Predictors and consequences of HIV status disclosure to adolescents living with HIV in Eastern Cape, South Africa: a prospective cohort study

Introduction The World Health Organization recommends full disclosure of HIV-positive status to adolescents who acquired HIV perinatally (APHIV) by age 12. However, even among adolescents (aged 10–19) already on antiretroviral therapy (ART), disclosure rates are low. Caregivers often report the child being too young and fear of disclosure worsening adolescents’ mental health as reasons for non-disclosure. We aimed to identify the predictors of disclosure and the association of disclosure with adherence, viral suppression and mental health outcomes among adolescents in sub-Saharan Africa. Methods Analyses included three rounds (2014–2018) of data collected among a closed cohort of adolescents living with HIV in Eastern Cape, South Africa. We used logistic regression with respondent random-effects to identify factors associated with disclosure, and assess differences in ART adherence, viral suppression and mental health symptoms between adolescents by disclosure status. We also explored differences in the change in mental health symptoms and adherence between study rounds and disclosure groups with logistic regression. Results Eight hundred and thirteen APHIV were interviewed at baseline, of whom 769 (94.6%) and 729 (89.7%) were interviewed at the second and third rounds, respectively. The proportion aware of their HIV-positive status increased from 63.1% at the first round to 85.5% by the third round. Older age (adjusted odds ratio [aOR]: 1.27; 1.08–1.48) and living in an urban location (aOR: 2.85; 1.72–4.73) were associated with disclosure between interviews. There was no association between awareness of HIV-positive status and ART adherence, viral suppression or mental health symptoms among all APHIV interviewed. However, among APHIV not aware of their status at baseline, adherence decreased at the second round among those who were disclosed to (N = 131) and increased among those not disclosed to (N = 151) (interaction aOR: 0.39; 0.19–0.80). There was no significant difference in the change in mental health symptoms between study rounds and disclosure groups. Conclusions Awareness of HIV-positive status was not associated with higher rates of mental health symptoms, or lower rates of viral suppression among adolescents. Disclosure was not associated with worse mental health. These findings support the recommendation for timely disclosure to APHIV; however, adherence support post-disclosure is important

Adolescent Motherhood and HIV in South Africa: Examining Prevalence of Common Mental Disorder

The mental health of adolescents (10–19 years) remains an overlooked global health issue, particularly within the context of syndemic conditions such as HIV and pregnancy. Rates of pregnancy and HIV among adolescents within South Africa are some of the highest in the world. Experiencing pregnancy and living with HIV during adolescence have both been found to be associated with poor mental health within separate explorations. Yet, examinations of mental health among adolescents living with HIV who have experienced pregnancy/parenthood remain absent from the literature. As such, there exists no evidence-based policy or programming relating to mental health for this group. These analyses aim to identify the prevalence of probable common mental disorder among adolescent mothers and, among adolescents experiencing the syndemic of motherhood and HIV. Analyses utilise data from interviews undertaken with 723 female adolescents drawn from a prospective longitudinal cohort study of adolescents living with HIV (n = 1059) and a comparison group of adolescents without HIV (n = 467) undertaken within the Eastern Cape Province, South Africa. Detailed study questionnaires included validated and study specific measures relating to HIV, adolescent motherhood, and mental health. Four self-reported measures of mental health (depressive, anxiety, posttraumatic stress, and suicidality symptomology) were used to explore the concept of likely common mental disorder and mental health comorbidities (experiencing two or more common mental disorders concurrently). Chi-square tests (Fisher’s exact test, where appropriate) and Kruskal Wallis tests were used to assess differences in sample characteristics (inclusive of mental health status) according to HIV status and motherhood status. Logistic regression models were used to explore the cross-sectional associations between combined motherhood and HIV status and, likely common mental disorder/mental health comorbidities. 70.5% of participants were living with HIV and 15.2% were mothers. 8.4% were mothers living with HIV. A tenth (10.9%) of the sample were classified as reporting a probable common mental disorder and 2.8% as experiencing likely mental health comorbidities. Three core findings emerge: (1) poor mental health was elevated among adolescent mothers compared to never pregnant adolescents (measures of likely common mental disorder, mental health comorbidities, depressive, anxiety and suicidality symptoms), (2) prevalence of probable common mental disorder was highest among mothers living with HIV (23.0%) compared to other groups (Range:8.5–12.8%; Χ2 = 12.54, p = 0.006) and, (3) prevalence of probable mental health comorbidities was higher among mothers, regardless of HIV status (HIV & motherhood = 8.2%, No HIV & motherhood = 8.2%, Χ2 = 14.5, p = 0.002). Results identify higher mental health burden among adolescent mothers compared to never-pregnant adolescents, an increased prevalence of mental health burden among adolescent mothers living with HIV compared to other groups, and an elevated prevalence of mental health comorbidities among adolescent mothers irrespective of HIV status. These findings address a critical evidence gap, highlighting the commonality of mental health burden within the context of adolescent motherhood and HIV within South Africa as well as the urgent need for support and further research to ensure effective evidence-based programming is made available for this group. Existing antenatal, postnatal, and HIV care may provide an opportunity for mental health screening, monitoring, and referral

3D DOCUMENTATION AND VIRTUAL ARCHAEOLOGICAL RESTORATION OF MACEDONIAN TOMBS

Archaeology as a science is based on finding and displaying the remains of the past. In recent years, with the progress of technology, the science of archeology has been expanding and evolving. Three-dimensional digitization has become an integral part of the archiving, documentation and restoration effort of cultural heritage, offering important benefits in studies for reconstruction and restoration tasks of architectural creations, archaeological sites, historic monuments and objects of art in general. The three-dimensional models are now available for many applications. In this paper such 3D models of two prominent Macedonian tombs in Northern Greece were exploited for their virtual restoration. Virtual restoration of monuments is of special importance to archaeological research, as it provides the necessary tools to investigate alternative solutions to the serious issue of archaeological restoration. These solutions do not interfere with the real monument, thus respecting its value and the international conventions. Digital 3D models have begun to be more beneficial in a science such as archaeology as they offer easy access to both archaeological and geometric information to a wider audience as well as a high degree of interaction possibilities with the user

Locomotor hyperactivity in 14-3-3Zeta KO mice is associated with dopamine transporter dysfunction

Dopamine (DA) neurotransmission requires a complex series of enzymatic reactions that are tightly linked to catecholamine exocytosis and receptor interactions on pre- and postsynaptic neurons. Regulation of dopaminergic signalling is primarily achieved through reuptake of extracellular DA by the DA transporter (DAT) on presynaptic neurons. Aberrant regulation of DA signalling, and in particular hyperactivation, has been proposed as a key insult in the presentation of schizophrenia and related neuropsychiatric disorders. We recently identified 14-3-3ζ as an essential component of neurodevelopment and a central risk factor in the schizophrenia protein interaction network. Our analysis of 14-3-3ζ-deficient mice now shows that baseline hyperactivity of knockout (KO) mice is rescued by the antipsychotic drug clozapine. 14-3-3ζ KO mice displayed enhanced locomotor hyperactivity induced by the DA releaser amphetamine. Consistent with 14-3-3ζ having a role in DA signalling, we found increased levels of DA in the striatum of 14-3-3ζ KO mice. Although 14-3-3ζ is proposed to modulate activity of the rate-limiting DA biosynthesis enzyme, tyrosine hydroxylase (TH), we were unable to identify any differences in total TH levels, TH localization or TH activation in 14-3-3ζ KO mice. Rather, our analysis identified significantly reduced levels of DAT in the absence of notable differences in RNA or protein levels of DA receptors D1–D5. Providing insight into the mechanisms by which 14-3-3ζ controls DAT stability, we found a physical association between 14-3-3ζ and DAT by co-immunoprecipitation. Taken together, our results identify a novel role for 14-3-3ζ in DA neurotransmission and provide support to the hyperdopaminergic basis of pathologies associated with schizophrenia and related disorders.H Ramshaw, X Xu, EJ Jaehne, P McCarthy, Z Greenberg, E Saleh, B McClure, J Woodcock, S Kabbara, S Wiszniak, Ting-Yi Wang, C Parish, M van den Buuse, BT Baune, A Lopez and Q Schwar

‘Yummy or crummy?': the multisensory components of medicines-taking among HIV-positive youth

The global rollout of Antiretroviral Treatment (ART) has revealed an urgent need to understand the medicines-taking practices of HIV-positive adolescents. In the last decade, the literature on the social determinants of health has broadened the evidence-base on ART adherence. Interdisciplinary studies have expanded conceptions of medicines-taking beyond clinical or health systems frameworks, recognising the importance of socio-structural conditions and of patients’ beliefs and experiences. Participatory research techniques which foreground the perspectives of adolescents provide greater insights still into their adherence. This article explores the use of participatory methods within a broader study on the social determinants of ART adherence among HIV-positive adolescents in South Africa. We describe how participatory methods were incorporated into this study (n = 1,059 in the quantitative baseline). We focus on an exercise, ‘Yummy or crummy?’, that explored the multisensory dimensions of medicines-taking, including their colour, smell, shape, and delivery mechanism. We describe two principal findings: first, adolescents’ preference for greater understanding of the chemical workings of medicines, manifested in their preferences for colour, taste and shape of medicines; and second, the vital relationship between sensory preferences and the social imperatives of discretion and confidentiality regarding HIV-status

Medical Pluralism Predicts Non-ART Use among Parents in Need of ART: A Community Survey in KwaZulu-Natal, South Africa

Despite documented common use of traditional healers and efforts to scale up antiretroviral treatment (ART) in sub-Saharan Africa, evidence on whether medical pluralism predicts ART use is inconclusive and restricted to clinic settings. This study quantitatively assesses whether medical pluralism predicts ART use among parents in need of ART in South Africa. 2,477 parents or primary caregivers of children were interviewed in HIV-endemic communities of KwaZulu-Natal. Analysis used multiple logistic regression on a subsample of 435 respondents in need of ART, who reported either medical pluralism (24.6 %) or exclusive public healthcare use (75.4 %). Of 435 parents needing ART, 60.7 % reported ART use. Medical pluralism emerged as a persistent negative predictor of ART utilization among those needing it (AOR [95 % CI] = .556 [.344 - .899], p = .017). Use of traditional healthcare services by those who need ART may act as a barrier to treatment access. Effective intersectoral collaboration at community level is urgently needed

NUDT2 Disruption Elevates Diadenosine Tetraphosphate (Ap4A) and Down-Regulates Immune Response and Cancer Promotion Genes.

Regulation of gene expression is one of several roles proposed for the stress-induced nucleotide diadenosine tetraphosphate (Ap4A). We have examined this directly by a comparative RNA-Seq analysis of KBM-7 chronic myelogenous leukemia cells and KBM-7 cells in which the NUDT2 Ap4A hydrolase gene had been disrupted (NuKO cells), causing a 175-fold increase in intracellular Ap4A. 6,288 differentially expressed genes were identified with P < 0.05. Of these, 980 were up-regulated and 705 down-regulated in NuKO cells with a fold-change ≥ 2. Ingenuity® Pathway Analysis (IPA®) was used to assign these genes to known canonical pathways and functional networks. Pathways associated with interferon responses, pattern recognition receptors and inflammation scored highly in the down-regulated set of genes while functions associated with MHC class II antigens were prominent among the up-regulated genes, which otherwise showed little organization into major functional gene sets. Tryptophan catabolism was also strongly down-regulated as were numerous genes known to be involved in tumor promotion in other systems, with roles in the epithelial-mesenchymal transition, proliferation, invasion and metastasis. Conversely, some pro-apoptotic genes were up-regulated. Major upstream factors predicted by IPA® for gene down-regulation included NFκB, STAT1/2, IRF3/4 and SP1 but no major factors controlling gene up-regulation were identified. Potential mechanisms for gene regulation mediated by Ap4A and/or NUDT2 disruption include binding of Ap4A to the HINT1 co-repressor, autocrine activation of purinoceptors by Ap4A, chromatin remodeling, effects of NUDT2 loss on transcript stability, and inhibition of ATP-dependent regulatory factors such as protein kinases by Ap4A. Existing evidence favors the last of these as the most probable mechanism. Regardless, our results suggest that the NUDT2 protein could be a novel cancer chemotherapeutic target, with its inhibition potentially exerting strong anti-tumor effects via multiple pathways involving metastasis, invasion, immunosuppression and apoptosis