Kigozi IM, Dobkin LM, Martin JN, Geng EH, Muyindike W, Emenyonu NI, et al. Late-disease stage at presentation to an HIV clinic in the era of free antiretroviral therapy in Sub-Saharan Africa. J Acquir Immune Defic Syndr 2009; 52:280–289.
15. Farley J, Miller E, Zamani A, Tepper V, Morris C, Oyegunle M, et al. Screening for hazardous alcohol use and depressive symptomatology among HIV-infected patients in Nigeria: prevalence, predictors, and association with adherence. J Int Assoc Physicians AIDS Care (Chic) 2010; 9:218–226.
16. Beyene KA, Gedif T, Gebre-Mariam T, Engidawork E. Highly active antiretroviral therapy adherence and its determinants in selected hospitals from south and central Ethiopia. Pharmacoepidemiol Drug Saf 2009; 18:1007–1015.
17. Amberbir A, Woldemichael K, Getachew S, Girma B, Deribe K. Predictors of adherence to antiretroviral therapy among HIV-infected persons: a prospective study in Southwest Ethiopia. BMC Public Health 2008; 8:265.
18. Campos LN, Guimarães MD, Remien RH. Anxiety and depression symptoms as risk factors for nonadherence to antiretroviral therapy in Brazil. AIDS Behav 2010; 14:289–299.Epub 2008 Jul 22.
19. Wang H, Zhou J, He G, Luo Y, Li X, Yang A, et al. Consistent ART adherence is associated with improved quality of Life, CD4 counts, and reduced hospital costs in central China. AIDS Res Hum Retroviruses 2009; 25:757–763.
20. Abera K, Gedif T, Engidawork E, Gebre-Mariam T. Quality of life of people living with HIV/AIDS and on highly active antiretroviral therapy in Ethiopia. Afr J AIDS Res 2010; 9:31–40.
21. Wisaksana R, Indrati AK, Fibriani A, Rogayah E, Sudjana P, Djajakusumah TS, et al. Response to first-line antiretroviral treatment among human immunodeficiency virus-infected patients with and without a history of injecting drug use in Indonesia. Addiction 2010; 105:1055–1061.Epub 2010 Mar 10.
22. Shin S, Muñoz M, Espiritu B, Zeladita J, Sanchez E, Callacna M, et al. Psychosocial impact of poverty on antiretroviral nonadherence among HIV-TB coinfected patients in Lima, Peru. J Int Assoc Physicians AIDS Care (Chic) 2008; 7:74–81.Epub 2008 Mar 4.
23. Bhat VG, Ramburuth M, Singh M, Titi O, Antony AP, Chiya L, et al. Factors associated with poor adherence to antiretroviral therapy in patients attending a rural health centre in South Africa. Eur J Clin Microbiol Infect Dis 2010; 29:947–953.Epub 2010 May 14.
24. Nakimuli-Mpungu E, Mutamba B, Othengo M, Musisi S. Psychological distress and adherence to highly active antiretroviral therapy (HAART) in Uganda: a pilot study. Afr Health Sci 2009; 9 (Suppl 1):S2–7.
25. Sharma M, Singh RR, Laishram P, Kumar B, Nanao H, Sharma C, Ahmed T. Access, adherence, quality and impact of ARV provision to current and ex-injecting drug users in Manipur (India): an initial assessment. Int J Drug Policy 2007; 18:319–325.Epub 2007 Jun 21.
26. Do NT, Phiri K, Bussmann H, Gaolathe T, Marlink RG, Wester CW. Psychosocial factors affecting medication adherence among HIV-1 infected adults receiving combination antiretroviral therapy (cART) in Botswana. AIDS Res Hum Retroviruses 2010; 26:685–691.
27. Byakika-Tusiime J, Crane J, Oyugi JH, Ragland K, Kawuma A, Musoke P, Bangsberg DR. Longitudinal antiretroviral adherence in HIV+ Ugandan parents and their children initiating HAART in the MTCT-Plus family treatment model: role of depression in declining adherence over time. AIDS Behav 2009; 13 (Suppl 1):82–91.Epub 2009.
28. Venkatesh KK, Srikrishnan AK, Mayer KH, Kumarasamy N, Raminani S, Thamburaj E, et al. Predictors of nonadherence to highly active antiretroviral therapy among HIV-infected South Indians in clinical care: implications for developing adherence interventions in resource-limited settings. AIDS Patient Care STDS 2010; 24:795–803.Epub 2010 Nov 22.
29. Adewuya AO, Afolabi MO, Ola BA, Ogundele OA, Ajibare AO, Oladipo BF, Fakande I. The effect of psychological distress on medication adherence in persons with HIV infection in Nigeria. Psychosomatics 2010; 51:68–73.
30. Tadios Y, Davey G. Antiretroviral treatment adherence and its correlates in Addis Ababa, Ethiopia. Ethiop Med J 2006; 44:237–244.
31. Dahab M, Charalambous S, Karstaedt AS, Fielding KL, Hamilton R, La Grange L, et al. Contrasting predictors of poor antiretroviral therapy outcomes in two South African HIV programmes: a cohort study. BMC Public Health 2010; 10:430.
32. Abaynew Y, Deribew A, Deribe K. Factors associated with late presentation to HIV/AIDS care in South Wollo Zone Ethiopia: a case-control study. AIDS Res Ther 2011; 8:8.
33. Marcellin F, Boyer S, Protopopescu C, Dia A, Ongolo-Zogo P, Koulla-Shiro S, et al. EVAL Study GroupDeterminants of unplanned antiretroviral treatment interruptions among people living with HIV in Yaoundé, Cameroon (EVAL survey, ANRS 12-116). Trop Med Int Health 2008; 13:1470–1478.Epub 2008 Nov 5.
34. Martinez P, Andia I, Emenyonu N, Hahn JA, Hauff E, Pepper L, Bangsberg DR. Alcohol use, depressive symptoms and the receipt of antiretroviral therapy in southwest Uganda. AIDS Behav 2008; 12:605–612.Epub 2007 Oct 30.
35. Jordan MR, La H, Nguyen HD, Sheehan H, Lien TT, Duong DV, et al. Correlates of HIV-1 viral suppression in a cohort of HIV-positive drug users receiving antiretroviral therapy in Hanoi, Vietnam. Int J STD AIDS 2009; 20:418–422.
36. Olley BO, Seedat S, Stein DJ. Persistence of psychiatric disorders in a cohort of HIV/AIDS patients in South Africa: a 6-month follow-up study. J Psychosom Res 2006; 61:479–484.
37. Stangl AL, Wamai N, Mermin J, Awor AC, Bunnell RE. Trends and predictors of quality of life among HIV-infected adults taking highly active antiretroviral therapy in rural Uganda. AIDS Care 2007; 19:626–636.
38. Bajunirwe F, Tisch DJ, King CH, Arts EJ, Debanne SM, Sethi AK. Quality of life and social support among patients receiving antiretroviral therapy in western Uganda. AIDS Care 2009; 21:271–279.
39. Wig N, Lekshmi R, Pal H, Ahuja V, Mittal CM, Agarwal SK. The impact of HIV/AIDS on the quality of life: a cross sectional study in north India. Indian J Med Sci 2006; 60:3–12.
40. Kaharuza FM, Bunnell R, Moss S, Purcell DW, Bikaako-Kajura W, Wamai N, et al. Depression and CD4 cell count among persons with HIV infection in Uganda. AIDS Behav 2006; 10 (4 Suppl):S105–S111.
41. Khochak HE, Noorifard M, Kashi AH, Arbabi M, Kheirandish P, Badie BM, Rasoolinejad M. Evaluation of depression in HIV/AIDS patients refering to behavioral counselling center of Imam Khomeini Hospital. Acta Medica Iranica 2009; 47:193–196.
42. Yu XN, Lau JT, Mak WW, Cheng YM, Lv YH, Zhang JX. Risk and protective factors in association with mental health problems among people living with HIV who were former plasma/blood donors in rural China. AIDS Care 2009; 21:645–654.
43. Boivin MJ, Busman RA, Parikh SM, Bangirana P, Page CF, Opoka RO, Giordani B. A pilot study of the neuropsychological benefits of computerized cognitive rehabilitation in Ugandan children with HIV. Neuropsychology 2010; 24:667–673.
44. Wang H, Zhou J, Huang L, Li X, Fennie KP, Williams AB. Effects of nurse-delivered home visits combined with telephone calls on medication adherence and quality of life in HIV-infected heroin users in Hunan of China. J Clin Nurs 2010; 19:380–388.
45. Olley BO. Improving well being through psycho-education among voluntary counseling and testing seekers in Nigeria: a controlled outcome study. AIDS Care 2006; 18:1025–1031.
46. Futterman D, Shea J, Besser M, Stafford S, Desmond K, Comulada WS, Greco E. Mamekhaya: a pilot study combining a cognitive-behavioral intervention and mentor mothers with PMTCT services in South Africa. AIDS Care 2010; 22:1093–1100.
47. Andersen L. Effectiveness of cognitive-behavioral therapy on the reduction of depression in people infected with HIV/AIDS in South Africa HOFSTRA University; 2009.
48. Papas RK, Sidle JE, Martino S, Baliddawa JB, Songole R, Omolo OE, et al. Systematic cultural adaptation of cognitive-behavioral therapy to reduce alcohol use among HIV-infected outpatients in western Kenya. AIDS Behav 2010; 14:669–678.
49. Van Winghem J, Telfer B, Reid T, Ouko J, Mutunga A, Jama Z, Vakil S. Implementation of a comprehensive program including psycho-social and treatment literacy activities to improve adherence to HIV care and treatment for a pediatric population in Kenya. BMC Pediatr 2008; 8:52.
50. Mills EJ, Nachega JB, Bangsberg DR, Singh S, Rachlis B, Wu P, et al. Adherence to HAART: a systematic review of developed and developing nation patient-reported barriers and facilitators. PLoS Med 2006; 3:e438Review.
51. Cook JA, Grey D, Burke J, Cohen MH, Gurtman AC, Richardson JL, et al. Depressive symptoms and AIDS-related mortality among a multisite cohort of HIV-positive women. Am J Public Health 2004; 94:1133–1140.
52. Azar MM, Springer SA, Meyer JP, Altice FL. A systematic review of the impact of alcohol use disorders on HIV treatment outcomes, adherence to antiretroviral therapy and healthcare utilization. Drug Alcohol Depend 2010; 112:178–193.Epub 2010 Aug 11. Review.
53. Hendershot CS, Stoner SA, Pantalone DW, Simoni JM. Alcohol use and antiretroviral adherence: review and meta-analysis. J Acquir Immune Defic Syndr 2009; 52:180–202.Review.
54. Baum MK, Rafie C, Lai S, Sales S, Page JB, Campa A. Alcohol use accelerates HIV disease progression. AIDS Res Hum Retroviruses 2010; 26:511–518.
55. Prince M, Patel V, Saxena S, Maj M, Maselko J, Phillips MR, Rahman A. No health without mental health. Lancet 2007; 370:859–877.Review.
56. Himelhoch S, Medoff DR, Oyeniyi G. Efficacy of group psychotherapy to reduce depressive symptoms among HIV-infected individuals: a systematic review and meta-analysis. AIDS Patient Care STDS 2007; 21:732–739.Review.
57. Scott-Sheldon LA, Kalichman SC, Carey MP, Fielder RL. Stress management interventions for HIV+ adults: a meta-analysis of randomized controlled trials, 1989 to 2006. Health Psychol 2008; 27:129–133.
58. Crepaz N, Passin WF, Herbst JH, Rama SM, Malow RM, Purcell DW, Wolitski RJ. HIV/AIDS Prevention Research Synthesis TeamMeta-analysis of cognitive-behavioral interventions on HIV-positive persons’ mental health and immune functioning. Health Psychol 2008; 27:4–14.
59. Safren SA, O’Cleirigh C, Tan JY, Raminani SR, Reilly LC, Otto MW, Mayer KH. A randomized controlled trial of cognitive behavioral therapy for adherence and depression (CBT-AD) in HIV-infected individuals. Health Psychol 2009; 28:1–10.
60. Johnson MO, Charlebois E, Morin SF, Remien RH, Chesney MA. National Institute of Mental Health Healthy Living Project TeamEffects of a behavioral intervention on antiretroviral medication adherence among people living with HIV: the healthy living project randomized controlled study. J Acquir Immune Defic Syndr 2007; 46:574–580.
61. Gonzalez JS, Penedo FJ, Llabre MM, Durán RE, Antoni MH, Schneiderman N, Horne R. Physical symptoms, beliefs about medications, negative mood, and long-term HIV medication adherence. Ann Behav Med 2007; 34:46–55.
62. Horne R, Cooper V, Gellaitry G, Date HL, Fisher M. Patients’ perceptions of highly active antiretroviral therapy in relation to treatment uptake and adherence: the utility of the necessity-concerns framework. J Acquir Immune Defic Syndr 2007; 45:334–341.
63. Lovejoy TI, Suhr JA. The relationship between neuropsychological functioning and HAART adherence in HIV-positive adults: a systematic review. J Behav Med 2009; 32:389–405.Epub 2009 Mar 17. Review.
64. Brinkhof MW, Dabis F, Myer L, Bangsberg DR, Boulle A, Nash D, et al. ART-LINC, IeDEAEarly loss of HIV-infected patients on potent antiretroviral therapy programmes in lower-income countries. Bull World Health Organ 2008; 86:559–567.
65. Amuron B, Namara G, Birungi J, Nabiryo C, Levin J, Grosskurth H, et al. Mortality and loss-to-follow-up during the pretreatment period in an antiretroviral therapy programme under normal health service conditions in Uganda. BMC Public Health 2009; 9:290.
66. Carrico AW, Riley ED, Johnson MO, Charlebois ED, Neilands TB, Remien RH, et al. Psychiatric risk factors for HIV disease progression: the role of inconsistent patterns of antiretroviral therapy utilization. J Acquir Immune Defic Syndr 2011; 56:146–150.
adherence; alcohol; depression; engagement with services; low and middle income settings; mental health interventions
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