Associations Between Patterns of Alcohol Use and Viral Load Suppression Amongst Women Living with HIV in South Africa.

This study aimed to identify alcohol use patterns associated with viral non-suppression among women living with HIV (WLWH) and the extent to which adherence mediated these relationships. Baseline data on covariates, alcohol consumption, ART adherence, and viral load were collected from 608 WLWH on ART living in the Western Cape, South Africa. We defined three consumption patterns: no/light drinking (drinking ≤ 1/week and ≤ 4 drinks/occasion), occasional heavy episodic drinking (HED) (drinking > 1 and ≤ 2/week and ≥ 5 drinks/occasion) and frequent HED (drinking ≥ 3 times/week and ≥ 5 drinks/occasion). In multivariable analyses, occasional HED (OR 3.07, 95% CI 1.78-5.30) and frequent HED (OR 7.11, 95% CI 4.24-11.92) were associated with suboptimal adherence. Frequent HED was associated with viral non-suppression (OR 2.08, 95% CI 1.30-3.28). Suboptimal adherence partially mediated the relationship between frequent HED and viral non-suppression. Findings suggest a direct relationship between frequency of HED and viral suppression. Given the mediating effects of adherence on this relationship, alcohol interventions should be tailored to frequency of HED while also addressing adherence.

The Impact of HIV-Associated Neurocognitive Impairment on Driving Performance in Commercial Truck Drivers.

Driving ability can be diminished amongst people with HIV with associated neurocognitive impairment (NCI). We explore the relationship between HIV status, NCI and driving ability in professional truck drivers. Forty male professional drivers (20 HIV-positive; mean age = 39.20 ± 7.05) completed a neuropsychological test battery, two driving simulator tasks that assessed driving ability, and a driving history and habits questionnaire. A higher proportion of HIV-positive drivers exhibited impaired overall cognitive performance (p ≤ 0.001). Overall, drivers with NCI (defined as z ≤ 1.00) were more likely than those without NCI to crash (p = 0.002). There were no significant between-group (HIV-positive versus HIV-negative) differences with regard to self-reported on-road driving events. Professional drivers with NCI, as measured on a driving simulator, are at increased risk of making driving errors under high-risk conditions compared to their neurocognitively normal counterparts. These data should inform driver health management with regard to annual medical screening and surveillance.

RESUMEN: La capacidad de conducción puede verse disminuida entre las personas con VIH con deterioro neurocognitivo asociado (neurocognitive impairment, NCI). Exploramos la relación entre la situación frente al VIH, el NCI y la capacidad de conducción en conductores profesionales de camiones. Cuarenta conductores profesionales masculinos (20 seropositivos, edad media = 39.20 ± 7.05) completaron una batería de pruebas neuropsicológicas, dos tareas de simulador de conducción que evaluaron la capacidad de conducción y un cuestionario de hábitos y antecedentes de conducción. Una mayor proporción de conductores VIH positivos exhibió un desempeño cognitivo general deficiente (p ≤ 0.001). En general, los conductores con NCI (definido como z ≤ 1.00) tenían más probabilidades de chocar que aquellos sin NCI (p = 0.002). No hubo diferencias significativas entre los grupos (VIH positivo frente a VIH negativo) con respecto a los eventos autoinformados de conducción en carretera. Los conductores profesionales con NCI, según lo medido en un simulador de conducción, tienen un mayor riesgo de cometer errores de conducción en condiciones de alto riesgo en comparación con sus homólogos neurocognitivamente normales. Estos datos deberían informar a la gestión de la salud del conductor en lo que respecta a la vigilancia y los exámenes médicos anuales.

Detecting Depression in People Living with HIV in South Africa: The Factor Structure and Convergent Validity of the South African Depression Scale (SADS).

Screening measures for depression developed in high-income countries have not always demonstrated strong psychometric properties in South Africa and with people living with HIV (PLWH). The present study explored the psychometric properties of the 16-item South African Depression Scale (SADS) comprised of idioms of distress specific to isiXhosa culture in PLWH. The SADS was administered to 137 Xhosa-speaking PLWH who met diagnostic criteria for major depressive disorder (MDD) together with the Hamilton Depression Scale (HAM-D) and the Center for Epidemiological Studies Depression Scale (CES-D). We conducted exploratory factor analysis, correlation, and reliability statistics. Four factors of the SADS emerged: Sadness, lethargy/burdened, anhedonia/withdrawal, and cognitive/somatic. All factors correlated significantly with the HAM-D and CES-D. Internal consistency of the overall measure was high (α = .89). The SADS promises to be a robust measure of depression in isiXhosa-speaking PLWH in South Africa likely due to the inclusion of local idioms of distress.

'I went back to being myself': acceptability of a culturally adapted task-shifted cognitive-behavioural therapy (CBT) treatment for depression (Ziphamandla) for South African HIV care settings.

There is a need for a culturally adapted, evidence-based, psychotherapy treatment that is effective, acceptable, and feasible for integration into primary care in South Africa. This qualitative study used exit interviews to examine participants' experiences of an adapted cognitive-behavioural therapy treatment for adherence and depression, task-shifted and delivered by nurses in two peri-urban HIV clinics near Cape Town. Nine semi-structured exit interviews were conducted with isiXhosa-speaking females and analysed using thematic analysis. Overall, participants responded positively to the treatment, viewing it as acceptable and beneficial and as a catalyst to returning to normalcy. Results indicated that participants viewed the treatment as being effective in ameliorating their depressive symptoms and improving their adherence to ART . Additional benefits described included improvements in subjective wellbeing and social and occupational functioning. Several began or resumed employment, an important behavioural indicator of the treatment's capacity to facilitate positive change and cost saving. Recommendations to improve the treatment included using video material and educating others about depression. These findings have positive implications regarding the acceptability and cultural applicability of the treatment for use in South Africa.

Self-Seeding Microwells to Isolate and Assess the Viability of Single Circulating Tumor Cells.

The availability of viable tumor cells could significantly improve the disease management of cancer patients. Here we developed and evaluated a method using self-seeding microwells to obtain single circulating tumor cells (CTC) and assess their potential to expand. Conditions were optimized using cells from the breast cancer cell line MCF-7 and blood from healthy volunteers collected in EDTA blood collection tubes. 43% of the MCF-7 cells (nucleus+, Ethidium homodimer-1-, Calcein AM+, α-EpCAM+, α-CD45-) spiked into 7.5 mL of blood could be recovered with 67% viability and these could be further expanded. The same procedure tested in metastatic breast and prostate cancer patients resulted in a CTC recovery of only 0⁻5% as compared with CTC counts obtained with the CellSearch® system. Viability of the detected CTC ranged from 0⁻36%. Cell losses could be mainly contributed to the smaller size and greater flexibility of CTC as compared to cultured cells from cell lines and loss during leukocyte depletion prior to cell seeding. Although CTC losses can be reduced by fixation, to obtain viable CTC no fixatives can be used and pore size in the bottom of microwells will need to be reduced, filtration conditions adapted and pre-enrichment improved to reduce CTC losses.

Empowering Lay-Counsellors with Technology: Masivukeni, a Standardized Multimedia Counselling Support Tool to Deliver ART Counselling.

Lay-counsellors in resource-limited settings convey critical HIV- and ART-information, and face challenges including limited training and variable application of counselling. This study explored lay-counsellors and Department of Health (DoH) perspectives on the utility of a multimedia adherence counselling program. Masivukeni, an mHealth application that provides scaffolding for delivering standardized ART counselling was used in a 3-year randomized control trail at two primary health care clinics in Cape Town, South Africa. In this programmatic and descriptive narrative report, we describe the application; lay-counsellors' response to open-ended questions regarding their experience with using Masivukeni; and perspectives of the City of Cape Town and Western Cape Government DoH, obtained through ongoing engagements and feedback sessions. Counsellors reported Masivukeni empowered them to provide high quality counselling. DoH indicated strong support for a future implementation study assessing feasibility for larger scale roll-out. Masivukeni has potential as a counselling tool in resource-limited settings.

The dopamine-related polymorphisms BDNF, COMT, DRD2, DRD3, and DRD4 are not linked with changes in CSF dopamine levels and frequency of HIV infection.

We showed previously that higher levels in CSF dopamine in HIV patients are associated with the presence of the dopamine transporter (DAT) 10/10-repeat allele which was also detected more frequently in HIV-infected individuals compared to uninfected subjects. In the current study, we investigated further whether other genetic dopamine (DA)-related polymorphisms may be related with changes in CSF DA levels and frequency of HIV infection in HIV-infected subjects. Specifically, we studied genetic polymorphisms of brain-derived neurotrophic factor, catechol-O-methyltransferase, and dopamine receptors DRD2, DRD3, and DRD4 genetic polymorphisms in uninfected and HIV-infected people in two different ethnical groups, a German cohort (Caucasian, 72 individuals with HIV infection and 22 individuals without HIV infection) and a South African cohort (Xhosan, 54 individuals with HIV infection and 19 individuals without HIV infection). We correlated the polymorphisms with CSF DA levels, HIV dementia score, CD4+ T cell counts, and HIV viral load. None of the investigated DA-related polymorphisms was associated with altered CSF DA levels, CD4+ T cell count, viral load, and HIV dementia score. The respective allele frequencies were equally distributed between HIV-infected patients and controls. Our findings do not show any influence of the studied genetic polymorphisms on CSF DA levels and HIV infection. This is in contrast to what we found previously for the DAT 3'UTR VNTR and highlights the specific role of the DAT VNTR in HIV infection and disease.

A Comparison of Five Brief Screening Tools for HIV-Associated Neurocognitive Disorders in the USA and South Africa.

Screening for HIV-associated neurocognitive disorders (HAND) is important to improve clinical outcomes. We compared the diagnostic sensitivity and specificity of the mini-mental state examination, International HIV dementia scale (IHDS), Montreal cognitive assessment, Simioni symptom questionnaire and cognitive assessment tool-rapid version (CAT-rapid) to a gold standard neuropsychological battery. Antiretroviral-experienced participants from Cape Town, South Africa, and Baltimore, USA, were recruited. The sensitivity and specificity of the five tools, as well as those of the combined IHDS and CAT-rapid, were established using 2 × 2 contingency tables and ROC analysis. More than a third (65165) had symptomatic HAND. In detecting HIV-D, the CAT-Rapid had good sensitivity (94 %) and weak specificity (52 %) (cut-point ≤10), while the IHDS showed fair sensitivity (68 %) and good specificity (86 %) (cut-point ≤10). The combined IHDS and CAT-rapid showed excellent sensitivity and specificity for HIV-D at a cut-off score of ≤16 (out of 20; 89 and 82 %). No tool was adequate in screening for any HAND. The combination IHDS and CAT-rapid tool appears to be a good screener for HIV-D but is only fairly sensitive and poorly specific in screening for any HAND. Screening for milder forms of HAND continues to be a clinical challenge.

Understanding the experience and manifestation of depression in people living with HIV/AIDS in South Africa.

Understanding the experience of depression in people living with HIV/AIDS (PLWH) could aid in the detection and treatment of the disorder. Yet, there is limited knowledge of the subjective experience of depression amongst PLWH in low- and middle-income countries despite high rates of this disorder in this population. In the current study, semi-structured interviews were conducted with depressed adults living with HIV attending a primary infectious disease clinic in South Africa. Interview transcripts were thematically analyzed. The construct of depression was consistent with DSM-IV criteria; however, the symptom presentation was distinctive. Somatic symptoms were most prominent in participants' initial presentations because participants perceived them as medically relevant. Affective, cognitive, and behavioral symptoms were not readily reported as participants did not perceive these symptoms as pertinent to their medical treatment. We identified several idioms of distress that could assist in screening for depression in this population. A valid, contextually developed screener for depression in PLWH awaits further investigation. Such a measure could play a key role in formulating a logistically feasible method of detection and treatment for depression in this population.

Isolation of Single Circulating Tumor Cells Using VyCAP Puncher System.

Tumor heterogeneity has a major role in the development of tumor evasion and resistance to treatments. To study and understand the intrinsic heterogeneity of cancer cells, the use of single-cell isolation technology has had a major boost in recent years, gaining ground to bulk analysis in the study of solid tumors. In the liquid biopsy field, the use of technologies for single-cell analysis has represented a major advance in the study of the heterogeneity of circulating tumor cells (CTCs), providing relevant information about therapy-resistant CTCs. However, single-cell analysis of CTCs is still challenging due to the weakness and scarcity of these cells. In this chapter, we describe a protocol for CTCs isolation at a single-cell level using the VyCAP Puncher system.

ImpACT+, a coping intervention to improve clinical outcomes for women living with HIV and sexual trauma in South Africa: study protocol for a randomized controlled trial.

BACKGROUND: Addressing sexual trauma in the context of HIV care is essential to improve clinical outcomes and mental health among women in South Africa. Women living with HIV (WLH) report disproportionately high levels of sexual trauma and have higher rates of posttraumatic stress disorder. Adherence to antiretroviral therapy (ART) may be difficult for traumatized women, as sexual trauma compounds the stress associated with managing HIV and is often comorbid with other mental health disorders, further compromising care engagement and adherence. ART initiation represents a unique window of opportunity for intervention to enhance motivation, increase care engagement, and address the negative effects of trauma on avoidant coping behaviors. Mental health interventions delivered by non-specialists in low- and middle-income countries have potential to treat depression, trauma, and effects of intimate partner violence among WLH. This study will examine the effectiveness of Improving AIDS Care after Trauma (ImpACT +), a task-shared, trauma-focused coping intervention, to promote viral suppression among WLH initiating ART in a South African clinic setting. METHODS: This study will be conducted in Khayelitsha, a peri-urban settlement situated near Cape Town, South Africa. Using a hybrid type 1 effectiveness-implementation design, we will randomize 350 WLH initiating ART to the ImpACT + experimental condition or the control condition (three weekly sessions of adapted problem-solving therapy) to examine the effectiveness of ImpACT + on viral suppression, ART adherence, and the degree to which mental health outcomes mediate intervention effects. ImpACT + participants will receive six once-a-week coping intervention sessions and six monthly maintenance sessions over the follow-up period. We will conduct mental health and bio-behavioral assessments at baseline, 4, 8, and 12 months, with care engagement data extracted from medical records. We will explore scalability using the Consolidated Framework for Implementation Research (CFIR). DISCUSSION: This trial is expected to yield important new information on psychologically informed intervention models that benefit the mental health and clinical outcomes of WLH with histories of sexual trauma. The proposed ImpACT + intervention, with its focus on building coping skills to address traumatic stress and engagement in HIV care and treatment, could have widespread impact on the health and wellbeing of individuals and communities in sub-Saharan Africa. TRIAL REGISTRATION: Clinicaltrials.gov NCT04793217 . Retrospectively registered on 11 March 2021.

Measurement of the Drug Sensitivity of Single Prostate Cancer Cells.

The treatment of cancer faces a serious challenge as cancer cells within patients are heterogeneous and frequently resistant to therapeutic drugs. Here, we introduce a technology enabling the assessment of single cancer cells exposed to different drugs. PCa cells were individually sorted in self-seeding microwells, cultured for 24 h, and then exposed to several drugs to induce (R1881) or inhibit (Enzalutamide/Abiraterone) the secretion of a protein (PSA). Cell viability and PSA secretion of each individual prostate cell were monitored over a 3-day period. The PSA protein secreted by each cell was captured on a PVDF membrane through a pore in the bottom of each well. The basal PSA secretion was found to be 6.1 ± 4.5 and 3.7 ± 1.9 pg/cell/day for LNCaP and VCaP, respectively. After exposure to R1881, the PSA secretion increased by ~90% on average and was not altered for ~10% of the cells. PSA production decreased in the majority of cells after exposure to enzalutamide and abiraterone.

The treatment gap for mental disorders in adults enrolled in HIV treatment programmes in South Africa: a cohort study using linked electronic health records.

AIMS: Mental disorders are common in people living with HIV (PLWH) but often remain untreated. This study aimed to explore the treatment gap for mental disorders in adults followed-up in antiretroviral therapy (ART) programmes in South Africa and disparities between ART programmes regarding the provision of mental health services. METHODS: We conducted a cohort study using ART programme data and linked pharmacy and hospitalisation data to examine the 12-month prevalence of treatment for mental disorders and factors associated with the rate of treatment for mental disorders among adults, aged 15-49 years, followed-up from 1 January 2012 to 31 December 2017 at one private care, one public tertiary care and two pubic primary care ART programmes in South Africa. We calculated the treatment gap for mental disorders as the discrepancy between the 12-month prevalence of mental disorders in PLWH (aged 15-49 years) in South Africa (estimated based on data from the Global Burden of Disease study) and the 12-month prevalence of treatment for mental disorders in ART programmes. We calculated adjusted rate ratios (aRRs) for factors associated with the treatment rate of mental disorders using Poisson regression. RESULTS: In total, 182 285 ART patients were followed-up over 405 153 person-years. In 2017, the estimated treatment gap for mental disorders was 40.5% (95% confidence interval [CI] 19.5-52.9) for patients followed-up in private care, 96.5% (95% CI 95.0-97.5) for patients followed-up in public primary care and 65.0% (95% CI 36.5-85.1) for patients followed-up in public tertiary care ART programmes. Rates of treatment with antidepressants, anxiolytics and antipsychotics were 17 (aRR 0.06, 95% CI 0.06-0.07), 50 (aRR 0.02, 95% CI 0.01-0.03) and 2.6 (aRR 0.39, 95% CI 0.35-0.43) times lower in public primary care programmes than in the private sector programmes. CONCLUSIONS: There is a large treatment gap for mental disorders in PLWH in South Africa and substantial disparities in access to mental health services between patients receiving ART in the public vs the private sector. In the public sector and especially in public primary care, PLWH with common mental disorders remain mostly untreated.

The mechanics of setting up a COVID-19 response: Experiences of the COVID-19 epidemic from Groote Schuur Hospital, Cape Town, South Africa.

The SARS-CoV-2 pandemic has challenged the provision of healthcare in ways that are unprecedented in our lifetime. Planning for the sheer numbers expected during the surge has required public hospitals to de-escalate all non-essential clinical services to focus on COVID-19. Western Cape Province was the initial epicentre of the COVID-19 epidemic in South Africa (SA), and the Cape Town metro was its hardest-hit geographical region. We describe how we constructed our COVID-19 hospital-wide clinical service at Groote Schuur Hospital, the University of Cape Town's tertiary-level teaching hospital. By describing the barriers and enablers, we hope to provide guidance rather than a blueprint for hospitals elsewhere in SA and in low-resource countries that face similar challenges now or during subsequent waves.

Normal-pressure hydrocephalus presenting with psychiatric symptoms.

A 62-year-old man presented with a 2-month history of psychiatric symptoms. These were preceded by cognitive deterioration, urinary incontinence and an abnormal gait. A diagnosis of normal-pressure hydrocephalus (NPH) was made, and the patient improved after surgery.

Generating evidence to narrow the treatment gap for mental disorders in sub-Saharan Africa: rationale, overview and methods of AFFIRM.

There is limited evidence on the acceptability, feasibility and cost-effectiveness of task-sharing interventions to narrow the treatment gap for mental disorders in sub-Saharan Africa. The purpose of this article is to describe the rationale, aims and methods of the Africa Focus on Intervention Research for Mental health (AFFIRM) collaborative research hub. AFFIRM is investigating strategies for narrowing the treatment gap for mental disorders in sub-Saharan Africa in four areas. First, it is assessing the feasibility, acceptability and cost-effectiveness of task-sharing interventions by conducting randomised controlled trials in Ethiopia and South Africa. The AFFIRM Task-sharing for the Care of Severe mental disorders (TaSCS) trial in Ethiopia aims to determine the acceptability, affordability, effectiveness and sustainability of mental health care for people with severe mental disorder delivered by trained and supervised non-specialist, primary health care workers compared with an existing psychiatric nurse-led service. The AFFIRM trial in South Africa aims to determine the cost-effectiveness of a task-sharing counselling intervention for maternal depression, delivered by non-specialist community health workers, and to examine factors influencing the implementation of the intervention and future scale up. Second, AFFIRM is building individual and institutional capacity for intervention research in sub-Saharan Africa by providing fellowship and mentorship programmes for candidates in Ethiopia, Ghana, Malawi, Uganda and Zimbabwe. Each year five Fellowships are awarded (one to each country) to attend the MPhil in Public Mental Health, a joint postgraduate programme at the University of Cape Town and Stellenbosch University. AFFIRM also offers short courses in intervention research, and supports PhD students attached to the trials in Ethiopia and South Africa. Third, AFFIRM is collaborating with other regional National Institute of Mental Health funded hubs in Latin America, sub-Saharan Africa and south Asia, by designing and executing shared research projects related to task-sharing and narrowing the treatment gap. Finally, it is establishing a network of collaboration between researchers, non-governmental organisations and government agencies that facilitates the translation of research knowledge into policy and practice. This article describes the developmental process of this multi-site approach, and provides a narrative of challenges and opportunities that have arisen during the early phases. Crucial to the long-term sustainability of this work is the nurturing and sustaining of partnerships between African mental health researchers, policy makers, practitioners and international collaborators.

HIV-associated neurocognitive disorders: antiretroviral regimen, central nervous system penetration effectiveness, and cognitive outcomes.

BACKGROUND: The human immunodeficiency virus (HIV) can give rise to a spectrum of neuropsychological impairments known collectively as HIV-associated neurocognitive disorders (HAND). Although antiretroviral therapy (ART) has reduced the incidence of HIV dementia, the prevalence of milder forms of HAND has increased. It has been postulated that incomplete central nervous system (CNS) viral suppression or potential drug toxicity, both of which could be related to the CNS penetration effectiveness (CPE) of ART regimens, may contribute to this phenomenon. OBJECTIVE: This study compared cognitive outcomes in clade C-infected HIV patients in South Africa treated for 1 year with ART regimens with differing CPE scores. METHODS: We assessed 111 HIV-positive patients with varying levels of cognitive function at baseline (pre-ART) and then a year later. A neuropsychological battery was administered at both visits to derive global deficit scores. ART regimen data were collected at the follow-up visit. Some participants remained ART-naïve during this period, thus providing a non-treatment control group. RESULTS: Significantly more ART recipients maintained or improved cognitive function compared with patients not on ART (p=0.017). There was no significant difference in cognitive outcomes between higher and lower CPE regimen groups (p=0.473). CONCLUSIONS: ART preserves or improves cognition in HIV-infected patients after 1 year, irrespective of the regimen's CPE. South Africa's current low CPE-scored first-line regimen performed as well as higher CPE-scored regimens. These findings are reassuring for South Africa, but larger, longer-term studies would be more definitive.

The accuracy of interpreting key psychiatric terms by ad hoc interpreters at a South African psychiatric hospital.

OBJECTIVE: This study examined the competence and accuracy of ad hoc interpreters in interpreting key psychiatric terms at a South African psychiatric hospital METHODS: Nine individuals were asked to translate key psychiatric terms from English to Xhosa. These translations were then back-translated by independent translators, who do not have knowledge of psychiatric terminology. These back-translations were then compared with the original English. RESULTS: It was clear that not all the participants were fully competent in English. None had formal training in interpreting or psychiatric terminology. Not all of the participants were familiar with the psychiatric concepts that clinicians use and they often made mistakes while interpreting. CONCLUSION: The competency levels of interpreters are unsatisfactory to ensure the optimal delivery of mental health care. It is clear that there is a need for trained interpreters in South Africa, as the continuous use of untrained interpreters compromises the effectiveness of mental health care and could lead to adverse health outcomes.

Integrating mental health into general health care: lessons from HIV.

Mental disorders are highly prevalent across all health settings. Where they are co-morbid with other chronic physical disorders, a complex bidirectional relationship exists between them. While mental disorders may result in an increase in adverse healthrelated outcomes, they are amenable to cost-effective treatments. In resource-limited settings, many barriers to the detection and treatment of mental disorders exist. One approach to the effective targeting of the available resources is to utilize a "risk-flag" approach, wherein individuals at-risk of treatment failure are identified and routed into more intensive mental health screening and intervention. This paper discusses how lessons from HIV services may inform how to improve mental health care and integration in HIV settings, as well as in other chronic diseases.