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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.

Diagnosing HIV-associated neurocognitive impairment in most high-burden, but resource-constrained, settings is difficult due to the unavailability of specialist neurologists and neuropsychologists in primary health care centers. New tests that are easy to perform, based on virological and host immune response biomarkers, may be valuable in the diagnosis of HIV-associated neurocognitive disorder. The receiver operator characteristic curve analysis was used to investigate the diagnostic accuracy of threshold/cutoff concentrations for the peripheral lymphocyte proviral load and plasma biomarkers as diagnostic candidates for neurocognitive impairment in 133 HIV-infected individuals, using global deficit scores as the clinical gold standard. Forty-five (33.83%) of the participants had HIV-associated neurocognitive impairment, with 17.29% being mildly impaired and 16.54% moderately impaired. IL-2 had the best performance as a diagnostic tool for neurocognitive impairment with sensitivity of 67% and specificity of 52%, while the lowest performance was IL-6 with 65% sensitivity and 39% specificity. MIP-1α had the highest precision for the cutoff value, as indicated by the narrow 95% confidence interval (CI) (2.23-3.27), followed by IL-2 with 95% CI (3.02-5.12). RANTES had least precision, as shown by the widest 95% CI (135-9,487.61). For clinical markers of HIV diagnosis and monitoring, the lymphocyte proviral load cutoff value of 145 genome copies/million cells had the highest accuracy with 60% sensitivity and 51% specificity. The plasma viral load had an imperfect balance of 46% sensitivity and 78% specificity. The study demonstrated low to medium diagnostic accuracy of plasma cytokine biomarker cutoff values for defining neurocognitive impairment in people living with HIV.

Objective Although many studies report that women with HIV (WWH) are more vulnerable to cognitive impairment than men with HIV (MWH), this trend is not described consistently in the literature. In this systematic review and meta-analysis, we investigated whether the weight of evidence supports the existence of a significant sex difference in cognitive functioning among people with HIV and, if so, whether specific domains are affected. Method A systematic literature search retrieved 4,062 unique articles published between January 2000 and June 2019. Eligibility criteria were that studies directly compared adult WWH and MWH using a neuropsychological test battery. After extensive screening, we included 11 studies in the systematic review (N = 3,333) and 6 in the meta-analysis (N = 2,852). Results Six studies included in the systematic review found WWH performed significantly more poorly on measures of cognitive performance than MWH; the other five found no sex differences. Meta-analytic results indicated that WWH performed significantly more poorly than MWH in three cognitive domains (psychomotor coordination, visuospatial learning, and memory), but magnitudes of effect sizes were small (d = −.16, −.43, and − .30, respectively). Analyses detected no sex differences in global cognitive functioning and in the other cognitive domains. Conclusions Sex differences in cognitive performance are small, and sociodemographic and psychiatric characteristics of WWH and MWH differ between studies. Cognitive differences between WWH and MWH may be explained by sex-based variation in these characteristics, the impact of which seems to outweigh that of HIV-related clinical variables (e.g., CD4 count and viral load).

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.

Central nervous system dysfunction, associated with human immunodeficiency virus (HIV) infection, remains a significant clinical concern, affecting at least 50% of infected people. Imbalances in cytokine expression levels have been linked to HIV-associated neurocognitive disorders. The aim of this study was to evaluate plasma cytokine levels as predictor neurocognitive impairment in HIV infection using a multiplex profiling kit. Stepwise regression model was used to identify cytokine biomarkers of overall and domain-specific cognitive performance. Higher interleukin (IL)-2 (

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

The 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.

Driving ability can be diminished amongst people with HIV with associated neurocognitive impairment (NCI). We explore the relationship between HIV status, NCI and driving ability in professional truck drivers. Forty male professional drivers (20 HIV-positive; mean age = 39.20 ± 7.05) completed a neuropsychological test battery, two driving simulator tasks that assessed driving ability, and a driving history and habits questionnaire. A higher proportion of HIV-positive drivers exhibited impaired overall cognitive performance (p ≤ 0.001). Overall, drivers with NCI (defined as z ≤ 1.00) were more likely than those without NCI to crash (p = 0.002). There were no significant between-group (HIV-positive versus HIV-negative) differences with regard to self-reported on-road driving events. Professional drivers with NCI, as measured on a driving simulator, are at increased risk of making driving errors under high-risk conditions compared to their neurocognitively normal counterparts. These data should inform driver health management with regard to annual medical screening and surveillance.La capacidad de conducción puede verse disminuida entre las personas con VIH con deterioro neurocognitivo asociado (neurocognitive impairment, NCI). Exploramos la relación entre la situación frente al VIH, el NCI y la capacidad de conducción en conductores profesionales de camiones. Cuarenta conductores profesionales masculinos (20 seropositivos, edad media = 39.20 ± 7.05) completaron una batería de pruebas neuropsicológicas, dos tareas de simulador de conducción que evaluaron la capacidad de conducción y un cuestionario de hábitos y antecedentes de conducción. Una mayor proporción de conductores VIH positivos exhibió un desempeño cognitivo general deficiente (p ≤ 0.001). En general, los conductores con NCI (definido como z ≤ 1.00) tenían más probabilidades de chocar que aquellos sin NCI (p = 0.002). No hubo diferencias significativas entre los grupos (VIH positivo frente a VIH negativo) con respecto a los eventos autoinformados de conducción en carretera. Los conductores profesionales con NCI, según lo medido en un simulador de conducción, tienen un mayor riesgo de cometer errores de conducción en condiciones de alto riesgo en comparación con sus homólogos neurocognitivamente normales. Estos datos deberían informar a la gestión de la salud del conductor en lo que respecta a la vigilancia y los exámenes médicos anuales.

South Africa (SA) has the most people living with HIV/AIDS (PLWH) globally and prevalent alcohol use. Beliefs that mixing alcohol and antiretroviral therapy (ART) can lead to adverse reactions may promote ART nonadherence. Healthcare providers (n = 11) and patients (n = 19) recruited from primary HIV and substance use care in SA described their messages, beliefs, and behaviors around simultaneous use of alcohol and ART. Transcripts were analyzed using thematic analysis: (1) most providers indicated a message shift to reflect harm reduction principles: PLWH should manage alcohol use but not let it interfere with taking ART; however, (2) patients recalled conflicting messages from their providers and some displayed interactive toxicity beliefs and behaviors. Despite progress demonstrated by 2016 national adherence guidelines and shifted provider messaging, interactive toxicity beliefs remain a barrier to ART adherence. Results have implications for the adaptation of adherence counseling to minimize the impact of alcohol use on HIV treatment.

South Africa (SA) has the largest HIV/AIDS burden globally. In SA, substance use is prevalent and interferes with HIV treatment adherence and viral suppression, yet is not routinely treated in HIV care. More research is needed to adapt scalable, evidence-based therapies for substance use for integration into HIV care in SA. Behavioral activation (BA), originally developed as an efficacious therapy for depression, has been feasibly delivered to treat depression in low- and middle-income countries (LMICs) and to treat substance use in high-income settings. Yet, to date, there is limited research on implementing BA for substance use in LMICs. Guided by the ADAPT-ITT framework, this study sought to adapt BA therapy for substance use in HIV care in SA. We conducted semi-structured individual interviews with patients (n=19), and HIV care providers and substance use treatment therapists (n=11) at two clinic sites in a peri-urban area of Cape Town. We enrolled patients with moderate/severe substance use (WHO-ASSIST≥4) and detectable viral load, and HIV providers and substance use treatment therapists across roles and disciplines. We assessed patient and provider/therapist views on the appropriateness of the BA therapy model and sought feedback on Xhosa-translated BA therapy components. Participants identified the central role of boredom in contributing to substance use and saw the BA therapy model as highly appropriate. Participants identified church and religious practices, sports, and yard and housework as relevant substance-free activities in this community. These findings will inform adaptations to BA therapy for substance use and HIV medication adherence in this setting.

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.

BACKGROUND: Despite HIV and problematic drinking often co-occurring in South Africa (SA), limited research has examined how HIV stigma relates to alcohol outcomes, how alcohol stigma relates to HIV outcomes, or moderators of these associations. This study examined the intersection of HIV/alcohol stigmas on HIV/alcohol outcomes and the role of avoidant behavior in moderating these relationships in SA. METHODS: We assessed biomarker-verified measures of antiretroviral therapy (ART) adherence, HIV viral load (VL), and alcohol consumption, and self-reported measures of internalized HIV/alcohol stigmas, avoidant behavior, ART adherence, and problematic drinking—alcohol use that will likely lead to health or other problems—cross-sectionally among people with HIV (PWH) and problematic drinking (N=64). Regression analyses with interaction terms were conducted. FINDINGS: A significant relationship was found between internalized alcohol stigma and VL suppression, with higher levels of alcohol stigma associated with a lower likelihood of suppression (OR=1.68, 95%CI[1.11–2.65], p=0.02). Avoidance significantly moderated the relationship between internalized HIV stigma and problematic drinking. Higher HIV stigma was associated with lower problematic drinking only at low levels of avoidance (b(SE)=−1.92(.85), p=0.03). CONCLUSIONS: This study is the first to examine associations between HIV and alcohol stigmas, avoidance, and both HIV and alcohol outcomes in SA. Findings contribute to our understanding of how alcohol stigma relates to biological HIV outcomes, and the role of avoidance in the relationship between internalized HIV stigma and problematic drinking. Findings may inform future clinical interventions to reduce the impact of stigma on HIV treatment outcomes and alcohol use among PWH in SA.

Dysregulated expression of neuro-immune markers has previously been linked to HIV-associated neurocognitive impairment. We undertook an exploratory approach in a HIV clade-C cohort, investigating the association between eight immune markers and neurocognitive performance in 99 HIV+ and 51 HIV- participants. Markers were selected on preliminary and putative evidence of their link to key neuro-immune functions. Cognitive performance was established using a battery of tests sensitive to HIV-associated neurocognitive impairment, with domain-based scores utilized in analysis. The markers Thymidine phosphorylase (TYMP) and Neutrophil gelatinase-associated lipocalin (NGAL) were significantly higher while Matrix Metalloproteinase (MMP)9 was significantly lower in HIV+ participants. Our results further showed that in the HIV+ group, worse psychomotor processing speed was associated with higher TYMP and NGAL levels and worse motor function was associated with higher NGAL levels. Future studies should explore the underlying mechanisms of these markers in HIV-associated neurocognitive impairment. Graphical Abstract The association of peripheral immune markers with neurocognitive performance in South African HIV-positive patients.

South Africa is home to the largest number of people living with HIV/AIDS in the world. Alongside the HIV/AIDS epidemic, problematic alcohol and other drug (AOD) use is prevalent and associated with poor HIV treatment and secondary HIV prevention outcomes. International guidelines and local policy both support the integration of mental health care and AOD treatment into HIV care, yet barriers exist to implementation. This study aimed to explore patient and provider perspectives on the integration of HIV and AOD treatment services in Cape Town, South Africa. This included barriers and facilitators to task sharing AOD treatment in HIV care and preferences for a task shared approach to integrating AOD treatment in HIV care, including who should deliver the behavioural intervention. We conducted thirty semi-structured qualitative interviews with HIV and AOD treatment staff, providers, and people living with HIV/AIDS (PLWH) with moderate, problematic AOD use and difficulties (personal or structural) adhering to HIV treatment. Findings illustrated several key themes: (1) the separation between AOD and HIV services (a "siloed treatment experience"), even in the context of geographic co-location; (2) low AOD treatment literacy among HIV patients and providers, including a low awareness of existing AOD use services, even when co-located; (3) substance use stigma as a barrier to HIV and AOD treatment integration; (4) a strong patient preference for peer interventionists; and (5) the role of community health workers (CHWs) in detecting AOD use among some PLWH who had not followed up in HIV care. These findings will inform a future type 1 hybrid effectiveness-implementation trial, guided by the RE-AIM framework, to evaluate a task shared, evidence-based intervention to address problematic AOD use and improve HIV medication adherence in this setting.

HIV-infected women who have experienced sexual violence face unique challenges in their HIV care engagement and adherence to antiretroviral medications (ARVs). Improving AIDS Care after Trauma (ImpACT) is a brief counseling intervention aimed at reducing the negative impact of sexual trauma and HIV, building coping skills, and improving long-term HIV care engagement. We conducted a randomized controlled pilot trial of ImpACT with 64 women initiating ARVs in Cape Town, South Africa, with results suggesting the intervention can reduce PTSD symptoms and increase motivation to adhere to ARVs. For the current study, we abstracted data from ImpACT worksheets completed by 31 participants during intervention sessions, and qualitative responses from post-intervention surveys, to examine mechanisms, facilitators, and barriers to change in the intervention. Data included participant descriptions of the values informing their care, barriers to participation, and perceived benefits of the intervention related to coping with trauma and improving care engagement. During the first session, women reported feelings of shame, sadness, and anger that led to social isolation, mistrust, and damaged relationships. Barriers to participation included work and school demands, issues with transportation, finances, and discomfort in talking about HIV and trauma, particularly in group sessions. Despite these challenges, several women stated they developed more positive thinking, felt more confident, and improved their interpersonal relationships. Participants also reported substantial positive impact on symptoms of sexual trauma and motivation to continue with long-term HIV care, and clearer understanding of barriers and facilitators to ARV adherence. ImpACT is a promising intervention model for building adaptive coping skills and adherence to HIV treatment, informed by personal values, among women with a history of trauma in this high-risk setting. The data also offer insights into strategies to strengthen the intervention, overcome barriers to participation, encourage the practical application of skills, and promote long-term HIV care engagement.

Most measures developed in high income countries to screen for major depressive disorder (MDD) among people living with HIV (PWH) demonstrate suboptimal psychometric properties when utilized in non-western, resource limited settings due to their high false positive rates. For standardized MDD screening to be implementable in local settings, a measure is needed that reduces diagnostic burden by being highly sensitive while limiting false positives. This study sought to evaluate the ability of the locally developed South African Depression Scale (SADS) to screen for MDD in PWH in Cape Town. The SADS was administered along with the SCID-5-RV as gold standard to 236 PWH. It demonstrated good discriminating ability in detecting MDD with an area under the curve of 0.85. A cut-off of 27 yielded 78.2% sensitivity and 54.4% PPV. Given its robust psychometric properties, routine use of the SADS in community clinics to screen at-risk PWH, combined with evidence-based depression treatment, could improve the health outcomes and well-being of PWH in South Africa.ResumenLa mayoria de las medidas desarrolladas en paises de ingresos altos para detectar el trastorno depresivo mayor (TDM) entre las personas que viven con el VIH (PVV) demuestran propiedades psicometricas suboptimas cuando se utilizan en entornos no occidentales de recursos limitados debido a sus altas tasas de falsos positivos. Para que la deteccion de TDM estandarizada sea implementable en entornos locales, se necesita una medida que reduzca la carga diagnostica al ser altamente sensible mientras limita los falsos positivos. Este estudio trato de evaluar la capacidad de la Escala de Depresion Sudafricana (SADS, por sus siglas en ingles) desarrollada localmente para detectar TDM en PVV en Ciudad del Cabo. El SADS se administro junto con el SCID-5-RV como el test de referencia a 236 PWH. Demostro una buena capacidad discriminatoria en la deteccion de TDM con un area bajo la curva de 0,85. Un corte de 27 produjo un 78,2% de sensibilidad y un 54,4% de VPP. Dadas sus solidas propiedades psicometricas, el uso rutinario del SADS en clinicas comunitarias para detectar las PVV en riesgo, combinado con un tratamiento de depresion basado en la evidencia, podria mejorar los resultados de salud y el bienestar de las PVV en Sudafrica.

Introduction South Africa (SA) has the highest number of people living with HIV (PLWH) globally, and a significant burden of alcohol and other drug use (AOD). Although integrating AOD treatment into HIV care may improve antiretroviral therapy (ART) adherence, this is not typically routine practice in SA or other low‐resource settings. Identifying interventions that are feasible and acceptable for implementation is critical to improve HIV and AOD outcomes. Methods A pilot randomized hybrid type 1 effectiveness‐implementation trial (N = 61) was conducted to evaluate the feasibility and acceptability of Khanya, a task‐shared, peer‐delivered behavioral intervention to improve ART adherence and reduce AOD in HIV care in SA. Khanya was compared to enhanced treatment as usual (ETAU), a facilitated referral to on‐site AOD treatment. Implementation outcomes, defined by Proctor’s model, included feasibility, acceptability, appropriateness and fidelity. Primary pilot effectiveness outcomes were ART adherence at post‐treatment (three months) measured via real‐time electronic adherence monitoring, and AOD measured using biomarker and self‐report assessments over six months. Data collection was conducted from August 2018 to April 2020. Results and discussion Ninety‐one percent of participants (n = 56) were retained at six months. The intervention was highly feasible, acceptable, appropriate and delivered with fidelity (>90% of components delivered as intended by the peer). There was a significant treatment‐by‐time interaction for ART adherence (estimate = −0.287 [95% CI = −0.507, −0.066]), revealing a 6.4 percentage point increase in ART adherence in Khanya, and a 22.3 percentage point decline in ETAU. Both groups evidenced significant reductions in alcohol use measured using phosphatidylethanol (PEth) (F(2,101) = 4.16, p = 0.01), significantly decreased likelihood of self‐reported moderate or severe AOD (F(2,104) = 7.02, p = 0.001), and significant declines in alcohol use quantity on the timeline follow‐back (F(2,102) = 21.53, p

Objective Most research investigating reinforcement in alcohol use is from high-income countries. The current study sought to understand the association of different reinforcement types (alcohol-specific reward, environmental reward, behavioral activation) with multiple measures of alcohol use and cravings among individuals living with HIV in South Africa. Method Baseline data were obtained from a substance use clinical trial in Cape Town (N = 65). Unhealthy alcohol use was measured using the biomarker phosphatidylethanol (PEth), Alcohol Use Identification Test (AUDIT-C), average number of drinks from the timeline follow back (TLFB), and self-reported cravings. Reinforcement was measured using the proportion of income spent on alcohol (alcohol-specific reward), both subscales of the Reward Probability Index (environmental reward), and the Behavioral Activation Depression Scale (activation). Poisson and linear regression analyses were conducted. Results Each percentage point increase in income spent on alcohol was significantly associated with PEth, RR = 1.004 [95% CI (1.001, 1.007)], which translates to a 13.6% increase in the relative risk of unhealthy alcohol use for the average person in the study. More alcohol-specific reward was significantly associated with higher scores on the AUDIT-C, higher average number of drinks on the TLFB, and more cravings. Higher activation was associated with lower scores on the AUDIT-C. Neither subscale of environmental reward was associated with model outcomes. Conclusion Greater alcohol-specific reward and less behavioral activation were associated with more frequent and unhealthy alcohol use in this setting, but not environmental reward. Findings highlight how different reinforcement types potentially influence alcohol use in a low-resource global setting. (PsycInfo Database Record (c) 2021 APA, all rights reserved).

Introduction Major depressive disorder, highly prevalent among people with HIV (PWH) globally, including South Africa, is associated with suboptimal adherence to antiretroviral therapy. Globally, there are insufficient numbers of mental health providers and tested depression treatments. This study's aim was to test task‐shared cognitive‐behavioural therapy for adherence and depression (CBT‐AD) in HIV, delivered by clinic nurses in South Africa. Methods This was a two‐arm randomized controlled effectiveness trial (recruitment: 14 July 2016 to 4 June 2019, last follow 9 June 2020). One‐hundred‐sixty‐one participants with clinical depression and virally uncontrolled HIV were recruited from primary care clinics providing HIV care, in Khayelitsha, South Africa. Arm 1 was task‐shared, nurse‐delivered CBT‐AD; and arm 2 was enhanced treatment as usual (ETAU). Primary outcomes (baseline to 4 months) were blinded Hamilton Depression Rating Scale (HAM‐D) scores, and weekly adherence via real‐time monitoring (Wisepill). Secondary outcomes were adherence and depression over 4‐, 8‐ and 12‐month follow‐ups, proportion of participants with undetectable viremia and continuous CD4 cell counts at 12 months. Additional analyses involved viral load and CD4 over time. Results At 4 months, the HAMD scores in the CBT‐AD condition improved by an estimated 4.88 points more (CI: –7.86, –1.87, p = 0.0016), and for weekly adherence, 1.61 percentage points more per week (CI: 0.64, 2.58, p = 0.001) than ETAU. Over follow‐ups, CBT‐AD had an estimated 5.63 lower HAMD scores (CI: –7.90, –3.36, p < 0.001) and 23.56 percentage points higher adherence (CI: 10.51, 34.21, p < 0.001) than ETAU. At 12 months, adjusted models indicated that the odds of having an undetectable viremia was 2.51 greater at 12 months (CI: 1.01, 6.66, p = 0.047), and 3.54 greater over all of the follow‐ups (aOR = 3.54, CI: 1.59, 20.50; p = 0.038) for those assigned CBT‐AD. CD4 was not significantly different between groups at 12 months or over time. Conclusions Task‐shared, nurse‐delivered, CBT‐AD is effective in improving clinical depression, ART adherence and viral load for virally unsuppressed PWH. The strategy of reducing depression to allow patients with self‐care components of medical illness to benefit from adherence interventions is one to extend. Implementation science trials and analyses of cost‐effectiveness are needed to translate findings into clinical practice. Trial Registration ClinicalTrials.gov Identifier: NCT02696824 https://clinicaltrials.gov/ct2/show/NCT02696824

HIV-1 is responsible for the development of a spectrum of cognitive impairments known as HIV-associated neurocognitive disorder (HAND). In the era of antiretroviral therapy (ART), HAND remains prevalent in people living with HIV (PLWH), despite low or undetectable viral loads. Persistent neuroinflammation likely plays an important role in the contributing biological mechanisms. Multiple cerebrospinal fluid (CSF) immune markers have been studied but it is unclear which markers most consistently correlate with neurocognitive impairment. We therefore conducted a systematic review of studies of the association of CSF immune markers with neurocognitive performance in ART-experienced PLWH. We aimed to synthesize the published data to determine consistent findings and to indicate the most noteworthy CSF markers of HAND. Twenty-nine studies were included, with 20 cross-sectional studies and 9 longitudinal studies. From the group of markers most often assayed, specific monocyte activation (higher levels of Neopterin, sCD163, sCD14) and neuroinflammatory markers (higher levels of IFN-γ, IL-1α, IL-7, IL-8, sTNFR-II and lower levels of IL-6) showed a consistent direction in association with HIV-associated neurocognitive impairment. Furthermore, significant differences exist in CSF immune markers between HIV-positive people with and without neurocognitive impairment, regardless of viral load and nadir/current CD4+ count. These markers may be useful in furthering our understanding of the neuropathology, diagnosis and prognosis of HAND. Studies using prospective designs (i.e. pre- and post-interventions), "multi-modal" methods (e.g. imaging, inflammation and neurocognitive evaluations) and utilizing a combination of the markers most commonly associated with HAND may help delineate the mechanisms of HAND.

Background South Africa adopted a universal test and treatment program for HIV infection in 2015. The standard of care that people living with HIV receive consists of 3 sessions of readiness counseling delivered by lay counselors (LCs). In the largest antiretroviral therapy (ART) program worldwide, effective and early HIV and ART education and support are key for ensuring ART adoption, adherence, and retention in care. Having LCs to deliver readiness counseling allows for the wide task-sharing of this critical activity but carries the risks of loss of standardization, incomplete content delivery, and inadequate monitoring and supervision. Systems for ensuring that a minimum standard of readiness counseling is delivered to the growing number of people living with HIV are essential in the care cascade. In resource-constrained, high-burden settings, mobile health (mHealth) apps may potentially offer solutions to these treatment gaps by providing content structure and delivery records. Objective This study aims to explore, at a large Cape Town–based nonprofit HIV care organization, the staff’s perceived preimplementation barriers and facilitators of an mHealth intervention (Masivukeni) developed as a structured app for ART readiness counseling. Methods Masivukeni is a laptop-based app that incorporates written content, graphics, short video materials, and participant activities. In total, 20 participants were included in this study. To explore how an mHealth intervention might be adopted across different staff levels within the organization, we conducted 7 semistructured interviews (participants: 7/20, 35%) and 3 focus groups (participants in 2 focus groups: 4/20, 20%; participants in 1 focus group: 3/20, 15%) among LCs, supervisors, and their managers. In total, 20 participants were included in this study. Interviews lasted approximately 60 minutes, and focus groups ranged from 90 to 120 minutes. The Consolidated Framework for Implementation Research was used to explore the perceived implementation barriers and facilitators of the Masivukeni mHealth intervention. Results Several potential facilitators of Masivukeni were identified. Multimedia and visual elements were generally regarded as aids in content delivery. The interactive learning components were notably helpful, whereas facilitated updates to the adherence curriculum were important to facilitators and managers. The potential to capture administrative information regarding LC delivery and client logging was regarded as an attractive feature. Barriers to implementation included security risks and equipment costs, the high volume of clients to be counseled, and variable computer literacy among LCs. There was uncertainty about the app’s appeal to older clients. Conclusions mHealth apps, such as Masivukeni, were perceived as being well placed to address some of the needs of those who deliver ART adherence counseling in South Africa. However, the successful implementation of mHealth apps appeared to be dependent on overcoming certain barriers in this setting.

Objective:Food insecurity is a structural barrier to HIV care in peri-urban areas in South Africa (SA), where approximately 80 % of households are moderately or severely food insecure. For people with HIV (PWH), food insecurity is associated with poor antiretroviral therapy adherence and survival rates. Yet, measurement of food insecurity among PWH remains a challenge.Design:The current study examines the factor structure of the nine-item Household Food Insecurity Access Scale (HFIAS, isiXhosa-translated) among PWH in SA using a restrictive bifactor model.Setting:Primary care clinics in Khayelitsha, a peri-urban settlement in Cape Town, SA.Participants:Participants (n 440) were PWH who received HIV care in Khayelitsha screening for a clinical trial. Most were categorised as severely (n 250, 56·82 %) or moderately (n 107, 24·32 %) food insecure in the past 30 d.Results:Revised parallel analysis suggested a three-factor structure, which was inadmissible. A two-factor structure was examined but did not adequately fit the data. A two-factor restrictive bifactor model was examined, such that all items loaded on a general factor (food insecurity) and all but two items loaded on one of two specific additional factors, which adequately fit the data (comparative fit index = 0·995, standardised root mean square residual = 0·019). The two specific factors identified were: anxiety/insufficient quality and no food intake. Reliability was adequate (ω = 0·82).Conclusions:Results supported the use of a total score, and identified two specific factors of the HFIAS, which may be utilised in future research and intervention development. These findings help identify aspects of food insecurity that may drive relationships between the construct and important HIV-related variables.

Introduction Addressing the intersection between mental health and HIV is critical for the wellbeing of persons living with HIV (PLWH). This systematic review synthesized the literature on mental health interventions for PLWH in low‐ and middle‐income countries (LMICs) to determine intervention components and explore their relationship with intervention effectiveness. Methods We included only controlled clinical trials of interventions aiming to improve the mental health of PLWH. We conducted a search in the following databases: PubMed, CINAHL, PsycINFO and EMBASE for eligible studies describing the evaluation of interventions for mental health problems among PLWH in LMICs published through August 2020. Two reviewers independently screened references in two successive stages of title/abstract screening and then full‐text screening for references meeting title/abstract criteria. Results We identified a total of 30 eligible articles representing 6477 PLWH who were assigned to either the intervention arm (n = 3182) or control arm (n = 3346). The mental health interventions evaluated were psychological (n = 17, 56.67%), pharmacological (n = 6, 20.00%), combined psychological and pharmacological (n = 1, 3.33%) and complementary/alternative treatments (n = 6, 20.00%). The mental health problems targeted were depression (n = 22, 73.33 %), multiple psychological symptoms (n = 1, 3.33%), alcohol and substance use problems (n = 4, 13.33%), post‐traumatic stress disorder (n = 1, 3.33%) and HIV‐related neuro‐cognitive impairment (n = 2, 6.67%). Studies of interventions with significant effects had significantly a higher number of active ingredients than those without significant effects [3.41 (2.24) vs. 1.84 (1.46) Mean (SD)] [Mean difference = −1.56, 95% CI = −3.03 to −0.09, p = 0.037]. Conclusions There continue to be advances in mental health interventions for PLWH with mental illness in LMICs. However, more research is needed to elucidate how intervention components lead to intervention effectiveness. We recommend scale up of culturally appropriate interventions that have been successfully evaluated in low‐ and middle‐income countries.

Immune activation, which is accompanied by the production of proinflammatory cytokines, is a strong predictor of disease progression in HIV infection. Inflammation is critical in neuronal damage linked to HIV-associated neurocognitive disorders. We examined the relationship between plasma cytokine levels and deficits in neurocognitive function. Multiplex profiling by Luminex

Key Points Question Are HIV plasma markers that are universally used to monitor immune function and treatment response associated with subcortical brain volumes in clinically and demographically heterogeneous HIV-infected individuals? Findings In this cross-sectional study of 1203 HIV-infected adults, lower current CD4+ T-cell counts were associated with smaller hippocampal and thalamic volumes independent of treatment status, although in the subset of participants not receiving treatment, they were associated with smaller putamen volumes. Across all participants, detectable viral load was associated with smaller hippocampal volumes, but in the subset of participants receiving HIV treatment, detectable viral load was also associated with smaller amygdala volumes. Meaning In a heterogeneous population of HIV-infected individuals, volumes of structures in the limbic system were consistently associated with plasma markers., Importance Despite more widely accessible combination antiretroviral therapy (cART), HIV-1 infection remains a global public health challenge. Even in treated patients with chronic HIV infection, neurocognitive impairment often persists, affecting quality of life. Identifying the neuroanatomical pathways associated with infection in vivo may delineate the neuropathologic processes underlying these deficits. However, published neuroimaging findings from relatively small, heterogeneous cohorts are inconsistent, limiting the generalizability of the conclusions drawn to date. Objective To examine structural brain associations with the most commonly collected clinical assessments of HIV burden (CD4+ T-cell count and viral load), which are generalizable across demographically and clinically diverse HIV-infected individuals worldwide. Design, Setting, and Participants This cross-sectional study established the HIV Working Group within the Enhancing Neuro Imaging Genetics Through Meta Analysis (ENIGMA) consortium to pool and harmonize data from existing HIV neuroimaging studies. In total, data from 1295 HIV-positive adults were contributed from 13 studies across Africa, Asia, Australia, Europe, and North America. Regional and whole brain segmentations were extracted from data sets as contributing studies joined the consortium on a rolling basis from November 1, 2014, to December 31, 2019. Main Outcomes and Measures Volume estimates for 8 subcortical brain regions were extracted from T1-weighted magnetic resonance images to identify associations with blood plasma markers of current immunosuppression (CD4+ T-cell counts) or detectable plasma viral load (dVL) in HIV-positive participants. Post hoc sensitivity analyses stratified data by cART status. Results After quality assurance, data from 1203 HIV-positive individuals (mean [SD] age, 45.7 [11.5] years; 880 [73.2%] male; 897 [74.6%] taking cART) remained. Lower current CD4+ cell counts were associated with smaller hippocampal (mean [SE] β = 16.66 [4.72] mm3 per 100 cells/mm3; P, This cross-sectional study examines structural brain associations with CD4+ T-cell count and viral load in HIV-positive individuals taking and not taking combination antiretroviral therapy.

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

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.

Neurocognitive impairment (NCI) associated with the human immunodeficiency virus (HIV) remains prevalent amongst people living with HIV. Testing for HIV-associated NCI in routine clinical care is limited in South Africa and reasons for this are unclear. We conducted an online survey amongst healthcare workers (HCW) to assess HIV-associated NCI knowledge and current practices. The final sample included four hundred surveys (n=400). Chi-square analyses were used to explore HCW knowledge of HIV-associated NCI and screening tools. One-way ANOVA was used to compare mean responses between HCW categories. We observed low awareness of HIV-associated NCI terminology and screening tools. HCW seldom suspected NCI among patients and screening practices were uncommon. Referrals for further NCI investigations were never requested. HCW expressed a desire to receive further training to identify HIV associated NCI. The current study highlights the context of HIV-associated NCI knowledge and practices among front-line HIV HCW in resource-limited settings.

First-time antiretroviral therapy (ART) initiators may be more vulnerable to poor ART adherence because they may be coping with a new HIV diagnosis, facing logistical challenges to accessing and adhering to ART for the first time, and have not yet developed support networks or the skills to support long-term adherence. We recruited 324 participants in two HIV clinics near Cape Town, South Africa. Sociodemographic/psychosocial factors were measured at baseline and self-reported adherence at the 6 month follow-up. We conducted multivariable regression to determine which baseline factors were associated with 6-month adherence. A better patient-clinic relationship score (OR: 1.08 [95% CI: 1.05–1.11]) was associated with higher adherence. A drug use problem (0.51 [0.29–0.87]), higher social isolation (0.93 [0.87–0.99]), and greater number of years living with HIV before initiating ART (0.92 [0.86–1.00]) were associated with adherence levels below 90%. Patient-clinic relationships and social support are key psycho-social factors in early adherence behavior. Reducing drug use problems through targeted screening and early intervention may improve ART adherence.

Rapid maturation of major white matter pathways occurs in the first 2 years of life, indicating a critical neuronal developmental period. The impact of initiating antiretroviral therapy (ART) in children perinatally infected with HIV-1, after the age of 2 years on neurocognitive functioning and white matter development in adolescence has not been studied. Forty-six adolescents who initiated ART during the first 2 years of life ( 2 years) and 79 adolescents who initiated ART after 2 years of age ( 2 years), with perinatally acquired HIV were enrolled in the Cape Town Adolescent Antiretroviral Cohort. Adolescents completed a comprehensive neurocognitive battery testing a number of cognitive domains. Diffusion tensor imaging (DTI) was done to determine fractional anisotropy (FA), mean diffusivity (MD), axial diffusion (AD), and radial diffusion (RD) in a region of interest analysis. Neurocognitive performance was similar between adolescents who initiated ART 2 years or 2 years. There was a trend towards attention (p = .07) and working memory (p = .05) being poorer in the group who initiated ART 2 years. FA was lower in the 2-year group in the superior corona radiata (p = .03), and the external capsule (p = .04). MD was higher in the 2-year group in the cerebral peduncle (p = .02), the superior corona radiata (p = .01), and the superior fronto-occipital fasciculus (p = .03). RD was higher in the 2-year group in the superior corona radiata (p = .02), the cerebral peduncle (p = .01), and the superior fronto-occipital fasciculus (p = .01). However, the higher AD in the 2-year group in the superior corona radiata was not in the expected direction (p = .01). Initiation of ART after the neuronal development period of the second postnatal year is associated with white matter alterations on neuroimaging.

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

It is not known if proviral DNA in the periphery corresponds to cognitive status in clade C as it does in clade B and recombinant forms. A cross-sectional study was conducted on participants investigated for HIV-associated neurocognitive impairment in South Africa. HIV-1 proviral DNA was quantified using a PCR assay targeting a highly conserved HIV-1 LTR-gag region. Fifty-four (36.7%) participants were cognitively impaired and 93 (63.3%) were not impaired. Forty-three (79.6%) of the cognitively impaired participants were female and 11 (20.4%) were male. There was no significant age difference between cognitively impaired and unimpaired participants (p = 0.42). HIV-1 DNA in cognitively impaired PLWH was significantly higher than in cognitively normal individuals (p = .016). Considering impaired participants, lymphocyte HIV-1 DNA was significantly higher in males than females (p = 0.02). There was a modest positive correlation between lymphocyte HIV-1 DNA and global deficit scores (GDS) r = 0.176; p = 0.03). The two measures of viral load, lymphocyte HIV-1 DNA copies/million and plasma RNA copies/ml, were positively correlated (r = 0.39; p p value = 0.010. The burden of HIV-1 peripheral blood lymphocyte proviral DNA corresponds to neurocognitive impairment among individuals infected with clade C disease. Therefore, therapeutic strategies to reduce the HIV-1 proviral DNA reservoir in lymphocytes may improve neurocognitive outcomes in PLWH.

A spectrum of cognitive impairments known as HIV-associated neurocognitive disorders (HAND) are consequences of the effects of HIV-1 within the central nervous system. Regardless of treatment status, an aberrant chronic neuro-immune regulation is a crucial contributor to the development of HAND. However, the extent to which inflammation affects brain structures critical for cognitive status remains unclear. The present study aimed to determine associations of peripheral immune markers with cortical thickness and surface area. Participants included 65 treatment-naive HIV-positive individuals and 26 HIV-negative controls. Thickness and surface area of all cortical regions were derived using automated parcellation of T1-weighted images acquired at 3 T. Peripheral immune markers included C-C motif ligand 2 (CCL2), matrix metalloproteinase 9 (MMP9), neutrophil gelatinase-associated lipocalin (NGAL), thymidine phosphorylase (TYMP), transforming growth factor (TGF)-β1, and vascular endothelial growth factor (VEGF), which were measured using enzyme-linked immunosorbent assays. Associations of these markers with thickness and surface area of cortical regions were evaluated. A mediation analysis examined whether associations of inflammatory markers with cognitive functioning were mediated by brain cortical thickness and surface area. After controlling for multiple comparisons, higher NGAL was associated with reduced thickness of the bilateral orbitofrontal cortex in HIV-positive participants. The association of NGAL with worse motor function was mediated by cortical thickness of the bilateral orbitofrontal region. Taken together, this study suggests that NGAL plays a potential role in the neuropathophysiology of neurocognitive impairments of HIV.

Pregnancy represents a time of increased risk for intimate partner violence (IPV), and an HIV diagnosis further increases the vulnerability of this at-risk group. This study explores experiences of recent IPV using qualitative interviews with N = 12 HIV-positive pregnant women recruited from a clinical setting in South Africa, a location with a high global prevalence of IPV and HIV. Partner dynamics around IPV resulted in HIV shame and stigma and adversely affected engagement in HIV care and HIV treatment behaviors. The results highlight the challenges women face in navigating disclosure of both IPV and HIV, accessing necessary support, and engaging in both HIV-related and pregnancy-related care in the context of an abusive relationship.

For women enrolled in prevention of mother-to-child transmission (PMTCT) programs, non-disclosure of their HIV status can be a significant barrier to sustained HIV care engagement. To explore decision-making surrounding HIV disclosure among HIV-infected pregnant women, we conducted repeated in-depth interviews during pregnancy and postpartum with 20 women recruited from a PMTCT clinic in Cape Town, South Africa. Three domains were examined using thematic analysis: (1) disclosure experiences, (2) challenges associated with partner disclosure, and (3) implications of nondisclosure. All women had disclosed to someone by the time of the baby’s birth, typically limiting their disclosure to trusted individuals. Only half of participants disclosed to the father of the child. Nondisclosure, particularly to partners, was a significant source of worry and stress. Women used pregnancy as an explanation for using medication and attending frequent clinic appointments, and recognized impending challenges in the postpartum period when this excuse would no longer apply. Results suggest that PMTCT programs have a key role to play in helping individuals to make decisions about HIV disclosure, and assisting patients to navigate the disclosure process, especially with partners.

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

Women with severe mental illness (SMI) in South Africa face numerous psychosocial challenges and alcohol use is widely used in this population as a coping strategy. Although hazardous alcohol use has a documented negative effect on medication adherence or chronic illness, research has mostly ignored the role of alcohol on psychotropic medication adherence in women with SMI. The primary aim of this study was to explore the association of hazardous alcohol use on psychotropic medication adherence in adult women living with SMI (N = 119), attending a psychiatric clinic for treatment in Cape Town. Medication adherence was based on self-report and hazardous alcohol use was measured with the Alcohol Use Disorders Identification Test (AUDIT). Poisson regression analyses (controlling for education, relationship status, and psychiatric hospitalisations) indicated that hazardous alcohol use was significantly associated with a greater likelihood of psychotropic medication non-adherence. Similar findings were observed for HIV medication non-adherence in the HIV-positive subsample. Study findings highlight the role of alcohol use for medication non-adherence in women with SMI and should be addressed in psychiatric care.

Improving AIDS Care after Trauma (ImpACT), a coping intervention for HIV-infected women with sexual abuse histories, was evaluated for feasibility and potential efficacy in a public clinic in Cape Town, South Africa. Sixty-four participants were enrolled prior to starting antiretroviral therapy (ART). After completing baseline assessments, participants were randomly assigned to standard of care (SoC: three adherence counseling sessions) or ImpACT (SoC plus four individual and three group sessions). Participants completed assessments at 3 months (after individual sessions) and 6 months post-baseline. In exploratory analysis of primary outcomes, ImpACT participants, compared to SoC, reported greater reductions in avoidance and arousal symptoms of PTSD and greater increases in ART adherence motivation at 3 months. Clinically significant decreases in overall PTSD symptoms were also demonstrated at 3 months. These effects continued as trends at the 6-month assessment, in addition to increases in social/spiritual coping. In analysis of secondary outcomes, high levels of non-adherence to ART and poor care engagement were evident at 6 months, with no differences between study arms. A trauma-focused, culturally-adapted individual intervention delivered by a non-specialist in the HIV care setting is feasible and acceptable. Preliminary findings suggest ImpACT has potential to reduce PTSD symptoms and increase ART adherence motivation, but a more intensive intervention may be needed to improve and maintain care engagement among this population. Trial Registration: ClinicalTrials.gov NCT02223390.

Antiretroviral therapy (ART)-readiness counseling has been deemed critical to adherence, instilling knowledge, and promoting positive beliefs and attitudes. In the landscape of changing policy in South Africa, some ART initiators have had prior ART-readiness counseling (e.g., for prevention-of-mother-to-child-transmission [PMTCT] programs). The extent to which previous counseling resulted in retained knowledge and belief is unknown, which may be important to the promotion of women’s ART adherence. We compared 320 women living with HIV and initiating ART, with and without prior PMTCT on HIV knowledge, treatment, beliefs, and attitudes. The PMTCT group held more accurate beliefs and more positive attitudes about ART. Both groups lacked understanding of basic HIV biology. Non-disclosure of HIV status was high. Thus, in individuals re-initiating therapy, some knowledge about HIV and its treatment was not well retained. Tailored education and counseling may be critical to adherence, with a focus on biological concepts that impact ART resistance.

Background Therapeutic drug monitoring (TDM) is essential practice when dosing drugs with a narrow therapeutic index in order to achieve a plasma drug concentration within a narrow target range above the efficacy concentration but below the toxicity concentration. However, TDM with dose individualisation is challenging during a double-blind clinical trial with laboratory staff and investigators blinded to treatment arm allocation. Methods Drug concentrations were simulated for participants in the placebo arm by an unblinded independent statistician, utilising the measured values from the treatment arm participants. Simulated and actual concentrations were re-blinded and passed on to a dose-adjusting investigator, who made dose adjustment recommendations but was not directly responsible for clinical care of participants. Results A total of 257 sham lithium plasma concentrations were simulated utilising 242 true lithium plasma concentrations in real time as the trial progressed. The simulated values had a median (interquartile range) of 0.59 (0.46, 0.72) compared to 0.53 (0.39, 0.72) in the treatment arm. Blinding of the laboratory staff and dose-adjusting investigator was maintained successfully. Conclusions We succeeded in simulating sham lithium plasma concentrations while maintaining blinding. Our simulated values have a smaller range than the observed data, which can be explained by the challenges with respect to drug adherence and dose timing that were experienced. Trial registration Pan African Clinical Trials Registry, PACTR201310000635418 . Registered on 30 August 2013.

Infection with human immunodeficiency virus (HIV) is associated with neuroimaging alterations. However, little is known about the topological organization of whole-brain networks and the corresponding association with cognition. As such, we examined structural whole-brain white matter connectivity patterns and cognitive performance in 29 HIV+ young adults (mean age = 25.9) with limited or no HIV treatment history. HIV+ participants and demographically similar HIV− controls (n = 16) residing in South Africa underwent magnetic resonance imaging (MRI) and neuropsychological testing. Structural network models were constructed using diffusion MRI-based multifiber tractography and T1-weighted MRI-based regional gray matter segmentation. Global network measures included whole-brain structural integration, connection strength, and structural segregation. Cognition was measured using a neuropsychological global deficit score (GDS) as well as individual cognitive domains. Results revealed that HIV+ participants exhibited significant disruptions to whole-brain networks, characterized by weaker structural integration (characteristic path length and efficiency), connection strength, and structural segregation (clustering coefficient) than HIV− controls (p

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

Sexual trauma is highly prevalent among women living with HIV in South Africa, and there is a great need for psychotherapeutic interventions to address these concerns. Improving AIDS Care After Trauma (ImpACT) is a manualized intervention, based on stress and coping theories, that builds skills for coping with sexual trauma and HIV to promote long-term HIV care engagement. Using qualitative case study methodology, we report the case of Xoliswa, a 34-year-old woman with a complex history of sexual trauma and alcohol use who was diagnosed with HIV 1 year prior to enrollment in ImpACT. The interventionist, a lay counselor, worked with Xoliswa in a primary care clinic to address her concerns by exploring personal values, managing barriers to HIV care, and teaching active coping. Xoliswa's drinking reduced, symptoms of trauma and depression improved, and she maintained strong HIV care engagement. The interventionist experienced stress and emotional challenges in delivering ImpACT to Xoliswa and other highly traumatized women, and the interventionist's skill development and support received through training and supervision are briefly discussed. The case demonstrates the feasibility of ImpACT in a resource-limited setting and highlights themes and barriers in therapy, which can inform future interventions for women living with HIV. (PsycINFO Database Record (c) 2020 APA, all rights reserved).

HIV-associated neurocognitive impairments (HANI) are a spectrum of neurological disorders due to the effects of HIV-1 on the central nervous system (CNS). The HIV-1 subtypes; HIV-1 subtype B (HIV-1B) and HIV-1 subtype C (HIV-1C) are responsible for the highest prevalence of HANI and HIV infections respectively. The HIV transactivator of transcription (Tat) protein is a major contributor to the neuropathogenesis of HIV. The effects of the Tat protein on cells of the CNS is determined by the subtype-associated amino acid sequence variations. The extent to which the sequence variation between Tat-subtypes contribute to underlying mechanisms and neurological outcomes are not clear. In this review of the literature, we discuss how amino acid variations between HIV-1B Tat (Tat B) and HIV-1C Tat (Tat C) proteins contribute to the potential underlying neurobiological mechanisms of HANI. Tat-C is considered to be a more effective transactivator, whereas Tat-B may exert increased neurovirulence, including neuronal apoptosis, monocyte infiltration into the brain, (neuro)inflammation, oxidative stress and blood-brain barrier damage. These findings support the premise that Tat variants from different HIV-1 subtypes may direct neurovirulence and neurological outcomes in HANI.

OBJECTIVE We explored the prevalence of HIV infection in older rural South Africans and its associations, as well as the point prevalence of dementia and its associations with HIV and aging. DESIGN We utilized a cross-sectional analytic design. METHODS Using the brief Community Screening Instrument for Dementia together with a rapid HIV test, we conducted a home-based screening survey among 1150 older South Africans. We explored the prevalence of HIV and dementia, and their associations using descriptive statistics and logistic regression analysis. RESULTS The HIV prevalence was 4.78%. Overall, participants were on average 71.3 years old, with nearly 70% having no primary school education. HIV+ participants were significantly younger, more likely to be single and had lower BMI. The overall dementia prevalence was 11.04%. HIV+ participants had higher rates of dementia compared with HIV- participants (18.18 vs. 10.68%) but the difference was NS. In adjusted analysis, screened dementia was associated with older age, the presence of self-reported depression and HIV+ status. Participants were also more likely to self-report cognitive impairment if they were older, depressed and had objective evidence of dementia. CONCLUSION Infection with HIV in rural older South Africans is a prevalent problem, and together with older age, is a significant contributor to cognitive impairment. It is possible that HIV infection contributes to dementia on the basis of an acceleration of degeneration - because our HIV-infected participants were younger - AND an accentuation of aging - because of the higher rates of impairment for similar age groups.

South African women have disproportionately high rates of both sexual trauma and HIV. To understand how sexual trauma impacts HIV care engagement, we conducted in-depth qualitative interviews with 15 HIV-infected women with sexual trauma histories, recruited from a public clinic in Cape Town. Interviews explored trauma narratives, coping behaviors and care engagement, and transcripts were analyzed using a constant comparison method. Participants reported multiple and complex traumas across their lifetimes. Sexual trauma hindered HIV care engagement, especially immediately following HIV diagnosis, and there were indications that sexual trauma may interfere with future care engagement, via traumatic stress symptoms including avoidance. Disclosure of sexual trauma was limited; no women had disclosed to an HIV provider. Routine screening for sexual trauma in HIV care settings may help to identify individuals at risk of poor care engagement. Efficacious treatments are needed to address the psychological and behavioral sequelae of trauma.

Depression is prevalent among people living with HIV in South Africa and interferes with adherence to antiretroviral therapy. This study evaluated a nurse-delivered, cognitive behavioral therapy intervention for adherence and depression among antiretroviral therapy users with depression in South Africa ( n = 14). Primary outcomes were depression, antiretroviral therapy adherence, feasibility, and acceptability. Findings support robust improvements in mood through a 3-month follow up. Antiretroviral therapy adherence was maintained during the intervention period. Participant retention supports acceptability; however, modest provider fidelity despite intensive supervision warrants additional attention to feasibility. Future effectiveness research is needed to evaluate this nurse-delivered cognitive behavioral therapy intervention for adherence and depression in this context.