The salience of structural barriers and behavioral health problems to ART adherence in people receiving HIV primary care in South Africa.

Multilevel factors (individual and structural) influence adherence to antiretroviral therapy, particularly in high HIV prevalence areas such as South Africa. The present study examined the relative importance of structural barriers to HIV care and behavioral health factors, depression and alcohol use, in Khayelitsha, Cape Town, South Africa. People receiving HIV care in six primary care clinics in Khayelitsha (N = 194) completed the Center for Epidemiologic Studies Depression Scale, the Alcohol Use Disorders Identification Test, the Structural Barriers to Medication Taking questionnaire, and a qualitative rating of past-two-week adherence. Correlations were employed to examine associations among these variables, and hierarchical regression analysis was used to examine the unique effects of structural barriers over and above depression and alcohol use as predictors of adherence. Participants were primarily Black South African (99%) women (83%), and 41 years old on average. All four variables were significantly correlated. The hierarchical regression analysis showed that among behavioral health predictors, alcohol use alone significantly predicted ART adherence (b = -.032, p = .002). When structural barriers was added to the model, it was the only significant unique predictor of ART adherence (b = -1.58, p < .001). Findings highlight the need to consider structural vulnerabilities in HIV care in South Africa when developing behavioral health interventions.

Cognitive Impairment in Tuberculous Meningitis.

BACKGROUND: Cognitive impairment is reported as a common complication in adult tuberculous meningitis (TBM), yet few studies have systematically assessed the frequency and nature of impairment. Moreover, the impact of impairment on functioning and medication adherence has not been described. METHODS: A cognitive test battery (10 measures assessing 7 cognitive domains) was administered to 34 participants with human immunodeficiency virus (HIV)-associated TBM 6 months after diagnosis. Cognitive performance was compared with that a comparator group of 66 people with HIV without a history of tuberculosis. A secondary comparison was made between participants with TBM and 26 participants with HIV 6 months after diagnosis of tuberculosis outside the central nervous system (CNS). Impact on functioning was evaluated, including through assessment of medication adherence. RESULTS: Of 34 participants with TBM, 16 (47%) had low performance on cognitive testing. Cognition was impaired across all domains. Global cognitive performance was significantly lower in participants with TBM than in people with HIV (mean T score, 41 vs 48, respectively; P < .001). These participants also had lower global cognition scores than those with non-CNS tuberculosis (mean global T score, 41 vs 46; P = .02). Functional outcomes were not significantly correlated with cognitive performance in the subgroup of participants in whom this was assessed (n = 19). CONCLUSIONS: Low cognitive performance following HIV-associated TBM is common. This effect is independent of, and additional to, effects of HIV and non-CNS tuberculosis disease. Further studies are needed to understand longer-term outcomes, clarify the association with treatment adherence, a key predictor of outcome in TBM, and develop context-specific tools to identify individuals with cognitive difficulties in order to improve outcomes in TBM.

Comparing dedicated and designated approaches to integrating task-shared psychological interventions into chronic disease care in South Africa: a three-arm, cluster randomised, multicentre, open-label trial.

BACKGROUND: Community health workers (CHWs) are increasingly providing task-shared psychological interventions for depression and alcohol use in primary health care in low-income and middle-income countries. We aimed to compare the effectiveness of CHWs dedicated to deliver care with CHWs designated to deliver care over and above their existing responsibilities and with treatment as usual for patients with a chronic physical disease. METHODS: We did a three-arm, cluster randomised, multicentre, open-label trial done in 24 primary health-care clinics (clusters) within the Western Cape province of South Africa. Clinics were randomly assigned (1:1:1) to implement dedicated care, designated care, or treatment as usual, stratified by urban-rural status. Patients with HIV or type 1 or type 2 diabetes were eligible if they were 18 years old or older, taking antiretroviral therapy for HIV or medication to manage their diabetes, had an Alcohol Use Disorders Identification Test (AUDIT) score of eight or more or a Center for Epidemiologic Studies Depression Scale score of 16 or more, and were not receiving mental health treatment. In the intervention arms, all participants were offered three sessions of an evidence-based psychological intervention, based on motivational interviewing and problem-solving therapy, delivered by CHWs. Our primary outcomes were depression symptom severity and alcohol use severity, which we assessed separately for the intention-to-treat populations of people with HIV and people with diabetes cohorts and in a pooled cohort, at 12 months after enrolment. The Benjamini-Hochberg procedure was used to adjust for multiple testing. The trial was prospectively registered with the Pan African Clinical Trials Registry, PACTR201610001825403. FINDINGS: Between May 1, 2017, and March 31, 2019, 1340 participants were recruited: 457 (34·1%) assigned to the dedicated group, 438 (32·7%) assigned to the designated group, and 445 (33·2%) assigned to the treatment as usual group. 1174 (87·6%) participants completed the 12 month assessment. Compared with treatment as usual, the dedicated group (people with HIV adjusted mean difference -5·02 [95% CI -7·51 to -2·54], p<0·0001; people with diabetes -4·20 [-6·68 to -1·72], p<0·0001) and designated group (people with HIV -6·38 [-8·89 to -3·88], p<0·0001; people with diabetes -4·80 [-7·21 to -2·39], p<0·0001) showed greater improvement on depression scores at 12 months. By contrast, reductions in AUDIT scores were similar across study groups, with no intervention effects noted. INTERPRETATION: The dedicated and designated approaches to delivering CHW-led psychological interventions were equally effective for reducing depression, but enhancements are required to support alcohol reduction. This trial extends evidence for CHW-delivered psychological interventions, offering insights into how different delivery approaches affect patient outcomes. FUNDING: British Medical Research Council, Wellcome Trust, UK Department for International Development, the Economic and Social Research Council, and the Global Challenges Research Fund.

Blood and cerebrospinal fluid biomarker changes in patients with HIV-associated neurocognitive impairment treated with lithium: analysis from a randomised placebo-controlled trial.

HIV-associated neurocognitive disorders (HAND) persist in the era of antiretroviral therapy (ART). Thus, ART does not completely halt or reverse the pathological processes behind HAND. Adjuvant mitigating treatments are, therefore, prudent. Lithium treatment is known to promote neuronal brain-derived neurotrophic factors (BDNF). Lithium is also an inhibitor of glycogen synthase kinase-3 beta (GSK-3-ß). We analyzed biomarkers obtained from participants in a randomized placebo-controlled trial of lithium in ART-treated individuals with moderate or severe HAND. We assayed markers at baseline and 24 weeks across several pathways hypothesized to be affected by HIV, inflammation, or degeneration. Investigated biomarkers included dopamine, BDNF, neurofilament light chain, and CD8 + lymphocyte activation (CD38 + HLADR +). Alzheimer's Disease (AD) biomarkers included soluble amyloid precursor protein alpha and beta (sAPPα/ß), Aß38, 40, 42, and ten other biomarkers validated as predictors of mild cognitive impairment and progression in previous studies. These include apolipoprotein C3, pre-albumin, α1-acid glycoprotein, α1-antitrypsin, PEDF, CC4, ICAM-1, RANTES, clusterin, and cystatin c. We recruited 61 participants (placebo = 31; lithium = 30). The age baseline mean was 40 (± 8.35) years and the median CD4 + T-cell count was 498 (IQR: 389-651) cells/µL. Biomarker concentrations between groups did not differ at baseline. However, both groups' blood dopamine levels decreased significantly after 24 weeks (adj. p < 002). No other marker was significantly different between groups, and we concluded that lithium did not confer neuroprotection following 24 weeks of treatment. However, the study was limited in duration and sample size.

Intersecting Relationships of Psychosocial and Structural Syndemic Problems Among People with HIV in South Africa: Using Network Analysis to Identify Influential Problems.

In South Africa, little is known about interrelationships between syndemic problems among people with HIV (PWH). A better understanding of syndemic problems may yield important information regarding factors amenable to mitigation. We surveyed 194 PWH in Khayelitsha, outside of Cape Town, South Africa. We used network analysis to examine the frequency of 10 syndemic problems and their interrelationships. Syndemic problems among PWH in South Africa were common; 159 (82.8%) participants reported at least 2 co-occurring syndemic problems and 90 (46.9%) endorsed 4 or more. Network analysis revealed seven statistically significant associations. The most central problems were depression, substance use, and food insecurity. Three clusters of syndemics were identified: mood and violence; structural factors; and behavioral factors. Depression, substance use, and food insecurity commonly co-occur among PWH in sub-Saharan Africa and interfere with HIV outcomes. Network analysis can identify intervention targets to potentially improve HIV treatment outcomes.

RESUMEN: En Sudáfrica, poco se sabe sobre interrelaciones entre problemas sindémicos entre personas con VIH (PCV). Un major entendimiento de los problemas sindémicos puede arrojar información importante sobre los factores susceptibles de mitigación. Utilizamos el análisis de redes para examinar la frecuencia de 10 problemas sindémicos y sus interrelaciones. Problemas sindémicos entre PCV en Sudáfrica eran communes; 159 (82.8%) participantes presentaron al menos 2 problemas sindémicos concurrentes y 90 (46.9%) presentaron 4 o más. El análisis de red reveló siete asociaciones estadísticamente significativas. Los problemas más centrales fueron la depresión, el uso de sustancias y la inseguridad alimentaria. Se indetificaron tres grupos de sindemias: estado de ánimo y violencia; factores estructurales; y factores de comportamiento. La depresión, el uso de sustancias y la inseguridad alimentaria comúnmente ocurren simultáneamente entre las PCV en el África subsahariana e interfieren con los resultados del VIH. El análisis de redes puede identificar objetivos de intervención para potencialmente mejorar los resultados del tratamiento del VIH.

Cognitive Performance, as well as Depression, Alcohol Use, and Gender, predict Anti-Retroviral Therapy Adherence in a South African Cohort of People with HIV and Comorbid Major Depressive Disorder.

Depression and cognitive impairment, which commonly coexist in people with HIV (PWH), have been identified as potential barriers to optimal antiretroviral therapy (ART) adherence. We investigated associations between cognitive performance, depression (as well as other sociodemographic, psychosocial and psychiatric variables) and ART adherence in a South African cohort of PWH with comorbid major depressive disorder (MDD). Cognitive performance and ART adherence were assessed at two time points 8 months apart (Nbaseline = 105, Nfollow-up = 81). Adherence was indicated by self-report, objective measures (Wisepill usage and plasma tenofovir-diphosphate levels), and HIV viral suppression. Mixed-effects regression models examined associations across both time points. Univariate models detected no significant associations between cognitive performance (globally and within-domain) and ART adherence. Multivariate modelling showed increased depression severity (ß = - 0.54, p < 0.001) and problematic alcohol use (ß = 0.73, p = 0.015) were associated with worse adherence as measured subjectively. Being female (OR 0.27, p = 0.048) and having better global cognitive performance (OR 1.83, p = 0.043) were associated with better adherence as indicated by viral suppression. This study identifies poor global cognitive performance, as well as depression and problematic alcohol use, as potential barriers to optimal ART adherence in PWH and comorbid MDD. Hence, clinicians could consider assessing for cognitive deficits, depression, and problematic alcohol use, and should endeavour to provide the appropriate support so as to improve adherence.

Mental Health, ART Adherence, and Viral Suppression Among Adolescents and Adults Living with HIV in South Africa: A Cohort Study.

We followed adolescents and adults living with HIV aged older than 15 years who enrolled in a South African private-sector HIV programme to examine adherence and viral non-suppression (viral load > 400 copies/mL) of participants with (20,743, 38%) and without (33,635, 62%) mental health diagnoses. Mental health diagnoses were associated with unfavourable adherence patterns. The risk of viral non-suppression was higher among patients with organic mental disorders [adjusted risk ratio (aRR) 1.55, 95% confidence interval (CI) 1.22-1.96], substance use disorders (aRR 1.53, 95% CI 1.19-1.97), serious mental disorders (aRR 1.30, 95% CI 1.09-1.54), and depression (aRR 1.19, 95% CI 1.10-1.28) when compared with patients without mental health diagnoses. The risk of viral non-suppression was also higher among males, adolescents (15-19 years), and young adults (20-24 years). Our study highlights the need for psychosocial interventions to improve HIV treatment outcomes-particularly of adolescents and young adults-and supports strengthening mental health services in HIV treatment programmes.

RESUMEN: Monitoreamos adolescentes y adultos mayores de 15 años que viven con VIH y que están registrados en un programa privado Surafricano para el tratamiento del VIH. Nuestro propósito fue examinar adherencia a los medicamentos y supresión viral (carga viral < 400 copias/mL) en los participantes con (20,743, 38%) y sin (33,635, 62%) diagnósticos de salud mental. Los diagnósticos de salud mental estuvieron asociados con patrones de adherencia desfavorables. Comparados con pacientes sin diagnósticos de salud mental, el riesgo de no supresión viral fue más alto entre pacientes con desórdenes mentales orgánicos [riesgo relativo ajustado (aRR) 1.55, 95% intervalo de confidencia (CI) 1.22­1.96], desórdenes en el uso de sustancias (aRR 1.53, 95% CI 1.19­1.97), desórdenes mentales serios (aRR 1.30, 95% CI 1.09­1.54), y depresión (aRR 1.19, 95% CI 1.10­1.28). El riesgo de no supresión viral también fue más alto en hombres que en mujeres, en adolescentes (15­19 años), y en adultos jóvenes. Nuestro estudio resalta la necesidad de intervenciones psicosociales para mejorar los resultados del tratamiento contra el VIH ­particularmente en adolescentes y adultos jóvenes­, y respalda el fortalecimiento de servicios de salud mental como parte de los programas para el tratamiento del VIH.

Acceptability and Feasibility of Providing Adherence Feedback Based on Tenofovir Diphosphate in Dried Blood Spots: Results from a Pilot Study Among Patients and Providers in Cape Town, South Africa.

Tenofovir diphosphate (TFV-DP) concentrations in dried blood spots (DBS) predict viral breakthrough, but their use remains understudied in real-world clinic settings. This pilot study examined acceptability, feasibility, and initial adherence outcomes of providing adherence feedback using TFV-DP concentrations on patient- and provider-levels in Cape Town, South Africa. We enrolled 60 persons with HIV (PWH) receiving tenofovir-containing ART attending a primary health clinic. They were randomized 1:1 to an intervention receiving TFV-DP concentration feedback by research staff vs. no feedback at monthly visits for 4 months. Acceptability among medical providers and level of clinical follow-up of TFV-DP results was examined. Patient acceptability was assessed descriptively. Mean electronic adherence (EA), as measured by WisePill device, and TFV-DP in DBS were compared between the two arms. All participants in the intervention group (100%) reported finding TFV-DP feedback helpful and 86% reported changing adherence behaviors. Medical providers indicated high acceptability of incorporating TFV-DP concentration feedback into the clinic, yet among 29 results < 1000 fmol/punch, only 2 were reviewed with no follow-up actions performed. In the intervention arm, mean TFV-DP concentrations were significantly higher (t = 2.5, p < .01) during follow-up and EA in upper quartile (96-100%) was greater compared to controls (x2 = 7.8, p ≤ .05). This study found high acceptability among patients for receiving adherence feedback based on TFV-DP concentrations. TFV-DP and EA data demonstrated greater adherence in the intervention group. Providers indicated high acceptability of incorporating TFV-DP feedback into the clinic, but few providers reviewed results, which could impact clinic-level feasibility.

Mental and cognitive healthcare training targeting primary healthcare workers providing HIV services in Africa: a scoping review.

Mental health and neurocognitive functioning remain a concern among people living with HIV. Symptomatic neurocognitive impairment (NCI) and mental illness can cause difficulties in daily functioning, including problems adhering to treatment. However, many healthcare workers in resource-limited settings have limited knowledge about the relationship between HIV and NCI. A synthesis of available literature on mental health and NCI training provided to healthcare workers delivering HIV services in Africa, is lacking. We conducted a scoping review of published literature to identify training interventions which targeted healthcare workers providing careto people with HIV in Africa. Ten studies met the inclusion criteria. One study focused on NCI, two studies mentioned HIV-associated dementia and seven studies were centred on common mental health disorders. Most studies used a multi-method training approach, with pre-and post-testing as the main evaluation technique. This review highlights the gap in training interventions addressing NCI in Africa. Although there is some commitment to building capacity for mental health and NCI assessment among healthcare workers in this setting, this review suggests that there is a need for research to develop and evaluate training interventions for healthcare workers delivering HIV services in Africa.

Exploring HIV status as a mediator in the relationship of psychological distress with socio-demographic and health related factors in South Africa: findings from the 2012 nationally representative population-based household survey.

BACKGROUND: Psychological distress as measured by mental disorders like depression and anxiety is more prevalent in people living with HIV (PLHIV) than in the general population. However, the relationship between mental disorders and HIV is complex and bidirectional. Improved understanding of the relationship between mental disorders and HIV is important for designing interventions for this group. This paper explores the interrelationships of psychological distress with HIV and associated socio-demographic and health-related factors. METHODS: This secondary data analysis used the 2012 South African population-based household survey on HIV collected using a cross-sectional multi-stage stratified cluster sampling design. Generalized structural equation modelling (G-SEM) path analysis was used to explore the direct and indirect relationships of socio-demographic, health and HIV-related factors with psychological distress as measured by Kessler 10 scale using HIV status as a moderator variable. RESULTS: A total of 20,083 participants were included in the study, 21.7% reported psychological distress, of whom (32.6%) were HIV positive. In the final path model with HIV status as a moderator, psychological distress was significantly more likely among age group 25-49 years (AOR: 1.4 [95% CI 1.3-1.6]), age 50 years and older, (AOR: 1.4 [95% CI 1.2-1.6]), females (AOR: 1.6 [95% CI 1.4-1.8]), high risk drinkers (AOR: 1.9 [1.6-2.2]) hazardous drinkers (AOR: 4.4 [95% CI 3.1-6.3]), ever tested for HIV (AOR: 1.2 [95% CI 1.1-1.3]). Psychological distress was significantly less likely among the married [AOR: 0.8 (0.7-0.9)], other race groups [AOR: 0.5 (0.5-0.6)], those with secondary level education (AOR: 0.9 [95% CI 0.8-0.9]), and tertiary level education (AOR: 0.7 [95% CI 0.6-0.9]), those from rural informal [AOR: 0.8 (0.7-0.9)], and rural formal [AOR: 0.8 (0.7-0.9)] areas and those who rated their health as excellent/good [AOR: 0.4 (0.4-0.5)]. CONCLUSION: The findings highlight the importance of designing tailored interventions targeted at psychological distress among PLHIV especially the elderly, females, those with no education and / or low education attainment and those residing in informal urban areas.

South Africa's Psychiatric training capacity in 2008 and in 2018. Has training capacity improved?

Background: There is a deficit of psychiatrists in South Africa, and to our knowledge, there is no situational analysis of training posts for psychiatrists in the country. Aim: To compare the number of specialists and subspecialists in training and training posts available in 2008 and 2018. Setting: South African medical schools with departments of psychiatry. Methods: A situational analysis involving data collection through a survey completed by eight heads of academic psychiatric departments followed by a comparative analysis of the two aforementioned years. Results: Data shows an 11% increase in funded and unfunded posts combined and a 9.3% increase in funded posts. The occupancy of funded posts decreased (92% in 2008 to 82% in 2018). When considering both funded and unfunded posts, only three more psychiatrists were being trained in 2018. Supernumeraries appointed in unfunded posts can be expected to return to their countries of origin. As such, a decrease in filled funded posts likely reflects a decrease in training psychiatrists destined to work in South Africa. While child and adolescent psychiatry was the only sub-speciality with accredited training posts in 2008, all sub-specialities included on the questionnaire had accredited training posts in 2018, and the number of accredited training posts in child and adolescent psychiatry doubled. That said, many of the posts were unfunded and vacant. Conclusion: While there was an increase in posts from 2008 to 2018, many posts remained unfilled. As such, not only are additional funded training posts required but also strategies to increase post-occupancy and successful completion of training. Contribution: This study is the first situational analysis of specialist and subspecialist training posts in Psychiatry in South Africa, at two time points over a 10 year period, that draws on academic heads of departments of psychiatry as respondents. The study highlights the nominal increase in funded training posts over this period, especially subspecialist training posts. The majority of Health Professions Council of South Africa (HPCSA) accredited subspecialities in Psychiatry have no funded training posts which is particularly concerning.

Pharmacokinetic and pharmacogenetic associations with dolutegravir neuropsychiatric adverse events in an African population.

BACKGROUND: Dolutegravir has been associated with neuropsychiatric adverse events (NPAEs), but relationships between dolutegravir concentrations and NPAEs are unclear. OBJECTIVES: To determine in an African population whether a concentration-response relationship exists between dolutegravir and treatment-emergent NPAEs, and whether selected loss-of-function polymorphisms in genes encoding UDP-glucuronosyltransferase-1A1 (the major metabolizing enzyme for dolutegravir) and organic cation transporter-2 (involved in neurotransmitter transport and inhibited by dolutegravir) are associated with NPAEs. METHODS: Antiretroviral therapy-naive participants randomized to dolutegravir-based therapy in the ADVANCE study were enrolled into a pharmacokinetic sub-study. Primary outcome was change in mental health screening [modified mini screen (MMS)] and sleep quality from baseline to weeks 4, 12 and 24. Dolutegravir exposure was estimated using a population pharmacokinetic model. Polymorphisms analysed were UGT1A1 rs887829 and SLC22A2 rs316019. RESULTS: Data from 464 participants were available for pharmacokinetic analyses and 301 for genetic analyses. By multivariable linear regression, higher dolutegravir exposure was associated with worsening sleep quality only at week 12 [coefficient  = -0.854 (95% CI -1.703 to -0.005), P = 0.049], but with improved MMS score at weeks 12 and 24 [coefficient = -1.255 (95% CI -2.250 to -0.261), P = 0.013 and coefficient = -1.199 (95% CI -2.030 to -0.368), P = 0.005, respectively]. The UGT1A1 and SLC22A2 polymorphisms were not associated with change in MMS score or sleep quality. CONCLUSIONS: Only at week 12 did we find evidence of a relationship between dolutegravir exposure and worsening sleep quality. However, higher dolutegravir exposure was associated with improved MMS scores, suggesting a possible beneficial effect.

Limited evidence for a moderating effect of HIV status on brain age in heavy episodic drinkers.

We set out to test the hypothesis that greater brain ageing will be observed in people with HIV (PWH) and those who engage in heavy episodic drinking (HED), with their combined effects being especially detrimental in cognitive control brain networks. We correlated measures of "brain age gap" (BAG) and neurocognitive impairment in participants with and without HIV and HED. Sixty-nine participants were recruited from a community health centre in Cape Town: HIV - /HED - (N = 17), HIV + /HED - (N = 14), HIV - /HED + (N = 21), and HIV + /HED + (N = 17). Brain age was modelled using structural MRI features from the whole brain or one of six brain regions. Linear regression models were employed to identify differences in BAG between patient groups and controls. Associations between BAG and clinical data were tested using bivariate statistical methods. Compared to controls, greater global BAG was observed in heavy drinkers, both with (Cohen's d = 1.52) and without (d = 1.61) HIV. Differences in BAG between HED participants and controls were observed for the cingulate and parietal cortex, as well as subcortically. A larger BAG was associated with higher total drinking scores but not nadir CD4 count or current HIV viral load. The association between heavy episodic drinking and BAG, independent of HIV status, points to the importance of screening for alcohol use disorders in primary care. The relatively large contribution of cognitive control brain regions to BAG highlights the utility of assessing the contribution of different brain regions to brain age.

HIV-1 subtype C Tat exon-1 amino acid residue 24K is a signature for neurocognitive impairment.

Variation and differential selection pressures on Tat genes have been shown to alter the biological function of the protein, resulting in pathological consequences in a number of organs including the brain. We evaluated the impact of genetic variation and selection pressure on 147 HIV-1 subtype C Tat exon 1 sequences from monocyte-depleted peripheral lymphocytes on clinical diagnosis of neurocognitive impairment. Genetic analyses identified two signature amino acid residues, lysine at codon 24 (24K) with a frequency of 43.4% and arginine at codon 29 (29R) with a frequency of 34.0% in individuals with HIV-associated neurocognitive impairment. The analyses also revealed two signature residues, asparagine, 24 N (31.9%), and histidine, 29H (21.3%), in individuals without neurocognitive impairment. Both codons, 24 and 29, were associated with high entropy but only codon 29 was under positive selection. The presence of signature K24 increased by 2.08 times the risk of neurocognitive impairment, 3.15 times higher proviral load, and 69% lower absolute CD4 T-cell count compared to those without the signature. The results support a linkage between HIV-1 C Tat N24K polymorphism, proviral load, immunosuppression, and neurocognitive impairment. The signature may induce more neurotoxic effects, which contributes to establishment and severity of HIV-associated neurocognitive impairment.

Cognitive performance in a South African cohort of people with HIV and comorbid major depressive disorder.

Cognitive performance in people with HIV (PWH) may be affected by brain injury attributable to the infection itself, by other medical and psychiatric comorbidities (including major depressive disorder; MDD), and by psychosocial factors (e.g., education, food insecurity). We investigated effects of these variables on cognitive performance in a South African cohort of PWH with comorbid MDD and incomplete adherence to antiretroviral therapy (ART). We also examined (a) associations of depression severity with cognitive performance, and (b) whether improvement in depression led to improved cognitive performance. Participants (N = 105) completed baseline neuropsychological, psychiatric, and sociodemographic assessments. Subsequently, 33 were assigned to a cognitive-behavioural therapy for ART adherence and depression (CBT-AD) and 72 to standard-of-care treatment. Eight months post-baseline, 81 (nCBT-AD = 29) repeated the assessments. We investigated (a) baseline associations between sociodemographic, medical, and psychiatric variables and cognitive performance, (b) whether, from baseline to follow-up, depression and cognitive performance improved significantly more in CBT-AD participants, and (c) associations between post-intervention improvements in depression and cognitive performance. At baseline, less education (ß = 0.62) and greater food insecurity (ß = -0.20) predicted poorer overall cognitive performance; more severe depression predicted impairment in the attention/working memory domain only (ß = -0.25). From baseline to follow-up, depression decreased significantly more in CBT-AD participants (p = .017). Improvement over time in depression and cognitive performance was not significantly associated except in the attention/working memory domain (p = .026). Overall, factors associated with cognitive performance were unrelated to brain injury. We conclude that clinicians examining PWH presenting with cognitive difficulties must assess depression, and that researchers investigating cognitive impairment in PWH must collect information on psychosocial factors.

Gender Moderates Results of a Randomized Clinical Trial for the Khanya Intervention for Substance Use and ART Adherence in HIV Care in South Africa.

Little is known about gender effects of alcohol and drug use (AOD) among people living with HIV (PLWH) in resource-limited settings. Using multilevel models, we tested whether gender moderated the effect of Khanya, a cognitive-behavioral therapy-based intervention addressing antiretroviral (ART) adherence and AOD reduction. We enrolled 61 participants from HIV care and examined outcomes at 3- and 6-months compared to enhanced treatment as usual (ETAU). Gender significantly moderated the effect of Khanya on ART adherence (measured using electronically-monitored and biomarker-confirmed adherence), such that women in Khanya had significantly lower ART adherence compared to men in Khanya; no gender differences were found for AOD outcomes. Exploratory trajectory analyses showed men in Khanya and both genders in ETAU had significant reductions in at least one AOD outcome; women in Khanya did not. More research is needed to understand whether a gender lens can support behavioral interventions for PLWH with AOD.Trial registry ClinicalTrials.gov identifier: NCT03529409. Trial registered on May 18, 2018.

The Relationship Between Harmful Alcohol Use and Antiretroviral Non-adherence in People Accessing HIV Treatment in Cape Town, South Africa: An Event-Level Analysis.

Harmful alcohol consumption can significantly compromise adherence to antiretroviral therapy (ART). Prior research has identified aggregate relationships between alcohol use and ART non-adherence, largely relying on concurrent assessment of these domains. There is relatively limited evidence on more nuanced day-level associations between alcohol use and ART non-adherence, despite potentially important clinical implications. We recruited adults with HIV treatment adherence challenges and harmful alcohol use (n = 53) from HIV care in South Africa. We examined relationships between alcohol use and same and next day ART adherence, accounting for the role of weekends/holidays and participant demographics, including gender. Results demonstrated that ART adherence was significantly worse on weekend/holiday days. Next day adherence was significantly worse in the context of weekend alcohol use and among men. These results suggest the importance of tailoring intervention strategies to support ART adherence during weekend drinking and for men engaged in heavy episodic drinking.

Exploring HIV-Associated Neurocognitive Impairment in the Era of Effective Antiretroviral Therapy: A Primary Healthcare Perspective.

The prevalence of HIV-associated neurocognitive impairment (H-NCI) is concerning. Individuals on effective antiretroviral therapy (ART) may still be at risk for H-NCI as they experience longer life expectancies. There are, however, few professionals with knowledge and skills to identify H-NCI, in low- and middle-income countries. We explored qualitatively, primary healthcare workers' knowledge and views of H-NCI, in the era of effective ART, particularly their views toward task-sharing of H-NCI screening from specialists to mid-level or lay healthcare providers. The first phase of data collection involved two focus group discussions (FGDs) 23 primary healthcare workers from two facilities in the Western Cape participated in the FGDs. In the second phase of data collection12 individual, in-depth interviews were conducted in KwaZulu-Natal. Using thematic analysis, several key themes emerged. Although healthcare providers were unable to specifically identify H-NCI, they described several HIV disease and treatment related or mental health comorbidities that could be responsible for the symptoms. Despite healthcare workers reporting low frequencies of H-NCI, they favoured receiving training to screen for H-NCI with a view toward providing holistic care.

Adapting a Behavioral Intervention for Alcohol Use and HIV Medication Adherence for Lay Counselor Delivery in Cape Town, South Africa: A Case Series.

Human immunodeficiency virus (HIV) and problematic alcohol use are two ongoing and interconnected epidemics in South Africa, with untreated problematic alcohol use associated with poorer HIV treatment outcomes and disease progression. A lack of trained mental health providers is a primary barrier to increasing access to evidence-based treatment in this setting. To address this gap, we integrated evidence-based intervention components for problematic alcohol use and antiretroviral therapy (ART) adherence, adapted for lay provider delivery in an HIV primary care setting in Cape Town, South Africa. The intervention, locally termed "Khanya" in isiXhosa, which means glow, direction, or light, comprises Life Steps adherence counseling, motivational interviewing, behavioral activation, and relapse prevention, including mindfulness-based relapse prevention components. In this case series, we present a detailed description of the intervention and provide three clinical cases of individuals who received the Khanya intervention to showcase necessary clinical adaptations and the supervision needed for optimal treatment delivery, flexibility in intervention delivery, and overall successes and challenges. We present descriptive data on alcohol use and ART adherence outcomes for the cases to supplement the narrative discussion. Successes of intervention delivery included participant uptake of mindfulness skills, reductions in alcohol use despite varying levels of motivation, and interventionist mastery over various clinical skills. Challenges included delivering the intervention within the allotted time and the strong influence of substance-using social networks. Overall, a pragmatic approach to intervention delivery was necessary, as was ongoing support for the interventionist to promote fidelity to both treatment components and therapeutic skills. Trial registration: ClinicalTrials.gov identifier: NCT03529409. Trial registered on May 18, 2018.

Moving on From HAND: Why We Need New Criteria for Cognitive Impairment in Persons Living With Human Immunodeficiency Virus and a Proposed Way Forward.

Human immunodeficiency virus (HIV)-associated neurocognitive disorders (HAND) criteria are frequently used to describe cognitive impairment in persons living with HIV (PLWH) across diverse populations globally. These criteria typically find 20-60% of PLWH meet criteria for HAND, which does not tally with clinical observations in the modern era that cognitive disorders present relatively infrequently. Most with HAND have asymptomatic neurocognitive impairment; however, the significance of low cognitive test performance without symptoms is uncertain. Methods underlying HAND criteria carry a false-positive rate that can exceed 20%. Comorbidities, education, and complex socioeconomic factors can influence cognitive test performance, further increasing the potential for misclassification. We propose a new framework to characterize cognitive impairment in PLWH that requires a clinical history and acknowledges the multifactorial nature of low cognitive test performance. This framework is intended to be applicable across diverse populations globally, be more aligned with clinical observations, and more closely represent HIV brain pathology.