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There is increasing evidence that HIV-1 viral protein R (Vpr) plays an important role in the pathogenesis of cognitive impairment. We investigated the relationship between HIV-1 sub-type C Vpr sequence variation and HIV-associated neurocognitive impairment as measured by global deficit score (GDS) in treatment naive individuals. We used different bioinformatic tools and statistical models to correlate vpr variation and cognitive function. We identified a Tyrosine at position 45 (45Y) as signature for neurocognitive impairment and Histidine (45H) as a signature in the non-impaired indviduals. The presence of signature 45Y was associated by 3.66 times higher GDS, 525 times higher plasma viral load, 15.84 times higher proviral load and 60% lower absolute CD4-T cell count compared those without the signature. Additionally, we identified 4 conserved Vpr fragment sequences, PEDQGPQREPYNEWTLE (5 to 21), LGQYIY(42 to 47), TYGDTW (49 to 54), PEDQGPQREPYNEW (5 to 18) that were associated with higher plasma viral load and proviral load. The implication of these findings is that variation of Vpr leads to neurocognitve impairment in HIV infection and worsens the progression of disease in general by promoting the production of provirus, promoting HIV replication and depletion of CD4+ T cells in the periphery. Key words: HAND, Vpr, entropy, signature amino acid residue, Tyrosine, Histidine.

Although mental health screenings are not routinely conducted in rugby, the Sport Concussion Assessment Tool - Fifth Edition (SCAT-5) is widely performed and measures affective, cognitive, sleep, and physical symptoms. This study investigated the psychometric properties of the SCAT-5 to explore its potential as a mental health screening tool.During preseason for the 2021 Western Province Super League A in South Africa, clinicians conducted mental health assessments of 71 adult male rugby union players. The SCAT-5 Symptom Evaluation, Baron Depression Screener for Athletes (BDSA), Athlete Psychological Strain Questionnaire (APSQ), Center for Epidemiologic Studies-Depression (CES-D), and Generalized Anxiety Disorder-7 (GAD-7) were compared to each other and to fully structured diagnostic interviews by mental health professionals using the Mini International Neuropsychiatric Interview (MINI) 7.0.2.Lifetime MINI-defined mental disorders were common, being identified in 33.8% (95% CI 22.79-46.17%). Only 4.29% of participants had a previous diagnosis. Exploratory Factor Analysis indicated a mental health construct of depression/anxiety being measured by the SCAT-5. The SCAT-5 had strong internal consistency (α = 0.94) and showed moderate convergent validity with the CES-D (r = 0.34; p = 0.008) and GAD-7 (r = 0.49; p 0.0001). The area under the curve for the ability of the SCAT-5 to identify current disorders was 0.87 (p = 0.003), on par with the CES-D and GAD-7.Since the SCAT-5 has the potential to identify depression and anxiety, it may allow mental health screening without the need for additional measures. Follow-up studies should further explore its discriminative ability in larger samples.

BACKGROUND: The intellectually demanding modern workplace is often dependent on good cognitive health, yet there is little understanding of how neurocognitive dysfunction related to HIV presents in employed individuals working in high risk vocations like driving. HIV-associated neurocognitive impairment is also associated with poorer long term cognitive, health and employment outcomes. SETTING: This study, set in Cape Town, South Africa, assessed the effects of HIV on neuropsychological test performance in employed male professional drivers. METHOD: We administered a neuropsychological test battery spanning seven cognitive domains and obtained behavioral data, anthropometry, and medical biomarkers from three groups of professional drivers (68 men with HIV, 55 men with cardiovascular risk, and 81 controls). We compared the drivers’ cognitive profiles, and used multiple regression modelling to investigate whether between-group differences persisted after considering potentially confounding sociodemographic and clinical variables (i.e., income, home language, depression, and Framingham Risk Score). RESULTS: Relative to other study participants, professional drivers with HIV performed significantly more poorly on tests assessing processing speed (p

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.

Contains fulltext : 248376.pdf (Publisher’s version ) (Open Access) For many traits, males show greater variability than females, with possible implications for understanding sex differences in health and disease. Here, the ENIGMA (Enhancing Neuro Imaging Genetics through Meta-Analysis) Consortium presents the largest-ever mega-analysis of sex differences in variability of brain structure, based on international data spanning nine decades of life. Subcortical volumes, cortical surface area and cortical thickness were assessed in MRI data of 16,683 healthy individuals 1-90 years old (47% females). We observed significant patterns of greater male than female between-subject variance for all subcortical volumetric measures, all cortical surface area measures, and 60% of cortical thickness measures. This pattern was stable across the lifespan for 50% of the subcortical structures, 70% of the regional area measures, and nearly all regions for thickness. Our findings that these sex differences are present in childhood implicate early life genetic or gene-environment interaction mechanisms. The findings highlight the importance of individual differences within the sexes, that may underpin sex-specific vulnerability to disorders.

Special Issue: The ENIGMA Consortium: the first 10 years., Delineating the association of age and cortical thickness in healthy individuals is critical given the association of cortical thickness with cognition and behavior. Previous research has shown that robust estimates of the association between age and brain morphometry require large-scale studies. In response, we used cross-sectional data from 17,075 individuals aged 3–90 years from the Enhancing Neuroimaging Genetics through Meta-Analysis (ENIGMA) Consortium to infer age-related changes in cortical thickness. We used fractional polynomial (FP) regression to quantify the association between age and cortical thickness, and we computed normalized growth centiles using the parametric Lambda, Mu, and Sigma method. Interindividual variability was estimated using meta-analysis and one-way analysis of variance. For most regions, their highest cortical thickness value was observed in childhood. Age and cortical thickness showed a negative association; the slope was steeper up to the third decade of life and more gradual thereafter; notable exceptions to this general pattern were entorhinal, temporopolar, and anterior cingulate cortices. Interindividual variability was largest in temporal and frontal regions across the lifespan. Age and its FP combinations explained up to 59% variance in cortical thickness. These results may form the basis of further investigation on normative deviation in cortical thickness and its significance for behavioral and cognitive outcomes., European Community's Seventh Framework Programme, Grant/Award Numbers: 278948, 602450, 603016, 602805; US National Institute of Child Health and Human Development, Grant/Award Numbers: RO1HD050735, 1009064, 496682; QIMR Berghofer Medical Research Institute and the Centre for Advanced Imaging, University of Queensland; ICTSI NIH/NCRR, Grant/Award Number: RR025761; European Community's Horizon 2020 Programme, Grant/Award Numbers: 667302, 643051; Vici Innovation Program, Grant/Award Numbers: #91619115, 016-130-669; NWO Brain & Cognition Excellence Program, Grant/Award Number: 433-09-229; Biobanking and Biomolecular Resources Research Infrastructure (Netherlands) (BBMRI-NL); Spinozapremie, Grant/Award Number: NWO-56-464-14192; Biobanking and Biomolecular Resources Research Infrastructure, Grant/Award Numbers: 184.033.111, 184.021.007; Netherlands Organization for Health Research and Development (ZonMW), Grant/Award Numbers: 480-15-001/674, 024.001.003, 911-09-032, 056-32-010, 481-08-011, 016-115-035, 31160008, 400-07-080, 400-05-717, 451-04-034, 463-06-001, 480-04-004, 904-61-193, 912-10-020, 985-10-002, 904-61-090; NIMH, Grant/Award Number: R01 MH090553; Geestkracht programme of the Dutch Health Research Council, Grant/Award Number: 10-000-1001; FP7 Ideas: European Research Council; Nederlandse Organisatie voor Wetenschappelijk Onderzoek, Grant/Award Numbers: NWO/SPI 56-464-14192, NWO-MagW 480-04-004, 433-09-220, NWO 51.02.062, NWO 51.02.061; National Center for Advancing Translational Sciences, National Institutes of Health, Grant/Award Number: UL1 TR000153; National Center for Research Resources; National Center for Research Resources at the National Institutes of Health, Grant/Award Numbers: NIH 1U24 RR025736-01, NIH 1U24 RR021992; NIH Institutes contributing to the Big Data to Knowledge; U.S. National Institutes of Health, Grant/Award Numbers: R01 CA101318, P30 AG10133, R01 AG19771; Medical Research Council, Grant/Award Numbers: U54EB020403, G0500092; National Institute of Mental Health, Grant/Award Numbers: R01MH117014, R01MH042191; Fundación Instituto de Investigación Marqués de Valdecilla, Grant/Award Numbers: API07/011, NCT02534363, NCT0235832; Instituto de Salud Carlos III, Grant/Award Numbers: PI14/00918, PI14/00639, PI060507, PI050427, PI020499; Swedish Research Council, Grant/Award Numbers: 523-2014-3467, 2017-00949, 521-2014-3487; South-Eastern Norway Health Authority; the Research Council of Norway, Grant/Award Number: 223273; South Eastern Norway Regional Health Authority, Grant/Award Numbers: 2017-112, 2019107; Icahn School of Medicine at Mount Sinai; Seventh Framework Programme (FP7/2007-2013), Grant/Award Number: 602450; National Institutes of Health, Grant/Award Numbers: R01 MH116147, R01 MH113619, R01 MH104284; South London and Maudsley NHS Foundation Trust; the National Institute for Health Research (NIHR)

BackgroundDespite a high prevalence of problematic substance use among people living with HIV in South Africa, there remains limited access to substance use services within the HIV care system. To address this gap, our team previously developed and adapted a six-session, peer-delivered problem-solving and behavioral activation-based intervention (Khanya) to improve HIV medication adherence and reduce substance use in Cape Town. This study evaluated patient and provider perspectives on the intervention to inform implementation and future adaptation.MethodsFollowing intervention completion, we conducted semi-structured individual interviews with patients (n = 23) and providers (n = 9) to understand perspectives on the feasibility, acceptability, and appropriateness of Khanya and its implementation by a peer. Patients also quantitatively ranked the usefulness of individual intervention components (problem solving for medication adherence ‘Life-Steps’, behavioral activation, mindfulness training, and relapse prevention) at post-treatment and six months follow-up, which we triangulated with qualitative feedback to examine convergence and divergence across methods.ResultsPatients and providers reported high overall acceptability, feasibility, and appropriateness of Khanya, although there were several feasibility challenges. Mindfulness and Life-Steps were identified as particularly acceptable, feasible, and appropriate components by patients across methods, whereas relapse prevention strategies were less salient. Behavioral activation results were less consistent across methods.ConclusionsFindings underscore the importance of examining patients’ perspectives on specific intervention components within intervention packages. While mindfulness training and peer delivery models were positively perceived by consumers, they are rarely used within task-shared behavioral interventions in low- and middle-income countries.

Background: Normative modeling is a statistical approach to quantify the degree to which a particular individual-level measure deviates from the pattern observed in a normative reference population. When applied to human brain morphometric measures it has the potential to inform about the significance of normative deviations for health and disease. Normative models can be implemented using a variety of algorithms that have not been systematically appraised. Methods: To address this gap, eight algorithms were compared in terms of performance and computational efficiency using brain regional morphometric data from 37,407 healthy individuals (53% female; aged 3-90 years) collated from 87 international MRI datasets. Performance was assessed with the mean absolute error (MAE) and computational efficiency was inferred from central processing unit (CPU) time. The algorithms evaluated were Ordinary Least Squares Regression (OLSR), Bayesian Linear Regression (BLR), Generalized Additive Models for Location, Scale, and Shape (GAMLSS), Parametric Lambda, Mu, Sigma (LMS), Gaussian Process Regression (GPR), Warped Bayesian Linear Regression (WBLG), Hierarchical Bayesian Regression (HBR), and Multivariable Fractional Polynomial Regression (MFPR). Model optimization involved testing nine covariate combinations pertaining to acquisition features, parcellation software versions, and global neuroimaging measures (i.e., total intracranial volume, mean cortical thickness, and mean cortical surface area). Findings: Statistical comparisons across models at PFDR

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.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) 1.22–1.96], desórdenes en el uso de sustancias (aRR 1.53, 95% CI 1.19–1.97), desórdenes mentales serios (aRR 1.30, 95% CI 1.09–1.54), y depresión (aRR 1.19, 95% CI 1.10–1.28). El riesgo de no supresión viral también fue más alto en hombres que en mujeres, en adolescentes (15–19 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.

Pregnant and postpartum women (PPW) in sub-Saharan Africa are at disproportionately high risk of HIV infection compared to non-pregnant women. When used consistently, pre-exposure prophylaxis (PrEP) can prevent HIV acquisition and transmission to the foetus or infant during these critical periods. Recent studies have demonstrated associations between mental health challenges (e.g. depression and traumatic stress associated with intimate partner violence) and decreased PrEP adherence and persistence, particularly among adolescents, younger women and women in the postpartum period. However, mental health is not currently a major focus of PrEP implementation research and programme planning for PPW.PrEP implementation programmes for PPW need to assess and address mental health barriers to consistent PrEP use to ensure effectiveness and sustainability in routine care. We highlight three key research priorities that will support PrEP adherence and persistence: (1) include mental health screening tools in PrEP implementation research with PPW, both to assess the feasibility of integrating these tools into routine antenatal and postpartum care and to ensure that limited resources are directed towards women whose symptoms may interfere most with PrEP use; (2) identify cross-cutting, transdiagnostic psychological mechanisms that affect consistent PrEP use during these periods and can realistically be targeted with intervention in resource-limited settings; and (3) develop/adapt and test interventions that target those underlying mechanisms, leveraging strategies from existing interventions that have successfully mitigated mental health barriers to antiretroviral therapy use among people with HIV.For PPW, implementation of PrEP should be guided by a robust understanding of the unique psychological difficulties that may act as barriers to uptake, adherence and persistence (i.e. sustained adherence over time). We strongly encourage PrEP implementation research in PPW to incorporate validated mental health screening tools and ultimately treatment in routine antenatal and postnatal care, and we stress the potential public health benefits of identifying women who face mental health barriers to PrEP use.

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.

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.

The coronavirus disease 2019 (COVID-19) pandemic and ensuing restrictions have negatively affected the mental health and well-being of the general population, and there is increasing evidence suggesting that lockdowns have led to a disruption of health services. In March 2020, South Africa introduced a lockdown in response to the COVID-19 pandemic, entailing the suspension of all non-essential activities and a complete ban of tobacco and alcohol sales. We studied the effect of the lockdown on mental health care utilisation rates in private-sector care in South Africa.We conducted an interrupted time-series analysis using insurance claims from 1 January 2017 to 1 June 2020 of beneficiaries 18 years or older from a large private sector medical insurance scheme. We calculated weekly outpatient consultation and hospital admission rates for organic mental disorders, substance use disorders, serious mental disorders, depression, anxiety, other mental disorders, any mental disorder and alcohol withdrawal syndrome. We calculated adjusted odds ratios (OR) for the effect of the lockdown on weekly outpatient consultation and hospital admission rates and the weekly change in rates during the lockdown until 1 June 2020.710 367 persons were followed up for a median of 153 weeks. Hospital admission rates (OR 0.38; 95% confidence interval (CI) 0.33-0.44) and outpatient consultation rates (OR 0.74; 95% CI 0.63-0.87) for any mental disorder decreased substantially after the introduction of the lockdown and did not recover to pre-lockdown levels by 1 June 2020. Health care utilisation rates for alcohol withdrawal syndrome doubled after the introduction of the lockdown, but the statistical uncertainty around the estimates was large (OR 2.24; 95% CI 0.69-7.24).Mental health care utilisation rates for inpatient and outpatient services decreased substantially after the introduction of the lockdown. Hospital admissions and outpatient consultations for alcohol withdrawal syndrome increased after the introduction of the lockdown, but statistical uncertainty precludes strong conclusions about a potential unintended effect of the alcohol sales ban. Governments should integrate strategies for ensuring access and continuity of essential mental health services during lockdowns in pandemic preparedness planning.

IntroductionMental disorders are highly prevalent among people living with HIV and are associated with adverse HIV treatment outcomes. We assessed HIV treatment outcomes in patients with and without mental health diagnoses by sex and age.MethodsUsing hospital, outpatient and pharmacy claims and laboratory data from 2011 to 2020, we followed HIV-positive adolescents and adults aged ≥15 years who enrolled in a South African private sector HIV treatment programme. We performed a longitudinal trajectory analysis to identify patients with similar adherence patterns and examined associations between mental health diagnoses and adherence patterns using multinomial logistic regression. We examined non-adherence and viral non-suppression (VNS, viral load >400 copies/mL) in patients with and without mental health diagnoses by sex and age using mixed-effects Poisson regression models.Results54,378 patients were followed for a median of 3.5 years (IQR 1.9-6.4), 20,743 (38%) of whom had received a mental health diagnosis. 90% of patients had HIV viral load ConclusionOur study highlights the need for psychosocial interventions to improve HIV treatment outcomes, particularly for adolescents and young adults, and supports strengthening mental health services in paediatric and general HIV treatment programs.

AimsIn March 2020, South Africa introduced a lockdown in response to the COVID-19 pandemic, entailing the suspension of all non-essential activities and a complete ban of tobacco and alcohol sales. We studied the effect of the lockdown on mental health care utilisation rates in private-sector care in South Africa.MethodsWe did an interrupted time series analysis using insurance claims from January 1, 2017, to June 1, 2020 of beneficiaries 18 years or older from a large private sector medical aid scheme. We calculated weekly outpatient consultation and hospital admission rates for organic mental disorders, substance use disorders, serious mental disorders, depression, anxiety, other mental disorders, any mental disorder, and alcohol withdrawal syndrome. We calculated adjusted odds ratios (OR) for the effect of the lockdown on weekly outpatient consultation and hospital admission rates and the weekly change in rates during the lockdown until June 1, 2020.Results710,367 persons were followed up for a median of 153 weeks. Hospital admission rates (OR 0.38; 95% CI 0.33–0.44) and outpatient consultation rates (OR 0.74; 95% CI 0.63–0.87) for any mental disorder decreased substantially after the lockdown and did not recover to pre-lockdown levels until June 1, 2020. Health care utilisation rates for alcohol withdrawal syndrome doubled after the introduction of the lockdown, but the statistical uncertainty around the estimates was large (OR 2.24; 95% CI 0.69-7.24).ConclusionsReduced mental health care contact rates during the COVID-19 lockdown likely reflect a substantial unmet need for mental health services with potential long-term consequences for mental health patients and their families. Steps to ensure access and continuity of mental health services during future lockdowns should be considered.

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.

INTRODUCTION: Despite efforts to detect and treat problematic substance use (SU) among people living with HIV (PLWH) in South Africa, integration of HIV and SU services is limited. We sought to understand whether PLWH and problematic SU were: (a) routinely referred to SU treatment, a co-located Matrix clinic, (b) used SU treatment services when referred, and (c) the individual amount spent on SU. METHODS: Guided by the RE-AIM implementation science framework, we examined patient-level quantitative screening and baseline data from a pilot clinical trial for medication adherence and problematic SU. Qualitative data came from semi-structured interviews with HIV care providers (N = 8), supplemented by patient interviews (N = 15). RESULTS: None of the screened patient participants (N = 121) who were seeking HIV care and had problematic SU were engaged in SU treatment, despite the freely available co-located SU treatment program. Only 1.5% of the enrolled patient study sample (N = 66) reported lifetime referral to SU treatment. On average, patients with untreated SU spent 33.3% (SD=34.5%) of their monthly household income on substances. HIV care providers reported a lack of clarity about the SU referral process and a lack of direct communication with patients about patients' needs or interest in receiving an SU referral. DISCUSSION: SU treatment referrals and uptake were rare among PLWH reporting problematic SU, despite the high proportion of individual resources allocated to substances and the co-located Matrix site. A standardized referral policy between the HIV and Matrix sites may improve communication and uptake of SU referrals.

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.