Cognitive performance, neuropsychiatric symptoms, and cerebrospinal fluid viral control following programmatic switch from efavirenz-based to dolutegravir-based antiretroviral therapy in South Africa (CONNECT): a prospective cohort study.

BACKGROUND: Both efavirenz and dolutegravir have been associated with neuropsychiatric side-effects and cognitive impairment. Furthermore, cerebrospinal fluid (CSF) HIV RNA escape has not been comprehensively studied in African populations. We aimed to examine changes in cognition, neuropsychiatric symptoms, and CSF viral control associated with the widespread switch from efavirenz-based to dolutegravir-based antiretroviral therapy (ART). METHODS: This prospective cohort study of people with HIV and people without HIV recruited adults with HIV (aged 18-55 years) from the Gugulethu Community Health Centre in a low-income periurban area of Cape Town, South Africa. Eligible participants had been receiving efavirenz-based ART for at least 1 year and were identified by the clinic to switch to dolutegravir-based ART as part of the national programmatic switch. Participants were studied at baseline and followed up at 1 year after switch to dolutegravir. People without HIV were recruited from the same area, matched for age and gender, and followed up at the same time interval. People with HIV and people without HIV underwent comprehensive cognitive testing over seven domains and measures of functioning, mood, anxiety, and sleep. People with HIV had CSF sampling for HIV RNA quantification. FINDINGS: Between Aug 12, 2019, and Sept 16, 2022, we recruited 178 people with HIV and 95 people without HIV. 145 (81%) of 178 people with HIV and 40 (66%) of 60 people without HIV who were offered underwent follow-up. Global cognitive performance was 2·57 T score points lower in people with HIV than in people without HIV at baseline (p=0·0008). At follow-up, cognition in people with HIV improved more than practice effects observed in people without HIV (coefficient 1·40, 95% CI 0·48-2·32, p=0·0028) and no significant difference in cognitive performance between groups was apparent (51·43 vs 52·73; p=0·22). Sleep quality improved following the switch (risk ratio 0·90, 95% CI 0·84-0·95; p=0·0002), driven mainly by indicators of disturbed sleep. There were nine incident cases of depression, although baseline differences were present. There was one case (1%) of CSF escape at baseline and three cases (4%) at follow-up; all were at low levels or resolved with repeated sampling. INTERPRETATION: Improvements in cognition and sleep are probably related to switching from efavirenz. However, the possible increase in depression warrants further examination. Cognitive performance in virally supressed African people with HIV receiving dolutegravir-based therapy is similar to people without HIV. CSF escape is uncommon on both efavirenz-based and dolutegravir-based therapy. FUNDING: South African Medical Research Council and UK Medical Research Council, Newton Fund.

Piloting Siyakhana: A community health worker training to reduce substance use and depression stigma in South African HIV and TB care.

South Africa has one of the highest rates of HIV/tuberculosis (TB) co-infection, and poor engagement in HIV/TB care contributes to morbidity and mortality. In South Africa, community health workers (CHWs) are tasked with re-engaging patients who have dropped out of HIV/TB care. CHWs have described substantial challenges with substance use (SU) and depression among their patients, while patients have described CHW stigma towards SU and depression as barriers to re-engagement in care. Yet, CHWs receive little-to-no training on SU or depression. Therefore, we piloted Siyakhana, a brief CHW training to reduce stigma related to SU and depression while improving skills for re-engaging these patients in HIV and/or TB care. This study evaluated the preliminary effectiveness (stigma towards SU and depression; clinical competence assessed via roleplay) and implementation (quantitative ratings of feasibility, acceptability, appropriateness, adoption; semi-structured written qualitative feedback) of Siyakhana among CHWs and supervisors (N = 17) at pre- and post-training assessments. SU stigma significantly decreased (F(1,16) = 18.94, p < 0.001, ηp2 = 0.54). Depression stigma was lower than SU stigma at both timepoints and did not significantly decrease after training. CHW clinical competency towards patients with SU/depression significantly improved (t(11) = -3.35, p = 0.007, d = 1.00). The training was rated as feasible, acceptable, appropriate, and likely to be adopted by CHWs and their supervisors. Nonjudgmental communication was commonly described as the most useful training component. Based on this pilot, the training is being refined and evaluated in a larger randomized stepped-wedge clinical trial.

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.

Community health worker training to reduce mental health and substance use stigma towards patients who have disengaged from HIV/TB care in South Africa: protocol for a stepped wedge hybrid type II pilot implementation trial.

BACKGROUND: South Africa has deployed community health workers (CHWs) to support individuals to enter and stay in HIV/TB care. Although CHWs routinely encounter patients with mental health (particularly depression) and substance use (SU) conditions that impact their engagement in HIV/TB care, CHWs are rarely trained in how to work with these patients. This contributes to mental health and SU stigma among CHWs, a known barrier to patient engagement in care. Mental health and SU training interventions could reduce CHW stigma and potentially improve patient engagement in care, but evidence of the feasibility, acceptability, and preliminary effectiveness of these interventions is scarce. Therefore, we designed a hybrid type 2 effectiveness-implementation pilot trial to evaluate the implementation and preliminary effectiveness of a CHW training intervention for reducing depression and SU stigma in the Western Cape, South Africa. METHODS: This stepped wedge pilot trial will engage CHWs from six primary care clinics offering HIV/TB care. Clinics will be block randomized into three-step cohorts that receive the intervention at varying time points. The Siyakhana intervention involves 3 days of training in depression and SU focused on psychoeducation, evidence-based skills for working with patients, and self-care strategies for promoting CHW wellness. The implementation strategy involves social contact with people with lived experience of depression/SU during training (via patient videos and a peer trainer) and clinical supervision to support CHWs to practice new skills. Both implementation outcomes (acceptability, feasibility, fidelity) and preliminary effectiveness of the intervention on CHW stigma will be assessed using mixed methods at 3- and 6-month follow-up assessments. DISCUSSION: This trial will advance knowledge of the feasibility, acceptability, and preliminary effectiveness of a CHW training for reducing depression and SU stigma towards patients with HIV and/or TB. Study findings will inform a larger implementation trial to evaluate the longer-term implementation and effectiveness of this intervention for reducing CHW stigma towards patients with depression and SU and improving patient engagement in HIV/TB care. TRIAL REGISTRATION: ClinicalTrials.gov NCT05282173. Registered on 7 March 2022.

A Supervision Framework for Task-Shared Mental Health Workers: Implications for Clinical Trials and Beyond.

The rise in task-shared interventions that address the mental health treatment gap in low- and middle-income countries (LMICs) has highlighted the need for additional support and supervision of nonspecialist mental health workers (NHWs). The supervision of NHWs in most resource-limited settings is still primarily disorganized, without clear guidelines that provide the necessary structure for supervision. The need for supervision is even greater for NHWs working in the context of trauma, not only to provide training and ensure adequate delivery of care but also to provide support to minimize the psychological impact of their work. In South Africa, women face intersecting epidemics of HIV, intimate partner violence, and sexual trauma. This syndemic highlights the importance of integrating mental health treatment in HIV care, especially in settings like South Africa, where mental health services are limited. In this context, our group developed and is evaluating the effectiveness of ImpACT+, a task-shared coping intervention to improve clinical and mental health outcomes among HIV-infected women with sexual trauma in South Africa. We describe the ImpACT+ supervision model that is currently being implemented in the context of a hybrid effectiveness-implementation clinical trial. Combining experiences from clinical psychology, task-shared interventions, and trauma-informed care, the supervision model integrates formal elements of clinical supervision into categories that are suitable for use in task-shared trauma interventions in low-resource settings. To the best of our knowledge, such a trauma-informed supervision approach has not been widely documented in the literature, particularly in task-shared interventions in LMICs. In this article, we describe the ImpACT+ intervention, provide an overview of the supervision model, and provide illustrative examples of how the supervision model has been implemented.

Sex Differences in the Cognitive Performance of a South African Cohort of People With HIV and Comorbid Major Depressive Disorder.

Women with HIV (WWH) may be more vulnerable to cognitive impairment than men with HIV (MWH), which may be explained by the direct effects of HIV or by sociodemographic and psychiatric characteristics. We recruited 105 people with HIV (PWH; 76 women) with incomplete antiretroviral therapy adherence, comorbid major depressive disorder, and socioeconomically disadvantaged backgrounds. Participants completed neuropsychological testing and measures gathering sociodemographic, medical, and psychiatric information. We compared WWH and MWH cognitive performance using unadjusted and adjusted regressions, and within each respective group, we explored predictors of cognitive performance. Results showed no significant between-sex differences in cognitive performance, both globally and within domains. Fewer years of education (ß = 0.94), illiteracy (ß = 4.55), and greater food insecurity (ß = -0.28) predicted lower cognitive performance in WWH but not MWH. We conclude that sex differences in PWH are likely due to sample characteristics representing broader inequalities, rather than true biological differences.

"Trajectories of treatment response in a cognitive-behavioral therapy intervention for depression and adherence in persons with HIV in South Africa".

BACKGROUND: People with HIV (PHW) are at greater risk of depression than the general population. Insight into the time-to-treatment-response and predictors of response to psychotherapy may improve implementation in primary care. METHODS: We assessed depression treatment response among 80 participants in a trial of cognitive-behavioral therapy for adherence and depression (CBT-AD) for PWH with MDD and suboptimal antiretroviral therapy (ART) adherence. Participants self-reported depressive symptoms (CESD) at each therapy session. Clinicians assessed participants' depression (HAMD), along with potential predictors of response, every four months for one year. Latent class analyses examined classes of responders for the active and the post-treatment phases. Regression analyses identified predictors of class membership for each phase. RESULTS: During the active treatment phase (CESD) we identified an early response (at session 2 and with continued trajectory of improvement) and a non-response group. There were also two classes during post-treatment (HAM-D): early responders (4-month) and late responders (12-month). Distress aversion was associated with lower likelihood of early response to CBT-AD (aOR = 0.74, 95%CI[0.56-0.90], p = .009), and social support was associated with increased likelihood of early response (aOR = 2.24, 95%CI[1.07-5.46], p = .045). LIMITATIONS: Self-reported depression during the treatment phase may have resulted from social desirability bias. CONCLUSIONS: Most participants responded to CBT-AD early during treatment (89 %) and had sustained improvements in depression by 4 months (80 %). Distress aversion was a risk factor for late response, and social support was protective. Future research is needed to assess the optimal dose of CBT-AD in resource limited settings.

Life years lost associated with mental illness: A cohort study of beneficiaries of a South African medical insurance scheme.

BACKGROUND: People with mental illness have a reduced life expectancy, but the extent of the mortality gap and the contribution of natural and unnatural causes to excess mortality among people with mental illness in South Africa are unknown. METHODS: We analysed reimbursement claims from South African medical insurance scheme beneficiaries aged 15-85 years. We estimated excess life years lost (LYL) associated with organic, substance use, psychotic, mood, anxiety, eating, personality, developmental or any mental disorders. RESULTS: We followed 1,070,183 beneficiaries for a median of three years, of whom 282,926 (26.4 %) received mental health diagnoses. Men with a mental health diagnosis lost 3.83 life years (95 % CI 3.58-4.10) compared to men without. Women with a mental health diagnosis lost 2.19 life years (1.97-2.41) compared to women without. Excess mortality varied by sex and diagnosis, from 11.50 LYL (95 % CI 9.79-13.07) among men with alcohol use disorder to 0.87 LYL (0.40-1.43) among women with generalised anxiety disorder. Most LYL were attributable to natural causes (men: 3.42, women: 1.94). A considerable number of LYL were attributable to unnatural causes among men with bipolar (1.52) or substance use (2.45) disorder. LIMITATIONS: Mental diagnoses are based on reimbursement claims. CONCLUSIONS: Premature mortality among South African individuals with mental disorders is high. Our findings support interventions for the prevention, early detection, and treatment of physical comorbidities in this population. Targeted programs for suicide prevention and substance use treatment, particularly among men, can help reduce excess mortality from unnatural causes.

Cognitive impairment in people living with HIV: consensus recommendations for a new approach.

Current approaches to classifying cognitive impairment in people living with HIV can overestimate disease burden and lead to ambiguity around disease mechanisms. The 2007 criteria for HIV-associated neurocognitive disorders (HAND), sometimes called the Frascati criteria, can falsely classify over 20% of cognitively healthy individuals as having cognitive impairment. Minimum criteria for HAND are met on the basis of performance on cognitive tests alone, which might not be appropriate for populations with diverse educational and socioeconomic backgrounds. Imprecise phenotyping of cognitive impairment can limit mechanistic research, biomarker discovery and treatment trials. Importantly, overestimation of cognitive impairment carries the risk of creating fear among people living with HIV and worsening stigma and discrimination towards these individuals. To address this issue, we established the International HIV-Cognition Working Group, which is globally representative and involves the community of people living with HIV. We reached consensus on six recommendations towards a new approach for diagnosis and classification of cognitive impairment in people living with HIV, intended to focus discussion and debate going forward. We propose the conceptual separation of HIV-associated brain injury - including active or pretreatment legacy damage - from other causes of brain injury occurring in people living with HIV. We suggest moving away from a quantitative neuropsychological approach towards an emphasis on clinical context. Our recommendations are intended to better represent the changing profile of cognitive impairment in people living with HIV in diverse global settings and to provide a clearer framework of classification for clinical management and research studies.

Behavioural Medicine: Strengthening approaches to address co-morbid chronic physical and mental disorders.

South Africa is confronted with multi-morbid chronic physical and mental disorders. The relationships between these conditions are often multidirectional and result in a variety of adverse mental and physical health outcomes. The risk factors and perpetuating conditions in multi-morbidity are potentially modifiable through effective behaviour change. However, in South Africa, interventions and clinical care that address these co-occurring factors have traditionally functioned in a vacuum, created by a lack of formalised multidisciplinary collaboration. In high-income settings, the field of Behavioural Medicine was established in recognition of the importance of psychosocial factors in illness and assumes that the presence of physical concerns can be influenced by psychological and behavioural factors. The large body of evidence supporting Behavioural Medicine has afforded the field global recognition. Yet, it remains an emerging field in South Africa and on the African continent. The purpose of this paper is to contextualise the field of Behavioural Medicine in South Africa and present a way forward to establish the field in our context.

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.

The Clinical Impact and Cost-Effectiveness of Clinic-Based Cognitive Behavioral Therapy for People With HIV, Depression, and Virologic Failure in South Africa.

BACKGROUND: Depression affects 25%-30% of people with HIV (PWH) in the Republic of South Africa (RSA) and is associated with both antiretroviral therapy (ART) nonadherence and increased mortality. We evaluated the cost-effectiveness of task-shifted, cognitive behavioral therapy (CBT) for PWH with diagnosed depression and virologic failure from a randomized trial in RSA. SETTING: RSA. METHODS: Using the Cost-Effectiveness of Preventing AIDS Complications model, we simulated both trial strategies: enhanced treatment as usual (ETAU) and ETAU plus CBT for ART adherence and depression (CBT-AD; 8 sessions plus 2 follow-ups). In the trial, viral suppression at 1 year was 20% with ETAU and 32% with CBT-AD. Model inputs included mean initial age (39 years) and CD4 count (214/µL), ART costs ($7.5-22/mo), and CBT costs ($29/session). We projected 5- and 10-year viral suppression, quality-adjusted life-years (QALYs), lifetime costs, and incremental cost-effectiveness ratios (ICERs: $/QALY [discounted 3%/yr]; cost-effectiveness threshold: ≤$2545/QALY [0.5× per capita GDP]). In sensitivity analyses, we determined how input parameter variation affected cost-effectiveness. RESULTS: Model-projected 5- and 10-year viral suppression were 18.9% and 8.7% with ETAU and 21.2% and 9.7% with CBT-AD, respectively. Compared with ETAU, CBT-AD would increase discounted life expectancy from 4.12 to 4.68 QALYs and costs from $6210/person to $6670/person (incremental cost-effectiveness ratio: $840/QALY). CBT-AD would remain cost-effective unless CBT-AD cost >$70/session and simultaneously improved 1-year viral suppression by ≤4% compared with ETAU. CONCLUSIONS: CBT for PWH with depression and virologic failure in RSA could improve life expectancy and be cost-effective. Such targeted mental health interventions should be integrated into HIV care.

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.

Comparing Predictive Ability of Two Objective Adherence Measures in a Community-Based Cohort on Antiretroviral Therapy in South Africa: Tenofovir Diphosphate Concentrations and Electronic Adherence Monitors.

BACKGROUND: Electronic adherence (EA) and tenofovir diphosphate (TFV-DP) in dried blood spots (DBS) are objective measures of antiretroviral therapy (ART) adherence. We characterized the association between these measures in a prospective cohort of persons with HIV (PWH) on ART. SETTING: Four primary health clinics in Cape Town, South Africa. METHODS: We enrolled 250 virally suppressed PWH receiving tenofovir-based ART. We collected EA data, monthly viral load, and TFV-DP in DBS for 12 months. We used logistic regression to estimate the adjusted odds ratio (aOR) and 95% confidence intervals (CIs) for future viral breakthrough (VB) (>400 copies/mL) for each adherence measure. Receiver operating characteristics (ROCs) provided the predictive power of these measures. RESULTS: Participants had a median (IQR) age of 34 (27-42); 78% were women. Twenty-one (8%) developed VB. Logistic regression showed that when percent EA and TFV-DP concentrations increased, the odds of VB decreased. This relationship was consistent at the time of VB (aOR of 0.41 [95% CI: 0.25 to 0.66] for TFV-DP and aOR of 0.64 [95% CI: 0.54 to 0.76] for EA) and for up to 2 months before VB. Both adherence measures predicted future VB at both 1 month and 2 months before viral load measurement. CONCLUSION: We established that 2 objective adherence measures, EA and TFV-DP in DBS, have a positive association with, and are both strongly predictive of, VB in a community-based South African cohort on ART. Future research is needed to determine the feasibility of implementing these adherence measures in resource-limited settings to facilitate adherence interventions.

Patient and stakeholder perspectives on impacts of the COVID-19 pandemic on HIV and mental health care delivery in South Africa.

BACKGROUND: The COVID-19 pandemic had a global impact on health systems and the delivery of health services, including for chronic conditions such as HIV. In South Africa, impacts on HIV services have widely been quantitatively described. Across different health settings, patients have also qualitatively described numerous negative impacts to their HIV care. However, patient perspectives on COVID-19 impacts to HIV care in South Africa, the largest HIV care system in the world, have been little explored to date. METHODS: We conducted 29 semi-structured individual interviews with people living with HIV (n = 24) and providers (n = 5) in Cape Town, South Africa. RESULTS: While most patient participants reported continued access to HIV treatment during the pandemic, many described perceiving that the quality of their care declined. Increased structural barriers were described as one contributing factor to this change. Additionally, patients described that reduced privacy in clinical interactions was a key factor negatively influencing their experience of receiving care. CONCLUSION: Findings underscore the importance of ensuring patient privacy for HIV services even during the rearrangement of services in emergencies. It is also important to continue developing models to integrate community mental health services within HIV care delivery in South 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.

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.

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.