Sleep health is a good indicator to a person’s overall health status and general well-being. Proper sleep is one of the most important factors to healthy immunity. Protecting and restoring sleep quality are vital to well-being. Problems such as insomnia, obstructive sleep apnea, fatigue, and hypersomnia can all affect the quality of a person’s sleep. There are over 35 million people living with HIV/AIDS infection in the world. These people suffer from many of the same sleep problems and often have more frequent or more severe symptoms. It is not clear if this is from the disease, the medications, or some other factors. HIV-positive persons need good sleep quality to maintain their immune system and help keep the disease from progressing. Treatments for sleep disorders in HIV need to be considered carefully. Interventions should start with the least invasive progress to more invasive therapies and be monitored carefully.

Dissertation submitted to the FacuIty ofArts for the Masters degree in Clinical Psychology in the Department of Psychology at the University of Zululand, 1997. / This report documents a qualitative description of the special needs expressed by persons with late stage AIDS in the Richards Bay area. A phenomenological research design and methods were employed to impose rigour on this event. Once the needs of persons with late stage AIDS had been made explicit, these were collated with services rendered or planned through state and welfare structures in the Richards Bay area in an effort to identify salient unfulfilled needs that could be addressed through the establishment of an AIDS Care Centre. This provided important cues regarding the types of services and facilities required at the AIDS Care Centre. Additionally the unstructured interviews employed in the research provided the interviewees with an opportunity to suggest a format of care at the AIDS Care Centre that would be most suitable for them.

A DISSERTATION SUBMITTED IN PARTIAL FULFILMENT OF THE REQUIREMENT FOR THE DEGREE: MASTERS IN EDUCATIONAL PSYCHOLOGY IN THE DEPARTMENT OF EDUCATIONAL PSYCHOLOGY AND SPECIAL EDUCATION UNIVERSITY OF ZULULAND, 2007 / The purpose of this study was to investigate teachers' attitudes towards the HIV/AIDS programmes, which the government had supplied to the schools a few years ago. This concern was triggered by the researcher's own experience in dealing with these teachers whom he found to be protective, passionate about the disabled children and often treated them as separate from those of the regular school system. To collect data, a questionnaire was administered to teachers at all the three special schools in the education district. In the questionnaire, items sought to establish whether or not teachers ever received training in HTV7AIDS prevention programmes as well as their knowledge about how HIV was transmitted. Findings showed that these teachers were not trained in HTV/AIDS prevention programmes but there was a strong positive correlation between their knowledge about HIV/AIDS and positive attitude. It was also revealed that they were not involved in any HTV/AIDS prevention programme at their schools. Many of them were not even aware of the material said to have been provided by the Department of Education to be used in raising awareness programmes.

Purpose: To compare the presenting symptoms and the outcomes of root canal therapy between HIV positive and HIV negative endodontic patients over a 6-12 month period. Methods: Fifty-nine HIV negative and 46 HIV positive patients presented for endodontic treatment. Signs and symptoms were noted and compared for both groups of patients, together with demographic data and CD4 counts for the HIV positive patients. Endodontic procedures were evaluated after an 18-month period. Endodontic treatment was assessed using clinical factors (palpation, percussion, sensitivity to hot and cold, swellings, excessive bleeding), and radiographic factors (periapical radiolucency, root resorption, periodontal ligament space). Results: There was no statistically significant difference in the preoperative presenting symptoms of endodontic infections/conditions between HIV positive and HIV negative patients. The prevalence of radiographic caries in the presenting teeth was only 24% in the HIV positive patients compared with 95% in the HIV negative patients. For the HIV positive patients, the treatment time required to resolution of the endodontic infection was nearly twice (113 minutes) that of the HIV negative patients (52 minutes). Amongst the HIV positive patients still experiencing symptoms at 18 months, pain was more severe in those patients with lower CD4 counts (significance at the 90% level of confidence). Conclusion: Within the limitations of this study the following conclusions emerge: 1. Although the success rate was lower over the period of this study in HIV positive patients, the rate is sufficiently high to warrant treatment. 2. Patients who are HIV positive may present with more severe symptoms and during treatment more bleeding may be expected. 3. In keeping with best practice for immuno-compromised patients, it would be advantageous to put HIV positive patients on antibiotic cover during treatment. 4. The process of anachoresis may explain the high incidence of endodontic infections in teeth with no history of trauma or caries in the HIV positive group.

A thesis submitted to the Faculty of Health Sciences, University of the Witwatersrand, Johannesburg, in fulfillment of the requirements for the degree of Doctor of Philosophy Johannesburg, South Africa 2016 / Introduction: Neonatal infections contribute to 25% of all neonatal deaths, which account for approximately 44% of all under-5 childhood deaths globally. Pathogens responsible for sepsis in neonates and young infants can be acquired vertically prior to or during labour, or from the environment (community or hospital). This project evaluated the burden and aetiology of sepsis in neonates and young infants (≤90 days), and explored this association to in-utero exposure to human immunodeficiency virus. The study also included a specific focus on the epidemiology of invasive Group B Streptococcal disease in young infants. Additionally, we assessed the efficacy of intrapartum chlorhexidine vaginal washes for: (i) preventing early-onset neonatal sepsis; and (ii) vertical transmission of potentially pathogenic bacteria to the newborns. Furthermore, we evaluated risk factors for poor outcomes due to neonatal sepsis. Materials and methods: (i) A bacterial surveillance system was established at Chris Hani Baragwanath Academic Hospital (CHBAH) from 2004-2008 to identify young infants with bacterial sepsis hospitalised in the neonatal and paediatric wards. Medical and microbiological records were utilised to obtain clinical and laboratory data. Maternal HIV results were obtained from antenatal testing records or admission records. (ii) A blinded, randomised, placebo-controlled trial of 0.5% chlorhexidine maternal vaginal intrapartum wipes and newborn skin wipes was conducted at CHBAH between 2004 and 2007. Consented, eligible participants were randomised during labour to receive either chlorhexidine vaginal wipes or water external genitalia wipes. Newborns received either chlorhexidine full-body wipes (intervention arm) or foot wipes (control arm). Maternal and infant participants were followed up for admissions during the first month after delivery/ birth. A subset of 5144 maternal participants had an intrapartum lower vaginal swab collected, and skin swabs were collected from their newborns to assess colonisation with potentially pathogenic bacteria (Group B streptococcus, Escherichia coli and Klebsiella pneumoniae). Results: Group B streptococcus (GBS) was the most commonly isolated bacterial pathogen, causing 35.2% of culture-confirmed sepsis in infants ≤90 days, 41.6% of early-onset disease (EOD, 0-6 days), 40.5% of late-onset neonatal disease (LOD, 7-27 days) and 18.7% of young-infant community-acquired disease (YI-CAD, 28-90 days). Staphylococcus aureus (S. aureus), Escherichia coli (E. coli) and Klebsiella pneumoniae (K. pneumoniae) contribute 16.2%, 12.2% and 3.4% to sepsis in young infants. Overall, incidence (per 1000 live births) of invasive GBS disease was 2.72 (95% confidence interval [95% CI]: 2.46 to 3.01), including an incidence of 1.50 and 1.22, respectively, in infants 0-6 days and 7-90 days of age. HIV-exposed infants were at greater risk of EOD (Relative risk [RR]: 1.69; 95% CI: 1.28-2.24) and LOD (RR= 3.18; 95% CI: 2.34-4.36) than HIV-unexposed infants. GBS serotypes Ia and III caused 84.0% of invasive GBS disease in young infants. Intrapartum chlorhexidine interventional wipes was not efficacious in prevention of any of: (i) vertical transmission of pathogenic bacteria (54% vs. 55%; efficacy -0.05, 95% CI: -9.5 to 7.9) to the newborns; (ii) sepsis in first 3 days of life (3% vs. 4%; p=0.65,); (iii) sepsis in the later neonatal period (both <1%; p=0.4444); or (iv) maternal puerperal sepsis(both <1%; p=0.56). Conclusion: GBS, S. aureus, E. coli and K. pneumoniae are the most commonly isolated bacterial pathogens in neonates and infants ≤90 days old. HIV-exposed infants are at greater risk of GBS sepsis. Intrapartum chlorhexidine intervention was not efficacious in reducing vertical transmission of pathogenic bacteria, neonatal or maternal sepsis. Alternative interventions to prevent sepsis in young infants, including maternal immunisation, need to be investigated in setting such as ours where there is a high prevalence of maternal HIV infection. / MT2017

MSc (Med), Faculty of Health Sciences, University of the Witwatersrand, 2006

We hypothesized that higher levels of felt or enacted stigma would be related to poorer medication adherence, and that this relationship would be mediated by indicators of HIVrelated quality of life (HIV-QOL) including medication concerns, disclosure concerns, and perceptions of health provider treatment. 98 people living with HIV (PLWH) who were all currently taking ART medications completed an online survey that included measures of demographics, HIV-related stigma, medication, and HIV-QOL. Results suggested that concerns about medication accounted for the relationship between enacted HIV-related stigma and medication adherence.

Circulating monocytes have the capacity to mature into either macrophages or dendritic cells in tissue, both of which play important roles in the induction and effector phase of immune response. In TB, the macrophages are the central player in the host-bacteria interaction as the main mycobacterial reservoir. In HIV disease, monocyte lineage cells are one of the two main cell types (along with CD4+ T-cells) in sustaining intracellular HIV infection. Monocytes are heterogeneous population with three functionally distinct subsets namely classical, intermediate and non-classical monocytes. The three subsets exist in a continuum, and have a certain plasticity or flexibility to develop into multiple roles depending on the local and tissue environment. In the current study we sought to evaluate the frequencies of these three subsets in participants with TB, HIV and TB/HIV co-infection. While previous studies had shown that the intermediate and non-classical monocyte subsets were elevated relative to classical monocytes, very little had been done in these disease groups regarding more comprehensive characterization of these subsets. In particular, we wished to quantitate the expression of multiple sets of cell surface and intracellular molecules of high relevance using multi-parameter flow cytometry from a functional point of view. In publication I, we evaluated Toll-like receptors (TLRs) expression in each of the study cohorts. TLRs are vital pattern recognition receptors by monocyte lineage cells and signal the induction of crucial functions. We focused on three such TLRs (TLR2, TLR4 and TLR9) which have been shown to be involved in many monocyte lineage cell interactions with mycobacterial and HIV infections. We observed enhanced expression of TLR2 and TLR4, but not TLR9 in TB and HIV. TLR4 was particularly high in patients with TB, but also in HIV. We observed comparable increase of TLR4 irrespective of monocyte subset. However, TLR2 expression exhibited a different pattern. Levels among the most prominent classical monocyte subsets were identical in all four cohorts, healthy controls (HC), HIV, TB, and TB/HIV co-infection. In contrast, TLR2 expression was significantly elevated in both participants with HIV and TB, but not with participants with TB/HIV co-infection in the intermediate monocyte subset. We also observed correlations between TLRs and plasma cytokines that were disease and TLR specific. In publication II, we observed elevated chemokine receptors (CRs) expression which above healthy controls and exhibit a pattern of disease preference. Thus, CCR2 and CX3CR1 were the highest in participants with TB, followed by HIV and TB/HIV co-infection, whereas CCR4 and CCR5 were highest in participants with HIV, and less elevated in TB. CCR2 and CX3CR1 are critical for migration of monocytes to sites of TB infection, as determined by murine models. CCR4 and especially CCR5 have been implicated in migration of cells to distant organs but more as co-receptors for HIV infection. Thus, the observed pattern of CRs expression in these monocytes in different disease states would predict greater availability of these cells or their receptors for interaction with either TB or HIV organisms. From the perspective of the pathogen this would lead to enhanced “substrate”, whereas from the perspective of the host, this could lead to greater immune potential. As a final point, we also observed that the pattern of disease association of CRs was independent of the monocyte subset. In publication III, we explored the expression of Programmed cell death-ligand 1 (PDL1) on the three monocyte subsets. Like many of the other molecules we have addressed in this thesis, PDL1 expression was enhanced in participants with HIV, TB, and TB/HIV co-infection. Among participants with HIV, PDL1 was correlated with HIV-1 viral load. The enhanced expression was apparent in all three subsets, but it was particularly prominent in the intermediate monocyte subset. Moreover, PDL1 expression was the highest in participants with TB/HIV co-infection. The implications behind these observations is that the subset thought to have the greatest potential for T cell antigen presentation had the highest levels of the T cell down-regulatory PDL1 molecule in the cohort of patients particularly participants with TB/HIV co-infection. Participants with TB/HIV co-infection have the greatest potential to be immuno-compromised and as a result the very need for enhanced not depressed APCs function. In addition, we also observed the PDL1 levels were correlated with multiple plasma, mostly pro-inflammatory,cytokines. We analyzed cytokine mRNA levels of total monocytes to address the source of the cytokines but mRNA levels did correlate with neither plasma cytokine nor PDL1 levels. Considering all the phenotype analysis in each of the three studies together we could see two patterns emerging. In one scenario,surface molecules expression patterns were disease specific but independent of monocyte subset expression. In other words, whatever the underlying mechanism(s) involved in their regulation, those mechanisms apparently acted similarly in all three subsets. In another scenario, expression of surface molecules showed disease specific patterns, but molecules were particularly enhanced in the intermediate monocyte subsets. These findings imply that there exist mechanisms to modulate surface phenotypes and functions that are unique to a given subset. In conclusion, we have comprehensively defined the density of multiple molecules expressed by different subsets of monocytes and explored their differences in participants with TB, HIV and TB/HIV co-infection, as well as their correlations with microbial indices and plasma cytokines. Many molecules levels were elevated to some extent in all disease cohorts, but we observed patterns of expression which were particularly elevated in TB (CCR2, CX3CR1, and TLR2), those in HIV (CCR4, CCR5) and those on both (TLR4, PDL1). Molecule-disease associations were either independent of monocyte subset, or most readily revealed in a single monocyte subset. TB/HIV co-infection did not follow a consistent pattern in association with monocytes markers, in some cases more resembling TB, in others HIV, in others neither. Finally, to proof one possible mechanism of association between disease and monocyte phenotype, we explored correlations between monocyte markers and plasma cytokines. We observed significant positive and negative associations, frequently unique to a single monocyte subset or disease cohort, such as TB/HIV co-infected cohort. Collectively, the results imply that there are likely multiple mechanisms involved at many levels regulating the phenotype and function of monocytes, and these differ in different disease states.:Abbreviations ............................................................................................................ 3 Abstract ..................................................................................................................... 4 1. Introduction ........................................................................................................... 6 1.1 Epidemiology of Tuberculosis and Human Immunodeficiency virus ................... 6 1.2 The immunological response to TB and HIV ....................................................... 7 1.2.1 Innate immunity of TB ...................................................................................... 7 1.2.2 Innate immunity of HIV .................................................................................... 11 1.2.3 Immune checkpoint regulation in TB and HIV.................................................. 13 1.3 The role of monocytes in TB, HIV and TB/HIV ................................................... 14 1.3.1 Monocytes ....................................................................................................... 14 1.3.2 Abnormalities of monocytes in TB ................................................................... 15 1.3.3 Abnormalities of monocytes in HIV ................................................................. 16 1.3.4 Abnormalities on monocytes in TB/HIV co-infection ....................................... 17 1.4 The rationale for the thesis ................................................................................ 17 2. Objectives ............................................................................................................ 19 3. Publications .......................................................................................................... 20 4. Summary .............................................................................................................. 65 References ............................................................................................................... 69 Annex I: Author contribution ..................................................................................... 76 Annex II: Declaration of independent writing of the work ......................................... 77 Annex III: Curriculum Vitea ....................................................................................... 78 Annex V: Acknowledgment........................................................................................ 82 Annex VI ................................................................................................................... 84

Bakgrund Hiv är en av vår tids största sjukdomar med miljoner drabbade människor. Att drabbas av obotlig sjukdom påverkar patientens livskvalitet. Som sjuksköterska är det viktigt att ha kunskap om livskvaliteten hos patienter med hiv för att kunna ge en god och individanpassad omvårdnad. Vald teoretisk referensram utgörs av Siri Naess definition av livskvalitet. Syfte Att utifrån Naess definition av livskvalitet beskriva faktorer som påverkar livskvaliteten hos vuxna patienter med hiv. Metod I denna litteraturöversikt lokaliserades nio, relevanta artiklar i databasernaCinahl, Pubmed och PsycINFO som analyserades genom en manifest innehållsanalysoch därefter utgick vi från en deduktiv ansats utifrån Naess (1987) teori om livskvalitet. Resultat Faktorer identifierades och delades in i Naess (1987) definition av livskvalitet. Faktorerna vi kom fram till var till exempel att utbildning, sociala relationer och stöd, depression och stigmatisering påverkade livskvaliteten. Slutsats Livskvalitet är ett komplext begrepp där många faktorer spelar in och samverkar för att patienter med hiv ska känna att de upplever hög livskvalitet. Resultatet erbjuder sjuksköterskan kunskap om vad som påverkar livskvaliteten hos patienter med hiv och kan utifrån detta få ökad möjlighet att förbättra livskvaliteten hos dessa patienter.

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