Depressed mood as a transdiagnostic target relevant to anxiety and/or psychosis: a scoping review protocol.

INTRODUCTION: Depressed mood is a psychological state characterised by sadness or loss of interest in activities. Depressed mood is a highly prevalent symptom across major mental disorders. However, there is limited understanding of the burden and management of comorbid depressed mood across major mental disorders. Therefore, this scoping review aims to summarise knowledge on depressed mood among persons with anxiety and/or psychosis. The specific aims are to describe the epidemiology and risk factors of depressed mood as a transdiagnostic target among persons with anxiety and/or psychosis, to identify commonly used outcome measures for depressed mood and to outline initial evidence of psychometric robustness and to identify and summarise the effectiveness of commonly applied depressed mood modification interventions. Our hope is that the proposed review will provide insights into the burden of depressed mood in persons with anxiety and psychosis and help to identify evidence gaps and recommendations for future research. METHODS AND ANALYSIS: This scoping review will be conducted per Arksey and O'Malley's framework. We will first search for peer-reviewed articles and grey literature published from 2004 to 2023 in PubMed, Scopus, Web of Science, Africa-Wide Information, CINAHL, PsycINFO, Academic Search Premier, Humanities International Complete, Sabinet, SocINDEX, Open Grey and Google Scholar. We will include articles reporting depressed mood (subthreshold depression) among persons with anxiety and/or psychosis. Studies recruiting participants meeting depression diagnostic criteria and those published in non-English languages will be excluded. Two independent researchers will extract the data. We will analyse and chart data collaboratively with researchers with lived experiences of depressed mood. ETHICS AND DISSEMINATION: This study does not require ethical approval as it is a literature review. The results will be submitted for publication in a peer-reviewed journal.

Cognitive performance in depression in low- and middle-income countries: A systematic review with meta-analytic components.

BACKGROUND: Depression is highly prevalent in low- and middle- income countries (LMIC) and associated with significant cognitive dysfunction across multiple domains. However, little is known about neurocognitive tests used in people with depression in LMIC. We aimed to investigate cognitive performance and cognitive tests in depression research in LMIC. METHODS: APA PsycInfo, Embase, Ovid MEDLINE, and Global Health were systematically searched for studies that implemented a cognitive performance test in a depressed, LMIC population. Tool quality was assessed using an adapted scale for quality of measures in cross-cultural settings. Data extracted included demographics, depression and cognitive performance measures, and cognitive performance comparisons between depression and control groups. RESULTS: 29 studies met eligibility criteria, involving a total of 19,100 participants from 11 LMIC. 93.1 % of studies were conducted in upper middle-income countries. 67 cognitive performance tools were implemented. Reliability was reported for 5.6 % of cognitive performance tests and validity was reported for 8.3 %. 36.1 % of tests used were culturally adapted. 75.9 % of included studies implemented at least one memory test. Cognitive deficits were observed in all depressed groups, especially in memory (Cohen's d = -1.60, 95 % CI -2.02 to -1.18). LIMITATIONS: Heterogeneity between studies; averaged results across memory subtypes; no assessment of depression severity and cognitive deficits associations; restrictive search terms. CONCLUSIONS: Cognitive impairments in depression, especially in memory, are prevalent in LMIC. This research has drawn attention to the burden of cognitive dysfunction in depression in LMIC, and to the disparate research gap in LMIC. PROSPERO registration CRD42022315397.

Task-sharing with lay counsellors to deliver a stepped care intervention to improve depression, antiretroviral therapy adherence and viral suppression in people living with HIV: a study protocol for the TENDAI randomised controlled trial.

INTRODUCTION: Non-adherence to antiretroviral therapy (ART) is the main cause of viral non-suppression and its risk is increased by depression. In countries with high burden of HIV, there is a lack of trained professionals to deliver depression treatments. This paper describes the protocol for a 2-arm parallel group superiority 1:1 randomised controlled trial, to test the effectiveness and cost effectiveness of the TENDAI stepped care task-shifted intervention for depression, ART non-adherence and HIV viral suppression delivered by lay interventionists. METHODS AND ANALYSIS: Two hundred and ninety people living with HIV aged ≥18 years with probable depression (Patient Health Questionnaire=>10) and viral non-suppression (≥ 1000 HIV copies/mL) are being recruited from HIV clinics in towns in Zimbabwe. The intervention group will receive a culturally adapted 6-session psychological treatment, Problem-Solving Therapy for Adherence and Depression (PST-AD), including problem-solving therapy, positive activity scheduling, skills to cope with stress and poor sleep and content to target barriers to non-adherence to ART. Participants whose score on the Patient Health Questionnaire-9 remains ≥10, and/or falls by less than 5 points, step up to a nurse evaluation for possible antidepressant medication. The control group receives usual care for viral non-suppression, consisting of three sessions of adherence counselling from existing clinic staff, and enhanced usual care for depression in line with the WHO Mental Health Gap intervention guide. The primary outcome is viral suppression (<1000 HIV copies/mL) at 12 months post-randomisation. ETHICS AND DISSEMINATION: The study and its tools were approved by MRCZ/A/2390 in Zimbabwe and RESCM-18/19-5580 in the UK. Study findings will be shared through the community advisory group, conferences and open access publications. TRIAL REGISTRATION NUMBER: NCT04018391.

Validity of Digital Assessments in Screening for HIV-Related Cognitive Impairment: a Review.

PURPOSE OF REVIEW: While traditional neuropsychological tests are the gold standard in screening for HIV-related cognitive impairment, computerized neuropsychological assessment devices (CNADs) offer an alternative to these time- and resource-intensive batteries and may prove to be particularly useful for remote assessments or longitudinal monitoring. This review seeks to describe the benefits, limitations, and validity of CNADs in the evaluation of HIV-associated neurocognitive disorder (HAND). RECENT FINDINGS: We identified eight CNADs that have undergone validity testing for cognitive impairment in the setting of HIV. Included among these are batteries that have been modeled after the traditional neuropsychological exam, as well as others that implement new technologies, such as simulated reality and daily ecological assessments in their testing. Currently, these digital batteries do not yet have the ability to supplant gold standard neuropsychological tests in screening for HAND. However, many have the potential to become effective clinical screening tools.

Survival following screening and preemptive antifungal therapy for subclinical cryptococcal disease in advanced HIV infection.

OBJECTIVES: Our study's primary objective was to compare 1-year survival rates between serum cryptococcal antigen (sCrAg)-positive and sCrAg-negative HIV-positive individuals with CD4+ cell counts less than 100 cells/µl without symptoms of meningitis in Zimbabwe. DESIGN: This was a prospective cohort study. METHODS: Participants were enrolled as either sCrAg-positive or sCrAg-negative and followed up for 52 weeks or less, with death as the outcome. Lumbar punctures were recommended to all sCrAg-positives and inpatient management with intravenous amphotericin B and high-dose fluconazole was recommended to those with disseminated Cryptococcus. Antiretroviral therapy was initiated immediately in sCrAg-negatives and after at least 4 weeks following initiation of antifungals in sCrAg-positives. Multivariable logistic regression models were used to determine risk factors for mortality. RESULTS: We enrolled 1320 participants and 130 (9.8%) were sCrAg positive, with a median sCrAg titre of 1 : 20. Sixty-six (50.8%) sCrAg-positives had lumbar punctures and 16.7% (11/66) had central nervous system (CNS) dissemination. Cryptococcal blood cultures were performed in 129 sCrAg-positives, with 10 (7.8%) being positive. One-year (48-52 weeks) survival rates were 83.9 and 76.1% in sCrAg-negatives and sCrAg-positives, respectively, P = 0.011. Factors associated with increased mortality were a positive sCrAg, CD4+ cell count less than 50 cells/µl and having presumptive tuberculosis (TB) symptoms. CONCLUSION: Our study reports a high prevalence of subclinical cryptococcal antigenemia and reiterates the importance of TB and a positive sCrAg as risk factors for mortality in advanced HIV disease (AHD). Therefore, TB and sCrAg screening remains a crucial component of AHD package, hence it should always be part of the comprehensive clinical evaluation in AHD patients.

The transient effect of a peer support intervention to improve adherence among adolescents and young adults failing antiretroviral therapy in Harare, Zimbabwe: a randomized control trial.

BACKGROUND: Adolescents and young adults living with HIV in sub Saharan Africa are at high risk of poor adherence to antiretroviral therapy (ART) and virologic failure (VF). METHODS: We conducted a randomized control trial among adolescents and young adults on ART with VF to assess the effectiveness of a community-based peer support intervention aimed at improving VF. Viral load (VL) levels were obtained at 12, 24 and 36 weeks. A subset of the participants had baseline HIV drug resistance (HIVDR) genotyped using Sanger sequencing. RESULTS: The participants' median (interquartile range (IQR)) age was 18.1 (IQR: 15.1-20.0) years and half (50.5%, n = 107) were male. At week 24, the proportion of subjects with a detectable viremia was significantly lower in the intervention arm than in the standard of care (SOC) arm (76.0% (n = 79) vs. 89.0% (n = 96), p = 0.013). At Week 36, there remained a difference in the proportion of subjects with a detectable VL between the intervention arm (68.3%, n = 71) and SOC arm (79.6%, n = 86), which was trending towards statistical significance (p = 0.059). There was no difference in the probability of having a detectable VL over time between the intervention and SOC groups (adjusted odds ratio: 1.14, p = 0.439). Baseline HIVDR was observed in 44.0% of the participants in the intervention and 56.0% in the SOC group (p = 0.146). CONCLUSION: A transient effect of the peer support intervention in improving VF was observed among adolescents and young people failing ART. TRIAL REGISTRATION: This study is registered with www.clinicaltrials.gov under the reference number: NCT02833441.

A Cascade of Interventions to Promote Adherence to Antiretroviral Therapy in African Countries.

PURPOSE OF REVIEW: We reviewed interventions to improve uptake and adherence to antiretroviral therapy (ART) in African countries in the Treat All era. RECENT FINDINGS: ART initiation can be improved by facilitated rapid receipt of first prescription, including community-based linkage and point-of-care strategies, integration of HIV care into antenatal care and peer support for adolescents. For people living with HIV (PLHIV) on ART, scheduled SMS reminders, ongoing intensive counselling for those with viral non-suppression and economic incentives for the most deprived show promise. Adherence clubs should be promoted, being no less effective than facility-based care for stable patients. Tracing those lost to follow-up should be targeted to those who can be seen face-to-face by a peer worker. Investment is needed to promote linkage to initiating ART and for differentiated approaches to counselling for youth and for those with identified suboptimal adherence. More evidence from within Africa is needed on cost-effective strategies to identify and support PLHIV at an increased risk of non-adherence across the treatment cascade.

Neurocognitive impairment in treatment-experienced adults living with HIV attending primary care clinics in Zimbabwe.

BACKGROUND: HIV affects the central nervous system resulting in HIV associated neurocognitive impairment (NCI) in approximately 50% of people living with HIV. It typically affects memory, learning, working memory, fine motor skills, speed of information processing, verbal fluency and executive functioning cognitive domains. NCI can affect adherence to antiretroviral therapy (ART), employability, driving ability and activities of daily living. NCI is not routinely screened for in Zimbabwe, and the burden is not known in this setting. The objectives of this study were: 1) To determine NCI prevalence using a comprehensive neuropsychological battery at two primary health care clinics in Harare; 2) To assess the pattern of cognitive impairment across cognitive domains using a gold standard neuropsychological (NP) battery in HIV-positive patients compared to HIV-negative controls. METHODS: Inclusion criteria: 18 years or older; minimum 7 years education; no neurological or psychiatric disorders. HIV-positive participants were on ART for ≥3 months; HIV-negative participants had a confirmed HIV negative status in the past month. A comprehensive NP battery, functional assessments, demographic and medical history questionnaires were administered. The NP battery consisted of tests assessing memory, learning, working memory, fine motor skills, speed of information processing, verbal fluency and executive functioning. RESULTS: Two-hundred-and-thirty-one participants were recruited. Of those, 155 were HIV-positive (Female = 70%, Age M = 37.8; SD 11.2) and 76 HIV-negative (Female = 63%, Age M = 31.2; SD 9.9). HIV-positive participants were on ART for an average of 6 years. NCI was present in 49.7% HIV positive participants. Compared to HIV-negative participants, the HIV-positive group had significantly poorer scores in 5 out of 7 cognitive domains. A good level of education is negatively correlated with NCI. CONCLUSIONS: NCI prevalence in HIV-positive population Zimbabwe is consistent with global estimates. NCI persists in adults who are on ART. Routine assessment of NCI in adults attending primary care clinics using this adapted battery is therefore important so that they are identified early and are provided the necessary interventions.

A Task-Shifting Problem-Solving Therapy Intervention for Depression and Barriers to Antiretroviral Therapy Adherence for People Living With HIV in Zimbabwe: Case Series.

HIV is prevalent in Sub-Saharan Africa, and depression frequently co-occurs. Depression is one of the most important predictors of poor adherence to antiretroviral therapy (ART). Little has been done to develop integrated interventions that are feasible and appropriate for task-shifting to nonspecialists that seek to address both depression and barriers to ART adherence in Sub-Saharan Africa. This case series describes an integrated intervention for depression and ART adherence delivered by a lay adherence counselor and supervised by a local psychologist. The 6-session intervention was based on problem-solving therapy for depression and for barriers to adherence (PST-AD), with stepped care for those whose depression did not recover with PST-AD. Primary outcomes were acceptability and depression. Acceptability was measured by participant attendance to the 6 sessions. Three case studies illustrate the structured intervention, solutions identified to adherence barriers and to problems underlying low mood, and changes seen in the clients' psychological symptoms. Acceptability of the intervention was high and common mental disorder symptoms scores measured using the SRQ-8 decreased overall. An integrated intervention for depression and adherence to ART appeared feasible in this low-income setting. An RCT of the intervention versus an appropriate comparison condition is needed to evaluate clinical and cost-effectiveness.

Assessment of neurocognitive deficits in people living with HIV in Sub Saharan Africa: A systematic review.

Objective: People living with HIV (PLWH) are at risk for HIV-Associated Neurocognitive Disorders (HAND)/Neurocognitive Impairment (NCI). HIV prevalence in Sub-Saharan Africa (SSA) is high, but neuropsychological screening and testing for NCI among HIV-infected individuals is not done frequently. This systematic review aims to establish how NCI among HIV-infected individuals is being assessed in SSA, if and how the tests are adapted, if norms exist and identify personnel who administer them.Method: We searched PubMed, Medline, EBSCO, PsycINFO, and Web of Science. Two reviewers screened the articles for inclusion and risk of bias. We included studies from SSA with a comprehensive neuropsychological assessment battery.Results: We retrieved 212 articles and 23 articles met inclusion criteria. The most commonly used tests were the Color Trails Test 1, Color Trails Test 2, and the WAIS III Digit Symbol Test. Some tests were translated into French (Cameroon), Luganda (Uganda), Chichewa (Malawi), isiXhosa (South Africa), and Afrikaans (South Africa). Some verbal learning tests were adapted to reflect culturally appropriate language. Test administrators were either non-specialized personnel supervised by clinical neuropsychologists or clinical psychologists.Conclusion: Overall, the tests used are similar to the tests being used globally to assess NCI among HIV-infected individuals and there is a general consistency across countries. However, there is generally a lack of norms for the tests and the process of adaptation is not always well described. Future research should establish whether these tests measure neuropsychological constructs as successfully as they do in western populations where the tests were developed.

Feasibility and Acceptability of a Task-Shifted Intervention to Enhance Adherence to HIV Medication and Improve Depression in People Living with HIV in Zimbabwe, a Low Income Country in Sub-Saharan Africa.

Using a pilot trial design in an HIV care clinic in Zimbabwe, we randomised 32 adults with poor adherence to antiretroviral therapy and at least mild depression to either six sessions of Problem-Solving Therapy for adherence and depression (PST-AD) delivered by an adherence counsellor, or to Enhanced Usual Care (Control). Acceptability of PST-AD was high, as indicated by frequency of session attendance and through qualitative analyses of exit interviews. Fidelity was >80% for the first two sessions of PST-AD but fidelity to the adherence component of PST-AD dropped by session 4. Contamination occurred, in that seven patients in the control arm received one or two PST-AD sessions before follow-up assessment. Routine health records proved unreliable for measuring HIV viral load at follow-up. Barriers to measuring adherence electronically included device failure and participant perception of being helped by the research device. The study was not powered to detect clinical differences, however, promising change at 6-months follow-up was seen in electronic adherence, viral load suppression (PST-AD arm 9/12 suppressed; control arm 4/8 suppressed) and depression (Patient Health Questionnaire-4.7 points in PST-AD arm vs. control, adjusted p value = 0.01). Results inform and justify a future randomised controlled trial of task-shifted PST-AD.

Cultural adaptation of a cognitive-behavioural intervention to improve adherence to antiretroviral therapy among people living with HIV/AIDS in Zimbabwe: Nzira Itsva.

Few evidence-based interventions to improve adherence to antiretroviral therapy have been adapted for use in Africa. We selected, culturally adapted and tested the feasibility of a cognitive-behavioural intervention for adherence and for delivery in a clinic setting in Harare, Zimbabwe. The feasibility of the intervention was evaluated using a mixed-methods assessment, including ratings of provider fidelity of intervention delivery, and qualitative assessments of feasibility using individual semi-structured interviews with counsellors (n=4) and patients (n=15). The intervention was feasible and acceptable when administered to 42 patients and resulted in improved self-reported adherence in a subset of 15 patients who were followed up after 6months.

'I was thinking too much': experiences of HIV-positive adults with common mental disorders and poor adherence to antiretroviral therapy in Zimbabwe.

OBJECTIVE: To document the lived experiences of people with both poor mental health and suboptimal adherence to antiretroviral therapy in high HIV prevalence settings. METHODS: In-depth qualitative interviews were conducted with 47 (female = 31) HIV-positive adults who scored above the cut-point on a locally validated scale for common mental disorders (CMDs). Purposive sampling was used to recruit participants with evidence of poor adherence. Six additional key informant interviews (female = 6) were conducted with healthcare workers. Data were collected and analysed inductively by an interdisciplinary coding team. RESULTS: The major challenges faced by participants were stressors (poverty, stigma, marital problems) and symptoms of CMDs ('thinking too much', changes to appetite and sleep, 'burdened heart' and low energy levels). Thinking too much, which appears closely related to rumination, was the symptom with the greatest negative impact on adherence to antiretroviral therapy among HIV-positive adults with CMDs. In turn, thinking too much was commonly triggered by the stressors faced by people living with HIV/AIDS, especially poverty. Finally, participants desired private counselling, access to income-generating activities and family engagement in mental health care. CONCLUSIONS: Better understanding of the local expression of mental disorders and of underlying stressors can inform the development of culturally sensitive interventions to reduce CMDs and poor adherence to antiretroviral therapy.