The aim of the study was to delineate, discuss and analyze major challenges that affect children between the ages of 13 and 18 in the Nyandeni area due to HIV/AIDS. This exploratory study was also performed to identify the categories of children made vulnerable by HIV/AIDS. One of the objectives was to provide a descriptive and analytical interpretation of the day to day experiences of children affected by HIV/AIDS. In shaping the sample size, 50 respondents were selected from three wards (2, 3 and 16) of the Nyandeni Local Municipality in the Nyandeni area in the Eastern Cape.The researcher made use of the interview technique to collect data from the respondents. In analysing data, the researcher made use of the quantitative and qualitative measures.The outcome of the study points out that HIV/AIDS is the major threat to children and that there is a significant increase in number of child headed families as a result of HIV/AIDS.

A thesis submitted to the Faculty of Humanities (University of the Witwatersrand, Johannesburg), in fulfillment of the requirements for the degree of Doctor of Philosophy by thesis in the field of Psychology. University of the Witwatersrand, Johannesburg, 2015 / Conventional psychometric measures, such as the IQ score, have significant limitations in addressing the assessment needs of linguistically and culturally diverse communities. In response, working memory assessment has been identified as a promising alternative to these constraints. It is a better predictor of scholastic success than IQ, and is essential in the acquisition of fundamental literacy and numeracy concepts in school beginners. While there is a lot of theoretical and empirical support for working memory performance in typically developing populations, less is known about its functioning in the context of atypical development; particularly in children who are infected with, or exposed to HIV in utero. This study compared the working memory (AWMA) and general neuropsychological functioning (NEPSY-II) of 273 South African school beginners (6-8 years). The sample consisted of both HIV-infected (n = 95), and HIV-exposed (n = 86) children, as well as an uninfected, unexposed typically developing control group (n = 92). Significant differences were found between the three groups on measures of working memory and general neurocognitive functioning, where the processing component of working memory appeared to be particularly impaired in the two HIV-affected atypical groups. A within-group analysis of the relative strengths and weaknesses of each of the three groups showed that both storage and processing skills in the verbal domain appeared to be general weaknesses, while visuospatial working memory was a relative strength. The former is believed to be influenced by issues of linguistic test bias in the multilingual sample, while the latter is posited to be a consequence of this very multilingualism, which affords these children an executive functioning advantage. The two HIV-affected samples also showed significant deviations in the structure of their working memory when compared to the typically developing control group. However, within-group structural comparisons of a number of working memory models showed that the four factor model comprising separate components of the verbal and visuospatial simple and processing components of working memory was still favoured, even in conditions of atypical development. The study contributes to the growing body of working memory research by presenting the working memory profiles of HIV-infected and HIV-exposed, uninfected children. It also assists in identifying HIV-exposed, uninfected children as a vulnerable and under-researched clinical group which could benefit from further intervention, as well as foregrounding working memory as a less biased alternative in the assessment of paediatric cognitive functioning. / MT2016

Abstract Powerful and diverse countertransference reactions in psychotherapy group work with HIV positive children can be understood to indicate a site of mourning in the life of the group. Data from six interviews with five individuals conducting broadly psychodynamic group work with HIV positive children was analysed according to Thematic Content Analysis. The countertransference responses of the participants are understood as communications of the group unconscious, as well as expressions of the participants’ own unresolved unconscious difficulties. Working with HIV positive children confronts the participants with mortality and activates their earliest losses. A sense of strangeness and displacement, denial, idealisation, feelings of persecution, fantasies of rescue, rage, despair and hopelessness emerge in the countertransference and can be considered indicative of defences against mourning. These defences alternate with an engagement with the work of mourning and are represented in the countertransference as the relinquishment of omnipotence, awareness of fusion, containment, the recognition of the child’s resilience and uniqueness and the promotion of the child’s autonomy and expression. These findings may facilitate containment for therapists working with HIV positive children by offering an explanation of powerful and diverse countertransference responses as indicating a site of mourning, thereby promoting increased receptivity to unexpressed grief in therapy with these children.

<p><font face="Times-Roman"> <p align="left">According to the findings of this study, childcare workers caring for HIV-positive children working in a residential care setting, have similar experiences and challenges to nurses, community-based caregivers and primary caregivers, such as coping with loss and contagion fear. Nonetheless, caring for HIV-positive children poses unique challenges for the caregiver, calling for flexibility and situation-dependent coping strategies.</p> </font></p>

<p><font face="Times-Roman"> <p align="left">According to the findings of this study, childcare workers caring for HIV-positive children working in a residential care setting, have similar experiences and challenges to nurses, community-based caregivers and primary caregivers, such as coping with loss and contagion fear. Nonetheless, caring for HIV-positive children poses unique challenges for the caregiver, calling for flexibility and situation-dependent coping strategies.</p> </font></p>

The 2013 case report of the “Mississippi baby,” who was started on antiretroviral therapy (ART) within 30 hours of life and maintained off-treatment remission for 27 months before HIV was once again detectable, generated renewed interest in the benefits of early ART, as well as optimism that HIV remission is a possibility if ART is started very early. The overarching goal of this dissertation was to advance our understanding of the relationship between early ART and three outcomes – the possibility of HIV remission, improved viral outcomes, and epigenetic changes – in HIV-infected infants and young children. First, a systematic review was conducted to assess current published data in support of the possibility of very early ART leading to HIV remission in infants. Evidence from this review suggested that although early ART does appear to be associated with better sustained virological control and smaller reservoir size, there are limited data at this time to support a strong link between early ART and HIV remission. Second, the association between age at ART initiation and virologic outcomes after ART initiation was empirically assessed using data from five cohorts of HIV-infected infants and young children initiating ART before 2 years of age in Johannesburg, South Africa. In three cohorts, there was no consistent evidence of an association between early ART initiation and rates of initial viral suppression. However, there was a consistent benefit of early treatment initiation on long-term viral control in two cohorts. Finally, an epigenome-wide association study was conducted to identify differential DNA methylation patterns between ART-treated HIV-infected and HIV-uninfected South African children. A total of 1,309 differentially methylated CpG sites associated with HIV status were selected (FDR q-value <0.05; |Δβ| >0.05), after adjustment for age, sex, and cell type proportions. In addition, 315 differentially methylated regions associated with HIV status were selected (Stouffer p-value <0.05, maximum |Δβ| change in the region >0.05, and containing at least two or more CpG sites). Many of the genes identified in both the site and region approaches were located in the major histocompatibility complex (MHC) region on chromosome 6, a region that plays an important role in the adaptive immune system. This novel study provided evidence of an association between perinatally-acquired HIV infection and a large number of changes in DNA methylation in school-aged children on ART, and highlighted potential new lines of investigation into the biologic pathways influenced by HIV and its treatment. Overall, this dissertation increased our understanding of the timing of early ART initiation in HIV-infected infants and addressed gaps in our knowledge relevant to outcomes associated with early ART initiation. As public health practice continues to move towards infant diagnosis of HIV at birth and early life initiation of ART, these findings help to inform future research that will guide HIV care in infants.

The manifestation of HIV-1 infection is different in children and adults. Most of the children who acquire HIV perinatally progress to disease within the first two years of life, while adults can remain asymptomatic for up to ten years. However, a small minority group of children can control the virus for years in the absence of antiretroviral therapy. We characterized CD8+ T cell responses critical for the containment of HIV infection in a cohort of infants HIV infected from birth using IFN- γ ELISPOT, multicolour flow cytometry and viral sequencing of the Gag protein. We investigated whether the age at the time of infection, specificity and functionality of the generated responses, genetic make up and the maternal immune responses to HIV, influenced disease progression in the child. We found that the majority of in-utero infected infants mounted CD8+ T cell responses from the first days of life. In contrast to chronically infected children or adults, the specificity of the initial response in acutely infected infants was directed towards Env and Rev proteins and CD4+ T cell responses were minimal during the first 6 months of life. Slow progression to disease was associated with possession of one of the protective HLA-B alleles by either the mother or the child (P=0.007) and targeting of Gag epitopes presented by the protective HLA-B alleles. Mothers who expressed protective alleles but whose children did not possess these alleles, transmitted less fit viruses that benefited their children. Furthermore, slow progressor children had more polyfunctional CD8+ T cell responses in early infection when compared to rapid progressors (P=0.05). The ability of infants to induce CD8+ T cell responses early in life is encouraging for vaccine interventions. The differences in the specificity of the initial responses between adults and children, insufficient priming of these responses as a result of minimal CD4+ T cell help during infancy and possession of non-protective HLA alleles shared between mother and child, may explain the rapid disease progression generally noted in most infants. However, slow progression to disease in the minority group of children may be attributed to functional capacity of the CD8+ T cells generated by the child, mediation by protective HLA alleles, acquisition of low fitness viruses from the mother or de novo attenuation of the virus by the child’s own immune responses. / Thesis (Ph.D.)-University of KwaZulu-Natal, Durban, 2011.

BACKGROUND Sub-Saharan Africa has the highest number of HIV-infected individuals and limited treatment programs. The use of Highly Active Antiretroviral Therapy (HAART) has resulted in a considerable decrease in morbidity and mortality among HIV-infected individuals. Long-term use of HAART has several limitations relating to cost, drug toxicity and adherence. Structured Treatment Interruption (STI) has been proposed as a therapeutic approach which limits the exposure to continuous HAART, but retains the benefits thereof. The role of HIV-specific Tcell responses in the control of viraemia has not been well studied in children and it is not clear when these responses become detectable or whether they are associated with improved viral control. Furthermore, antiretroviral drug resistance is well documented in adults infected with HIV-1 clade B virus but comparable information is lacking for chronic paediatric clade C virus infection. This pilot study focused on a chronic HIV-infected paediatric cohort from Durban, South Africa, to assess the immunologic and virologic responses in perinatal HIVinfected children undergoing STI. METHODS Thirty chronic HIV-infected treatment naïve children were enrolled and randomised into either the treatment interruption or continuous treatment group. Longitudinal measurements of viral loads and CD4 percentages were done at scheduled intervals. Peripheral blood mononuclear cells (PBMCs) were screened for cytotoxic T-lymphocyte (CTL) gamma interferon (IFN-?) enzyme-linked immunospot (ELISpot) assay responses using 410 peptides which spanned the entire HIV-1 clade C proteome. Intracellular cytokine staining (ICS) was done to distinguish between IFN-? Gag-specific T-helper and cytotoxic T cell responses. Pre-HAART drug resistance mutations testing and HLA typing were done for all children. RESULTS There was a significant increase in the median CD4 percentage after HAART was introduced. Six children randomized to the STI arm did not undergo treatment interruption because their viral loads remained detectable at the time of scheduled interruption. Most HIV proteins were targeted in this paediatric cohort. Gag was the most frequently targeted HIV-1 protein (93.1%). In both treatment groups, there were broadening of T-cell responses, however, the magnitude of T-cell responses decreased over time on HAART. Drug-resistant mutations were detectable in 4/29 children before initiation of HAART. CONCLUSION In this pilot study, the HIV-1-specific CD8+ and CD4+ T-cell responses were detected before and during HAART. Although the treatment interruption period was short, there were no adverse outcomes in either the continuous or treatment interruption groups in terms of death or other clinical outcomes. This study suggests that it is important to continue to explore alternative treatment strategies in order to reduce cost and toxicity as well as to enhance adherence. / Thesis (M.Med.Sc.)-University of KwaZulu-Natal, Durban, 2010.

Thesis (PhD)--Stellenbosch University, 2013. / Bibliography / ENGLISH ABSTRACT: Introduction: Lipoatrophy is a common adverse effect of stavudine and this effect is strongly dose-dependent. Stavudine remains the most commonly used paediatric antiretroviral drug in sub-Saharan Africa, yet when the current study began in 2009, the prevalence and severity of lipoatrophy in children on antiretroviral therapy in sub-Saharan Africa had never been studied. The development of lipoatrophy may have serious and far-reaching consequences for patients and their families. The off-label stavudine dosing method, prescribed to children whose caregivers do not have access to a refrigerator, in which the contents of an adult capsule is mixed into tap water, has potential for over-dosing or under-dosing. In addition, children on stavudine continue to be exposed to a disproportionately high dose out of line with the reduced adult dose. Aims: 1. a) To investigate the prevalence and risk factors for lipoatrophy in HIV-infected children in Southern Africa b) To identify a simple anthropometric screening tool to detect early lipoatrophy in children 2. To validate the off-label stavudine dosing method prescribed to children whose caregivers do not have access to a refrigerator, with a view to reducing the recommended dose and thereby the side-effects. Methods: 1. a) We recruited pre-pubertal children on antiretroviral therapy from a family HIV clinic in our facility. Lipoatrophy was identified by two experienced paediatric HIV clinicians using a standardized grading scale. A dietician performed dietary assessment and anthropometric measurements. Previous antiretroviral exposures were recorded. A subset of recruits received Dual-Energy X-ray Absorbtiometry scanning. b) Anthropometric measurements in children with and without lipoatrophy were compared using multivariate linear regression adjusting for age and gender. The most discerning anthropometric variables underwent Receiver Operating Characteristic curve analysis to identify the most appropriate diagnostic cut-off. 2. a) Accuracy of the standard off-label stavudine dosing method was investigated using high-performance liquid chromatography to recover active drug from solutions made up using the prescribed method. This was compared to the stated drug content of the capsules. b) Bioavailability was investigated by performing a randomized crossover pharmacokinetic study wherein healthy HIV-seronegative adult volunteers received one of two generic stavudine capsule formulations, either intact or mixed in water using the prescribed method. Plasma stavudine concentrations were assayed by liquid chromatography tandem mass spectrometry. Results: 1. a) Prevalence of lipoatrophy was 36%, and incidence was 12% per person-year. Adjusted odds ratio for developing lipoatrophy was 1.9 (CI: 1.3–2.9) for each additional year of accumulated exposure to standard-dose stavudine. b) Baseline biceps skin-fold thickness correlated well with maximum lipoatrophy grading score at any site, giving a partial correlation coefficient of 0.33 (p=0.0006), and a receiver operating characteristic area-under-curve value of 0.75 (CI: 0.64 – 0.84). Biceps skin-fold thickness <5mm at baseline had a sensitivity of 89% (CI: 67–100%) and a negative predictive value of 97% (CI: 91–100%) for predicting which children would go on to develop lipoatrophy by 15 month follow-up. Specificity was 60% (CI: 46–75%) and positive predictive value was 32% (CI: 14–50%). 2. a) Recovery of active drug from solution was 97.1%, 97.4% and 93.8% for the proprietary and two generic formulations respectively. b) Pharmacokinetic parameters of the off-label dosing method were well within the target range of intact capsule dosing for both generics. Conclusions: 1. a) The prevalence and incidence of lipoatrophy in pre-pubertal children on antiretroviral therapy in South Africa is high. Cumulative exposure to standard-dose stavudine was the greatest risk factor for lipoatrophy. b) Biceps skin-fold thickness provided reasonable sensitivity and specificity to detect and predict lipoatrophy in pre-pubertal children on antiretroviral therapy. 2. The off-label dosing method for stavudine prescribed to children whose caregivers do not have access to a refrigerator is reasonably accurate and is bioequivalent to intact capsule administration. / AFRIKAANSE OPSOMMING: Inleiding: Lipoatrofie is 'n algemene nadelige uitwerking van stavudien en hierdie effek is sterk dosis-afhanklike. Stavudien bly die mees algemeen gebruikte paediatriese antiretrovirale medikasie in sub-Sahara Afrika, maar toe ons studie begin het, was lipoatrofie in kinders op antiretrovirale terapie in sub-Sahara Afrika nog nooit voorheen bestudeer nie. Die ontwikkeling van lipoatrofie kan ernstige en verreikende gevolge vir die pasiënt en hul familie hê. Die af-etiket stavudien dosering metode voorgeskryf aan kinders wie se versorgers nie toegang tot 'n yskas het nie het 'n aansienlike potensiäal vir oor-dosering of onder-dosering. Daarbenewens, is kinders op stavudien blootgestel aan 'n disproporsionele hoë dosis uit-pas met die verminderde volwasse dosis. Doelwitte: 1. a) Om ondersoek in te stel na die voorkoms en risiko faktore vir lipoatrofie in MIV-geïnfekteerde kinders in Suid Afrika b) Om 'n eenvoudige antropometriese instrument te identifiseer om vroeë lipoatrofie op te spoor in kinders op antiretrovirale medikasie 2. Om die af-etiket stavudien dosering metode wat voorgeskryf is aan kinders wie se versorgers nie toegang tot 'n yskas het nie te valideer, met 'n oog op die vermindering van die aanbevole dosis Metodes: 1. a) Ons het 'n groep van onder-puberteitsjarige kinders op antiretrovirale terapie gewerf uit 'n familie MIV kliniek in ons fasiliteit. Lipoatrofie is geïdentifiseer deur twee ervare MIV pediaters deur gebruik van 'n gestandaardiseerde gradering skaal. 'n Diëetkundige het diëet assessering en antropometriese metings uitgevoer. Vorige antiretrovirale blootstellings is aangeteken. In 'n subset was Dual-energie X-straal Absorbtiometry (DXA) skandering uitgevoer. b) Antropometriese metings in kinders met en sonder lipoatrofie is vergelyk met behulp van meerveranderlike lineêre regressie aangepas vir ouderdom en geslag. Die mees kieskeurige antropometriese veranderlikes het Receiver Operating Curve analise ondergaan om die mees geskikte diagnostiese afgesnypunt te identifiseer. 2. a) Akkuraatheid is ondersoek deur gebruik te maak van hoë werkverrigting vloeistofchromatografie om aktiewe medikasie vanuit oplossings te herstel, wat gemeng is soos aangedui deur die voorgeskrewe af-etiket dosering metode. b) Biobeskikbaarheid is ondersoek deur die uitvoering van 'n ewekansige oorgesteekde farmakokinetiese studie waarin gesonde MIV- negatiewe volwasse vrywilligers een van twee generiese stavudien kapsule formulerings ontvang het, óf heel of in water gemeng soos aangedui deur die voorgeskrewe af-etiket dosering metode. Plasma stavudien konsentrasies is gemeet deur vloeistofchromatografie tandem massaspektrometrie. Uitslae: 1. a) Voorkoms van lipoatrofie was 36%, en insidensie was 12% per persoon-jaar. Aangepaste Odds ratio vir die ontwikkeling van lipoatrofie was 1,9 (CI: 1,3-2,9) vir elke addisionele jaar van opgehoopte blootstelling aan standaard dosis stavudien. b) Biceps vel-vou dikte <5mm het 'n sensitiwiteit van 89% (CI: 83-96%) en 'n negatiewe voorspellende waarde van 90% (CI: 84-96%) vir die opsporing en voorspelling van lipoatrofie. 2. a) Herwinning van aktiewe medikasie uit oplossings was 97,1%, 97,4% en 93,8% vir die oorspronklike en twee generiese formulerings onderskeidelik. b) Farmakokinetiese parameters van die af-etiket dosering metode was wel binne die teikenband van ongeskonde kapsule dosering vir beide generiese formulerings. Gevolgtrekkings: 1. a) Die voorkoms van lipoatrofie in onder-puberteitsjarige kinders op antiretrovirale terapie in Suid-Afrika is hoog. Die bedrag stavudien waaraan kinders blootgestel is moet hersien word. Die standaard stavudien dosis vir kinders moet herge-evalueer word. b) Biceps vel-vou dikte het redelike goeie sensitiwiteit en spesifisiteit om lipoatrofie op te spoor en te voorspel. 2. Die af-etiket dosering metode vir stavudien voorgeskryf aan kinders wie se versorgers nie toegang tot 'n yskas het nie is redelik akkuraat en is bio-ekwivalent aan ongeskonde kapsule administrasie.

Source: Masters Abstracts International, Volume: 46-05, page: 2670. Adviser: Palmer Beasley. Includes bibliographical references.