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Mental, Neurological, and Substance Use Disorders in People Living With HIV/AIDS in Low- and Middle-Income Countries

Chibanda, Dixon MD, MMed Psychiatry, MPH*,†; Benjamin, Laura MD, PhD‡,§,‖; Weiss, Helen A. BSc, MSc, PhD; Abas, Melanie MSc, MPhil, MD*,#

JAIDS Journal of Acquired Immune Deficiency Syndromes: September 1st, 2014 - Volume 67 - Issue - p S54–S67
doi: 10.1097/QAI.0000000000000258
Supplement Article
Free

Abstract: Depression, alcohol use disorders (AUD), and neurocognitive disorders are the 3 most prevalent mental, neurological, and substance use disorders in people living with HIV infection in low- and middle-income countries (LMICs). Importantly, they have an impact on everyday functions and on HIV outcomes. Many LMICs have validated tools to screen for and diagnose depression and AUD in the general population that can be used among people living with HIV infection. Current screening and diagnostic methods for HIV-associated neurocognitive disorders in the era of antiretroviral therapy are suboptimal and require further research. In our view, 2 research priorities are most critical. One is the development of an integrated screening approach for depression, AUD, and neurocognitive disorders that can be used by nonspecialists in LMICs. Second, research is needed on interventions for depression and AUD that also target behavior change, as these could impact on adherence to antiretroviral therapy and improve mental symptoms. Mentorship and fellowship schemes at an individual and institutional level need to be further supported to build capacity and provide platforms for research on HIV and mental, neurological, and substance use disorders in LMICs.

*Department of Psychiatry, University of Zimbabwe, Harare, Zimbabwe;

Zimbabwe Aids Prevention Project, Department of Community Medicine, University of Zimbabwe, Harare, Zimbabwe;

Institute of Infection and Global Health, University of Liverpool, Liverpool, United Kingdom;

§Malawi-Liverpool-Wellcome Major Overseas Clinical Research Programme, College of Medicine, University of Malawi, Blantyre, Malawi;

The Walton Centre NHS Foundation Trust, Department of Neurology, Liverpool, UK;

MRC Tropical Epidemiology Group, Faculty of Epidemiology and Population Health, London School of Hygiene and Tropical Medicine, London, United Kingdom; and

#King's College London Institute of Psychiatry, United Kingdom.

Correspondence to: Dixon Chibanda, MD, MMed Psychiatry, MPH, Department of Psychiatry, University of Zimbabwe, P.O. Box A178, Harare, Zimbabwe (e-mail: dichi@zol.co.zw).

D.C. is supported by a Fogarty Research Fellowship and a Grand Challenges Canada grant. L.B. is supported by the Wellcome Trust, United Kingdom. D.C. and M.A. are supported by the National Institute of Mental Health (1R21MH094156-01A1). H.A.W. is funded by the United Kingdom Medical Research Council.

The authors have no conflicts of interest to disclose.

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INTRODUCTION

Many mental, neurological, and substance use (MNS) disorders are more prevalent among people living with HIV infection (PLWH) than among non–HIV-infected persons, adding to disability and poor quality of life.1 Several MNS disorders also directly or indirectly increase the risk of HIV treatment failure, and some also increase the risk of HIV acquisition2,3 (Fig. 1). A focus on MNS is thus fundamental to addressing both the risk of contracting HIV and health outcomes for PLWH. This article will focus on 3 conditions considered to be high-priority MNS disorders by the World Health Organization (WHO)4: depression, alcohol use disorder (AUD), and neurocognitive disorders.

FIGURE 1

FIGURE 1

There is evidence that in low- and middle-income countries (LMICs), all 3 are more prevalent among PLWH than among the general population1,5 and that in these countries, the disorders predict worse HIV clinical outcomes for PLWH2,6 (Fig. 1). In this article, we review the evidence for the relationship of each of these interlinked conditions to HIV infection, antiretroviral therapy (ART) adherence, and HIV progression in LMICs, and we outline research priorities, making recommendations for interventions using an integrated approach that prevents and treats these conditions in resource-poor settings. Where data are lacking from LMICs, we will draw evidence from high-income countries (HICs).

Because of space constraints, this article will not review HIV MNS comorbidities such as epilepsy, stroke (discussed in this issue's article on cardiovascular and pulmonary diseases by Bloomfield et al7), peripheral neuropathy, psychotic disorders, anxiety disorders, and illicit drugs.

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METHODS

We used a combination of systematic reviews of MNS disorders in PLWH conducted globally since 2005 and epidemiologic studies in LMICs since 1995. We constructed search terms to ensure that we captured studies measuring our 3 conditions of particular interest: depression, alcohol use, and neurocognitive disorder/dementia/neurocognitive impairment. We used LMIC regional names, exploding them when the database allowed and adding developing countries and low-income countries. We searched MEDLINE, EMBASE, PsycINFO, and Global Health databases. We also included literature cited in publications, when relevant.

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Depression

Background

Depression is the most common psychiatric disorder found among PLWH in LMICs.1,8–10 It adversely impacts the lives and functionality of PLWH and their families6,11,12 but remains mainly undiagnosed because few HIV care settings carry out routine screening.

Depression is defined by diagnostic (Fifth Edition of the Diagnostic and Statistical Manual of Mental Disorders [DSM-V]; International Classification of Diseases, Tenth Edition) or screening criteria based on the number and severity of symptoms and behaviors, including sadness, loss of interest, lack of pleasure, poor sleep, concentration, and appetite, and impaired social and work roles. Screening tools for depression validated in LMICs in the general population are mostly those developed in HICs, such as the Hopkins Symptoms Checklist (HSCL-25) and the Patient Health Questionnaire (PHQ-9).13–18 Challenges of diagnosing depressive disorder in PLWH in LMICs include the overlap in symptoms with HIV infection (eg, fatigue, memory loss, and weight loss)19 and how to take into account locally meaningful symptoms of depression. For instance, in Zimbabwe, Tanzania, Rwanda, South Africa, and Zambia, “thinking too much” is an important symptom of depression19–22 but does not appear in tools such as PHQ-9,23–26 although it is now recognized in DSM-V.27 Somatic symptoms, which are common and can be metaphors for distress, such as having a “heavy heart” (in Zimbabwe), are often attributed to social problems.21,25,28 Cross-cultural methods have been used in a small number of settings, whereby local informants are consulted and indigenous idioms of distress are used to develop screening tools.19,24 However, in the absence of culturally specific tools, international tools are acceptable if they are translated, back translated, and adapted to ensure the meaning stays close to the original and that the questions are understandable. If they are validated, the methods used should take into account local concepts of mental disorder.18,19,25 In Uganda, a visual depression screening tool showed good psychometric properties among PLWH with low literacy.29

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Relationship Between Depression and HIV Infection

Data from HICs show that depression is more common among PLWH than in the general population, with an estimated prevalence of 5%–20%.30 However, the magnitude of the association of depression with HIV is difficult to estimate because of variability in diagnostic criteria and measures, lack of appropriate controls, and confounding factors.31 Most studies of depression among PLWH in LMICs consisted of small clinical samples with varying methods of measurement and wide variation in reported prevalence.32 For example, some studies report more than twice the prevalence of depression in PLWH compared with matched non–HIV-infected persons,33–36 and some report a depression prevalence in PLWH of more than 30%.6,20,35,37,38 Two large studies39,40 using internationally accepted diagnostic criteria found a prevalence of major depression of 7%–8% in PLWH. These discrepancies may be due to methodological issues such as sampling and difference in HIV clinical stages. Also, depression symptoms, such as self-criticism, may be part of common reactions to an HIV diagnosis, co-existing severe life events,35 or co-existing cognitive impairment and associated posttraumatic stress disorder symptoms rather than to a depressive disorder.41–44 More than 80% of Zambians recently commenced on ART were found to have anxiety and depression symptoms severe enough to warrant additional intervention or support, and a higher burden of this psychiatric morbidity was associated with early mortality.45

Although the direct effects of HIV on depression are not well understood, studies from HICs have postulated a biological mechanism for depression in HIV infection. For example, HIV virus penetration or HIV-induced exposure to proinflammatory cytokines of the brain's basal ganglia and hippocampal regions can cause depression symptoms such as insomnia, poor concentration, and psychomotor slowing.46–48 These symptoms also overlap with HIV-associated neurocognitive disorders (HAND), prompting some to question whether depression and HAND could be part of the same disease spectrum.49

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Depression and ART Adherence

A meta-analysis of 95 independent studies from HICs showed a consistent association between depression and ART nonadherence (P < 0.0001; 95% confidence interval: 0.14–0.25),50 as did 2 systematic reviews in LMICs.2,6 One of the systematic reviews showed that 5 of 6 prospective studies and 3 of 4 cross-sectional studies using multivariate analysis had adjusted odds ratios of 1.13–3.13 for association of depression and 1.75–3.36 for nonadherence to ART.2 Poor adherence to ART at least partially explains the association between depression and increased risk of HIV disease progression.50,51 Immunological effects of depression and stress may also hasten disease progression,52 and risky behavior may confound the association between depression and HIV mortality.53 Corollary effects of suicidal ideation and negative thinking, such as forgetfulness and poor concentration, or deficits in problem-solving that come about through a depressed mood, may contribute to poor adherence.53

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Interventions to Address Depression in PLWH

A systematic review of interventions for the treatment of depression in PLWH revealed that psychological and psychotropic interventions were effective, whereas social interventions alone were ineffective.54 In HICs, treatment of depression can also lead to improvements in HIV-related outcomes, especially when they are integrated with adherence interventions that make use of motivational and problem-solving approaches.55,56 The poor availability of antidepressants in most LMICs makes the use of psychotropic interventions a challenge.57,58 Clinical trials of psychological therapies among PLWH in Asia have demonstrated improved depression outcomes.59–62 Psychological therapies require the availability of skilled health professionals, who are not readily accessible in LMICs. However, task shifting approaches in both HIV and non-HIV populations show that lower-level cadres can deliver adapted forms of psychological interventions, which can be escalated to more intense psychotherapy or antidepressants for those who do not recover.63–67 Two studies from sub-Saharan Africa using simple structured approaches based on problem-solving therapy and other cognitive behavioral techniques provided preliminary evidence for the effectiveness of psychological interventions for depression in PLWH.68,69 Expanded provision of antidepressants in Africa, especially low-cost serotonin-reuptake inhibitors such as Fluoxetine, which have fewer side effects than tricyclic antidepressants, needs to be studied to assess their effectiveness.58

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Research Priorities

One research priority is the development and validation of screening tools for depression that are integrated with screening tools for cognitive impairment and alcohol abuse, particularly for use in primary health care in LMICs. Another key priority is randomized controlled trials (RCTs) of the effectiveness and cost-effectiveness of interventions for depression (Table 2) in HIV care programs in LMICs,70 especially those that can be delivered by lower-level cadres through stepped care or task shifting models.71 Evidence from HICs suggests that problem-solving approaches to ART adherence should be integrated with depression interventions.56

TABLE 1-a

TABLE 1-a

TABLE 1-b

TABLE 1-b

TABLE 1-c

TABLE 1-c

TABLE 1-d

TABLE 1-d

TABLE 1-e

TABLE 1-e

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Alcohol Use

Background

We focused on alcohol use because it is the most abused substance in sub-Saharan Africa, where 70% of PLWH reside globally, making this the substance use problem of greatest public health importance in the HIV population. However, we acknowledge that substance abuse varies by country and that a limitation of this review is that it does not address the occurrence of other important kinds of substance use among HIV-infected individuals.

AUD is defined by diagnostic (DSM-V; International Classification of Diseases, Tenth Edition) or screening criteria that include the pattern of drinking (quantity, frequency, binge drinking) and the consequences of use (eg, harmful drinking or dependence). A commonly used screening test in both HICs and LMICs is the Alcohol Use Disorders Identification Test (AUDIT),72 a 10-item test that categorizes high-scoring patients as hazardous, harmful, or alcohol-dependent drinkers. Alcohol use is the leading risk factor for mortality and disability-adjusted life years in several LMIC regions, including southern Africa, Eastern Europe, and Andean Latin America.73 The prevalence of AUD varies geographically, and many of the LMICs with the heaviest alcohol use burdens also have high HIV prevalence or rapidly emerging HIV epidemics, such as in Eastern Europe, where prevalence of AUD is estimated at 16%. In southern Africa, the region with the highest HIV prevalence globally, more than one third of adults are estimated to be engaged in heavy episodic drinking (defined as drinking at least 60 g of pure alcohol on at least 1 occasion in the past week).73

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Relationship Between Alcohol Use and HIV Infection

There is strong and consistent evidence that alcohol use is associated with HIV incidence and prevalence in LMICs. A recent meta-analysis of studies in sub-Saharan Africa identified 35 studies with a summary odds ratio of 1.61 (95% confidence interval: 1.44 to 1.80).74 The association held among both high-risk groups and the general population and was stronger among heavier drinkers. There are several possible mechanisms for this association: the biological plausibility that heavy alcohol use increases susceptibility to and severity of HIV infection through effects on innate and adaptive immune system aspects, the central nervous system (CNS), the liver, and other organ systems; the direct effect of alcohol consumption on cognitive capacity and its disinhibiting effect on behavior, which can affect consistent condom use or the ability to negotiate safe sex; the co-occurrence of alcohol use and risky sexual behavior among individuals with risk-taking personality characteristics75; and the dual character of places that sell alcohol, which are also sometimes meeting spots for potential sex partners (Fig. 1).

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Relationship to ART Adherence

In the ART era, the primary predictor of HIV-related mortality, morbidity, and treatment failure is nonadherence to ART.76 Systematic reviews have shown that alcohol use is strongly associated with poor adherence to ART,77,78 with alcohol users being around 50%–60% less likely to adhere to ART than nonusers. For example, a recent study from South Africa found that good adherence was reported by 65% of nondrinkers but only 39.7% of drinkers (P < 0.001).79 Adherence was lower still among hazardous or harmful drinkers (30.3%). The evidence for a causal effect of AUD on ART adherence is strengthened by dose–response and temporal relationships.79–82

The mechanisms by which alcohol consumption reduces ART adherence are similar to those that increase the risk of HIV acquisition, that is, cognitive factors (due to acute intoxication), personality factors (eg, risk taking), structural factors (eg, chaotic environment), and misconceptions about toxic interactions of alcohol use and ART.83 These factors can contribute to poor adherence when alcohol users taking medications off-schedule or missing doses, not renewing prescriptions, or having decreased access to ART.78,84

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Interventions to Address Alcohol Use Among PLWH

The primary evidence-based interventions to reduce AUD are structural interventions (eg, comprehensive policy measures to regulate the availability of alcohol and reduce demand through taxation and pricing mechanisms) and individual psychotherapeutic interventions (eg, screening and brief interventions by trained primary health care professionals). There have been few RCTs assessing the effects of psychotherapeutic interventions on alcohol use and ART adherence in HIV-infected alcohol users. One trial found a significant intervention effect on ART adherence and HIV virological and immunological outcomes at the 3-month follow-up, but not at 6 months,82 and a second trial found no significant intervention effects on adherence or virological endpoints.83,85 The difference may have been attributable to key variations between these trials, including the behavior change model used, the intensity and duration of the intervention, the type of counselor, the control condition, and the duration of follow-up. Another RCT found that a motivational enhancement intervention had a significant effect on HIV viral load at 6 months86 among PLWH aged 16–25 years, including a borderline significant reduction in alcohol use. Three other studies have evaluated the effect of motivational interview-based counseling on alcohol use among PLWH with AUD,87–90 but they did not measure ART adherence at HIV-related endpoints. Each of these studies found a large and significant intervention effect on alcohol use (Table 1). Further research is needed to refine and evaluate interventions to improve adherence among alcohol users in LMICs.

TABLE 2

TABLE 2

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Research Priorities

Further qualitative studies should be conducted to understand the role of alcohol in HIV acquisition through event-level data (eg, an in-depth examination of alcohol use and sexual activity occurring on particular occasions). Pilot studies are needed that would adapt alcohol-reduction interventions to suit HIV-infected populations in LMICs, followed by RCTs to evaluate the impact of such interventions on ART adherence and disease progression.

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HIV-Associated Neurocognitive Disorder (HAND)

Background

HAND is a general term that includes a number of disorders that are complications of HIV infection. The definition is based on the consensus opinion of experts in the field, and patients are diagnosed using a battery of neuropsychological tests.91 The term HAND includes asymptomatic neurocognitive impairment, mild neurocognitive disorder, and HIV-associated dementia.91

HIV-associated dementia is the severe form of HAND. Prevalence in HICs has declined after the introduction of ART.92 HIV-associated dementia is characterized by subcortical dementia, which involves motor and cognitive slowing, with a neuropathology consistent with HIV encephalitis.49 Prognosis is poor and survival is usually less than a year.93

Asymptomatic neurocognitive impairment and mild neurocognitive disorders are the most common manifestations of HAND in the era of ART in HICs.92 This phenotype is characterized by cortical symptoms such as memory loss and seems to be distinct from HIV-associated dementia; however, our understanding of this phenotype is still evolving.49,94 Unlike HIV-associated dementia, milder cognitive disorders are not associated with higher HIV viral load and lower CD4+ T-lymphocyte count, but they are associated with previous cardiovascular disease.92,95 A longitudinal study with a follow-up period of 3 years showed that symptoms were nonprogressive, but the very long-term prognosis is unclear.96 Postulated mechanisms for mild cognitive disorders include direct ART toxicity, chronic immune activation, or immune reconstitution syndrome.97,98 In addition to ART toxicity, the direct and indirect effects of HIV also play a role in cognitive disorders.49

The prevalence of HAND in LMICs varies, ranging from 6% to 64% in children and adults99–106 (Table 1). Not all of the individuals in these studies were on ART, which could partially account for the variation. Other factors that may also explain the differing prevalence rates are people's HIV subtypes, which may contribute to more severe forms of HAND, as seen in some subtypes found in Uganda107,108; the increasing burden of comorbidities related to cognition such as stroke109; demographic, educational, and cultural differences; or differing approaches to measurement of impairment. Because treatment of HIV infection is often delayed in LMICs, the added burden of opportunistic infections mimicking HAND (eg, cryptococcal infection, tuberculosis, meningitis, or neurosyphilis) is also a possibility. Notably, in HICs, the norm is screening non-HIV populations with cognitive impairment for infections like syphilis.110 However, in LMICs, screening is neither routine for non-HIV populations nor for individuals with HAND, which could mean that the burden of HAND is overestimated and that treatable conditions are being neglected.111

Neuropsychological tests are pivotal to the definition of HAND but have several restrictions. First, the diagnosis by neuropsychological tests does not account for disease mechanism. Importantly, it does not differentiate between progressive disease directly associated with HIV infection and nonprogressive disease owing to HIV-associated insult to the brain.49 Including the latter cases could overestimate the milder forms of HAND. Second, neuropsychological tests should have at least the following neurocognitive domains: verbal/language, attention/working memory, abstraction/executive function, learning/recall, speed of information processing, and motor skills. However, the choice of domains used varies between the different tests.112–115 Third, normative data for healthy age- and sex-matched community controls, crucial for the interpretation of neuropsychological tests, are limited in LMICs. Furthermore, these neuropsychological tests should be validated for the target population's culture and language and administered and interpreted by appropriately trained professionals; this is not always the case in LMICs.49,116 Each neuropsychological test varies in length, and weighing the need for lengthy and more sensitive tests versus shorter and more conveniently administered tests is challenging. Currently, there is no consensus on the best approach.112 Although the development of standardized tools is important, linking these tools to biomarkers of HAND would make them dynamic and more specific. Biomarkers for HAND are currently in the process of being identified, and those related to monocyte activation (eg, CD14) have shown promising results.49 Depression and AUD overlap with cognitive impairment (Fig. 1); integrating a screening tool that encompasses both disorders may be an efficient way forward.110 This approach could reduce the time spent screening for these noncommunicable diseases separately in busy and overstretched ART clinics.

Despite the availability of numerous, albeit limited, neuropsychological tools, routine screening in ART clinics in LMICs is still not the norm. This could have important implications for people who have HIV–dementia but are not eligible to start ART based on their CD4+ T-lymphocyte cell count. HIV–dementia is an AIDS-defining illness and justifies starting ART.

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Relationship to ART

Overall, ART has been beneficial for HAND in both HICs and LMICs. Eleven of 15 studies in a systematic review in 11 HICs and 4 LMICs showed improvement in neurocognitive status after treatment.111 The studies that showed no association were usually statistically underpowered and sometimes lacked appropriately matched normative data. Although ART may improve cognitive function in those with severe impairment, it does not seem to fully eradicate the milder forms of HAND.33,99,111,117,118

A multinational study evaluated the outcome of neurocognitive impairment and the degree of CNS penetration for 3 ART regimes (including WHO-recommended first-line treatments) in a large randomized trial.119 The study found no differences in the degree of CNS penetration of WHO-recommended ART regimens.119 Minocycline, a neuroprotective agent, was explored as an adjunct to ART in managing HAND in LMICs.120 Although this trial was unsuccessful, this should not discourage future trials from exploring the role of adjunctive neuroprotective/anti-inflammatory agents in reducing the burden of HAND.49

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Relationship to ART Adherence

A prospective cohort study in Zambia showed that 495 PLWH who had recently commenced ART had cognitive impairment and poorer ART adherence.45 In HICs, mild neurocognitive impairment was associated with poorer quality of life, unemployment, worse medication adherence, lower driving ability, and reduced survival.121 Furthermore, HAND may also be associated with adverse HIV outcomes, including HIV resistance and poor ART adherence due to prospective memory impairment.122 Alcohol misuse may coexist in patients with HAND, which could also impact on adherence. However, the extent to which these factors play a role in HIV acquisition and disease progression in LMICs has yet to be completely understood.

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Research Priorities

Of high priority is the development and validation of a standardized neuropsychological test that is resource appropriate, culturally tailored, and includes biomarkers of HAND to improve specificity (Table 2). Well-powered studies with appropriate normative data that examine the effect of ART in a well-characterized cohort (with brain imaging, exclusion of opportunistic infections, and autopsy confirmation of underlying pathologies) are needed in LMICs. Ideally, longitudinal studies should have a follow-up beyond the longest observation period of 3 years to determine the long-term prognosis of HAND in the ART era. In the meantime, screening for HAND needs to be instituted in clinics in LMICs, especially for patients not otherwise qualifying for ART.

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Research Platforms and Training Opportunities

Existing research and care platforms could be harnessed to conduct MNS studies. New scientific collaborations could be established, for instance, with Demographic Surveillance Systems, such as those in the INDEPTH Network (www.indepth-network.org), and HIV research centers in LMICs, such as those supported by the UK Medical Research Council, the Wellcome Trust, and the US National Institutes of Health. Opportunities exist for incorporating MNS research into existing HIV research platforms. For example, researchers could use the IeDEA network, AIDS clinical trials group sites, the WHO STEPS surveys, and the African Partnership for Chronic Diseases. Challenges in implementing such research may include the lack of awareness among many HIV researchers, funders, and policymakers of the importance of mental health in addressing HIV/AIDS.

Strengthening research capacity in many LMICs that have exceedingly low numbers of specialists in neurology and psychiatry, a situation exacerbated by the ongoing brain drain, will be important. New initiatives are supporting capacity building in mental health research, particularly the research hubs in Africa, Asia, and Latin America funded by the US National Institute of Mental Health (www.fic.nih.gov/programs/Pages/medical-education), consortia funded through the UK Department for International Development (www.prime.uct.ac.za), and Grand Challenges Canada (www.grandchallenges.ca), which funds projects and rising investigators in global mental health. The US President's Emergency Plan for AIDS Relief/National Institutes of Health–funded Medical Education Partnerships Initiative (MEPI)123 is another potential platform on which to build research capacity in HIV mental health and neurology in Africa. Existing initiatives such as Fogarty International Center fellowships (http://www.fic.nih.gov/programs/pages/scholars-fellows.aspx) and Wellcome Trust international training fellowships (www.liverpoolwttc.org.uk) also fund research and training of investigators in global mental health and neurology. At an institutional level, mentorship schemes are needed to pair clinical academics in psychiatry and neurology with centers requesting support. Examples of specific training priorities include grant writing, qualitative methods, formative research, cross-cultural methods in psychiatry, clinical trials training, database management, and biostatistics.

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CONCLUSION AND RECOMMENDATIONS

Addressing the burden of MNS conditions among PLWH in LMICs will contribute significantly to health, social, and economic outcomes as ART is scaled up. We focused this review on the 3 key MNS conditions most prevalent in HIV populations in LMICs, based on the current literature. Epilepsy, stroke, peripheral neuropathy, psychotic disorders, anxiety disorders (including post-traumatic stress disorder), and illicit drug use are other MNS conditions that we did not discuss in this review, but that are important areas for future research in LMICs.

Depression, AUD, and HAND contribute to poor HIV outcomes and are interlinked. Research is needed that improves our understanding of the underlying mechanism of these overlapping conditions. One research priority is to determine an integrated screening approach for depression, AUD, and neurocognitive disorders that can be used by nonspecialists in LMICs. Such a tool should ideally achieve a balance between time, skill needed to administer it, and the validity of the test. Another research priority is testing depression and AUD interventions that also target behavior change, as these could have an impact on ART adherence, accessing health care, and the improvement of mental symptoms. RCTs of such interventions, preceded by culturally informed formative work, are urgently needed.

Limited access to psychiatrists and neurologists in LMICs has been a long-standing issue; mentorship and fellowship schemes at an individual and institutional level do exist, but they need to be further supported. In the short-term, task shifting in the care of MNS disorders in HICs and LMICs has been successful and should be integrated into routine HIV care in LMICs.

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ACKNOWLEDGMENTS

The authors would like to thank Jessica Healy for her help with the literature search and Dr. Sam Nightingale for helpful discussions on the HAND section.

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REFERENCES

1. Brandt R. The mental health of people living with HIV/AIDS in Africa: a systematic review. Afr J AIDS Res. 2009;8:123–133.
2. Mayston R, Kinyanda E, Chishinga N, et al.. Mental disorder and the outcome of HIV/AIDS in low-income and middle-income countries: a systematic review. AIDS. 2012;26:S117–S135.
3. Kalichman SC, Rompa D, Cage M. Sexually transmitted infections among HIV seropositive men and women. Sex Transm Infect. 2000;76:350–354.
4. World Health Organization. mhGAP Mental Health Gap Action Programme: scaling up care for mental, neurological, and substance use disorders. 2008. Available at: http://www.who.int/mental_health/mhgap/en/. Accessed June 2013.
5. Maj M, Satz P, Janssen R, et al.. WHO Neuropsychiatric AIDS study, cross-sectional phase II. Neuropsychological and neurological findings. Arch Gen Psychiatry. 1994;51:51–61.
6. Nakimuli-Mpungu E, Bass J, Alexandre P, et al.. Depression, alcohol use and adherence to antiretroviral therapy in sub-Saharan africa: a systematic review. AIDS Behav. 2012:1–18.
7. Bloomfield GS, Khazanie P, Morris A, et al.. HIV and non-communicable cardiovascular and pulmonary diseases in low- and middle-income countries in the ART era: what we know and best directions for future research. J Acquir Immune Defic Syndr. 2014.
8. Breuer EML, Struthers H, Joska A. HIV/AIDS and mental health research in sub-Saharan Africa: a systematic review. Afr J AIDS Res. 2011;10:101–122.
9. Owe-Larsson B, Sall L, Salamon E, et al.. HIV infection and psychiatric illness. Afr J Psychiatry (johannesbg). 2009;12:115–128.
10. Wright E, Brew B, Arayawichanont A, et al.. Neurologic disorders are prevalent in HIV-positive outpatients in the Asia-Pacific region. Neurology. 2008;71:50–56.
11. Mast TC, Kigozi G, Wabwire-Mangen F, et al.. Measuring quality of life among HIV-infected women using a culturally adapted questionnaire in Rakai district, Uganda. AIDS Care. 2004;16:81–94.
12. Hughes J, Jelsma J, Maclean E, et al.. The health-related quality of life of people living with HIV/AIDS. Disabil Rehabil. 2004;26:371–376.
13. Kaaya SF, Fawzi MCS, Mbwambo JK, et al.. Validity of the Hopkins symptom Checklist-25 amongst HIV-positive pregnant women in Tanzania. Acta Psychiatr Scand. 2002;106:9.
14. Chibanda D, Mangezi W, Tshimanga M, et al.. Validation of the Edinburgh postnatal depression scale among women in a high HIV prevalence area in urban Zimbabwe. Arch Women's Ment Health. 2009;13:201–206.
15. Monahan PO, Shacham E, Reece M, et al.. Validity/reliability of PHQ-9 and PHQ-2 depression scales among adults living with HIV/AIDS in western Kenya. J Gen Intern Med. 2009;24:189–197.
16. Spies G, Kader K, Kidd M, et al.. Validity of the K-10 in detecting DSM-IV-defined depression and anxiety disorders among HIV-infected individuals. AIDS Care. 2009;21:1163–1168.
17. Akena D, Joska J, Obuku EA, et al.. Comparing the accuracy of brief versus long depression screening instruments which have been validated in low and middle income countries: a systematic review. BMC Psychiatry. 2012;12:187.
18. Weobong B, Akpalu B, Doku V, et al.. The comparative validity of screening scales for postnatal common mental disorder in Kintampo, Ghana. J Affective Disord. 2009;113:109–117.
19. Bolton P. Cross-cultural validity, reliability testing of a standard psychiatric assessment instrument without a gold standard. J Nervous Ment Dis. 2001;189:238.
20. Abas M, Broadhead JC, Mbape P, et al.. Defeating depression in the developing world: a Zimbabwean model. Br J Psychiatry. 1994;164:293–296.
21. Patel V, Simunyu E, Gwanzura F, et al.. The explanatory models and phenomenology of common mental disorders in primary care in Harare. Psychol Med. 1995;25:1191.
22. Kaaya SF, Mbwambo JK, Fawzi MC, et al.. Understanding women's experiences of distress during pregnancy in Dar es Salaam, Tanzania. Tanzan J Health Res. 2010;12:36–46.
23. Jelsma J, Mhundwa K, De Weerdt W, et al.. The reliability of the Shona version of the EQ-5D. Cent Afr J Med. 2001;47:8–13.
24. Patel V, Mann A. Etic and emic criteria for non-psychotic mental disorder: a study of the CISR and care provider assessment in Harare. Social Psychiatry Psychiatr Epidemiol. 1997;32:84.
25. Patel V, Simunyu E, Gwanzura F, et al.. The Shona symptom Questionnaire: the development of an indigenous measure of common mental disorders in Harare. Acta Psychiatrica Scand. 1997;95:469.
26. Kroenke K, Spitzer RL, Williams JB. The PHQ-9: validity of a brief depression severity measure. J Gen Intern Med. 2001;16:606–613.
27. Baarnhielm S. DSM-5 focuses on culture and context. Interview tool adapts psychiatry to the multicultural society. Lakartidningen. 2013;110:1916–1917.
28. Okello ES, Neema S. Explanatory models and help-seeking behavior: pathways to psychiatric care among patients admitted for depression in Mulago hospital, Kampala, Uganda. Qual Health Res. 2007;17:14–25.
29. Akena D, Joska J, Musisi S, et al.. Sensitivity and specificity of a visual depression screening instrument among HIV-positive individuals in Uganda, an area with low literacy. AIDS Behav. 2012;16:2399–2406.
30. Dube B, Benton T, Cruess DG, et al.. Neuropsychiatric manifestations of HIV infection and AIDS. J Psychiatry Neurosci. 2005;30:237–246.
31. Rabkin JG. HIV and depression: 2008 review and update. Curr Hiv/aids Rep. 2008;5:163–171.
32. Collins PY, Holman AR, Freeman MC, et al.. What is the relevance of mental health to HIV/AIDS care and treatment programs in developing countries? A systematic review. AIDS (London, England). 2006;20:1571.
33. Nakasujja N, Skolasky RL, Musisi S, et al.. Depression symptoms and cognitive function among individuals with advanced HIV infection initiating HAART in Uganda. BMC Psychiatry. 2010;10:44.
34. Adewuya AO, Afolabi MO, Ola BA, et al.. Psychiatric disorders among the HIV-positive population in Nigeria: a control study. J Psychosom Res. 2007;63:203–206.
35. Chibanda D, Mangezi W, Tshimanga M, et al.. Postnatal depression by HIV status among women in Zimbabwe. J Women's Health. 2010;19:2071–2077.
36. Sebit M, Tombe M, Siziya S, et al.. Prevalence of HIV/AIDS and psychiatric disorders and their related risk factors among adults in Epworth, Zimbabwe. East Afr Med J. 2004;80:503–512.
37. 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 Psychosomatic Res. 2006;61:479–484.
38. Myer L, Seedat S, Stein DJ, et al.. The mental health impact of AIDS-related mortality in South Africa: a national study. J Epidemiol Community Health. 2009;63:293–298.
39. Gaynes BN, Pence BW, Atashili J, et al.. Prevalence and predictors of major depression in HIV-infected patients on antiretroviral therapy in Bamenda, a semi-urban Center in Cameroon. PLoS ONE. 2012;7:e41699.
40. Kinyanda E, Hoskins S, Nakku J, et al.. Prevalence and risk factors of major depressive disorder in HIV/AIDS as seen in semi-urban Entebbe district, Uganda. BMC Psychiatry. 2011;11:205.
41. Akena DH, Musisi S, Kinyanda E. A comparison of the clinical features of depression in HIV-positive and HIV-negative patients in Uganda. Afr J Psychiatry (johannesbg). 2010;13:43–51.
42. Peterson K, Togun T, Klis S, et al.. Depression and posttraumatic stress disorder among HIV-infected Gambians on antiretroviral therapy. AIDS Patient Care STDS. 2012;26:589–596.
43. Klis S, Velding K, Gidron Y, et al.. Posttraumatic stress and depressive symptoms among people living with HIV in the Gambia. AIDS Care. 2011;23:426–434.
44. Adewuya AO, Afolabi MO, Ola BA, et al.. Post-traumatic stress disorder (PTSD) after stigma related events in HIV infected individuals in Nigeria. Soc Psychiatry Psychiatr Epidemiol. 2009;44:761–766.
45. Birbeck GL, Kvalsund MP, Byers PA, et al.. Neuropsychiatric and socioeconomic status impact antiretroviral adherence and mortality in rural Zambia. Am J Trop Med Hyg. 2011;85:782–789.
46. Lawson MA, Kelley KW, Dantzer R. Intracerebroventricular administration of HIV-1 Tat induces brain cytokine and indoleamine 2,3-dioxygenase expression: a possible mechanism for AIDS comorbid depression. Brain Behav Immun. 2011;25:1569–1575.
47. Castelo JM, Sherman SJ, Courtney MG, et al.. Altered hippocampal-prefrontal activation in HIV patients during episodic memory encoding. Neurology. 2006;66:1688–1695.
48. Berk M, Williams LJ, Jacka FN, et al.. So depression is an inflammatory disease, but where does the inflammation come from? BMC Med. 2013;11:200.
49. Clifford DB, Ances BM. HIV-associated neurocognitive disorder. Lancet Infect Dis. 2013;13:976–986.
50. Gonzalez JS, Batchelder AW, Psaros C, et al.. Depression and HIV/AIDS treatment nonadherence: a review and meta-analysis. J Acquir Immune Defic Syndr. 2011;58:181–187.
51. Antelman G, Kaaya S, Wei R, et al.. Depressive symptoms increase risk of HIV disease progression and mortality among women in Tanzania. JAIDS J Acquired Immune Deficiency Syndromes. 2007;44:470–477.
52. Leserman J, Leserman J. HIV disease progression: depression, stress, and possible mechanisms. Biol Psychiatry. 2003;54:295–306.
53. Hartzell JD, Janke IE, Weintrob AC. Impact of depression on HIV outcomes in the HAART era. J Antimicrob Chemother. 2008;62:246–255.
54. Sherr L, Clucas C, Harding R, et al.. HIV and depression–a systematic review of interventions. [Review]. Psychol Health Med. 2011;16:493–527.
55. Olatunji BO, Mimiaga MJ, O'Cleirigh C, et al.. Review of treatment studies of depression in HIV. Top HIV Med. 2006;14:112–124.
56. Safren SA, O'Cleirigh C, Tan JY, et al.. A randomized controlled trial of cognitive behavioral therapy for adherence and depression (CBT-AD) in HIV-infected individuals. Health Psychol. 2009;28:1–10.
57. WHO. Mental health Atlas. 2011.
58. Adams JL, Almond ML, Ringo EJ, et al.. Feasibility of nurse-led antidepressant medication management of depression in an HIV clinic in Tanzania. Int J Psychiatry Med. 2012;43:105–117.
59. SeyedAlinaghi S, Jam S, Foroughi M, et al.. Randomized controlled trial of mindfulness-based stress reduction delivered to human immunodeficiency virus-positive patients in Iran: effects on CD4(+) T lymphocyte count and medical and psychological symptoms. Psychosom Med. 2012;74:620–627.
60. Molassiotis A, Callaghan P, Twinn SF, et al.. A pilot study of the effects of cognitive-behavioral group therapy and peer support/counseling in decreasing psychologic distress and improving quality of life in Chinese patients with symptomatic HIV disease. AIDS Patient Care STDS. 2002;16:83–96.
61. Chan I, Kong P, Leung P, et al.. Cognitive-behavioral group program for Chinese heterosexual HIV-infected men in Hong Kong. Patient Educ Couns. 2005;56:78–84.
62. Li L, Lee SJ, Jiraphongsa C, et al.. Improving the health and mental health of people living with HIV/AIDS: 12-month assessment of a behavioral intervention in Thailand. Am J Public Health. 2010;100:2418–2425.
63. Chibanda D, Mesu P, Kajawu L, et al.. Problem-solving therapy for depression and common mental disorders in Zimbabwe: piloting a task-shifting primary mental health care intervention in a population with a high prevalence of people living with HIV. BMC Public Health. 2011;11:828.
64. Chibanda D, Shetty AK, Tshimanga M, et al.. Group problem-solving therapy for postnatal depression among HIV positive and HIV negative mothers in Zimbabwe. J Int Assoc Provid AIDS Care. 2013.
65. Araya R, Rojas G, Fritsch R, et al.. Treating depression in primary care in low-income women in Santiago, Chile: a randomised controlled trial. Lancet. 2003;361:995–1000.
66. Patel VH, Kirkwood BR, Pednekar S, et al.. Improving the outcomes of primary care attenders with common mental disorders in developing countries: a cluster randomized controlled trial of a collaborative stepped care intervention in Goa, India. Trials. 2008;9:4.
67. Rahman A, Malik A, Sikander S, et al.. Cognitive behaviour therapy-based intervention by community health workers for mothers with depression and their infants in rural Pakistan: a cluster-randomised controlled trial. Lancet. 2008;372:902–909.
68. Nakimuli-Mpungu E, Wamala K, Okello J, et al.. Developing a culturally sensitive group support intervention for depression among HIV infected and non-infected Ugandan adults : a qualitative study. J Affect Disord. 2014;163:10–17.
69. Kaaya SF, Blander J, Antelman G, et al.. Randomized controlled trial evaluating the effect of an interactive group counseling intervention for HIV-positive women on prenatal depression and disclosure of HIV status. AIDS Care. 2013;25:854–862.
70. Kaaya S, Eustache E, Lapidos-Salaiz I, et al.. Grand challenges: improving HIV treatment outcomes by integrating interventions for co-morbid mental illness. Plos Med. 2013;10:e1001447.
71. van Ginneken N, Tharyan P, Lewin S, et al.. Non-specialist health worker interventions for mental health care in low- and middle- income countries. Cochrane Database Syst Rev. 2011.
72. Bohn MJ, Babor TF, Kranzler HR. The Alcohol Use Disorders Identification Test (AUDIT): validation of a screening instrument for use in medical settings. J Stud Alcohol. 1995;56:423–432.
73. World health Organisation. Global status report on alcohol and health. 2011.
74. Woolf-King S, Steinmaus CM, Reingold AL, Hahn JA. An update on alcohol use and risk of HIV infection in sub-Saharan Africa: meta-analysis and future research directions. J Alcohol Drug Res. 2013;2:99–110.
75. Kalichman SC, Simbayi LC, Kaufman M, et al.. Alcohol use and sexual risks for HIV/AIDS in sub-Saharan Africa: systematic review of empirical findings. Prev Sci. 2007;8:141–151.
76. Ford N, Darder M, Spelman T, et al.. Early adherence to antiretroviral medication as a predictor of long-term HIV virological suppression: five-year follow up of an observational cohort. PLoS One. 2010;5:e10460.
77. Azar MM, Springer SA, Meyer JP, et al.. A systematic review of the impact of alcohol use disorders on HIV treatment outcomes, adherence to antiretroviral therapy and health care utilization. Drug Alcohol Depend. 2010;112:178–193.
78. Hendershot CS, Stoner SA, Pantalone DW, et al.: Review and meta-analysis. JAIDS J Acquired Immune Deficiency Syndromes. 2009;52:180–202.
79. Morojele NK, Kekwaletswe CT, Nkosi S. Associations Between Alcohol Use, et al (ART) adherence among south african ART Recipients. AIDS Behav. 2013.
80. Braithwaite RS, McGinnis KA, Conigliaro J, et al.. A temporal and dose-response association between alcohol consumption and medication adherence among veterans in care. Alcohol Clin Exp Res. 2005;29:1190–1197.
81. Lucas GM, Gebo KA, Chaisson RE, et al.. Longitudinal assessment of the effects of drug and alcohol abuse on HIV-1 treatment outcomes in an urban clinic. AIDS. 2002;16:767–774.
82. Parsons JT, Golub SA, Rosof E, et al.. Motivational interviewing and cognitive-behavioral intervention to improve HIV medication adherence among hazardous drinkers: a randomized controlled trial. J Acquir Immune Defic Syndr. 2007;46:443–450.
83. Kalichman SC, Amaral CM, White D, et al.. Prevalence and clinical implications of interactive toxicity beliefs regarding mixing alcohol and antiretroviral therapies among people living with HIV/AIDS. AIDS Patient Care STDS. 2009;23:449–454.
84. Cook RL, Sereika SM, Hunt SC, et al.. Problem drinking and medication adherence among persons with HIV infection. J Gen Intern Med. 2001;16:83–88.
85. Samet JH, Horton NJ, Meli S, et al.. A randomized controlled trial to enhance antiretroviral therapy adherence in patients with a history of alcohol problems. Antivir Ther. 2005;10:83–93.
86. Naar-King S, Parsons JT, Murphy DA, et al.. Improving health outcomes for youth living with the human immunodeficiency virus: a multisite randomized trial of a motivational intervention targeting multiple risk behaviors. Arch Pediatr Adolesc Med. 2009;163:1092–1098.
87. Hasin DS, Aharonovich E, O'Leary A, et al.. Reducing heavy drinking in HIV primary care: a randomized trial of brief intervention, with and without technological enhancement. Addiction. 2013;108:1230–1240.
88. Aharonovich E, Hatzenbuehler ML, Johnston B, et al.. A low-cost, sustainable intervention for drinking reduction in the HIV primary care setting. AIDS Care. 2006;18:561–568.
89. Papas RK, Sidle JE, Martino S, et al.. Systematic cultural adaptation of cognitive-behavioral therapy to reduce alcohol use among HIV-infected outpatients in western Kenya. AIDS Behav. 2009;14:669–678.
90. Velasquez MM, von Sternberg K, Johnson DH, et al.. Reducing sexual risk behaviors and alcohol use among HIV-positive men who have sex with men: a randomized clinical trial. J Consult Clin Psychol. 2009;77:657–667.
91. Antinori A, Arendt G, Becker JT, et al.. Updated research nosology for HIV-associated neurocognitive disorders. Neurology. 2007;69:1789–1799.
92. Heaton RK, Clifford DB, Franklin DR Jr, et al.. HIV-associated neurocognitive disorders persist in the era of potent antiretroviral therapy: CHARTER Study. Neurology. 2010;75:2087–2096.
93. Ellis RJ, Deutsch R, Heaton RK, et al.. Neurocognitive impairment is an independent risk factor for death in HIV infection. San Diego HIV Neurobehavioral Research Center Group. Arch Neurol. 1997;54:416–424.
94. Kanmogne GD, Kuate CT, Cysique LA, et al.. HIV-associated neurocognitive disorders in sub-Saharan Africa: a pilot study in Cameroon. BMC Neurol. 2010;10:60.
95. Wright EJ, Grund B, Robertson K, et al.. Cardiovascular risk factors associated with lower baseline cognitive performance in HIV-positive persons. Neurology. 2010;75:864–873.
96. Clifford DB, Evans S, Yang Y, et al.. Long-term impact of efavirenz on neuropsychological performance and symptoms in HIV-infected individuals (ACTG 5097s). HIV Clin Trials. 2009;10:343–355.
97. Mothobi NZ, Brew BJ. Neurocognitive dysfunction in the highly active antiretroviral therapy era. Curr Opin Infect Dis. 2012;25:4–9.
98. Holmes MV, Desai M, Dosekun O, et al.. Is the diagnosis at hand? Lancet. 2010;375:1134.
99. Gupta JD, Satishchandra P, Gopukumar K, et al.. Neuropsychological deficits in human immunodeficiency virus type 1 clade C-seropositive adults from South India. J Neurovirol. 2007;13:195–202.
100. Robertson K, Kumwenda J, Supparatpinyo K, et al.. A multinational study of neurological performance in antiretroviral therapy-naive HIV-1-infected persons in diverse resource-constrained settings. J Neurovirol. 2011;17:438–447.
101. Holguin A, Banda M, Willen EJ, et al.. HIV-1 effects on neuropsychological performance in a resource-limited country, Zambia. AIDS Behav. 2011;15:1895–1901.
102. Joska JA, Westgarth-Taylor J, Myer L, et al.. Characterization of HIV-associated neurocognitive disorders among individuals starting antiretroviral therapy in South Africa. AIDS Behav. 2011;15:1197–1203.
103. Lawler K, Jeremiah K, Mosepele M, et al.. Neurobehavioral effects in HIV-positive individuals receiving highly active antiretroviral therapy (HAART) in Gaborone, Botswana. PLoS One. 2011;6:e17233.
104. Patel VN, Mungwira RG, Tarumbiswa TF, et al.. High prevalence of suspected HIV-associated dementia in adult Malawian HIV patients. Int J STD AIDS. 2010;21:356–358.
105. Ruel TD, Boivin MJ, Boal HE, et al.. Neurocognitive and motor deficits in HIV-infected Ugandan children with high CD4 cell counts. Clin Infect Dis. 2012;54:1001–1009.
106. Nakku J, Kinyanda E, Hoskins S. Prevalence and factors associated with probable HIV dementia in an African population: a cross-sectional study of an HIV/AIDS clinic population. BMC Psychiatry. 2013;13:126.
107. Sacktor N, Nakasujja N, Skolasky RL, et al.. HIV subtype D is associated with dementia, compared with subtype A, in immunosuppressed individuals at risk of cognitive impairment in Kampala, Uganda. Clin Infect Dis. 2009;49:780–786.
108. Boivin MJ, Busman RA, Parikh SM, et al.. A pilot study of the neuropsychological benefits of computerized cognitive rehabilitation in Ugandan children with HIV. Neuropsychology. 2010;24:667–673.
109. Benjamin LA, Bryer A, Emsley HC, et al.. HIV infection and stroke: current perspectives and future directions. Lancet Neurol. 2012;11:878–890.
110. Hejl A, Hogh P, Waldemar G. Potentially reversible conditions in 1000 consecutive memory clinic patients. J Neurol Neurosurg Psychiatry. 2002;73:390–394.
111. Joska JA, Gouse H, Paul RH, et al.. Does highly active antiretroviral therapy improve neurocognitive function? A systematic review. J Neurovirol. 2010;16:101–114.
112. Mind Exchange Working Group. Assessment, diagnosis, and treatment of HIV-associated neurocognitive disorder: a consensus report of the mind exchange program. Clin Infect Dis. 2013;56:1004–1017.
113. Kamminga J, Cysique LA, Lu G, et al.. Validity of cognitive screens for HIV-associated neurocognitive disorder: a systematic review and an informed screen selection guide. Curr Hiv/aids Rep. 2013;10:342–355.
114. Haddow LJ, Floyd S, Copas A, et al.. A systematic review of the screening accuracy of the HIV Dementia Scale and International HIV Dementia Scale. PLoS One. 2013;8:e61826.
115. Cettomai D, Kwasa J, Kendi C, et al.. Utility of quantitative sensory testing and screening tools in identifying HIV-associated peripheral neuropathy in Western Kenya: pilot testing. PLoS One. 2010;5:e14256.
116. Kvalsund MP, Haworth A, Murman DL, et al.. Closing gaps in antiretroviral therapy access: human immunodeficiency virus-associated dementia screening instruments for non-physician healthcare workers. Am J Trop Med Hyg. 2009;80:1054–1059.
117. Sacktor N, Nakasujja N, Skolasky R, et al.. Antiretroviral therapy improves cognitive impairment in HIV+ individuals in sub-Saharan Africa. Neurology. 2006;67:311–314.
118. Joska JA, Westgarth-Taylor J, Hoare J, et al.. Neuropsychological outcomes in adults commencing highly active anti-retroviral treatment in South Africa: a prospective study. BMC Infect Dis. 2012;12:39.
119. Robertson K, Jiang H, Kumwenda J, et al.. Improved neuropsychological and neurological functioning across three antiretroviral regimens in diverse resource-limited settings: AIDS Clinical Trials Group study a5199, the International Neurological Study. Clin Infect Dis. 2012;55:868–876.
120. Nakasujja N, Miyahara S, Evans S, et al.. Randomized trial of minocycline in the treatment of HIV-associated cognitive impairment. Neurology. 2013;80:196–202.
121. Gorman AA, Foley JM, Ettenhofer ML, et al.. Functional consequences of HIV-associated neuropsychological impairment. Neuropsychol Rev. 2009;19:186–203.
122. Cysique LA, Brew BJ. Neuropsychological functioning and antiretroviral treatment in HIV/AIDS: a review. Neuropsychol Rev. 2009;19:169–185.
123. Mullan F, Frehywot S, Omaswa F, et al.. Medical schools in sub-Saharan Africa. Lancet. 2011;377:1113–1121.
124. Etienne M, Hossain M, Redfield R, et al.. 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.
    125. Abaynew Y, Deribew A, Deribe K. Factors associated with late presentation to HIV/AIDS care in South Wollo ZoneEthiopia: a case-control study. AIDS Res Ther. 2011;8:8.
      126. Beyene KA, Gedif T, Gebre-Mariam T, et al.. Highly active antiretroviral therapy adherence and its determinants in selected hospitals from south and central Ethiopia. Pharmacoepidemiol Drug Saf. 2009;18:1007–1015.
        127. Bonolo Pde F, Cesar CC, Acurcio FA, et al.. Non-adherence among patients initiating antiretroviral therapy: a challenge for health professionals in Brazil. AIDS. 2005;19(suppl 4):S5–S13.
          128. Dahab M, Charalambous S, Karstaedt AS, et al.. Contrasting predictors of poor antiretroviral therapy outcomes in two South African HIV programmes: a cohort study. BMC Public Health. 2010;10:430.
            129. Fritz K, McFarland W, Wyrod R, et al.. Evaluation of a peer network-based sexual risk reduction intervention for men in beer halls in Zimbabwe: results from a randomized controlled trial. AIDS Behav. 2011;15:1732–1744.
              130. Jaquet A, Ekouevi DK, Bashi J, et al.. Alcohol use and non-adherence to antiretroviral therapy in HIV-infected patients in West Africa. Addiction. 2010;105:1416–1421.
                131. Kalichman SC, Simbayi LC, Vermaak R, et al.. Randomized trial of a community-based alcohol-related HIV risk-reduction intervention for men and women in Cape Town South Africa. Ann Behav Med. 2008;36:270–279.
                  132. Kalichman SC, Cain D, Simbayi LC. Multiple recent sexual partnerships and alcohol use among sexually transmitted infection clinic patients, Cape Town, South Africa. Sex Transm Dis. 2011;38:18–23.
                    133. Papas RK, Sidle JE, Gakinya BN, et al.. Treatment outcomes of a stage 1 cognitive-behavioral trial to reduce alcohol use among human immunodeficiency virus-infected out-patients in western Kenya. Addiction. 2011;106:2156–2166.
                      134. Peltzer K, Davids A, Njuho P. Alcohol use and problem drinking in South Africa: findings from a national population-based survey. Afr J Psychiatry (johannesbg). 2011;14:30–37.
                        135. Sharma A, Sachdeva RK, Kumar M, et al.. Effects of lifetime history of use of problematic alcohol on HIV medication adherence. J Int Assoc Provid AIDS Care. 2013.
                          136. Venkatesh KK, Srikrishnan AK, Mayer KH, 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.
                            Keywords:

                            depression; alcohol use disorders; neurocognitive disorders; low- and middle-income countries

                            © 2014 by Lippincott Williams & Wilkins